Brain Cure: Balancing the Brain,

Balances Life

– A model for change for ADD/ADHD, Asperger’s,

Autism, Anxiety, Depression, Panic, Fear, Anger, Bi-
Polar, Chronic Fatigue, Chemical Imbalances and
Mood Disorders

Presented by Dr. Kevin Conners

Presentation from material of Dr. Robert Melillo, Dr. Frederick Carrick,
Dr. Michael Johnson
ADD/ADHD, Asperger’s, Autism, Anxiety, Depression, Panic, Fear, Anger, Bi-
Polar, Chronic Fatigue, Chemical Imbalances and Mood Disorders

Cure: 1. to heal someone 2. to treat successfully 3. to resolve a problem

Neurobehavioral disorders such as listed above, share many features in common, so

many that I and others who treat patients from a neurological perspective see them as a
spectrum or ‘circle’ of one disorder. I have never been in favor of giving patients a
diagnosis anyway; believing that a name given to a collection of symptoms simply
forces one to own the disability, I rather think it wiser to teach the patient to understand
‘why’ the symptoms are present and help them through the process of correcting the
reason they are there. In the past we referred to such neurobehavioral disorders as
Disabilities, Mood Disorders or Chemical Imbalances; currently these terms have fallen
the way of both neurological and political incorrectness.

Anxiety, Depression, Panic, Fear, Anger, Bi-Polar, Chronic Fatigue, Chemical

Imbalances and Mood Disorders fit directly into the same mold as attention deficit
disorder, attention deficit hyperactive disorder, pervasive developmental disorder,
obsessive-compulsive disorder, Asperger’s syndrome, and Autism to name but a few,
and may be viewed as points in a ‘circle’ of developmental disabilities in which those
points share features in common and possibly etiology as well, varying only in severity
and in the primary anatomical region of dysfunctional activity, i.e. the part of the brain
that is effected. I like to view these disorders as points on a circle:

ADD/ADHD

PDD-NOS Depression

OCD Anxiety
Bi-Polar

Panic Attacks Frontal Lobe Paranoia

Disconnect
Asperger’s Autism

Addictions Tourette-like

Dementia Loss of Empathy

Anger issues

As the neurological community currently understands the developmental disabilities of

this circle, let us explore some specific fundamentals:
• A PRIMARY PROBLEM IS IMBALANCE BETWEEN THE TWO HEMISPHERES.
The two halves of the brain are referred to as cerebral and cerebellar
hemispheres. These are separated into ‘lobes’ with particular and distinct
functions. When we are discussing the ‘circle’ listed above, we are mainly talking
about the frontal lobes, the part of the brain most forward, just behind the
forehead. There are common neurological deficits in all the Frontal Lobe
disorders even though patients may still present with different symptoms. The
primary problem relates to the imbalance between both right and left frontal
hemispheres. Normal (asymptomatic) individuals exhibit an asymmetric
distribution of nearly all human functions within the cerebral cortex including
cognitive, motor, sensory, neuro-hormonal, immune, autonomic, and endocrine
functions, i.e. the left side of the brain controls things that the right does not and
visa versa. Failure to develop and maintain this balance of inter-hemispheric
communication or damage affecting such balance between the two hemispheres
results in a form of ‘functional independence’ of each hemisphere. This may
result in high degrees of functioning in specific tasks and a concomitant
lesser function of others. One may term this imbalance of developmental
disabilities as a ‘functional disconnection syndrome’. Additionally, it will be noted
that in these individuals, global functions may not affected, but many specific
functions are decreased while others are enhanced, demonstrating region
specific brain effects.

• MOST CONDITIONS IN THIS CIRCLE OF DISORDERS ARE THE RESULT OF

A RIGHT HEMISHPERE DEFICIENCY. Most Frontal Lobe syndromes can
clearly be related to dysfunction or delay in development of the right hemisphere.
The right hemisphere is under-stimulated resulting in slower temporal processing
within that hemisphere, especially in the frontal and pre-frontal cortex. This
slower processing results, in turn, in decreased effectiveness of the right
hemisphere’s normal executive functions. Decrease in activity has been shown
with modern functional imaging of the brain, which has noted a decreased activity
in the right frontal and pre-frontal cortex with an asymmetric distribution of activity
in the basal ganglia (part of the midbrain) and cerebellum. This right
hemisphericity (right hypo-functioning) may also explain why males are affected
more than females. Almost all of the specific disorders described earlier are
found with significantly greater frequency in males. The frequency ranges from
approximately 6 to 1 in ADD to 50 to 1 in high functioning autistic individuals.
Male brains are more asymmetrical than female brains. Male brains are more
susceptible to prenatal and postnatal influences; these influences, which are
thought to consist of maternal prenatal levels of estrogen, create this left greater
than right cortical development characteristic of male brains. It has been further
noted that abnormal decreases in dopamine have a greater negative affect on
right frontal cortex function than left due to the asymmetrical distribution of
dopamine receptors in the brain (there are more dopamine receptors in the right
frontal lobe, hence, more susceptible to losses).

• ENVIRONMENTAL INFLUENCES CONTRIBUTE TO THE PROBLEM. Some

main factors in causation of frontal lobe disabilities are hypothesized to be
 environmental, especially in the more severely afflicted. Current socially
acceptable behaviors, primarily those which are sedentary, such as a high
proportion of time spent watching television, on the computer or playing video
games (all highly left brain stimulants), are at least a factor for the dramatic
increase in neurobehavioral problems. The human brain is extremely plastic
(moldable, changeable) allowing us to adapt to the environment in which we live.
The window of time for the greatest development is between conception and the
age of six. Motor activities facilitate this brain development, particularly in males.
A dramatic decrease in early motor activity in children will affect development of
gross motor behavior, which is more specific to right hemisphere development,
therefore, decreases in early motor activity equals decrease in right brain
development. In children, the increased use of TV, VCR, computers, game-boys,
and video entertainment coupled with working parents, and parental fears for
their children, all stimulate left-brain growth and lack of right brain stimulation.
Other environmental factors such as poor nutrition, increased poor caloric intake,
environmental toxins, and early sensory deprivation are other important factors.

• ALL OF THESE CONDITIONS ARE VARIATIONS OF THE SAME PROBLEM.

Most developmental disabilities are of similar etiology and are variations of the
same underlying problem. The frontal lobes, cerebellum, basal ganglia, and
thalamus have been implicated in all of these conditions. This has been
documented on static imaging such as CT scans and MRI, as well as functional
imaging such as PET scans and fMRI.

• THESE PROBLEMS ARE CORRECTABLE. As brain organization is plastic,

many aspects of neurobehavioral disorders do not have to result in permanent
impairment. Appropriate forms of environmental stimulation (Brain Based
Therapy) and behavioral modifications (Neural Cognitive Therapy) can
significantly improve or completely correct the underlying problem. Since motor
and cognitive dysfunction often coexist, improving the function of one effect
change in the other. Intervention strategies including Brain-based therapy and
Metabolic Therapy will effect objective change of the two cerebral hemispheres
that is associated with positive change in both the cognitive and motor
symptoms.

• HEMISPHERE SPECIFIC TREATMENT IS THE KEY TO SUCCESS. Besides

increasing motor performance, timing, endurance, and posture, we will finally
address the need for hemisphere specific treatment modalities. Brain Based
Therapy, sensory stimulation, and cognitive functions directed toward the under
functioning hemisphere are the most important consideration in treatment.
Achieving a balance of activity between the two hemispheres is critical for
allowing cognitive and bilateral motor binding to occur, which would reduce
hemispheric neglect (hypofunction). As the hemispheres achieve a normal
coherence and synchronization, motor and cognitive performance will improve.

Numerous investigators have reported that the incidence of autism spectrum disorders
and neurobehavioral developmental disabilities are on the rise (Chakrabarti &
Fombonne, 2001; Case-Smith & Miller, 1999; Fombonne, 1999). It also has been
reported that today’s children, in general, seem to have shorter attention span (Keren et
al., 2001; Chakrabarti & Fombonne, 2001), more impulsive behavior (Chakrabarti &
Fombonne, 2001), and decreasing scores in reading and language skills (Chakrabarti &
Fombonne, 2001) than they had as recently as ten years ago. It appears that these
problems are becoming epidemic.

They have also been noting, both clinically and as reported in the literature, an
increasing number of adult patients being diagnosed with ADD/ADHD, often following
physical trauma, such as an automobile accident (Arcia & Gualtieri, 1994).

Autistic spectrum disorders including ADD, ADHD and autism itself as well as other
learning disabilities are growing at a staggering rate in the United States. In January of
2001, it was reported Newsday, (2001) that 1 in 10 U.S. children have some sort of
mental health problem, but fewer than 1 in 5 of them are being treated. This claim was
made by the then Surgeon General of the United States, David Satcher, and reported in
the same article. Among the conditions that are reportedly under treated, include major
depression, considered one of the most common, attention deficit hyperactive disorder,
and obsessive-compulsive disorder. Satcher stated, “Short of those diagnosable
problems, are problems that children have in their development and functioning very
early.” Satcher proposed a complete overhaul of how mental health in children is
handled from training teachers and doctors, to better recognizing and understand these
disorders, to doing more research and translating that research into effective treatment
programs. Satcher is also quoted as noting, “In any given year it is estimated that fewer
than 1 in 5 of the children suffering from mental illness receive needed treatment.”

In an article in U.S. News and World Report (2000), it was stated that one in every six
children in America suffers from problems such as autism, aggression, dyslexia, and
attention deficit hyperactive disorder. In California, reported cases of autism rose 210
percent from 3,864 to 100,995 between 1987 and 1998. In New York, the number of
children purportedly with learning disabilities jumped 55 percent from 132,000 to
204,000 between 1983 and 1996. "In the past decade, there has been a significant
surge in the number of children diagnosed with autism throughout California,” states the
article. In August 1993 the article continues, "There were 4,911 cases of so-called level-
one autism logged in the state's Department of Developmental Services client-
management system. This figure does not include children with Asperger’s syndrome,
but only those who have received a diagnosis of classic autism. In the mid-'90s, the
caseload started spiraling up. In 1999, the number of clients was more than double what
it had been six years earlier. Then the curve started spiking. July 2001,there were
15,441 clients in the DDS database. Now there are more than seven new cases of
level-one autism - 85 percent of them children - entering the system every day.”

California is not alone. Rates of both classic autism and Asperger’s syndrome are
reportedly rising all over the world, which is certainly a cause for alarm and for the
urgent mobilization of research. Autism was once considered a rare disorder, occurring
in one out of every 10,000 births (Frombonne, 2003). Now it is reportedly more common
- perhaps 20 times more (Chakrabarti & Fombonne, 2001). However, according to local
authorities, the picture in California is particularly bleak in Santa Clara County. Here in
Silicon Valley, family support services provided by the DDS are brokered by the San
Andreas Regional Center, one of 21 such centers in the state.

Drug treatment is not a panacea neither is educational or psychological remediation

approaches. Some parents do not want to use medication because they are rightly
afraid of possible long-term side effects. For others, the medication does not work very
well or at all. While the vast majority of parents feel that psychological therapy is useful,
many report that behavioral interventions did not help their children as much as they
had hoped. They all feel there should be an alternative.

Most individuals with developmental neurobehavioral disorders do not have a good

understanding of the nature of the etiology of their dysfunction. They do not understand
what is “wrong” with their brain and often blame themselves, feel inadequate, and think
of themselves as “bad” people.

Subjective reports from experienced teachers have consistently yielded opinions that
while the ASD spectrum problem might be over diagnosed; there exists a growing
problem among significant numbers of children in their classrooms. Many have
indicated that today’s children are different now than children in their classes 20 or 30
years ago. The teachers claim to see a steady decline in the quality of the children’s
work over the last three decades and this trend seems to have been accelerating within
the past ten years. They find it much more difficult to teach because in today’s
classroom the children have a harder time paying attention or following instructions. The
percentage of children with severe behavioral and language problems is reportedly
increasing (USDHHS, 1997). Many teachers complain that children do not read as
much as earlier generations and their comprehension, when they did read, had
decreased significantly. The most frequent and consistent report of the many teachers
that have been interviewed is that it is harder to get children today to sit still.

The teachers report that at lunchtime they see children line up in the hallway outside the
nurse’s office for their medication. “Years ago,” one of the veteran teachers said, “…
maybe you had one or two children who were hyperactive or with attention problems per
class. Now in many instances, it is almost half the children who have problems.” They
all noted that many of their colleagues were opting for early retirement because they
could not take it any longer and felt ineffectual in their careers. They also believe the
problem is getting worse and they are powerless to change it.

When asked if they knew the basis of these subjectively noted changes in school
behavior the teachers, like many parents report that they do not really understand the
nature of the physiological problems. Teachers appear to be consistently in agreement
with each other. One teacher’s response characteristic of so many others is, “I don’t
know how it works, but I feel children don’t use their muscles as much as they used to.
At lunchtime, children do not play on the playground as they used to. They do not run
around, they just sit or stand there. They seem less physically active. If you drive
around any neighborhood, you do not see children outside. You used to see children
out on their bikes or roller skates, climbing trees or playing ball. You don’t see that any
more. It’s not that there are fewer children, in many cases there are more. They are
inside watching TV, playing Nintendo or computer games.” She continued, “I don’t know
exactly what the relationship is or how it works, but I believe that there is definitely some
connection.”

Another common response from teachers questioned was that teachers reported a
conjectural “cause and effect” relationship between increased developmental problems
and an increased number of children coming from families where both parents work.
Though this is a very ‘sticky subject’ the correlation does exist. They felt that increasing
numbers of children from these families have less parental stimulation and fewer
meaningful interpersonal relationships. Due to time constraints, parents do not talk to
their children as much as they did ten years ago, or read and spend time just being
together. This may even be true when one parent stays home; the stresses of modern
day ‘keep up with the Jones’ mentality and the seeming obsession Americans have with
new cars and the latest toys has changed so dramatically over the past two generations
that it is an oddity for a family to be without a cell phone, ipod, Wii, or the like. Because
of this, the baby-sitter is often the television, video games or the computer, intrinsically
solitary activities, so even talk with other people is greatly decreased. Parents attempt
to compensate for less time with their children by providing more stimulating activities,
or “quality” time between parent and child…just being together and talking and relating
with one another. Right-brain, imaginative play and creative communication falls by the
wayside.

Healey (1990) in her book Endangered Minds,” quotes many interviews with teachers
and some interesting studies with startling statistics. As an educator and administrator
with 30 years experience, she comments that modern children seem to have “changing
brains.” Healey notes that youngsters today seem different than those she used to
teach, even though the average IQ score has remained fairly stable. She became
convinced that the changes are due to the way children are now absorbing and
processing information.

Healey writes, “Children were likable, fun to be with, intuitive, and often amazingly self
aware.” Today, in her estimation, they seem harder to teach, less tuned to verbal
material both spoken and written. She discovered, “many admitted they didn’t read very
much, sometimes even the required homework.” They struggle with or avoid writing
assignments while teachers anguish over the results. One of the teachers she
interviewed stated, “I feel like children have one foot out the door with whatever they are
doing, they are incredibly easily distracted. I think there may have been a shift in the last
five years.” Healey (1990) developed a questionnaire requesting anecdotal information
of cognitive changes observed in students. She handed it out at national meetings and
conferences to experienced teachers working in schools where demographics had
remained relatively stable. Approximately 300 teachers responded and there was
unanimity in response. The consensus was that attention spans had become
perceptibly shorter and reading, writing, and oral language skills seem to be declining,
even in neighborhoods that are more affluent. Additionally, Healy indicated that no
matter how “bright,” students are less able to “bend their minds” around difficult
problems in math, science, and other subjects as they had been able to previously.
Statistics comparing math and science performance of students from Asia, Europe and
the United States, show that students in the US are at the “rock bottom,” particularly in
understanding complex interpretations of data (Healy, 1990). Healey goes on to quote a
cover story in Fortune magazine that indicating, “…In a high tech age where nations
increasingly compete on brain power, American schools are producing an army of
illiterates.”

The scholastic aptitude (SAT) test taken by students who intend to apply for college in
the United States has shown drastically declining scores (Choy, 2002), particularly in
the areas of higher level verbal and reasoning skills. Starting in 1965, the average SAT
verbal and math scores have declined steadily until the mid- 1980’s, where they leveled
off and then experienced a slight rise. Subsequent math scores have remained stable,
but verbal scores have begun another gradual decline. Overall, verbal declines have
been considerably greater, 47 points by 1988 as opposed to 22 for math (Choy, 2002).
In the past, it was shown that children from less privileged educational backgrounds had
poor scores on standardized tests. Recently, scores of minority populations are the only
ones showing consistent improvement, with African American Students in particular
making the most impressive gains (Choy, 2002). This steady decline in standardized
testing scores has occurred in spite of the proliferation of commercial courses that claim
to successfully prepare students for standardized tests like the SAT’s, and it happened
especially in the privileged groups, whose double income parents can afford the
additional expense. Educators agree that for all students, increased television watching
and decreased reading negatively influences verbal and attentional performance of
children (Ruff, et al., 1990; Kagan, 1971; White, 1975; Woody-Ramsey & Miller, 1988).
The National Assessment of Education Progress (NCES, 2001) has reported
deficiencies in higher order reasoning skills, including those necessary for advanced
reading, comprehension, math, and science. The NAEP’s (2001) most recent report
found that only 5 percent of high school graduates could satisfactorily master material
traditionally used at college level. Perhaps, it is no surprise that eighty percent of the
books in the United States are read by about 10 percent of the people. Cullinan (1997)
asked a group of typical fifth graders what percentage of time they spent outside of
school reading. Fifty percent read four minutes a day or less; 30 percent read two
minutes a day or less and 10 percent read nothing. Cullinan remarked that our society is
becoming increasingly “alliterate,” meaning that people know how to read, but choose
not to. Most alliterates watch television for their news and achieve only a superficial
level of understanding. Healey (1990) cites a report of a survey of 443 students entering
community college revealed that 50 percent were reading below ninth grade level. The
New York Times reported in March, 1988 (New York Times, 1988), that youngsters may
“sound out” words better than they used to, but actually understand less (cf. Kamil, et
al., 2000; Pappas & Brown 1987; Pearson, 1986).

Several of the teachers interviewed for by Healy felt that children from every
neighborhood come to class with fewer social skills, less language ability, less ability to
listen, and less motor ability and that in general, a frightening majority of children’s
attention spans have degenerated over recent years. Objective support for these
reported conclusions is supported in the literature by numerous studies (Ruff & Lawson,
1990; Schiffman, 2000; Woody-Ramsey & Miller, 1988). We conclude that sedentary
lifestyles, increased television viewing, and busy parents are major causes of these
dramatic statistical changes in cognitive, motor, and academic performance of present
day western school aged children.

Frontal Lobe discrepancies:

As stated, Anxiety, Depression and the rest of the ASD’s are primarily frontal lobe
disorders. Imbalance between the two hemispheres, a failure of reciprocal
communication, and typically a decrease frequency of firing of the right as compared to
left may be the cause of the collective symptoms. Though there may be many reasons
why this is occurring, from the emotional environment already discussed to the genetic
predisposition to auto-immune responses to metabolic stimuli, correction of the
imbalance must accompany the metabolic correction.

Tannock and Schachar (1996) note, “that there is a growing consensus that the
fundamental problems in (these conditions) are in self-regulation and that (it) is better
conceptualized as an impairment of higher-order cognitive processing known as
(executive function).”

Castallano (1999) also noted “unifying abstraction that currently best encompasses the
faculties principally affected in ADHD has been termed executive function (EF) which is
an evolving concept…. There is no impressive empirical support for its importance in
ADHD.” What is clear in the literature is that the main functions that are affected have
been termed executive functions and it is known that executive functions seem to
primarily reside in the frontal lobes. In fact, ADD is considered a name for a spectrum of
deficits of cognitive executive functions that may respond to similar treatments and are
often comorbid with a wide variety of psychiatric disorders, many of which may also be
spectrum disorders.

According to Brown (1991), this view of ADD as a cluster of attentional/executive

impairments that appear and may persist with or without psychiatric comorbidity is
consistent with Seidmans’ findings from neuropsychological testing of children and
adults with ADD (Seidmans et al., 1995a; 1995b; 1997a; 1997b; 1998).

Hudziack and Todd (1993) also noted that the rates of comorbidity in children for ADHD
and ODD was 35 percent, CD was 50 percent, mood disorders 15 percent-75 percent,
anxiety disorder 25 percent, and learning disabilities 10 percent-92 percent. It has also
been noted that individuals with attention deficit disorder have a significantly increased
probability of having increasingly additional psychiatric disorders (Biederman et al.
1991; Jensen et al. 1997).

Learning Disabilities
Although the relationship between learning disabilities and ADD is not completely
understood, there is nonetheless significant resource that shows significant elevation of
specific learning disorders such as reading disorder, math disorder and disorders of
written expression in individuals who are diagnosed with ADD (Cantwell & Baker, 1991).

OCD, Obsessive-Compulsive Disorder

Numerous authors have noted varying degrees of overlap between OCD and attention
deficit hyperactivity disorder. Percentage overlaps range from 6 percent (Toro et al.,
1992) up to 32 percent and 33 percent (Geller et al. 1995; 1996) respectively.

Tourette’s Syndrome

Most studies developmentally examining Tourette’s syndrome and its comorbidity with
ADHD demonstrate that between 25 and 85 percent of Tourette’s syndrome probands
have comorbid ADHD or ADD (Comings & Comings, 1984; 1985; 1986; 1987; 1988;
Shapiro et al. 1988). Another interesting finding is that in Tourette’s syndrome, as the
severity of symptoms increases, the frequency of comorbid ADD also increases. It has
also been noted that the combined prevalence of Tourette’s syndrome in males was 1 in
1400 and that males with Tourette’s syndrome 27 percent had ADHD, 27 percent had
sleep disorders, 17 percent had conduct disorders, 7 percent had obsessive-compulsive
disorder, 27 percent had repeated a grade, and 24 percent had learning disorder (Caine
et al., 1998). As we had noted earlier, the first signs of Tourette’s syndrome are not
necessarily vocal tics, but rather the diagnosis of ADHD.

PDD, Pervasive Developmental Disorder:

It has been noted that there also is a relationship between of ADD and severe autistic
and/or schizophrenic spectrum disorders (Luteijn et al., 2000). Luteijn and colleagues
examined differences and similarities between social behavior problems in children with
problems classified as pervasive developmental disorder not otherwise specified (PDD-
NOS) and a group of children with problems classified as ADHD, as measured by
parent questionnaires. In comparing the PDD-NOS group and the ADHD group, the
results demonstrated that both groups have severe problems in executing appropriate
social behavior. The two groups could be distinguished only by the nature and the
extent of these problems. Roeyers and colleagues (1998) also investigated early clinical
differences between children with a diagnosis of pervasive developmental disorder not
otherwise specified (PDD-NOS) and children with attention deficit/hyperactivity disorder
(ADHD). A differential diagnosis between the two disorders is often difficult in infancy or
early childhood. Twenty-seven children with PDD-NOS were matched with 27 children
with ADHD as to IQ and chronological age. Their parents were retrospectively
questioned on pre-, peri-, and postnatal complications and on atypical or delayed
development of the children between 0 and 4 years of age. This exploratory study
revealed almost no differences between both groups with respect to pregnancy or birth
complications.

Autism/Asperger’s Syndrome
The similarities between the symptoms and autistic spectrum disorders are actually
significant when one looks at the symptoms associated with ADHD. In fact, when we
examine them, they seem almost identical. It has been noted that autistic individuals
maybe hyperactive, but that they also present with executive dysfunction in attention,
impulsivity, and distractibility. It has also been noted that there is a similarity between
autistic disorder and Asperger’s syndrome and that Asperger’s syndrome goes under
many different types of names, some of the names are semantic-pragmatic disorder,
right hemisphere learning disability, nonverbal learning disability and schizoid disorder.

Much of this confusion has come about by the way we diagnose these problems. We
would like to believe that there is a lab test or an objective test somewhere that confirms
the diagnosis of ADHD, OCD, or Tourette’s; but in fact, the diagnosis is purely
subjective. There are no consistent anatomic or physical markers for these conditions.
Most often, a professional sitting down with a parent or teacher and reading to them a
list of symptoms and checking off if the parent or teacher believes that that the child
manifests the relevant symptoms diagnose these disorders. However, even this process
is not as clear-cut as it sounds. The list of symptoms is extremely vague and many of
these conditions are hard if not impossible to distinguish.

One problem, according to Linda Lotspeich (Lotspeich & Ciaranello, 1993; personal
communication, 2001), Director of the Stanford Pervasive Developmental Disorders
Clinic, is that the rules in the DSM-IV do not work. "The diagnostic criteria are
subjective, like marked impairment in the use of nonverbal behaviors such as eye-to-
eye gaze, facial expression, body posture, and gestures to regulate social interaction."
“How much 'eye-to-eye gaze' do you have to have to be normal?" asks Lotspeich. "How
do you define what 'marked' is? In shades of gray, when does black become white?
What is happening is that a group of symptoms is being called a disorder and if we add
or subtract a few symptoms or make a few more severe, then it is called a different
condition or syndrome. However, when we look at the areas of the brain involved in all
of these conditions, and the neurotransmitter systems involved, they are all basically the
same. Therefore, in reality, these are all possibly the same problem along a spectrum of
severity. The most common of all comorbidities is OCD, developmental coordination
disorder or more simply put “clumsiness” or motor incoordination. In fact, practically all
children in this spectrum have some degree of motor incoordination. The type of
incoordination is also usually the same. It involves primarily the muscles that control gait
and posture or gross motor activity. Sometimes to a lesser degree, we find fine motor
coordination also effected. Although it has been fairly well known that attention deficit
disorders are comorbid with psychiatric disorders such as the ones described above,
what is less known and what is more significant is the association between ADD and
motor controlled dysfunction (clumsiness) or what has been termed as developmental
coordination disorder (American Psychiatric Association, 1994). In the past, motor
clumsiness or OCD have not been looked at as being psychiatric in nature, but rather
being neurological and falling more under the realm of the pediatric neurologist. Motor
control problems were first noted in what was then called the minimal brain dysfunction
syndromes or MBD. BD was the term denoting children that had normal intelligence, but
who had comorbidity of attention deficit and motor dysfunction or “soft” neurological
signs.

Several studies by Denckla and others (Denckla & Rudel, 1978, Denckla et al., 1985;
Wolffet et al., 1990; Gillberg et al., 1982; 1993; Kadesjo & Gillberg, 1998; Landgren et
al., 1996) have shown that comorbidity exists between ADHD and OCD,
dyscoordination or motor perceptual dysfunction. Several Swedish studies have shown
that 50 percent of children with ADHD also had OCD (Brown, 2001).

In a Dutch study, (Hadders-Algar & Touwen, 1992) 15 percent of school age children
were judged to have mild minor neural developmental deviations and another 6 percent
demonstrated severe neural developmental deviations (occurring in boys twice as often
as in girls). Minor developmental deviations were noted to consist of dyscoordination,
fine motor deviations, choreiform movements, and abnormalities of muscle tone.
Researches that have dealt with these minor neural developmental deviations tend to
look at motor dysfunction as a sign of neurological disorder that may be associated with
other problems such as language and perception dysfunction. Motor dyscoordination
has also been noted as a significant sign in autistic spectrum disorders and in
Asperger’s syndrome. In fact, it has been speculated that the type of motor
incoordination might be able to differentiate high functioning autistic HSA individuals
from Asperger’s syndrome individuals (Green et al., 2002; Rutherford et al., 2002;
Gepner & Mestre, 2002). In Asperger’s syndrome, it has been noted that individual’s
have significant degrees of motor incoordination. In fact, in Wing’s original paper, she
noted that the 34 cases that she had diagnosed based on Asperger’s description, “90
percent were poor at games involving motor skill, and sometimes the executive
problems affect their ability to write or draw.” Although, gross motor skills are most
frequently affected, fine motor and specifically graphomotor skills were sometimes
considered significant in Asperger’s syndrome” (Wing, 1988; Wing & Edward, 1987).

Wing (1981) noted that posture, gait, and gesture incoordination was most often seen in
Asperger’s syndrome and that children with classic autism seem not to have the same
degree of balancing and gross motor skill deficits. However, it was also noted that the
agility and gross motor skills in children with autism seem to decrease as they get older
and may eventually present in similar or at the same level as Asperger’s syndrome.

Gillberg (1989) reported clumsiness to be almost universal among children that she had
examined for Asperger’s syndrome. The other symptoms she noted that were
associated with Asperger’s syndrome consisted of severe impairment and social
interaction difficulties, preoccupation with a topic, reliance on routines, pedantic
language, comprehension, and dysfunction of nonverbal communication. In subsequent
work, Gillberg included clumsiness as an essential diagnostic feature of Asperger’s
syndrome (Ehlers & Gillberg, 1993; Gillberg & Gillberg, 1989).

Tandam (1991) noted that 91 percent of the Asperger’s individuals in his study were
deemed clumsy and he reported that the most significant difference between Asperger’s
and not Asperger’s individuals was that ball catching was significantly poor in
Asperger’s individuals. Klime and colleagues (1995) noted that a significantly higher
percentage of Asperger’s rather than non-Asperger’s autistic individuals showed deficits
in both fine and gross motor skills either relative to norms or by clinical judgment. They
further noted that all 21 Asperger’s cases showed gross motor skill deficits, but 19 of
these also had impairment in manual dexterity which seem to suggest that poor
coordination was a general characteristic of Asperger’s. With studies like this, many
researches have looked at fine motor coordinative skills as being disrupted as a general
feature of autistic spectrum disorders. However, when we examine the condition from a
hemispheric perspective, as we will note later, gross motor skill dysfunctions are more
typical of right hemisphere involvement whereas fine motor skill dysfunctions are more
typical of left hemisphere involvement. We will demonstrate later that both classic
autism and Asperger’s syndrome are associated with right hemisphere deficits, and
thereby, would be expected to show a greater involvement of gross motor skill deficits. It
might seem somewhat confusing initially when fine motor skills seem to be disrupted at
almost equal levels. According to a neuropsychological model, this type of weakness
would be more indicative of a left hemisphere deficit. However, when examining the
literature closely, it has been noted (Szatmari et al., 1990) that manual dexterity is less
effective for high functioning autistics than for Asperger’s, but only for the non-dominant
hand. This suggests a lateralized difference. This would show that although fine motor
coordinative skill is decreased, it is decreased in the left hand more specifically, which is
associated with right hemisphere function. This is consistent with a hemispheric
imbalance model and specifically a right hemisphericity.

Manjiviona and Prior (1995) noted that 50 percent of autistics and 67 percent of their
Asperger’s group presented with significant motor impairment as defined by norms on a
test of motor impairment. However, the two autistic subgroups did not differ significantly.

Szatmari and colleagues (1990) also noted that autistic groups did not differ from
Asperger’s groups with respect to dominant hand speeds on type boards although both
were slower than psychiatric controls. Vilensky and associates (1981) analyzed the gait
pattern of a group of children with autism. They used film records and identified gait
abnormalities in these children that were not observed in a controlled group of normally
developing children or in small groups of “hyperactive/aggressive children.” Reported
abnormalities were noted to be similar to those associated with Parkinson’s. Hallet and
colleagues (1993) assessed the gait of five high functioning adults with autism
compared with age matched normal controls. Using a computer assisted video
kinematic technique; they found that gait was atypical in these individuals. The authors
noted that the overall clinical findings were consistent with a cerebellar rather than a
basal ganglionic dysfunction.

The Dopamine Connection:

Neural substrates, which may be especially important in executive function, working

memory, and ADD, are those of the nigrostriatal structures. Crinella and associates
(1997) reported findings from organism studies suggesting that nigrostriatal structures
contribute essential, superordinate control of functions such as shifting mental set,
planning action, and sequencing (i.e., executive functions). As Pennington and
colleagues (1996) pointed out, many developmental disorders may result from a general
change in some aspect of brain development such as neuronal number, structure,
connectivity, neurochemistry, or metabolism. Such a general change could have a
differential impact across different domains of cognition, with more complex aspects of
cognition, such as executive functions, being most vulnerable and other aspects being
less vulnerable. In this same context, Pennington and colleagues noted that the
executive function impairments associated with ADHD and some other developmental
disorders may all involve varying degrees of dopamine depletion in the prefrontal cortex
and in related areas.

In a review of findings from neuroimaging studies of the human brain, Posner and
Raichle (1994, pp. 154-179) showed evidence of at least three anatomic networks that
function separately and together to support various aspects of attention. The possibility
that attention impairments resulting from ADD may be closely related to dopamine
decreases in certain areas of the brain finds support in the numerous studies that have
demonstrated dopaminergic medications (e.g., methylphenidate, dextroamphetamine)
to be effective in alleviating a wide variety of inattention symptoms (see Levy, 1991).
Although noradrenergic medications (e.g., desipramine, nortriptyline) and alpha2-
agonist medications (e.g., clonidine, guanfadine) have been demonstrated to be
effective in alleviating hyperactivity-impulsivity symptoms of ADHD, there is some
evidence that these non-stimulant medications are less effective in alleviating
inattention symptoms (American Academy of Child and Adolescent Psychiatry, 1997;
Levy & Hobbes, 1988; Spencer et al., 1996). These findings suggest that a specific
neurotransmitter system, the dopaminergic system, may play a particularly important
role in inattention symptoms of ADD. Servan-Schreiber and associates (1998)
summarized the research literature on the impact of dopamine on specific neural
networks in human information processing. They developed and tested a model
demonstrating that dopamine has a direct positive effect on the gain in the activation
function of the neural networks underlying attentional processing. Additional evidence
for the critical role of dopamine in management of cognition comes from recent
laboratory studies summarized by Wickelgren (1997), which indicate that in many
species of dopamine plays a critical role in mobilizing attention, facilitating learning, and
motivating behavior that is critical for adaptation. The role of dopamine in facilitating
these functions may be far broader, subtle, and complex than had previously been
thought. Inattention symptoms of ADD may be reflecting impairments resulting primarily
from insufficient functioning of aspects of dopaminergic transmission in the human
brain.

What is the connection between the motor and the cognitive/emotional systems? In the
past, motor areas of the brain were thought to be distinct from areas that control
cognitive functions. However, over the last few years, those lines have blurred
significantly and it is now recognized that areas like the cerebellum and the basal
ganglia influence both motor function and non-motor function as well. Motor and
cognitive functions are closely related. In fact, it is thought that cognitive function, or
what we call thinking, is the internalization of movement and that cognition and
movement are really the same. We will attempt to better understand the connection
between motor control, cognition, and posture and how these connectivity’s may be
involved in learning and its dysfunction as well as in neurobehavioral disorders of
childhood.

Basic Structure of the Brain

• Neurons
• Dendrites
• Axons.

The basic cell or building block of the brain is the neuron. There are at best estimates
anywhere from 30 billions to 100 billions neurons in the human brain (Leisman, 1976a).
By comparison, our nearest relatives, the chimpanzees and gorillas have about 7-8
billion neurons (Nieuwenhuys et al., 1998). There are a few different categories of
neurons, but all areas of the brain are the same. The neuron has two basic jobs to
receive and to transmit information. It does these jobs through what is known as a nerve
impulse. A single neuron can handle as many as 50,000 messages per minute at least
(Leisman, 1976a; McClurkin & Optican, 1996). The neuron consists of a cell body,
which has one nucleus, long fibers at one end called the axons, which transmit
impulses, and short spine-like branches called dendrites, which receive information. The
neuron receives signal in the form of electrochemical impulses and then transmits the
impulse through the neuron by way of the axon ending at branched synaptic terminals.
The impulse can travel along the length of axons at speeds exceeding 100 miles/hour.
The axon comes close, but does not touch the dendrites of neighboring neurons. There
is a small gap or space between the axon and the dendrite known as a synapse. The
neuron has one cell body, but can have many or branches as well as many dendrites to
receive signals. A random section of the human cortex contains an enormous number of
synapses somewhere in the order of 600 millions per cubic millimeter (DeFelipe, 2002).
There are, therefore, estimated to be approximately 1010 synapses in the human
cortex. When one learns something new, one creates new lines of connections between
neurons Koch & Leisman 2000; Leisman & Koch 2000; Squire, 1991). As one increases
the number of connections, one increases the number of glial brain cells. These cells
act like glue to hold brain cells together and they are thought to act like “housekeeping”
cells. They help supply neurons with more energy to do more work and send more
signals.
Figure 2.1: The action potential.
 Figure 2.2: Neuronal function.

Neuron Theory

The ability for a neuron to transmit a message is due to the electrical and chemical properties of the nerve
cell. This is mostly because there is a difference between the electrochemical charges of the extracellular
fluid in reference to the intracellular fluid of the cell. The outside of a neuron carries a positive charge
relative to the inside. This charge is the product of certain ions that have a relatively high concentration
outside the cell. These are mostly sodium Na++ and chloride Cl-. Sodium is the most abundant ion
present in the extracellular fluid, potassium is also present but to a much lesser degree. Sodium carries a
positive charge; therefore, the outside of the cell is relatively positive. The inside of the neuron also
contains electrically charged ions primarily potassium and calcium and to a much lesser degree sodium.
The electrical charges of these ions are primarily positive, but the majority of the inside of the cell consists
of protein, which carries a negative charge.

Protein is the main constituent of the internal organelles as well as the cell membrane and
neurotransmitters. Therefore, the outside of a cell is positive with its main ion being sodium while the
inside is negative due to protein, but the main ion concentration in the intracellular fluid is potassium. The
separation of negative and positive charges across the membrane produces an electrical potential. This
potential in central cells is generally around –65 millivolts. There is approximately a 35:1 concentration of
sodium outside the cell to inside the cell. Potassium has an approximate 10:1 concentration on the inside
relative to the outside. When the difference between the charge of the inside and the outside becomes
less this is known as depolarization. When this becomes low enough it reaches threshold, an action
potential takes place, and a current is propagated down the nerve cell. Whether a nerve cell fires a signal
or not, is a product of incoming signals that cause changes in the relative flow of sodium and potassium
ions across the membrane.

When a cell is stimulated at its terminal end or dendrites, a local change in the
permeability of the cell occurs. If the permeability of the cell favors sodium rushing into
the cell, the cell will move closer to its firing threshold, which is approximately–45
millivolts. If the stimulus changes the permeability of the neuron and favors potassium
rushing out of the cell, the cell becomes hyperpolarized or more negative and it moves
the cell further away from its firing threshold. There are thousands of dendrites on the
end of each cell and they contact thousands of other cells. At any given time in the area
of the dendrite, there are thousands of signals some of which cause sodium to rush in,
depolarizing the cell, bringing it close to the threshold and there are also signals that
hyperpolarize an area of the cell making that area further away from threshold. The
integration of all of these different signals occurs in the cell body of the neuron. It adds
all the positive and negative impulses and assures either that a cell will not fire or
eventually if there is enough sodium rushing in, a wave of this change flows down the
cell body until it reaches an area where the cell body meets the axon. This area is
known as the axon hillock and it is significant because it is much more permeable to
sodium than any other area. In fact, it is approximately seven times more permeable to
sodium than to any other ion. Therefore, when this wave of depolarization makes its
way down the cell body to the axon hillock, there is a sudden rush of sodium in at the
axon hillock, an action potential takes place, and the signal is propagated down the
axon to the terminal end.

When an impulse reaches the end of the axon, spherical bodies called vesicles are
released and fused with the axon membrane. The vesicles then open and release
chemicals called neurotransmitters, which cross the space or synapse and cause the
neighboring cell to then send a signal along its axon. To end the signal, the axon
reabsorbs some neurotransmitters and enzymes in the synapse.

The neurotransmitter specifically contacts receptors on the post-synaptic neuron to take

one of the two actions: either it will cause sodium to rush in or potassium to rush out.
Either it will produce a local excitation of the cell or it will produce local inhibition of the
cell. No single neuronal input triggers an action potential; there is not enough power for
the flow of electrochemical signal to continue. It is the combination of excitation and
inhibition of thousands of synapses that gives the neuron a virtually limitless possibility
of combinations that may affect it. So just as the simple binary system in computing of 0
and 1s give computers tremendous processing capacity, the brain has a related process
of excitation and inhibition.

Plasticity
The brain has approximately 100 billion neurons with trillions of possible connections. It
has been estimated that there are more synaptic connections in one human brain than
there are stars in the known universe. This gives the brain virtually limitless processing
power. There is tremendous variability in this system. There are thousands of different
neurotransmitters, the number of dendrites and connectivities change with activity
(Eccles, 1987; Koch & Leisman, 1990). The type and the density of receptors can be
regulated up or down. Hormones can influence the sensitivity of the cells and/or
neurotransmitters and the number of synaptic connections can vary. The human brain
is extremely plastic, which means it is modifiable based on activity and
experiences. It can change its shape, size, number of branches, and number of
connections as well as the strength of its connections.

There is increasing evidence that the strengths of individual synapses in the different
regions of the human brain are enhanced by repeated activation (Eccles, 1987; Bliss &
Collingridge, 1993; Benke et. al, 1998). This provides strong support of the original
hypothesis by Hebb (1949) that generation of memory, for example, results from such a
process, as do other neuropsychological functions. The hippocampus is known to be
both the seat of short-term memory and the initiator of long-term memory through its
connections to the higher centers of the brain. While the means through which long-
term memory is implanted is not well settled, it is highly likely that recollection of
memories, once they are implanted, is a collective process of integration of information
distributively stored in different regions of the neocortex (Zola-Morgan & Squire 1993).
This idea is reinforced by the direct connections of specialized hippocampal cells (as
seen in recognition tasks in humans (Fried et. al., 1997), "place cells" in rats (Muller,
1996) and "spatial view" cells in primates (Rolls et. al., 1998)) to specific cortical areas
(Eccles, 1987; Zola-Morgan & Squire 1993).

Neurons in the brain are interconnected with many other neurons and, in turn, each
neuron receives input from many synapses of its dendrites and cell body. The resulting
neuronal loops according to Hebb (1980) contain neurons whose output signal may be
either excitatory or inhibitory. Although the neuronal loops are usually drawn as though
they were in the cortex, many of the loops probably run from the cortex to the thalamus
or other subcortical structures and back to the cortex. Because each neuron is thought
to both send and receive thousands of outputs and inputs, the number of possible
neuronal loops is truly immense.

In Hebb’s (1949, 1980) theory, each psychologically important event, whether a

sensation, percept, memory, thought, or emotion, is conceived to be the result of activity
flow in a given neuronal loop. Hebb proposed that the synapses in a particular path
become functionally connected to form a cell assembly. In Hebb’s view, the most
probable way in which one cell could become more capable of firing another is that
synaptic knobs grow or become more functional, increasing the area of contact between
the afferent axon and efferent cell body and dendrites.

Hebb assumed that if two neurons are excited together, they become linked
functionally. In Hebb’s view, the cell assembly is a system that is initially organized by a
particular sensory event but is capable of continuing its activity after the stimulation has
ceased. Hebb proposed that to produce functional changes in synaptic transmission,
the cell assembly must be repeatedly activated. After the initial sensory input, the
assembly would therefore reverberate. Repeated reverberations could then produce the
structural changes. Clearly this conception of information storage could explain the
phenomenon of short- and long-term memory: short-term memory is reverberation of
the closed loops of cell assemblies; long-term memory is more structural, a lasting
change in synaptic connections.

The magnitude of the post-synaptic response can be compared with the original
baseline and the time course of the decay of changes in response magnitude can be
measured as well. Two significant findings emerged from this study. First, response
magnitude markedly increased immediately after the high frequency stimulation. This
increase declined over time and returned to baseline. The rate of decline depends on
the details of stimulation. This short-term increase is called post-tetanic potentiation.
Second, the changes in response magnitude may not decline to baseline but instead
remain elevated, possibly for days or as long as is practical to measure it. This has
been called Long-Term Potentiation (LTP). In some cases, LTP may be present after
two months and Barnes (1988) has shown that LTP is prolonged by occasional
repetition of the high-frequency stimulation. The original studies of LTP were performed
on the hippocampus, but these phenomena can be demonstrated elsewhere in the
brain.

In addition, they have shown that there is a qualitative change in the synapses,
presumably including not only new ones but also existing ones that have been changed
by experience. These include changes in the size of various synaptic components, in
vesicle numbers, in the size of post-synaptic thickenings, and in the size of the dendritic
spines. (For a more complete review see Greenough & Chang, 1985.) Similar changes
have also been found in neurons exhibiting LTP, thus adding evidence that LTP may be
an analogue of normal learning.

With any stimulus to the cell, there is the activation of cellular immediate-early-gene
responses. These genetic responses regulate the production of protooncogenes that
are the precursors to the production of proteins within the cell. When the cell is
stimulated, it will produce more protein for production of membrane, neurotransmitters,
and organelles, like mitochondria. The increased protein makes the intracellular fluid
more negative and maintains a polarized state. This is important because neurons work
best when there is a clear delineation when the cell is “on” or “off.” This is also known as
signal-to-noise ratio; brain cells should have a high signal to noise ratio. Cells that do
not have a clear separation between activation and rest are thought to be “jumpy.” Cells
that are “jumpy” are much more likely to fire spontaneously as in epileptiform activity.
They also may fatigue or reach oxidative stress levels more quickly, where they may
cease to work, or they may produce free radicals, which can permanently damage or kill
the cell. The mitochondria provide more energy in the form of ATP, which gives the cell
the ability to work for longer periods before fatigue. The proteins that are formed are
also used to increase the density of dendritic spines, axonal branches, as well as
receptors on the membrane of the cell. These changes can increase the size and
density of the cell and the brain as a whole.

The most significant factors in plasticity are the frequency and duration of activation of
the cell. Integration at the neuronal level occurs because of a process known as
summation. Temporal summation occurs when the same input is triggered repeatedly
so that stimulus threshold is lowered to permit the cell to fire. Spatial summation results
when sufficiently different dendritic spines are stimulated simultaneously, so that firing
threshold is reached. In spatial summation, the more contacts that activate the cell
simultaneously, the greater likelihood the cell will depolarize enough to produce an
action potential. Temporal summation concerns the speed at which e contacts fire. Each
time a wave of polarization passes through the cell, it will degrade in approximately 15
msec. However, if we activate that cell before it degrades, we can then super add that
wave on top of previous waves.

Growth of the Human Brain

The human brain is extremely consistent in terms of its cellular makeup. The fact that
the brain cells are made up of the same basic cell structure in all areas is one of its
most striking features. Therefore, what is true for one brain cell is true for all brain cells
in all areas of the brain.

In order to function and grow, brain cells need two things. One is fuel in the form of
oxygen and glucose; and the second is stimulation. However, increasing fuel alone
does not cause brain cells to grow; only stimulation does. As the brain cells grow in
size, they require more fuel to have the ability to do more work. If we supply our brain
cells with an abundance of fuel in the form of oxygen and glucose, but fail to
stimulate it, the brain cells degenerate and die. Therefore, the most important
element in growth of brain cells, and the growth of the brain itself, is based on
increased stimulation. The most important aspect of stimulation is frequency, which
means that the more often a brain cell is stimulated the more it will grow (Snyder et al.,
2001; Sommer et al., 2002; Gemmell & O'Mara, 2002).

The human brain is larger than that of any other land mammal relative to body size.
What makes our brain truly unique is not just size, but its structure. The anatomy of our
brain is similar to that of primates, with the exception of our cerebral cortex and
cerebellum. Although we have an increased number of neurons in the human brain, the
increase in neurons is due to the brain’s greater size, not greater density. Humans have
only about 1.25 as many neurons per cubic centimeter as chimpanzees do
(Nieuwenhuys, 1998).

There are approximately 146,000 neurons per square millimeter of cortical surface. The
human brain has an area about 2,200 square centimeters and about thirty billion
neurons. Chimpanzees have brains that measure about five hundred square
centimeters with about six billion neurons. Gross anatomical examination shows that the
cerebral cortex is significantly larger and more complex in man than in the rest of
primates. This is accompanied with major changes in connectivities, especially the high
development of cortical projections (Nieuwenhuys, 1998). However, in contrast,
subcortical structures do not appear to achieve the same level of specialization in man,
although there are concurrent increases in areas of the cerebellum, thalamus, and basal
ganglia.

The human brain is about four times larger than those of primates, because the brain
cells or neurons are spread about (Blinkov & Glezer, 1968; Nieuwenhuys, et al., 1998).
The thicker cortices of the large mammals and humans as well, seem to be primarily a
function of larger nerve cell bodies, and more extensive dendritic and axonal systems,
and more numerous glial cells. Although neurons cannot reproduce after birth, glial cells
can. They reproduce based on increased metabolic demand of the neurons or
increased stimulation. This increase in growth of glial cells allows the neurons to make
more connections, which increases the ability and speed of the cell to transmit signal.
The increase in size and strength of connections allows both to happen more efficiently.
The growth and size and complexity of the human brain comes from the number of
supporting cells which in essence, feeds the neurons with more fuel and encourages
growth of new connections. It is not the increased number of neurons, but the increase
in connections between the cells and the increase in separating and supporting cells
that accounts for the large growth of the human brain. This is the very definition of
“plasticity.”

Plasticity is the ability of the brain to grow and whether it is growing on a short-term
basis or on a long-term basis. This can only mean that there was some increase in the
frequency, duration, and intensity of stimulation of the human brain over time for it to
have been created to have as uniquely as it has. There are two things that make
humans unique among other organisms: 1) we have a larger cortex and, 2) we stand
upright (bipedal). Assuming what we have thus far indicated is so, we must then
determine the source of the hypothesized increase in stimulation that may have created
the human brain as it now is and how is it relates to bipedalism?

Although the brain does provide itself with certain intense stimuli (e.g. dreams), when it
comes to functioning in the real world, the brain is a stimulus-based system. It is
dependent on outside sources for stimulation. Outside sources are the natural
environmental stimuli that are available: light, sound or vibration, odor or smells, food
and liquids for taste, heat and cold for temperature, and pressure or gravity for touch.
These are known as sensory input. We call the ability to use sensory input “senses,” of
which there are many.
One of these senses, proprioception is the ability to be aware of one’s body position in
space body movements in relation to gravity to be aware of body movement in
relationship to itself. This information is collected from the environment in specialized
structures known as mechanoreceptors. They are called receptors because they
receive information. Receptors are specific (for the most part) for different forms of
environmental stimuli. The retina has light receptors, rods, and cones; our ears possess
sound receptors, hair cells, and our joints and muscles possess receptors for movement
and gravity.

The more densely populated the receptor in an area, the more information or stimulation
can be collected from that area. These receptors are like buttons that are pushed by
environmental stimuli. Once the buttons are pushed, they send information through the
nerves to the spinal cord and up to the brainstem, cerebellum, thalamus, and ultimately
the cortex itself. The brain cells are then stimulated and the signal processed to decide
the best response to the environmental stimulus. The more a brain cell is stimulated the
more it will increase its size and strengthen its connections and the more supporting
cells will be produced (Ding et al., 2002; Chen et al., 2002; Carlen et al., 2002).

Three factors cause brain growth. The first is frequency of stimulation or how often
a cell is stimulated. The next is duration of stimulation, and the last is intensity or
how much stimulation the cells receive. Therefore, the impulses that stimulate the
cell most frequently, for the longest period of time, and the greatest degree of intensity
will have the greatest affect on the growth of the cells and the brain.

Most environmental stimuli are not constant, not always available to stimulate the brain
in the same way. Light, sound, taste, and temperature are all of variable frequency,
duration, and intensity. For example, sunlight is only present during the day. The only
constant source of stimulation from the environment is gravity. We live in what is known
as IG environment. We are compelled to resist gravity by using our muscles and joints
continuously because that is where the receptors for gravity and/or proprioception are
located. Because gravity steadily exerts force on us, and because we are perpetually
forced to resist it by using muscles and joints, the amount of time it stimulates our brain
based on frequency and duration is much greater than that of any other stimulus. Every
movement one make stimulates the brain. Simply standing upright involves responses
that not only allows us to see further, but also requires us to constantly resist gravity,
even when we are standing still. This simple condition steadfastly increases stimulation
to our brain therefore, accelerating its growth.

Receptors are not evenly distributed in all muscles and joints. Certain muscles and
joints have a greater density of receptors and therefore, supply a greater amount of
stimulation to the brain. Standing upright may well have been the single most important
act responsible for increasing our brain size. The greatest concentration of receptors in
human muscles and joints is found along the spine; the closer to the top of the spine, or
head, the greater the density of receptors in our muscles and joints. Imagine how
suddenly moving from a quadrupedal stance to standing erect would shift the degree of
gravitational force on our muscle and joint receptors up to the top of the spine where the
most receptors are located. In fact, Sperry (1964) has stated that it has been shown that
“…90 percent of the stimulation and nutrition to the brain is generated by the movement
of the spine. Kind of like a windmill generating electricity.” Envision how that enables us
to harness gravitational forces to an even greater degree and constantly increase the
stimulation to our brain cells. We have not only increased the frequency and duration of
stimulus, but we also significantly increased the intensity of stimulus. This is a
significant and dramatic increase beyond creatures that walk on all fours most of the
time.

Of all mammals, we exhibit the most dramatic increase in brain growth immediately after
birth, and we experience the longest interval of infantile helplessness. No other species
of mammals more than doubles its brain size by its first birthday, and no other species
requires fifteen months to begin to walk without parental support. The resemblance
between a human and a juvenile chimp, our relatively flat face, weak brow, and tall
forehead are among the juvenile traits of our ancestors that we retain into adulthood. In
fact, the proportions of fossil skulls of unknown gender reveal that Homo rodolfensis
had a much larger brain than this. The adult fossil skulls of this species had an
estimated capacity of 760 cubic centimeters (Ramirez Rozzi, 1998). This is quite large
compared to estimates for various skulls of Australopithecus, which range from about
430 to 485 cubic centimeters. A portion of another fossil skull of Homo rodolfensis,
points to an even larger brain size this hominid. Although this is only a large fragment of
skull, we can see that it belonged to a very small child with a very large brain. The
skull's cranial capacity, though not precisely measurable, would have approached 900
cubic centimeters in adulthood. While this adult figure is roughly 30 percent below the
modern human average (1,220 cubic centimeters for women and 1,420 for men), it is
nearly twice as large as the average estimate for skulls of Australopithecus. A delay of
the developmental process was probably the only mechanism by which evolution could
have produced the dramatic human encephalization. By using this mechanism, natural
selection made use of a pattern of growth the high rate of brain growth in utero that was
already present in the ancestral organism. All that was required was a change in timing.

Biomechanically, it was the change in the development of our spinal muscles and the
orientation of our spinal joints, as well as the hips, knees and feet that allowed us to
stand up. In doing this, the amount of gravitational force distributed through the joints
and muscles increased dramatically and therefore increased the stimulation to the brain.

If we look at the brain as a greedy master that will do anything to increase its own
stimulation and growth and that standing upright will maximally accomplish this, we can
see that the brain would augment the muscles it controls so that it can better
accommodate the upright position and increase its own stimulation, which in turn gives
it the ability for superior movement.

Effects of Gravity
Within short periods of time, when a human is not under the constant force of gravity, as
he is when in outer space, the body and all of its systems, especially the brain,
dysfunction significantly (Bock et al., 2001; Baroni et al., 2001; Casler & Cook, 1999).
There is a breakdown of the spinal muscles and the curves of the spine (Whalen, 1993).
In reported cases of “space dyslexia,” astronauts describe the same symptoms that we
see in children with Attention Deficit Hyperactive Disorder and other learning disabilities
and cognitive processing problems (Eddy et al., 1998; Casler & Cook, 1999). Humans
cannot survive for very long without gravity, whether in space, underwater, or lying in
bed. The results and the damage are similar. All of the physiological changes that we
see in astronauts, we also see in people who are in extended bed rest.

Organisms that have been sent up in space showed rapid and significant degeneration
of brain cells (Kosik, 1998; Holstein et al., 1999; D’Amelio et al., 1998a). The rats from
the University of California at Berkeley (D’Amelio et al., 1998b) showed increased
plasticity and growth of the brain when they used their muscles and joints in “novel and
interesting ways.” When the same type of rat goes into space however, they have
reverse plasticity and show rapid degeneration of their brain cells. It does not take more
than a small leap to understand that a child who is sedentary most of the time or who is
sitting in front of the television for several hours a day, is not maximizing his or her use
of gravity as a stimulus.

It is only in the past few decades that we see the development of sedentary
entertainment, such as television, computers, and computer games. As we become
more sedentary, there results a breakdown of the muscles and joints that allow us to
stand upright, the very action that enabled us to climb down from the trees. We see an
increase in spinal related disorders such as low back pain, neck pain, headaches, and
herniated disks. Low back surgeries because of back injuries have increased
dramatically over the past several years, probably due to the latest technology that
makes such surgery possible. Most of the ailments that we have today are life-style
diseases that are brought on by sedentary activity.

Most stimulation to the brain comes from muscles and joints, especially from the
postural muscles in the form of unconscious touch or proprioception. The source of this
stimulation is gravity, which is the only constant source of stimulation in our
environment. We discussed how changes in the genetic production of cells increased
the pool of cells in the early hominid brain, but required activation and increased
connectivities in order to survive. The bipedal posture of early hominids required a
larger cerebellum and cortex to coordinate and control this movement. This increased
size most likely provided new cortical cells with available connection sites. The cortical
cells also connected to other cortical cells forming association areas in the brain, which
in turn allowed for better cross communication and intra- and inter-hemisphericity.

For years, it was thought that areas of the brain, which control cognitive function, were
completely separate from areas that were responsible for motor function. Areas like the
cerebellum and basal ganglia were always considered purely motor areas of the brain
even the frontal lobes, where both cognitive and motor control have been known to
reside, were still not considered to be directly connected to each another. More recently,
however, it has been recognized that these areas have non-motor functions, every bit
as important as their motor functions that allow them to produce and control cognitive
and emotional behaviors as well as motor behaviors. This is important to note because
it is these very motor areas along with the frontal lobe of the cortex that seem to be
malfunctioning or developmentally delayed in many neurobehavioral disorders of
childhood.

This concept of interaction between motor and cognitive function has great clinical
implications for the diagnosis and treatment of these disorders. Motor dyscoordination,
especially of gait and posture, is the most consistent comorbid condition associated with
this spectrum of disorders. It tends to reason then that if we can administer therapeutic
intervention strategies to improve motor function and consequently improve the function
of motor areas of the brain we should thereby expect improvement in the cognitive
and/or behavioral abilities of the child as well.

In the late 19th century and early 20th centuries, there were two different opinions in
regard to execution of movements. The first proposed by William James was that
movement was reflexive dependent solely on the inputs from the sensory system.
Movement was thought to be driven and in response to sensory cues. Gram Brown
(1911; 1914; 1915) thought that movement was intrinsically generated, even in the
absence of sensory input, and that sensory input helps to modulate movement, but was
not necessary for the act of movement. He proposed that there were areas in the spinal
cord that acted as “pattern generators” that produce the ability to walk. Therefore, these
areas would initiate walking and sensory input was needed to modify walking so that we
did not fall. More recently, research has confirmed his initial observations that areas
within the brainstem and spinal cord are the basis of breathing and locomotion in
vertebrates (Kandel & Schwartz, 1991).

Llinas (2001) has proposed that in his conception, sensory input provides the specifics
of ongoing cognitive states or the context rather than the content. Therefore, the
importance of sensory information depends on the pre-existing environment of the brain
itself. Organisms must move in an intelligent way for movement to be beneficial to them.
The nervous system been created to have to provide organisms with a goal-oriented
plan that would make short-term prediction based on ongoing sensory input possible.
This allows the organism to move in a specific direction based on a sensory-motor
image. The concepts of corollary discharge, efference copies, spatial maps, contingent
negative variation, and expectancy, while beyond the scope of this section, speak to our
abilities as humans to predict what is likely to happen next in sensory-motor interaction
(Sommer & Wurtz, 2002; Leisman, 1976a; 1978; Robinson & Wurtz, 1976; Johnstone &
Mark, 1973; Evarts, 1971). It is precisely through these processes that we are capable
of descending a staircase without looking. We are capable of predicting the next likely
movement necessary by assuming something about the riser height of each step. When
we look at our feet, the motor programs that predict the next step need to be restarted.
The same mechanism also hold true in reading a printed page. Our eyes jump from
phrase to phrase until they reach the end of the line. The eyes then jump to the left
hand margin and overshoot the left-justified text, but only once; from then on, our eyes
successfully hit the left hand margin precisely each time.

The next critical point is an understanding of how the brain can perform prediction. In
prediction, the organism must anticipate the outcome of the movement depending on
sensory cues. A change in the environment must initiate an action or movement
(approach or withdrawal) for survival. Llinas states that this ability to predict the
outcome of future events, which is critical for successful movement, is the ultimate and
most common of all global brain functions. For prediction to be effective, it must be
centralized, which is what is thought to be the “self.” The nervous system to be able to
predict must first quickly compare all sensory input to gain an image of the world and it
must then convert this pre-motor image in to a specific movement strategy. However,
for prediction to be efficient, it cannot compare all sensory input and movement
possibilities at once. This would require too much time, processing space, and energy in
the brain. To understand how predictions been created to have coincidently with more
complex movement, we must understand how the control of movement takes place.

Even the most basic movement utilizes most of the body's muscles, which result in an
astronomical number of possible simultaneous or sequential muscle contractions and
directions. Llinas states that even the simple act of reaching for a carton of milk,
requires 10-15 combinations of muscle contractions. Along with this, there must be
1018 decisions that need to be made every second. This is obviously not feasible, as
this would overload the capacity of our brain. In addition, if the brain is required to be
“online” 100 percent of the time during movement this would put a tremendous strain,
both energetically and computationally, on the brain. The solution to these problems is
to have a system where movements are not continuous, but are made up of a series of
smaller movements that are synchronized. Movement would be discontinuous or
pulsatile, therefore the system would be online less, and it would turn off and on in
specific discrete timeframes. This is in fact the way that our movements take place. his
has been known since Shaffer (1886) realized that there is a clearly defined rhythmic
movement in adults at 8-13 Hz that exists in volitional movement (cf. Condon & Ogston,
1966; Condon & Sander, 1974; Leisman & Leisman, 1989). This has come to be known
as the physiological tremor and it takes place in all adult muscles at a rate of
approximately 8-13 times per second. This tremor is present not only during voluntary
movement, but also largely in either maintaining posture or at rest.

It is thought that these “rhythmic oscillation of muscles” allows for a mutual

synchronization involved in rhythmic movements, which is the basis of all movements.
In addition, voluntary movements occur in the direction of the phase of the tremor
(Condon, 1966; Leisman & Leisman, 1989), therefore it is simply an exaggeration of the
pre-existing movement. This pulsatile movement reduces the work overhead of the
nervous system. It brings in line a population of independent muscles, so that they may
act in a uniform fashion and it provides an inertial break to overcome frictional forces of
the muscle. It also allows for input and output to be bound in time. This allows the
sensory input and motor activity to be bound and integrated in the same system. As we
can see, evolution provided a brilliant solution. It was further shown that these pulsatile
movements were not based on an inherent property of muscle tissue itself, but rather a
reflection of a higher descending command from the brain. This pulsatile system brings
neurons and muscles closer to threshold for a particular action. This is thought to
compensate for the potential problems of discontinuities or choppy because there is a
synchronizing effect in all the independent parts and at all levels of the motor system.
This pulsatile activity occurs so quickly that it appears to any outside observer that our
movement is continuous and smooth even though it is actually discontinuous. Although
this physiological tremor is a reflection of a descending control system in the brain, it
does not spread out that way. Developmentally, the tremor is an intrinsic property of the
muscle itself. This is known as the myogenic movement of motricity, which takes place
before motor neurons even make contact with the muscles.

Let us examine this further Llinas uses the example of elasmobranchs (sharks). The
shark embryo is in an egg that allows oxygen to pass through. As the oxygen is
distributed evenly to all the tissues, there must be continuous movement of the fluid in
the egg, so the embryo must continually move rhythmically. However, at this point,
movement is not generated by the nervous system, in fact the muscle cells are not yet
innervated by motor neurons. At this stage of development, the muscle cells are
electrically coupled in a way similar to the nodal tissue of the heart.

In this way, the electrical signal that causes contraction of a single cell spreads easily
and quickly from one cell to the other produces rhythmic movements within the
organism, the myogenic stage of motricity. In the next stage of development, the spinal
cord begins sending axons from the motor neurons to innervate muscle cells. At this
point, the motor neurons in the spinal cord become electrotonically coupled. As they
innervate the muscle cells, the muscle cells cease being electrotonically coupled and
now movement is purely under control of motor neurons in the spinal cord. At this stage,
the movement of the muscle mass has been embedded in to the spinal cord known as
the stage of neurogenic motricity. Therefore, the capacity of the organism to interact
with its external environment has begun to be internalized in a nervous system. The
spinal cord motor neurons stay electrotonically coupled until the brainstem, which now
has become electrotonically coupled and makes its connection with spinal cord motor
neurons. At this point, the motor neurons in the spinal cord cease to be coupled as they
start to be innervated by other inputs of the nervous system that do not relate to specific
activities of muscle groups. These inputs relate to the total movement of the organism
as a whole and involve the vestibular system. These other inputs allow the organism to
relate its movement to a frame of reference outside of its own body, such as gravity, so
the organism starts to “think“ left and right, and up and down.

The next stage of development is encephalization. When the brain matures, the
organism starts to move forward along its long axis. In the front are developed
telereceptive sensory systems such as vision, hearing, and olfaction. At the front end, it
develops jaws and its head with a brain and skull for protection. The excretions of the
organism exit the rear in the opposite direction of the organism's forward movement.
Through these stages, we see that the organism take the initial properties of the muscle
and the outside world and internalize them, eventually projecting them up to the brain.
Most importantly, as Llinas states, this process gives us “the ability to think, which
arises from the internalization of movement.” “Thinking was the central event born out of
an increasing number of successful possible motor strategies. The issue is that thinking
ultimately represents movement, not just of body parts or of objects in the external
world, but of perceptions and complex ideas as well.” The next solution that evolution
developed to reduce energy and computational demands on the nervous system was to
use muscle collectives. The muscle collective is a group of muscles that are activated
simultaneously as when we pick up a carton of milk. If the brain moves groups of
muscles rather than individual muscles, the demand on the brain is significantly
reduced. The central control system during complex movement must then use muscle
collectives as necessary, transiently, and rapidly. Therefore, the brain must have an
area that can choose from a list of various muscle collectives that is efficient and
successful so that it does not waste time and energy on useless movements. We will
later examine the basal ganglia, the area of the brain that aids in controlling muscle
collectives or fixed actions patterns. We will see that these properties of the brain help
to more efficiently control movement and especially prediction, so that all these
properties can be understood as a single construct using cognitive binding or conscious
thought.

Specific areas of the brain, such as the inferior olive, have been created to have as
controller systems. In regard to controlling timing mechanisms or pacemaker activity,
these areas must possess oscillatory neuronal activities of individual cells as well as
oscillatory ensemble activity where a large group of neurons oscillate simultaneously
and they need to be functions associated closely with movement. Many types of
neurons in the nervous system are imparted with the ability to oscillate. Oscillations are
made up of ordinary volleys of nerve impulses that have been [previously discussed.
However, there is a different element that regularly repeats these impulses in the form
of bursts and the bursts repeat as well. These bursts are superimposed on an oscillating
generating system or “pacemaker” that causes a slow fluctuation in the membrane
potential of the neuron (Changeux, 1980; 1981; 1982; 1983; Eccles, 1987; Koch &
Leisman, 1990; 1996; 2001).

The membrane potential oscillates between two extreme values on either side of the
threshold for the nerve impulse. When the potential reaches the threshold an impulse is
generated and then repeats as long as the potential remains above threshold. If it falls
below threshold, the impulse stops, as does the burst. The pacemaker itself is a product
of two different molecular channels (Kandel & Schwartz, 1995). These channels open
slowly over several seconds and do so differently than channels involved in the
propagation of a typical nerve impulse, which acts over milliseconds. Additionally, their
selective permeability to ions is different from other type of channels. One is permeable
to potassium and the other to calcium. At the start of an oscillation, the electrical
potential decreases and consequently, the calcium channel, which is slow, opens.
Calcium then enters the cell, but before being pumped out again, it produces and opens
the other slow channel, which is specific for potassium. At this point, potassium leaves
the cell and in leaving the cell, it causes an increase in potential (Kandel & Schwartz,
1995). At this point, we are back to beginning of the oscillation. In this case, the
membrane potential oscillates slowly. If the oscillation is of sufficient amplitude for the
membrane potential to reach threshold for a nerve impulse, a burst will form on the crest
of each slow oscillation. Neuronal oscillators are regulated as much by the membrane
potential as by the internal calcium concentration (Changeux, 1985).

According to Llinas (2001), the peaks and valleys of the electrical oscillations of neurons
can dictate the waxing and waning of the cell’s responsiveness to incoming synaptic
signals. It may determine at any moment in time whether the cell chooses to “’hear’ and
respond to incoming electrical signal or ignore it.” Another property that is close in
relationship to neuronal oscillation is coherent rhythmicity and resonance. Neurons that
produce rhythmic oscillatory activity may entrain to each other through action potentials.
This then can produce neuronal groups that oscillate in phase or coherently which help
to support simultaneity of activity. There are several areas and groups of central nuclei,
such as the inferior olivary nucleus (IO), that plays an important role in the coordination
of movement.

In the case of the inferior olive, its neurons connect to the cerebellum. The fibers from
the inferior olivary nucleus branch project onto the main neurons of the Purkinje cells of
the cerebellar cortex. The connections are made through climbing fibers and connect to
the dendrites of the Purkinje cells. Most movement control processing occurs in the
cerebellum and the climbing fibers, which are some of the most powerful synaptic inputs
in the vertebrate central nervous system, playing an important role in that motor control
(Eccles et al., 1987). Damage to the inferior olive or to the climbing fibers causes
immediate severe and irreversible termination of many aspects of motor coordination,
especially timing of movement and in movements through three-dimensional space.

It has been shown that the inferior olive plays such an important role in timing that
organisms with damage to these nuclei have problems learning new motor behaviors
(Welsh et al., 1995; Welsh 1998). Intracellular recordings from cells in the IO have
shown that these cells oscillate spontaneously at 8-13 Hz. The IO cells fire their action
potential in a rhythmic fashion and it is thought that through its connection to the
cerebellum the IO is responsible for the timing signal that helps to control all
movements. It is thought that the oscillation of the inferior olive results in a slight tremor
of 10 Hz and occurs even when one is not moving (Llinas et al., 1975). This movement,
as previously described, is known as physiological tremor, allowing us to time
movements as a metronome, when we learn to play the piano. It also has been
demonstrated that with the experimental destruction of IO, behavioral tremor is
abolished (Llinas et al., 1975).

A similar type of timing mechanism is found in the cerebral cortex to help generate
conscious thought. We require a mechanism with which we will be able to bind
information from different sensory sources, so that the essential result will be an internal
representation or sensory motor image that can associate memories or thoughts with
this internal construct such as imagining or remembering. As Llinas (2001) states, the
task of cognition is to create an experience, which brings together elements that are
truly ours with elements that are truly foreign. This same oscillatory function occurs in
the brain and produces temporal coherence (Leisman, 1976a; 2002). Temporal
coherence according to Llinas is thought to be the neurological mechanism that
underlies perceptual unity, the binding together of independently derived sensory
information, or cognitive binding. This is a mechanism similar to that produced in motor
binding where through the inferior olive motricity precise temporal activation of muscles
is required in order to implement even the simplest movement correctly. Synchronous
activation of neurons that are spatially distant is most likely the mechanism that
improves the efficiency of the brain. Fixed action patterns set well-defined motor
patterns. This has been described as motor tapes or engrams that produce well-defined
and coordinated movements such as walking and swallowing. These patterns are called
fixed because they are stereotyped and relatively unchanged not only from individual to
individual, but within the species. These patterns, however, can be seen as simple or
complex motor patterns.

The fixed action patterns are seen as more elaborate reflexes that seem to group
lower reflexes together to achieve a more complex goal-oriented behavior (Leisman &
Koch, 2003). This allows the brain freedom efficiency and diminishes processing
capacity as the brain does not need to focus time and attention on each aspect of the
specific movement, only when it needs to modulate that movement due to change in
repetition. In other words, fixed action patterns allow the brain time to do and “think”
about other things rather than concentrate on a specific stereotyped movement. Fixed
action pattern are more sophisticated than simply the control mechanisms for walking,
which can be controlled by the brainstem and the spinal cord. Therefore, fixed action
patterns are thought to reside in the higher centers of the brain.

In the case of more complex fixed action patterns like playing an instrument, throwing a
ball, swinging a bat, it is thought that these are generated centrally by the basal ganglia
(Saint-Cyr et al., 1995; Hikosaka, 1998). It is thought that the basal ganglia acts as a
storehouse of motor programs, but how it actually works is not understood. As within the
cerebellum, the majority of connections within the basal ganglia are inhibitory and have
many reciprocal contacts. Neural pathology of these nuclei may be due to either
producing an excess of fixed action patterns thought to be seen in Tourette’s syndrome
or defect associated with loss of them as in Parkinson’s syndrome.

Very importantly, fixed action patterns have been created to have to improve the
survivability of organisms. A correct choice needs to be made and made quickly and
repetitively for an organism to move through the world successfully. Natural selection
has finely tuned this process and given us a mechanism in which can reduce the
possible alternatives. The underlying basis of movement is built around conflicting
alternatives such as approach-avoidance or approach-approach behaviors. These
potential conflicts require too much time to decide whether to approach or especially
avoid a predator. Significant decision time will not only prove inefficient, but deadly.
Therefore, natural selection has chosen a system proving for a reduction of choice and
decision time through fixed action patterns.

FAP’s require synchronous and coordinated activations of a number of different and

very specific muscle synergies, driving this motor event in a synchronous and
coordinative firing of very specific motor neurons with functionally specific firing
patterns, frequencies, and durations. However, the cerebral cortex has the ability to
override a fixed action pattern at any given time, which still allows us an enormous
degree of possibilities. Even language as well as emotions is considered a fixed action
pattern. Activities may not start out as fixed action patterns as learning how to play an
instrument, but through repetition they can become fixed action patterns and thereby
free up the cortex from the responsibility of control and it can focus on other things.
These differences are most clearly seen in the difference between letter and word-
habits in learning out to type or, in fact, the learning curve associated with any sensory
motor skill (Fitts, 1954; Fitts & Peterson, 1994; Leisman, 1989a; 1989b; 1989c; Leisman
& Vitori, 1990). Therefore, fixed action patterns are subject to modification, they can be
learned, remembered, and perfected.

Llinas (2001) considers that emotions are elements of fixed action patterns, but the
actions are not motor but rather pre-motor, similar to the way that muscle tone serves
as a basic platform for the execution of movements. Emotions represent the pre-motor
platform as either drives or deterrents to most of our actions. Therefore, emotions
provide motivation for our actions. The relationship between emotional state and the
motivation for action is extremely important because under usual conditions, it is some
emotional state that provides the trigger and the internal context for any specific action.
However, the pre-motor FAP does not only trigger an action as an FAP, it also
expressed in other forms of an accompanying type of motor FAP such as facial
expression which allows others to understand our motivation for the action that we are
taking. For example, when one touches a hot stove, pulling the hand back is a reflexive
fixed action pattern, but it is usually accompanied by a facial expression such as a
grimace, which is also a fixed action pattern and possibly even a "scream," which is yet
another fixed action pattern. With other fixed action patterns, emotions can be learned
and we can, in turn, learn how to suppress them as well. Therefore, emotional states
give context to motor behavior. It is interesting to note that children with autistic
spectrum disorders and even with attention deficit hyperactive disorder are known to
have stereotypical behaviors. We can look at these behaviors as being a release of
fixed action patterns, which can be associated with other hyperkinetic types of activities.
Emotions clearly relate to areas of the brain that are distinct and separate from the
basal ganglia, but are nonetheless closely associated with them (Saper, 1996; Heilman
& Gillmore, 1998). Emotions are linked to the motor aspects of fixed action patterns
through their access to the amygdala and hypothalamus and their associated
connections with the brainstem.

In summary, movement needs to be accomplished in an intelligent and coordinated

fashion to not overload the brain and nervous system as an information processor. The
brain seems to have been created to have two main strategies. The first was to develop
an internal clock or timing mechanism that would turn all of the muscles on and off
thereby reducing demand. The perceived temporal continuity of both sensory and motor
behavior, exemplified by the apparent smooth and coordinated fashion in which
muscles move, belies the fact that neither sensory nor motor function continuous in
actuality. This perceived continuity allows all muscles, which are not directly connected
to one another to be connected in time. Therefore, functionally connected but spatially
distant muscle groups could be coordinated into a purposeful movement. This is thought
to be the beginning of abstract thought. An abstraction is something that does not occur
in reality. Organisms coordinate their motor systems as one when they are, in fact,
made up of separate independent muscles that are not directly connected, is by
definition an abstraction. We have also shown how the external properties of muscles
eventually become imbedded in internal areas of the nervous system and eventually the
brain. This is then integrated with other sensory input to obtain a larger picture of the
organism (or self) and the surrounding world. This is then used to form a sensory motor
image of that world which is critical for the nervous system to predict the most important
function to be performed.

We can see that cognitive functions developed as ways to improve purposeful

movement for either approach or withdrawal behaviors. The properties of muscles were
imbedded deeper and deeper into the nervous system so that the nervous system
would be able to compare movement to other properties of the world and generate the
most accurate prediction proper response. These control mechanisms involved in
sensory-motor interaction are the largest and unique in humans and reside in the frontal
and prefrontal areas of the cerebral cortex. These areas perform executive functions
and it is this region of the brain that is primary affected in function and efficiency
in neurobehavioral disorders of childhood. The timing mechanism strategies that
developed to make motor activity more efficient were used to eventually allow us to
make sense of the world in cognitively. The pacemaker for muscles resides in the
inferior olive and cerebellum. The oscillator or pacemaker in the cognitive realm is the
thalamus. Just as muscles have no direct connection to one another, sensory
information is never fused together in the cortex (Koch & Leisman, 2002). There is no
one area in the brain to which all sensory input converges that allows for thinking and
emotional responsivity. Yet, to make sense of the world we need to combine sensations
and body movement to provide a temporally and spatially resolved reality.

Traditionally clinicians have looked at various disorders like attention deficit hyperactive
disorder, Tourette’s, and obsessive-compulsive disorder as separate and distinct clinical
entities. However, recently many of these disorders have been shown to have
significant overlap and many children that have one disorder will often be diagnosed
with at least one other. Neurobiological research and functional imaging tests have
given science a new way of examining the brain in its functional and dysfunctioning
states. These new tests have also revealed striking similarities in the brains of children
and adults with various cognitive and behavioral disorders. As a result, we are arriving
at the view that rather than consisting of separate processes, most of the common
cognitive and behavioral disorders of childhood rest along a continuum all with a similar
underlying mechanism. At one end of the spectrum is attention deficit disorder, then
attention deficit hyperactive disorder, learning disability, pervasive developmental
disorders, autism, obsessive-compulsive disorder, Tourette’s, and the schizophrenias.
From an anatomical and functional perspective, we find many of the same areas of the
brain are affected. Some regions are smaller or appear atrophied, other regions appear
to be functionally hyperactive, and some are hypoactive.

What seems to disturb parents and teachers alike and confuse many clinicians is that
they become overwhelmed by the wide variety of different symptoms that a child may
express. Most of these children do not present solely with behavioral problems or
learning disabilities although these may be of greatest concern or the most obvious.
These children usually exhibit a combination of emotional, behavioral, cognitive,
sensory, motor and autonomic symptoms. The broad range of symptoms causes even
more anxiety and confusion to parents and professionals and leads them to think that
the problem is overwhelming and insurmountable. Guiding principles in understanding
these conditions and in fomenting intervention strategies starts with the caveat that the
greater the number of symptoms, the more likely the problem is centered in the brain
where all bodily and behavioral systems are controlled. If one can isolate specific
dysfunctioning regions, one can then better understand the nature of the problem
making treatment more specific and effective.

While many of the same pathways are involved in disorders within the continuum, their
involvement appears restricted to either right-sided or left-sided hemispheric and
subcortical areas. Throughout the book, we have stressed a common theme of how the
brain functions including the existence of a baseline arousal level of subcortical and
cortical structures that appear to make up the contextual aspect of cognition, emotion,
and perception. Superimposed on this baseline arousal level we have described specific
pathways that convey content specific information to areas of the brain. Normal
functions can be disrupted if the contextual information, which is arousal dependent, or
the context specific information is disrupted in is progression through the nervous
system.

From a functional perspective, we can examine by brain imaging techniques and

standard neurological testing revealing underactive or overactive brain regions that in
turn relate to ineffectiveness of the arousal, non-specific system or the specific content
pathways. We have discussed how if neurons are active they will maintain normal
metabolic resting level. If neural pathways are not effectively stimulated they can
become underactive, and eventually relatively unstable. The result is that these neurons
will fatigue more quickly if fired upon and may even fire spontaneously as in the case of
seizures, hyperkinetic disorders, or spontaneous outbursts of action or thought.

From an anatomic perspective, we see that certain areas of the brain are physically
smaller and different from normal in children with these disorders (Aylward et al., 2002;
Blatt et al., 2001; Hardan et al., 2000; 2001a; 2001b; Saitoh & Courchesne, 1998;
Aoyama et al., 2000; Rosenberg et al., 1997; Castellanos et al., 2001; Singer et al.,
1993; Leisman & Ashkenazi, 1980). When an area is abnormally smaller, it either is
usually due to failure to develop properly or is a result of damage due to trauma,
inflammation (as in the case of Auto-Immune disease or toxicity), or some other disease
process. As with most areas of our body, when we use a structure it becomes larger
with use, when we do not use it, we will often see atrophy of that area. Even with lack of
development, we see that a region will fail to develop due to lack of exposure to stimuli,
which will promote a developmental delay of the growth of the under-stimulated region.

In most of the cognitive and behavioral disorders that we will discuss we will see that
there is a combination of alteration of function usually under-activity or hypoactive
states, as well as atrophy or smaller physical size of neural structures. We also will
recognize a common link between hypo-activity and atrophy of many of the same areas
in all of these disorders. The only difference is usually if they are restricted to left or right
side of the subcortical and cortical structures resulting in different symptoms. Many of
the symptoms result from lack of inhibition of one area resulting in that region’s
functional hyperactivity; this in turn we hypothesize to be due to the hypo-activity of a
region that would normally inhibit that function. In behavioral disorders, we know that
the limbic system, especially on the right, is responsible for the production of many
primitive or survival-driven emotions, such as fear, rage, anger, or approach and
avoidance behaviors. These brain regions in humans are normally modulated or
inhibited by higher centers in the neocortex, especially the prefrontal cortex.
Decreased stimulation or hypo-activity of the prefrontal cortex will reduce inhibitory
control over the limbic system which can result in abnormal behavior, uncontrollable
emotions especially aggression, increase in either avoidance or withdrawal behavior,
perseveration, inability to focus attention and hypo or hyperactivity in a way not unlike
that seen in the early Klüver-Bucy preparations in chimpanzees. The type of symptoms
will depend on which hemisphere is dysfunctional. Autonomic systems can be affected
or imbalanced due to dysfunction of the cortex and failure to modulate the limbic system
and the hypothalamus. Neurotransmitter systems, especially serotonin, norepinephrine
and dopamine systems can be dysfunctional, which system is affected is usually the
result of the side of the brain affected as there exists an asymmetric distribution of
neurotransmitters in the brain.

Finally, most of the development and normal function of the cerebrum is dependent on
subcortical structures especially the cerebellum, thalamus, and basal ganglia. A
failure to develop and or a dysfunction in these areas can affect both the nonspecific
arousal system as well as specific transfer of information in the brain. Dysfunction in
these areas will usually result in specific motor and sensory symptoms that are
commonly seen in children with cognitive or behavioral disorders. These brain regions
are often seen to be underactive or atrophied as well in these children. These cortical
loci have been shown to be connected with the prefrontal cortex, which have also often
been noted to be underactive or atrophied in children with the neurobehavioral
developmental disorders. The under-activity and or atrophy is usually either restricted to
the right or left side of the sub-cortex and cortex.

An imbalance of activity or arousal of one side of the cortex or the other can result in a
functional disconnection syndrome similar to what is seen in split-brain patients, this
could be an underlying source of many if not all of the symptoms that we see with
children with behavioral and cognitive disorders.

For example, post-mortem examinations have indicated structural differences between

the brains of good and impaired readers. High concentrations of micro-dysgenesis are
noted in the left temporoparietal regions of dyslexic brains. The concentration is most
evidenced in the planum temporale region (Galaburda et al., 1985; Kaufman &
Galaburda, 1989; Duane 1989). These micro-dysgeneses seriously impair the normal
pattern of architecture of dyslexics and remove the asymmetry normally observed
between the enlarged language areas of the left temporoparietal region and the smaller
homologous areas of the right hemisphere (Galaburda et al., 1985; Leisman &
Ashkenazi, 1980). The capacity for language is generally correlated with a significant
development in the magnitude of the left temporoparietal region and an attrition of
neurons in the right hemisphere. These neuronal casualties may produce the observed
asymmetry between corresponding areas in the left and right hemispheres (Geshwind &
Levitsky, 1968; Leisman & Ashkenazi, 1980). The relative symmetry in the dyslexics’
brains might reflect their impaired linguistic development.
In one study, (Leisman, 2002) left parieto-occipital EEG leads recorded a frequency
spectrum in dyslexics that is consistently different from the spectrum obtained from
normals. It is suggested that these effects represent significant differences in the
functional organization of these areas. EEG coherence values indicate that normals
have significantly greater sharing between hemispheres at symmetrical locations.
Dyslexics demonstrate significantly greater sharing within hemisphere than do normals
as evidenced in Figure 9.1 and Table 9.1. The data supports the notion that
developmental dyslexia is a functional hemispheric disconnection syndrome. Other
conditions in the spectrum of disorders that we are discussing yield similar results.

Figure 9.1: Mean values of EEG autospectral density by frequency recorded from P3-O1 electrode
placements for normal and dyslexic subjects. (From Leisman (2002)).

Table 9.1. Average frequency (in Hz), power (in dB), left-right asymmetry of power (in dB) between
hemisphere and within hemisphere coherence values at P3-O1/P4-O2 locations for dyslexics and
normals.
 Dyslexic Normal
Freq Power L-R Bilat. W/in Freq Power L-R Bilat. W/in
S
(Hz) (dB) (dB) Coher. Coher. (Hz) (dB) (dB) Coher. Coher.
1 09.2 12 -03 -- 1.1 09.2 28 -- -- 0.8
2 10.4 21 -04 -- 1.8 10.8 24 -- 2.4 --
2 10.4 21 -04 -- 1.8 10.8 24 -- 2.4 --
3 11.7 22 10 -- 2.4 12.7 18 -- 1.9 --
4 09.8 18 04 -- 1.6 10.9 20 -4 1.3 --
5 10.8 17 03 -- 1.4 08.6 16 -- 1.9 --
6 10.6 24 -01 -- 0.8 08.9 08 -- 1.8 --
7 10.6 28 -05 -- 1.5 11.2 11 -- 2.4 --
8 11.2 12 -07 -- 2.1 11.7 13 -2 1.5 1.8
9 12.0 19 -04 -- 1.9 10.0 12 -- 1.3 --
10 09.8 14 -- 0.7 0.6 10.7 15 -1 1.3 0.9
11 10.8 25 -02 -- 1.0 10.6 11 -- 1.2 1.4
12 11.7 22 -- 1.0 -- 12.0 09 -- 0.8 1.1
13 08.7 13 -01 -- 0.9 11.7 07 -- 1.0 --
14 09.0 27 08 -- 2.1 08.9 11 -- 1.9 --
15 10.7 13 -04 -- 2.4 09.5 10 -- 1.7 0.6
16 10.3 08 -06 -- 1.8 08.8 11 -2 2.1 --
17 09.5 22 -07 -- 2.0 08.6 14 -- 1.4 --
18 12.2 20 -07 -- 1.9 09.3 09 -- 1.8 --
19 11.9 09 -01 -- 0.9 12.4 12 -- 1.9 --
20 08.4 15 -04 -- 1.6 11.6 10 -- 0.9 --

This spectrum of childhood disorders that we are discussing generally relates to an

increase or decrease in activation of the brain and the balance of activation between
brain regions. These conditions result from two primary system effects: 1) primary
arousal deficit or imbalance, and 2) a specific activation deficit, imbalance, or
asynchrony.

The brain is driven by sensory input. We know that the brain receives more
simultaneous sensory input than it can possibly consciously process (Heilman, 1995;
Leisman, 1976a; Broadbent, 1958; 1965a; 1965b) In general the more stimulation a
brain cells receive the better their function allowing it to process more information faster,
for longer periods of time (Venables, 1989; Pascual & Figueroa, 1996; Szeligo &
Leblond, 1977; Mohammed et al., 2002; van Praag et al., 2000). Therefore all sensory
input is important although not all of it can be consciously processed and perceived. In
fact, without subconscious baseline inhibition higher conscious processing of sensory
stimuli would be difficult if not impossible.

Before higher brain centers can develop, the lesser supportive brain structures must
develop. In the cortex, Luria (1995) thought that lateralized cortical functions progress
from primary cortical areas to secondary and tertiary areas as the child matures (Luria,
1995). Going back even further we see that development of cortical areas and the
cortex itself are dependent on the anatomic and functional development of subcortical
areas especially the cerebellum and the thalamus. Studies suggest that intact cerebellar
functioning is required for normal cerebral functional and anatomical development (Rae
et al., 1998; Llinas, 1995). The same has been seen for the thalamus - that intact
thalamic function is necessary to cortical development and function (Castro-Alamancos,
2002; Alonzo, 2002, Amino et al., 2001; Young et al., 2000; Scannell et al., 1999; 2000;
Gil et al., 1999; Albe-Fessard et al., 1983; Kalivas et al., 1999; Macci et al., 1986).
Developmental dysfunction of the same brain areas as seen in acquired disorders such
as post-traumatic aphasia may be the basis of developmental learning disabilities and
neurobehavioral disorders (Dawson et al., 2002a; 2002b; 2001; 1982; Dawson, 1996;
1988; Obrzut, 1991).

As Orton (1937) had indicated, it is generally assumed that persons with learning
disabilities (including any and all Functional Disconnection Syndrome) have abnormal
cerebral organization including atypical or weak patterns of hemisphere specialization
(Bryden, 1988; Corballis, 1983; Obrzut, 1988). The developmental lag hypothesis
proposed by Lenneberg (1967) suggested that learning-disabled persons are slower to
develop basic language skills and demonstrate weak hemispheric specialization for
language tasks. In a reformulation of the progressive lateralization hypothesis (Satz et
al., 1990), it may be that subcortical and antero-posterior progressions have a
differential developmental course with learning disabled children and adults compared
to control subjects or those with acquired syndromes.

Since learning disabled children exhibit deficient performance on a variety of tests

thought to be a measure of perceptual laterality, evidence of weak laterality or failure to
develop laterality has been found across various modalities (audio, visual, tactile)
(Boliek & Obrzut, 1995). It is thought these children have abnormal cerebral
organization as suggested by Corballis (1983) and Obrzut (1988). The basic
assumption is that dysfunction in the central nervous system either prenatally or during
early postnatal development, results in abnormal cerebral organization and associated
dysfunctional specialization needed for lateralized processing of language function and
non-language skills. It is thought that cortical and subcortical dysfunction which results
from aberrant patterns of activation or arousal (Obrzut, 1991), inter- and
intrahemispheric transmission deficits, inadequate resource allocation (Keshner &
Peterson, 1988), or any combination of these may compromise hemispheric
specialization in those with cognitive and behavioral deficits (Bolick & Obrzut, 1995).
Development of higher processing areas in the cerebellar cortex would develop after
other more primary areas. For example, the lateral cerebellum would be dependent on
proper development of the more midline areas in the inter-medial and medial zones first.
Similarly, any region to which lateral cerebellum projected would be dependent on the
effective development of the lateral cerebellum and it in turn would be dependent on the
more medial cerebellar development. Therefore, if the medial aspects of the cerebellum
do not develop adequately, then the lateral areas would still grow however, they may be
smaller or atrophic, and dysfunction would be expected.

The cerebellum is thought to be part of a neuronal system that includes the thalamus,
basal ganglia, and prefrontal cortex (Thatch, 1980). Anatomic and functional
development of the nervous system is dependent on sensory input, which is associated
with growth of a given brain area and its associated connectivities with other brain
regions. Brain area growth and the capacity to make functional connectivities are highly
dependent on: continued regional stimulation and by global stimulation through
connected and coordinated function. If specific regions are inadequately stimulated,
then we may see failure of anatomic or functional development in that region with a
preservation of basic lower level functionality. Higher functions that depend on greater
areas of integrated stimulation may be lost or dysfunctional. If the sensory loss develops
after a critical period, these areas may still be smaller due to atrophy or reverse
plasticity, with either global or specific effects depending on the modality of dysfunction.
In children with learning disabilities or affective disorders, there are specific areas of the
nervous system that have been noted in imaging studies to be smaller than normal (von
Plessen et al., 2002; Frank & Pavlakis, 2001; Cohen et al., 2000; Chiron et al., 1999;
Larsen et al., 1990). Most often, these areas involve the prefrontal cortex, basal ganglia,
thalamus, and cerebellum.

Some neurophysiological experts regard the central nervous system as partly a closed
and part open system (Llinas, 1995). An open system is one that accepts input from the
environment, processes it, and returns it to the external environment. A closed system
suggests that the basic organization of the central nervous system is geared toward the
generation of intrinsic images and is primarily self-activating and capable of generating
a cognitive representation of the outside environment even without incoming sensory
stimuli. Although it is possible that a certain level of activation or stimulation will be
intrinsic to single neuronal cells and the nervous system as a whole, this stimulation
does not seem adequate to sustain a conscious, awake, individual. Behaviorally,
arousal is a term used to describe an organism that is prepared to process incoming
stimuli. From a physiologic standpoint, arousal also refers to the excitatory state or the
propensity of neurons to discharge when appropriately activated (neuronal preparation).
A non-aroused organism is comatose (Heilman, 1995). Therefore, an aroused alert
individual that is prepared to process information is in a state dependent on sensory
input with an attendant intrinsic excitability. Remove stimulation and the individual will
eventually lose conscious awareness and become comatose or at least inattentive. The
majority of brain activity associated with arousal comes from the ascending reticular
activating system. The majority of this activity is relayed by the non-specific thalamic
nuclei or intralaminar nuclei.
All sensory perception is based on the effectiveness of the arousal level of nonspecific,
mostly subconscious, activity of the brain. There can be no specific sensory modality
perception like vision or hearing without a baseline arousal level. The more stimulation
or greater frequency of stimulation the more aroused an individual will be. Low
frequency stimulation of midline thalamic non-specific nuclei produces inattention,
drowsiness, and sleep accompanied by slow wave synchronous activity and so called
spindle bursts. High frequency stimulation on the other hand has been shown to arouse
a sleeping subject or alert a waking organism (Tanaka et al., 1975; Arnulf et al., 2000;
Halboni, 2000). Specific sensory perception and processing is dependent on specific
thalamic relays, if one of the specific thalamic nuclei are damaged such as the lateral
geniculate body, that specific sensory modality is lost (e.g. blindness) but it does not
result in loss of other specific nuclei input like hearing. However, if lesions of the non-
specific intralaminar nuclei exist, patients cannot perceive or respond to any input by the
specific intact nuclei even though those pathways are intact. In essence, the person
does not exist from a cognitive standpoint (Llinas, 1995).

Luria postulated that the brain was divided into three functional units: 1) the arousal unit,
2) the sensory receptive and integrative unit, and 3) the planning and organizational
unit. He subdivided the last two into three hierarchic zones. The primary zone is
responsible for sorting and recording incoming sensory information. The secondary
zone organizes and codes information from the primary zone. The tertiary zone is where
data are merged from multiple sources of input and collated as the basis for organizing
complex behavioral responses (Luria, 1973). Luria's dynamic progression of lateralized
function is similar to Hughlings Jackson's Cartesian coordinates with respect to
progressive function from brainstem to cortical regions (Kinsbourne & Hiscock, 1983).

Satz and colleagues, 1990) have suggested that developmental invariance describes
the lateral (x-axis) dimension of asymmetry, whereas current formulation of equi-
potentiality and the progressive lateralization hypothesis better describes vertical
(subcortical-cortical) and horizontal (antero-posterior) progression during infancy and
early childhood. Interestingly it has been noted that most research designed to address
laterality issues in developmental disabilities (i.e. learning disabilities) has not dealt
systematically with subcortical-cortical development or antero-posterior progression, all
based on the concept of arousal unit.

The arousal unit is really the non-specific thalamic nuclei. We know that arousal is
dependent on external and internal environmental sensory input. The largest proportion
of subconscious sensory input passes between the thalamus, cerebellum, and dorsal
column from slowly adapting receptors found in muscles with a preponderance of slow-
twitch fibers - or slowly adapting muscle spindle receptors. The highest percentage of
these is found in anti-gravity postural muscles especially muscles of the spine and neck
(Guyton, 1986). The receptors, which provide the major source of input to the brain,
only receive sensory information. These receptors only work when muscles are
stretched or contracted with gravity being the most frequent and constant sensory
stimulus.
In summary, brain development and the adequacy of it continued functioning is
dependent on sensory input. Specific sensory perceptual processes like vision and
hearing are dependent on non-specific sensory input. This, in turn, creates a baseline
arousal and synchronization of brain activity (consciousness). This is a form of constant
arousal and is dependent on a constant flow of sensory input from receptors that are
found in muscles of the spine and neck. These receptors receive the majority of their
stimulation from gravity, creating a feedback loop that forms the basis of most if not all
of brain function. Sensory input drives the brain, and motor activity drives the sensory
system. Without sensory input the brain cannot perceive or process input. Without
motor activity provided by constant action of postural muscles a large proportion of
sensory stimuli are lost to further processing. This loop is the somatosensory system.

Higher processing is also dependent on the baseline sensory functions. For example, it
has been shown that when performing a complex task, it is likely that transfer of motor
commands to produce a final output is preceded to some degree, by transfer of
information between association areas, which in turn may precede transfer between
sensory regions (Banich, 1995).

Balance is Essential
It is clear that the sensory-motor system then cannot be separated. A dysfunction of the
sensory system results in a motor weakness or coordination deficit and a decrease in
motor tone or coordination which in turn decreases the sensitivity of the muscle receptor
and therefore the frequency of firing of the sensory pathways. The ability to sense body
movement or position in space relative to gravity is known as proprioception, or the
sense of subconscious touch. Proprioception is dependent on the amount of force or
functional state of somatosensory receptors of joints, tendons, and especially muscle
spindle receptors. These are pressure receptors similar to skin touch receptors for
tactile sensation, the only major difference is in the frequency of stimulation and the
resultant conscious or subconscious perception. Muscle tone may be defined as the
resistance of stretch of muscles. Muscle tone is a product of the output of the brain or its
level of activation and arousal. Output of the brain is directly related to input plus
arousal level. Effective muscle tone is characteristic of an aroused individual.
Proprioception and muscle tone are therefore related. The adequacy of proprioception
results from the effective sensitivity of muscle spindle receptors. High sensitivity of
muscle spindles is due to effective muscle tone, which in turn results from the adequacy
of brain output.

Of all the sensory input, proprioception constitutes the largest part. Many researchers
have noted that in learning disabled children, there often exists poor proprioception and
low muscle tone. Symptoms of poor proprioception and low muscle tone include poor
balance, posture, clumsiness, and poor coordination (Cammisa, 1994; Kohen-Raz,
1991; Kohen-Raz & Hiriatborde, 1979; Morris et al., 1988; Morrison et al., 1985; Conrad
et al., 1983; Hulme et al., 1982; Freides et al., 1980; Voronin et al., 1980; Ottenbacher,
1978; Njiokiktjien et al., 1976, Ayres, 1972; Kaluger & Heil, 1970). Jean Ayers (1973)
recognized over thirty years ago that these children demonstrated a variety of problems
that she thought were related to what she called poor sensory integration. She noted
then that these children possess different degrees of sensory deficits including hearing,
visual, tactile, and proprioceptive. Associated with these symptoms included speech
and language deficits, motor dysfunction, learning disabilities, and emotional problems.
She thought that the vestibular system was the principle source of the dysfunction.
Ayres arrived at this conclusion because she recognized that gravity plays a significant
role in proprioception and further concluded that the major gravity receptors, which
control balance, were primarily concentrated in the vestibular system. While her clinical
observations were keen, we now recognize, however, that the majority of proprioceptive
and gravity data arises from spinal and neck muscles, joints, and their sensory input to

While vestibular receptors do not change their sensitivity, the cerebellum may alter its
responsiveness to the vestibular apparatus based on the cerebellum's baseline arousal
level, which results mostly from spinal and neck motor activity (Matsushita & Xiong,
2001; Gdowski et al., 2001; Bruggencate, 1975). These midline motor structures of the
spine are connected to the midline cerebellar structures in the medial zone and fastigial
nuclei of the cerebellum and send sensory input directly back. The cerebellum
stimulates these midline muscles bilaterally. Signals then project to midline non-specific
nuclei in the thalamus, which then project to the entire cortex (Leisman, 1989a; 1989b).
This cerebellar feedback mechanism also connects through the vestibular nuclei and
proceeds to primarily affect the proximal trunk muscles. They also ascend to effect the
coordination of eye muscles. The intermediate and lateral cerebellum send more
specific information about extremity and distal muscles, which goes to specific thalamic
nuclei that are connected to the somatosensory cortex, prefrontal cortex, and
association cortices on the contralateral side of the body. These specific areas of
neocortex especially the frontal lobe then send fibers downwards to the ipsilateral
brainstem reticular formation which then sets global muscle tone of all muscles on that
side, both spinal and postural, as well as distal extremity muscles. It also sets the
balance of muscle tone between anterior and posterior compartment muscles on the
ipsilateral side of the body to help promote an upright bipedal posture.

Cerebellar lesions have been recognized since Gordon Holmes as resulting in problems
with proprioception and motor tone. Some of these symptoms effect the bilateral
coordination of muscles of the spine and eyes and occur primarily at the level of the
cerebellum, and always occur bilaterally due to both contralateral and ipsilateral fibers
(Ramnani et al., 2001; Ross et al., 1979). However, unilateral dys-coordination,
unilateral decreases in muscle tone in both postural and extremity muscles and the
balance of vestibular activity occur at the level of the cortex, dependent on contralateral
cerebellar input plus arousal activity (Leisman, 1989a; 1989b). Levinson (1988), in his
study of almost 4,000 learning disabled subjects showed that 94.1 percent presented
with what he termed cerebellar-vestibular dysfunction. His data suggested that learning
disabilities and dyslexia are C-V based and represent one disorder, that this C-V
dysfunction continues with increasing age and that the symptomatic overlap within
subjects and samples appear to reflect a common C-V basis rather than a group of
separate neurophysiological disorders. He went on to state that a variety of so called
"pure" disorders and terms such as dyslexia, dysgraphia, dyscalculia, dysphasia,
dysnomia, dyspraxia, attention deficit disorder (ADD), perceptual-motor disorder, etc.
merely reflect highly selected learning disabled symptoms and samples. Although he
recognized cerebellar dysfunction, he related many of these aforementioned problems
to a primary source in the inner ear of the vestibular system. He also did not consider
asymmetric cerebral lateralization and its development as a significant factor.

Therefore, a sensory deficit of proprioception and subsequent abnormality of muscle

tone may reflect a global decrease in global cerebellar, thalamic, and cortical arousal
levels.

Other specific sensory deficits may be result from the asymmetric arousal of these
areas, which would present with specific localized perceptual dysfunction. Since
proprioception is a subconscious sense, processed subconsciously through the
cerebellum, thalamus and somatosensory cortex, when cortical proprioceptive input is
decreased we are not consciously aware of the loss or dysfunction. However there are
symptoms that we may experience when the proprioceptive input becomes too low or
imbalanced. Dys-equilibrium, or the feeling of unsteadiness of gait, is one primary
symptom, poor balance, dizziness, or vertigo can be manifest if vestibular input is not
modulated effectively by the cerebellum.

In the past, most of the emphasis for balance dysfunction, such as vertigo, nystagmus,
or motion sickness, had been placed on the vestibular apparatus of the inner ear.
However, research suggests that as humans been created to have from quadrupeds to
bipeds the emphasis of control of balance, posture, and the coordination of head and
eye movements was shifted from the inner ear to the spinal muscles and joints. Wyke
(1979) notes that during the course of the evolution of the erect from the quadrupedal
posture, there has been a shift in the relative perceptual and reflexogenic significance of
the mechanoreceptors in the labyrinth of the internal ear and those located in the
cervical spinal joints in favor of the latter. This evolutionary decrease in the functional
significance of the vestibular system in man was first suggested by Rudolf Magnus
(1924) and is powerfully illustrated by the later clinical observations of Purdon Martin
(1967) which show, inter alia, that this system in man is of no significance at all in static
postural circumstances or in the production of reflex righting reactions. In this
connection, it may be relevant to note that the cervical articular mechanoreceptors
became functionally active in the developing human fetus long before the vestibular
mechanoreceptors (Wyke, 1975b; 1979). Wyke goes on to note that patients experience
a feeling of postural instability and unsteadiness of gait in situations of poor lighting after
these individuals have been provided with a cervical collar that affects their neck joints
and muscles (Wyke, 1979). He also notes that based on neuropsychological study
(Wyke, 1965) showing that, "precision of voluntary control of arm movement in the
absence of vision is markedly impaired by rotation of the head and neck to right and left
of central position.” It has also been observed by de Jong and colleagues (1977), and
others (Leisman, 1989a; 1989b) that local anesthetic infiltration of cervical spinal and
other joints in normal individuals results in a feeling of static body dysequilibrium (often
with vertigo). Also noted is kinesthesia, upon which the accurate control of voluntary
movements including walking depends even in the presence of a normally functioning
vestibular system (Wyke, 1979).

In regard to proprioceptive input and its relationship to various sources of input,

Carpenter and colleagues (2001) states "by far the most important proprioceptive
information needed for the maintenance of equilibrium comes from neck joint receptors
and muscles." Guyton (1986) also notes "mechanisms governing equilibrium and
orientation in three dimensional space proprioception are largely reflexive and
subconscious in character and depend on input from several sources. The most
important of these are as follows: kinesthetic sense conveyed by spino-cerebellar
system from receptors in muscles, tendons, and joints. Sense provided by the vestibular
organ of the inner ear and visual input from the retina."

The reason input of spinal muscles and joints are so important is that they are made up
of slowly adapting tonic receptors that continuously fire to the cerebellum and brain.
The sheer volume of stimulation because of continual firing more than any other source
of stimulus to the brain may be why the spinal muscles and joint have more neurons
than the rest of the nervous system. The spinal muscles and joints process more
information than any other region of the body, and is the only continuous source of
stimulus to the cerebellum and brain, not the inner ear or the eyes, only the muscles
that are forced to resist the forces of gravity.

What we have seen in multitudes of studies is that motion sickness, a severe symptom
of loss of proprioceptive input, is a common finding in micro-gravity situations. That the
loss of proprioceptive input is mostly the result of postural antigravity of the muscles of
the spine and lower extremity and this presents with a more powerful effect than loss of
vestibular input and active contraction, and use of these muscles can completely
compensate for the loss. We also see that this loss of proprioceptive input also results
in nystagmus of the eyes and an inability to efficiently control eye movement. Loss of
proprioceptive input can also result in significant abnormal autonomic reactions, which
again can be alleviated by increasing proprioceptive input from those specific muscles.
We have also seen that the loss of this input is thought to be mediated centrally through
the cerebellum and cortex. This loss of input in rats has been shown to cause rapid light
and dark degeneration of neurons in widespread areas of the brain - but especially the
neocortex. Areas of neocortex involved include the somatosensory and visual areas
especially.

Therefore, in children that present with signs and symptoms of proprioceptive loss,
which includes, disorders of balance and gait, abnormal muscle tone - especially
hypotonia, nystagmus, vertigo, dysequilibrium, nausea, motion-sickness symptoms,
etc., these symptoms are due essentially to a primary dysfunction of cerebellar-thalamo-
cortical input. The primary source of input to the cerebellum of proprioceptive input is
from muscles, joints, and tendons of spine and lower extremity, and postural antigravity
muscles. This input is more significant than vestibular input and can even compensate
for vestibular loss. Therefore, anything that may decrease the ongoing proprioceptive
input of postural antigravity muscles and/or vestibular input as seen in micro-gravity
experiments can result in sensory loss, degeneration or reverse plastic changes in the
cerebellum and neocortex. Such conditions have the possibility of affecting any or all
other brain regions but especially neocortical functions.
Tactile

Ayers (1989) and others (Cammisa, 1994; Kohen-Raz, 1991; Kohen-Raz & Hiriatborde,
1979; Morris et al., 1988; Morrison et al., 1985; Conrad et al., 1983; Hulme et al., 1982;
Freides et al., 1980; Voronin et al., 1980; Ottenbacher, 1978; Njiokiktjien et al., 1976,
Ayres, 1972; Kaluger & Heil, 1970) have noted that children with learning disabilities
and behavior disorders often have altered sense of touch or tactile sensations. Most
often, there exists a decrease in tactile sensitivity in these children, but others also
appear to have a hypersensitivity to touch. Interestingly, tactile sensory input or
conscious touch input travels much the same path as proprioceptive input. Therefore,
the same dysfunctioning mechanisms that affect proprioception can also affect tactile
perception. Both senses are mainly activate and are processed in the somatosensory
cortex, however for touch and spatial orientation there does appear to be asymmetric
lateralization favoring the right hemisphere. The somatosensory cortex is proximal to
the post-central gyrus and areas adjacent to it (Brodmann areas 1, 2, and 3). These
areas receive input from somatosensory pathways originating in the thalamus, which
transfer tactile information of, pain, temperature, and proprioception. The primary
somatosensory cortex (SI) is immediately caudal to the central sulcus, the secondary
somatosensory cortex (SII), which obtains most of its afferent input from SI, is located
ventral to SI. Somatosensory inputs projecting to the posterior parietal cortex arise from
SI and SII. Somatosensory input projecting to the thalamus and proceeding to the
primary somatosensory cortex transverses two main pathways: the antero-lateral
system for pain and temperature sense, and the dorsal column-medial lemniscal
pathway, which carries information about tactile proprioception and movement
sensation. Any process that physically disrupts the flow of information such as a lesion
at the receptor, nerve, spinal cord, brainstem, cerebellum, thalamus, or cortical level
can cause abnormalities in the attendant perceptual processes. Abnormal perception,
decreased arousal, or imbalance of arousal may result even with a physically intact
pathway.
Figure 9.4: Cortical source of hemispatial neglect syndromes, most often seen after large areas of
damage to right areas of parietal lobe. It is a frequent consequence of stroke on the right side of the brain
and thus neglect of everything on the left. It is also evidenced in other forms of brain dysfunction
especially with a right hemisphere source. Patients ignore everything on the side opposite to the lesion. It
is not blindness as patients can recognize and label objects appropriately and thus it is a disturbance in
the spatial distribution of directed attention. Patients frequently bump into objects, tend a not to groom
themselves, all on the side opposite the lesion. In the majority of patients, the lesion involves the
supermarginal gyrus in the inferior parietal lobe at the temporo-parietal junction. Although less frequently,
damage or dysfunction to the dorsolateral premotor and medial frontal regions can also bring about hemi-
neglect. Lesions confined to the primary motor, somatosensory, and visual cortices are not associated
with neglect. The posterior parietal component proves an internal sensory mechanism, the limbic
component regulates the spatial distribution, the frontal component coordinates the motor programs for
scanning, reaching, and exploring, and the reticular component provides levels of arousal.

Arousal level or attention is the foundation of all perception and without proper arousal, any or all effective
sensory perception can be impaired. These perceptual alterations and resultant inattention
syndromes are known as neglect, and can occur with or without spatial awareness, tactile, visual and
auditory sensations. In these cases, the physical pathways of the stimulus are intact but the cerebral
cortex does not integrate or perceive the information, in essence rendering the stimulus non-existent to
the individual. This can occur bilaterally, but more often, the result is a unilateral loss. The asymmetric
lateralization of the function, and the localization of the primary dysfunction will determine which sense
will be most affected, this helps us to localize the primary problem. There are numerous studies of various
asymmetries of tactile (haptic) perception, visual perception and of interference between two tasks
performed at the same time (Hiscock & Kinsbourne, 1995). Tactile inattention is also known as pseudo
hemi-anesthesia.

Vallar and colleagues (1991a) reported on a patient who had apparent contralateral hemi-anesthesia from
a large right hemisphere cerebral infarction. Although the patient denied being stimulated on the left side,
tactile stimulation did produce an electrochemical skin response. Three other patients were reported by
the same author (Vallar, 1991b). All three had left hemi-anesthesia from right hemisphere lesions;
however, all had normal evoked potentials recoded from the left side. This suggests that although the
pathways were intact, the tactile sensations were not perceived due to lesions in the right hemisphere.
Another study (Meador et al., 1988) using selective hemisphere anesthesia in 18 epileptic patients, found
that contralateral tactile inattention was present in eight patients after right hemisphere injection of
anesthesia but only in two subjects after left-sided injection.

Another form of tactile inattention is known as extinction to simultaneous stimulation. It has been
reported that as patients with neglect or hemi-inattention symptoms improve, they may develop extinction
to simultaneous stimuli. The difference is that individuals with inattention are not aware of tactile
stimulation to the side opposite the impaired hemisphere. However, patients with extinction are aware of
contralateral stimuli but are unable to perceive simultaneous bilateral stimulation, specifically failing to
perceive the stimulus to the contralateral side. In most cases, studied contralateral extinction was more
frequently associated with selective anesthesia of the right hemisphere than the left (Meador et al., 1988).

In spatial neglect, most commonly hemispatial neglect, patients with injury or dysfunction localized to one
hemisphere may not be able to perform normally on spatial tasks. This is usually found in the contralateral
hemi-space so that the stimuli to the left of the patient’s body are neglected more often than those to the
right side of the body (Heilman & Valenstein, 1979). Neglect of the environment may also occur so that
even when the individual lies on his or her side, the left half of the environment is neglected (Lodavas,
1987).

Spatial neglect is complex and can involve: 1) attentional disorders, 2) intentional or motor activation
disorders, or 3) representational disorders (Heilman, 1995). It has been hypothesized that hemispatial
neglect may have four possible attention related causes: 1) contralateral spatial inattention, 2) ipsilateral
attentional bias, 3) inability to disengage, and 4) reduced sequential attentional capacity or premature
habituation. One theory (Heilman & Watson, 1977) posits that patients with left hemispatial neglect are
unaware of stimuli presented to the left hemisphere because they may simply be less aware of stimuli on
the left than on the right resulting in an ipsilateral bias with attention being drawn to that side and away
from the neglected side. Another possibility for explaining neglect is that objects besides the critical
stimulus in ipsilateral space draw the patient’s attention with the bias becoming so strong that the
individual may not be able to disengage their attention (Posner et al., 1984). It is also possible, as
exemplified in one case, where bias or inattention may determine where stimuli are neglected, a limited
sequential capacity or inappropriate habituation may also lead to hemispatial neglect (Chatterjee et al.,
1992; Heilman, 1995).

Hemispatial neglect is seen more frequently with right hemisphere lesions (Ganotti et al., 1972; Costa et
al., 1969). Although several studies note that spatial neglect caused by right hemisphere lesions mostly
affects the left side of space or body, it may also affect the right side of space (Albert 1973; Heilman &
Valenstein, 1979; Weintraub & Mesulam, 1987). In humans, the inferior parietal lobe is more often
associated with disorders of attention (Critchley, 1966; Leisman, 1976a; Heilman, et al., 1983). Temporo-
parietal ablation in monkeys also results in contralesional attentional disorders, primarily extinction
(Heilman et al., 1970; Lynch, 1980). Therefore, it is suggested by this research that tactile as well as
spatial neglect can be a result of decreased or imbalanced arousal or attention. In the right hemisphere, a
lesion or dysfunction can result in neglect that affects both sides of the body or space with the left being
more frequently affected. The primary brain area reportedly responsible for the majority of cases is the
inferior parietal lobe or temporo-parietal areas.

Functionally, decreased afferent input in the absence of a physical lesion could be another reason for
neglect. In the parietal lobe, which is important in directing attention, it has been noted that the rate of cell
firing appears to be associated with the importance of the stimulus to the monkey, so that important
stimuli are associated with a higher firing rate than unimportant stimuli (Bushnell et al., 1981; Lynch 1980;
Motter & Mountcastle, 1981). It has been demonstrated that the activity of some parietal attentional
neurons are spatially selective. However, the parietal lobe also receives input from other sensory
modalities and the coding of spatial location is thought to be multimodal (Goldberg & Robinson, 1977;
Robinson et al., 1978). The primary sensory cortices project only to the association cortex. These single
modality primary sensory areas converge upon polymodal association areas in the monkey including the
frontal cortex (periarcuate, prearcuate, and orbitofrontal) and both banks of the superior temporal sulcus
(Pandya & Kypres, 1969). Multimodal association areas are important for sensory synthesis and cross-
modal association. These multimodal convergence areas project to the inferior parietal lobe (Mesulam et
al., 1977).

The cerebellum has also been noted to have a close connection to all association areas of the neocortex.
The cerebellum has also been implicated in tactile learning and sensory tactile deficits besides its primary
role in the processing of proprioceptive input. Leiner and colleagues (1991) have stated that,
"concomitant with the evolution of new association areas in the cerebral cortex, new neuronal
connections been created to have that descend (via enlarged structures in the brainstem) to new area 5
in the lateral cerebellum." It is further stated, "therefore, the neo-cerebellum can serve as a link between
the posterior and frontal language areas of the cerebral neocortex in effect the cerebellum provides the
cerebral cortex with an additional 'association area’.”

Blood flow studies during tactile learning of complicated geometrical objects show a
high activation in the lateral cerebellum (Roland et al., 1989). The activation of the
lateral cerebellum is thought to be due to cognitive processing during tactile learning,
whereas the medial cerebellar activity relates more to the actual movement (Fox et al.,
1985). The cerebellum has been specifically shown to be involved in sensory
perception; this has been shown during chronometric tests (Posner, 1988) of timing
functions. Cerebellar patients demonstrate deficits in perception of time intervals and
judgment of velocity of a moving stimulus. It has been postulated that one role of the
cerebellum is to modify motor performance to improve the efficiency of sensory
processing by the rest of the nervous system by means of arousal.

Arousal is a physiologic state that prepares an organism for sensory processing by

increasing sensitivity and signal-to-noise ratio (Heilman, 1995). This is an extremely
important concept because it forms the basis of all perception and perhaps even
consciousness itself. The baseline arousal of all cortical areas makes all of these cells
more active and therefore closer to threshold or more sensitive to incoming stimuli. The
closer to threshold, the better the signal-to-noise ratio resulting global or specific effects
on the brain. The results of such a process in turn could lower the effectiveness of
global possessing of the brain or one specific function may be affected more than
others. This can happen with an imbalance of arousal, where one side is too high in
relationship to the other.

Emotionally Significant

The significance of the stimulus requires knowledge of the meaning of the stimulation
and the motivational needs and goals of the individual (Heilman, 1995). The limbic
system provides the more primitive, motivation of immediate biologic needs, whereas
the frontal lobe is involved with goal directed behavior. The difference between the
limbic and frontal input to attentional or arousal systems, is that the frontal lobe may
provide motivation and goals that are of a higher level beyond the basic biological
needs of the child. It is thought that the frontal and limbic (cingulate gyrus) connections
with the frontal lobe may provide the neuronal basis for the ability of motivational states
to affect attentional systems and perception. Unilateral neglect in humans and
monkeys can be induced by lesions in the dorsolateral frontal and prefrontal
cortex (Heilman & Valenstein, 1972; Welch & Stateville 1958) as well as with cingulate
gyrus lesions (Heilman & Valenstein, 1972; Watson et al., 1973). Affective behaviors
have also been shown to be influenced by cerebellar dysfunction; especially midline
cerebellar atrophy (Gutzmann & Kuhl, 1987). The cerebellum is also known to be
connected to the dorsolateral frontal and prefrontal cortex. Not only can the cerebellum
affect global arousal, but it also has specific connections to association cortices for
multi-modal sensory processing. It has strong specific connections to the
somatosensory cortex in the parietal lobe, as well as the frontal lobe.

The overall neuronal preparedness and signal-to-noise ratio is dependent on arousal

input. The cerebellum may be the largest contributor to the arousal system. The
cerebellum also works to modify motor behavior to maximize all sensory input.
Therefore, the hemispatial neglect can be seen with all sensory input, not just tactile
and spatial, but also visual and auditory. Besides signal-to-noise ratio, neuronal
synchrony is essential for sensory perception to exist Koch & Leisman, 1990; 1996;
2001a; 2001b; Leisman & Koch, 2003). Liederman (1995) describes how
synchronization dysfunction may result in a neglect syndrome for any sensory modality.
She describes how cortico-cortical pathways can function to synchronize activity across
remote cortical regions. This synchronization then is thought to have the effect of
equilibratory activation between different regions. She is quoted, "thus disconnection
symptoms such as those seen in split-brain patients can be accounted for mainly by two
factors: the desynchronized and fragmented manner by which subcortical pathways
permit inter-hemispheric integration and the diminished arousal state of the non-viewing
hemisphere without the synchronizing influence of the cerebral commissures. The under
activated hemisphere displays an internal neglect that is marked by an abnormality of
processing of input after sensory reception it does not effectively process inputs to it (a)
directly from the contralateral side of space, or (b) indirectly from the opposite
hemisphere. These under-processed inputs are not consciously perceived though they
are reacted to on an implicit level."

Synchronization of a hemisphere is thought to result from 40 Hz. oscillations that arise

from the intralaminar thalamic nuclei. These subcortical oscillations in the thalamus
have been traced back and are thought to originate from the cerebellum and dorsal
column fibers that are thought to transmit information from slowly adapting receptors.
These types of receptors are found most commonly in slow-twitch muscle fibers of
postural spinal muscles. It is known that even in the intact brain the two hemispheres
can maintain different arousal levels as well if not more than differences within adjacent
areas of the same hemisphere. Large differences should not occur in a normally
functioning intact brain. However, in situations where stimulus conditions cause the
untrained or non-viewing hemisphere to be either busy or too minimally alert to
adequately subserve inter-hemispheric integration (Liederman, 1995) inter-hemispheric
arousal differences may exist.
It has been demonstrated that right parietal lobe lesions cause a deficit of integration
and not detection. It is thought that the neglect subjects do not have difficulty with
directing their attention to a single-feature target. They do appear, however, to have
difficulty with searching for conjunctions among distractions consisting of two elements,
which together would constitute a conjunctive stimulus and patients present with
deficiencies in their ability to integrate information after their attention has been focused
on the features. They do not have the ability to use selective attention as the glue to
bind these features (Prather et al., 1992).

Kinsbourne (1970) thought that each hemisphere directs attention to the contralateral
space and that a normal attentional system of one hemisphere inhibits the other
hemisphere. Therefore, if one hemisphere is injured or less active, the other becomes
attentionally hyperactive, and attention is biased to the side opposite the normal
hemisphere. This may be one of the explanations for the increased sensitivity to touch
that learning-disabled children exhibit. The right side of the brain is known to direct
attention to both sides of the body, therefore if it were functionally attentionally
hyperactive, the child may be hypersensitive to stimuli on both sides of the body
and space.

Another reason for hypersensitivity of tactile stimulation maybe that proprioceptive and
tactile input is inhibitory to pain input. Therefore, with decreased proprioceptive input, a
child would be more sensitive to pain and therefore even touch would be painful. This
would be compounded by the fact that loss of proprioceptive or arousal activity to the
neocortex would cause a decrease in inhibition of limbic autonomic output, which in turn
would result in increased sympathetic activity and increased adrenal catecholamine
release. These substances sensitize alpha 2 receptors found in pain transmitting fibers,
bringing the fibers closer to threshold globally. This may result in a child being
hypersensitive to touch because of decreased stimulation or arousal.

Occupational therapists for years have used brushing techniques where they lightly
brush the child's skin, the child eventually becomes “desensitized” to the stimulus, and
the child will not be as defensive to touch. This may not be due to actual
desensitization, but rather increased sensory input may result in an increased arousal
and reciprocal inhibition of each hemisphere so that one is not hyperactive and one is
not underactive. It may increase large afferent fiber input to produce inhibition of pain
directly as well as inhibition of sympathetic output in the spinal cord, and brain.

In summary, sensory processing is a product of multiple factors. The baseline arousal

level and signal-to-noise ratio or neuronal preparation, form the basis of all sensory
perception. This can be globally deficient and/or specifically decreased in a limited area.
It can be imbalanced from one side to the other with one side becoming hyperactive and
the other hypoactive. Any decrease in arousal will affect at least one sensory perceptual
process. The arousal level of a hemisphere is set by the subcortical structures
especially the thalamus and cerebellum. They receive most of their input from muscle
joint and tendon receptors in the postural and antigravity muscles. These receptors,
which are continually transducing gravitational forces into the central nervous system,
create the arousal level and the gamma oscillations that are the basis of all perception.
Hillyard (1999) indicated, "What you are asking about is the nature of neuronal codes
for sensory perceptual information. There is a general assumption that more activity-
greater firing rates etc. -within a nerve cell population means that more information is
being represented or processed by those cells. Conversely, a suppressed response
reflects diminished processing. ... In simple low-level sensory signals, greater physical
stimulus energy produces systematic increases in neuronal response amplitudes that
are paralleled by elevations in the perceived stimulus magnitude. Also signal detection
experiments in humans and monkeys have shown that moment-to-moment fluctuations
in neuronal response amplitudes can predict precisely whether the person or organism
detects a faint signal."

Children with learning disabilities have also been noted to demonstrate various types of
visual and auditory dysfunction. If we look at all sensory perception in light of Luria’s
theory (Luria, 1973) that the brain has three functional units: 1) the arousal unit, 2) the
sensory receptive or integrative unit, and 3) the planning and organizational unit, and
that the second and third are subdivided into three zones. The primary zone sorts and
records incoming sensory stimuli, the secondary zone organizes and codes information
from the primary zone, and lastly the tertiary zone is where data is merged from multiple
sources of input and collated as the basis for organizing complex behavioral responses.
These last two; especially the third or tertiary zones are what make humans unique. In
regard to vision, the primary zone gives us the ability to see, to perceive light at its most
basic level. The secondary zone allows us perform basic responses based on
immediate biologic needs -the limbic response. Most organisms have been created to
have to this level. However, the human neocortex, which fits Luria's description of
tertiary zone gives us the ability to put a higher meaning to this stimulus, to go beyond
basic primitive needs and motivations, and to utilize the stimulus to allow us to obtain
higher more complex goals. This higher goal directed behavior is supported by the
prefrontal cortex. This region allows us to put higher cognitive and emotional
significance to a stimulus like light or sound. The parietal lobes allow us to integrate this
information with other sensory stimuli before the meaning of it all is processed in the
frontal cortex. This area of integration is the seemingly occurs in the temporal, parietal,
and ¬occipital cortices (approximately Brodmann's area 39). The primary zone would
correspond to the primary visual cortex.
Figure 9.5: The human visual system. Goodale and Milner (1992) claim: "two cortical visual systems
have been created to have: a ventral stream for visual perception and a dorsal stream for the visual
control of skilled actions". Damage to the Ventral Pathway: Their case of D.F. demonstrates a complete
dissociation between visual form perception and visuomotor abilities. She can accurately reach for and
grasp an object, which she cannot identify. D.F. suffered anoxia and subsequent damage to the
ventrolateral regions of her cerebral cortex, with sparing of primary visual cortex and the dorsal pathway.
Damage to the Dorsal Pathway: Optic ataxia, difficulty reaching for and grasping objects, often results
from damage to superior portions of the parietal cortex. These patients can recognize and describe
objects. Thus, there is a double dissociation between the ventral/dorsal pathways and the
grasping/perceptual matching tasks. In the dorsal pathway, motion sensitive cells abound, particularly in
the areas MT and MST. Cells in posterior parietal cortex show evidence of anticipating the retinal
consequences of saccadic eye movements. Egocentric coding of these cells: Ventral pathway studies
show that inferotemporal cortex cells are tuned to highly specific forms, for example one IT area is
particularly responsive to face stimuli. These cells have extremely large receptive fields. These large cells
are thought to underly object-centered representations. In studies of dorsal pathways in brain-damaged
monkies, deficits in visually guided reaching resulted from damage to the posterior parietal cortex. In
studies of the ventral pathway, if the inferotemporal cortex is damaged or dysfunctioning bilaterally, the
monkies display severe difficulties in visual recognition and discrimination learning tasks.
 Figure 9.6: The human visual system’s network of pathways.

The final projection of the visual pathway is via the geniculo-cortical pathway. This group of axons exits
the lateral geniculate nucleus of the thalamus and proceeds to the cerebral cortex terminating in the
primary visual area of the occipital lobe (Brodmann’s area 17). This area is regular and stippled in
appearance hence its name the striate cortex. This area is also known as the primary visual area and it is
thought to be the region of the cortex where the first level of visual processing takes place. If the signal-to-
noise ratio is not high enough due to a decrease arousal in the occipital lobe, a child may appear to have
a primary visual deficit, even though the eyes and the visual pathway may be intact. A severe example of
this is related by Glen Doman (1974) in his book What to do about your Brain Injured Child notes that he
would often see children in his clinic who were apparently blind. They would have no apparent reaction
even to the brightest light. These brain-injured children were then placed on a program of therapy.
Surprisingly they noticed that many of these allegedly blind children improved in their visual function
coincident with improved movement ability. Doman assumed that this meant that the pathways
associated with vision in these children were always intact but for some reason this information was not
summating to the level of perception in the brain.

While Doman’s clinical observations were not examined under controlled circumstances, we can
postulate that as these children increased their movement or crawling, they increased the tone of postural
muscles and their feedback to the cerebellum and thalamus. This would increase the baseline arousal
increase signal-to-noise ratio and neuronal sensitivity so that with greater degrees of motor activity the
greater the degree of cerebellar feedback and the greater the effectiveness of sensory perception. The
fact that the primary pathways were intact could also be considered a visual neglect syndrome that would
be the same as tactile or spatial neglect, which would mean that the primary information may be effective
but under-processed and therefore ignored or neglected. This however, would be more characteristically
seen in a hemi-field of vision. Besides primary visual loss or visual neglect, there is an asymmetric
distribution of visual processes. The specificity of symptoms of visual loss, such as object identification
versus spatial localization, or global versus local effects, can help us to localize the problem to the right or
left hemisphere and ventral or dorsal systems.
Ungerleider and Mishkin (1982) proposed a model of cortical visual processing based on two parallel
visual systems, one thought to be directed ventrally to the infero-temporal cortex, and one directed
dorsally to the inferior parietal lobe. It has been shown in monkeys that lesions of inferior temporal cortex
produce severe deficits in performance in a variety of visual discrimination learning but not in visuo-spatial
tasks. However posterior parietal lesions cause severe impairments in visuo-spatial performance, such as
in visually guided reaching and in judging which of two objects is closer to a visual landmark, however
these lesions do not affect visual discrimination performance (Ungerleider & Mishkin, 1982). Some cells in
the parietal lobe are most active in the monkey when it fixes it gaze on an important object (fixation
neurons) other cells fire when the organism is visually tracking a moving object that is important (tracking
neurons) while others fire before a visual saccadic eye movement to a significant stimulus (saccadic
neurons). Finally, there are neurons that fire when important stimuli present to peripheral vision (light-
sensitive neurons) (Bushwell et al., 1981; (Lynch, 1980; Motter & Mountcastle, 1981).

The ventral visual pathway terminates in the inferior temporal lobe (area IT or TE). In TE area neurons, a
small percentage of cells respond selectively to high order complex stimuli, such as faces or hands. Most
of the neurons however respond specifically based on object features such as color, shape, and textures
rather than specific objects. IT area cells are thought to make up a network of cells that appear to be
involved with the representation of general object features. Lesions of the IT areas produce loss of
perceptual constancies and loss of visual memories (Mishkin et al., 1984). It is thought that memories of
visual inputs are limited to a habit learning system that involves the basal ganglia (Mishkin et al., 1984).

The Dorsal Visual Pathway This system provides the basis for peripheral vision, motion perception,
stereopsis, perception of three dimensionality based on perspective and shading, and most of the gestalt
phenomena of linking operations (Livingstone & Hubel, 1987). The dorsal pathway is thought to terminate
in area PG of the inferior parietal lobe and intra-parietal sulcus. In monkeys it has been shown that a
percentage of cells in the PG area fire when the organism fixates on interesting objects in a particular
region in space (Mountcastle, 1978). This is known as ambient vision (Motter & Mouncastle, 1981;
Trevarthen, 1968). Some cells in area P6 have been shown to increase their firing rate when the
organism expects a stimulus in a specific region of the visual field; this is called the enhancement effect
(Robinson et al., 1978). The posterior parietal cortex is involved in the control of spatial attention, lesions
or dysfunction in this region impair the ability to orient attention to the contralateral side with presentation
of invalid directional cues (Posner & Cohen, 1984; Posner et al., 1987). The two visual networks that have
been described are parallel hierarchies of sequential neocortical ¬cognitive representations, they are not
exclusively neocortical however and they are dependent on the function of the limbic system. The ventral
system has direct reciprocal connections to the amygdala and to the orbitofrontal cortex. The dorsal
system connects to the cingulate gyrus, the hippocampus, and surrounding limbic areas. These
connections are thought to provide the integration of emotional, motivational and interoceptive quality of
visual perception (Liottini & Tucker, 1995).

Bilateral damage to both TE and the amygdaloid complex produce severe long lasting recognition loss
(Mishkin, 1978; Zola-Morgan et al., 1982). The affective components are added to visual stimuli by
connections between neocortical aspects of the temporal lobe and amygdala. Without these connections,
it is not possible to associate reward conditions with visual stimuli. The amygdala may also play a role in
integrating perceptual and affective memories into a subjective experience (Gloor, 1990; Ledoux, 1987).

There exist monosynaptic connections from the thalamus to the amygdala (Ledoux, 1987). The thalamo-
amygdaloid system supports premature emotional reactions that are loosely coupled with the stimulus
that do not require object recognition. Inputs to the amygdala from multi-modal association areas can be
involved in evaluating object information integrated from different sensory modalities (Ledoux, 1987). The
orbito-frontal cortex possesses direct reciprocal connections with the temporal pole and amygdala and is
thought of to be the frontal extension of the ventral visual pathway. Severe impairments in visual object
learning have been noted because of orbito-frontal lesions in monkeys (Thorpe et al., 1983). Learning and
unlearning the emotional significance of sensory input may require close interaction with the amygdala
and orbital region.
The convergence of limbic inputs from the cingulate-retrosplenial cortex with
preprocessed sensory information may allow parietal neurons to recognize the
motivational relevance in complex sensory events (Mesulam, 1985). Monkeys with
unilateral cingulotomy display contralateral inattention in visual and somatosensory
modalities (Watson et al., 1973). Right parietal or medial frontal infarcts including the
cingulate cortex result in unilateral neglect for the left hemisphere (Heilman et al., 1983)
and significant inability with spatial memory in half the world (Mesulam, 1985). The
cingulate cortex may mediate adaptively significant attention as opposed to more
spatially oriented attention in the posterior parietal region. Bilateral cingulate infarcts in
humans produce an akinetic state and attentional dysfunction. Bilateral para-
hippocampal lesions result in decreased discrimination of complex geometric forms and
faces.

The right hemisphere is more connected to the dorsal system. The right hemisphere’s
primary role in humans is visual-spatial behavior. Visual-spatial behavior can be
disrupted by right posterior regions including the parietal lobe. Visual-spatial behavior
that is typically disrupted includes visual judgment of line orientation (Benton et al.,
1978a), maze performance (DeRenzi et al., 1977), and the ability to identify objects
presented from an unusual visual perspective (Warrington, 1982). Other functions of
visual processing associated with right posterior damage includes constructional
apraxia, dressing dyspraxia and prosopagnosia or disorders of face recognition
(Hécaen & Angelergues, 1962; Arrigoni & DeRenzi, 1964), depth perception (Kimura,
1961), spatial localization (DeRenzi, 1982), identification of complex geometric shapes
(Unilta et al., 1978) and exploratory eye movements (Sava et al., 1988). The network of
cortical and subcortical regions that control visual orienting in monkeys and humans are
functionally part of dorsal visual system and include the posterior parietal region, the
cingulate cortex, the dorsolateral frontal cortex, the pulvinar, and the inferior colliculus
(Heilman, 1979; Mesulam, 1981).

The right hemisphere stores global configurations of visual objects as opposed to local
features or details of objects. Line orientations are oblique (Umilta et al., 1974). The left
hemisphere is associated with the ventral visual pathway. Lesions in the left occipital-
temporal regions produce visual object agnosia (McArthy & Warrington, 1990). The left
hemisphere is also superior for object identification shown from a usual viewpoint. The
left hemisphere is better for line orientation when vertical, horizontal, or 45 degree
diagonal orientations are used (Umilta et al., 1974) generation of images of visual
objects (Farrah, 1984; Kosslyn, 1987). Patients with left-hemisphere lesions are unable
to assemble parts of visual image into a unified ensemble according to spatial and
temporal relation such as above-below right¬-left (Kosslyn, 1987), long term storage of
categorical, prepositional, or semantic knowledge concerning an object (Kosslyn, 1987),
and analysis of local levels or detection of visual scene, sequential analysis of local
information, or high spatial frequency.
Auditory Processing Symptoms
Many children with learning disabilities and behavioral disorders are also diagnosed
with auditory processing problems. It is most commonly described as a central auditory
processing disorder. In this case, many children have been diagnosed as having
hypersensitivity to various auditory stimuli (Geffen et al., 1992; Geffner et al., 1992).
Others have been thought to have decreased perception to sound. In most of these
cases, it appears that the peripheral pathway is intact and that the problem lies in the
central nervous system.

In 1895, Daniel David Palmer was studying the effects of spinal manipulation and
health. In the building where Palmer was conducting research, a janitor named Harvey
Lillard was working. Harvey Lillard was deaf and D. D. Palmer inquired of the man how
this came to be. Lillard explained that it happened all of a sudden while lifting
something, he heard a pop in his spine and from that time, he could not hear. As the
account goes D. D. Palmer went to the area of the spine pointed out by Mr. Lillard and
he performed the first chiropractic adjustment manipulating the man’s spine. Lillard's
hearing reportedly returned explained by Palmer on the basis a hypothesized
connection between spinal function and brain and nervous system function. We now
understand that spinal joints and muscles have the greatest concentration of receptors
that respond to gravity and movement with the largest degree of activity arising from
postural, antigravity muscles. We hypothesize that by increasing the movement of
spinal joints and allowing those muscles to stretch and contract against the forces of
gravity on a continuous basis, we would expect to increase the arousal level of the brain
through the cerebellar, thalamic and spinal pathways. The result should be an increase
in signal-to-noise ratio and the same level of sound that previously could not be
perceived, now is better able to summate and be processed. This is one simple
explanation.

The cerebellum and thalamus can influence the perception of sound in the same
manner that they are thought to influence vision. The cerebellum and thalamus not only
affect the arousal zone, but also the primary, secondary and tertiary zones, through
connection to association cortices, prefrontal lobe, limbic system, and the effect on the
ability to integrate and temporally bind auditory input with other sensory and emotional
events to perceive and remember these events. Besides these global effects, we must
consider the fact that as with visual and spatial functions, certain auditory functions are
asymmetrically localized in the brain. These specific pathways can also be affected, and
hemi-neglect symptoms may arise.

One method that is commonly used to test these asymmetric functions is the dichotic
listening task. Dichotic listening is a measure of temporal lobe function (Spreen &
Strauss, 1991), attention, and stimulus processing speed as well as a way to measure
hemispheric language asymmetry (Hugdahl, 1992a). It is thought that auditory
lateralization is probably not related to a single mechanism (Jancke et al., 1992), but is
thought to be related to several functions involving both perceptual and other cognitive
factors (Hugdahl, 1995). Hemispheric perceptors of sound are dependent on the level of
activation and attention. Hugdahl has indicated that the level of right ear advantage
(REA) in the DL task is significantly correlated with resting EEG asymmetry. Individuals
with larger left-than-right EEG resting activation also had better recall from the right as
compared to the left ear in DL (Hugdahl, 1995). DL is thought to be particularly effective
at testing frontal-temporal functional integrity (Hugdahl, 1988).

Dichotic listening has revealed a right ear advantage for consonant vowel (CV) syllables
in about 80 percent of subjects and in 65 percent of left-handers. This REA has been
found to be significant in children down to the age of 5 years. The REA for CV syllables
is thought to correlate with the left hemisphere advantage for language skills. REA is
thought to be related therefore to the integrity of the auditory system as well as to the
structural organization of the two cerebral hemispheres. However, it is clear that
dynamic cognitive and emotional factors can affect the level of the ear advantage. Also
attention, transient changes in activation, and arousal have also been shown to
influence the ear advantage. Emotional states especially the threat of negative events
have been shown to affect the ear advantage; this is thought to be due to the right
hemisphere advantage for negative emotions which change the balance between the
hemispheres in activation level for processing of dichotic stimuli.

Directed attention tests have been widely used with learning-disabled children and have
shown a lateralized performance difference between these children and control
children” (Boliek et al., 1988; Hugdahl & Anderson, 1987 Kershner & Micallef, 1992;
Obrzut et al., 1983). Using some form of behavioral task like dichotic listening, visual
half-field, and tactual dihaptic tasks, Bryden (1988) reviewed 51 studies and found 30 of
those studies indicate that learning-disabled children (poor readers) were less
lateralized than normal readers. In one study of 51 children ages 6-12 there were 34
normal control children and 17 learning disabled all of who had above average IQ's
(Mondor & Ueker, 1992). The learning disabled children all demonstrated disability in
reading and related language skills. A tone was presented to either one ear or the other
prior to every dichotic CV trial. In the control children, the results proved that the REA
for verbal functions that have been found in dichotic listening experiments is dependent
on attentional processes. A subgroup of mixed learning disabled and control children
had difficulty performing the dichotic task above chance levels because they could not
orient attention to the cue. It is thought that their inability to orient attention is related to
a possible underlying atypically organized functional (or structural) system or lack of
motivation. An interesting finding in the learning-disabled children who could perform
the task identified the to-be-attended and to-be-unattended items equally often, which is
thought to be indicative of children who exhibit selective attention deficits, but whose
performance tends to vary depending on what they are doing. The authors of this study
concluded that this data seems to support the notion that auditory perceptual
asymmetries in children are the result of the interaction of hemispheric ability and
attentional factors.

Furthermore, it has been postulated (Mondor & Ueker, 1992) that learning disabled
children may be less lateralized for both linguistic and non-linguistic tasks. The results
show that the learning disabled children demonstrate a significant disability in the
auditory-linguistic domain causing a significant dysfunction of reading and related
language skills. Dichotic listening tasks were used, and the results suggest that control
children possess the normal hemisphere shift in laterality (REA for CV's, LEA for tones).
In contrast, learning-disabled children show a processing bias to the same hemisphere
regardless of the stimulus characteristics. It was speculated based on these results that
performing both verbal and non-verbal processing with the same hemisphere is
problematic, and that children who do so are likely to show cognitive processing deficits
and are more likely to be labeled as learning disabled even though they may have
above average IQ's.

Hypersensitivity:

One of the symptoms of children with central auditory processing disorders is

hypersensitivity to certain frequencies. This may be explained by an arousal imbalance
where there may be an attentional bias to one ear. It may also be explained by a lack of
inhibition of one side by the other also due to a hemispheric imbalance of activation. A
decrease of activation of one side may also result from chronic ear infections, which
may interfere with development and produce a developmental lag due to decreased
sound stimulus.

Motor Symptoms

A large percentage of children with learning disabilities demonstrate motor symptoms.

These can range from poor tone, poor posture, slowness or unsteady gait, clumsiness,
high tone, hyperactive motor behavior, weakness, poor coordination, imbalance of
muscle tone, poor eye muscle control, tracking difficulty, poor handwriting, etc. These
motor symptoms involve both voluntary and involuntary motor control. The sensory
pathways of the nervous system that control motor activity involve the receptors in
muscles, tendons and joints that transmit information about various aspects of
movements to the cerebellum, thalamus, basal ganglia, somatosensory cortex and
frontal lobe. The majority of efferent flow of information from the cerebral cortex is
directed to the motor system, but the motor system can only respond appropriately
based on sensory feedback, therefore it makes sense that the majority of subconscious
input to the brain originates from the same motor system. Therefore, any interruption of
the flow of this loop that sends sensory input from the motor system to the brain and
then from the brain back to the motor system will have significant negative effects, not
just on the sensory-motor system but to motor, sensory, emotional, cognitive, and
autonomic functions as well. The majority of this sensory input and motor output is
subconscious, and is processed in the cerebellum, thalamus, and basal ganglia. Many
functions of the motor system are therefore reflexive, and are therefore a direct
reflection of the adequacy of brain activity. For example, resting muscle tone is reflexive
and subconscious and while we may be able to consciously modulate it, the baseline
muscle tone is a reflection of base output in a structurally intact system.

The basal ganglia, thalamus, and frontal lobe are intimately connected to one another
processing mostly somatosensory and motor input. If there exists a dysfunction of this
loop, we would expect to see typical basal ganglion motor symptoms of hypokinesia or
hyperkinesia, as well as dysfunction of motor and non-motor functions of the frontal
lobe. Although the global arousal and activity level is important, what is likewise
important and more often at fault is an imbalance of brain and motor activity. It is
essential that both sides of the brain and both sides of the motor system work together
in a balanced coordinated way. This balanced function is a product of evolution, the
survival of species, and related to the organism’s ability to develop goal directed
movement. To have goal directed controlled movement it is a prerequisite for an
organism to be bisymmetric.

Bisymmetry appears to be an adaptation for motility and therefore applies especially to

the locomotor system, including bones, joints and muscles, as well as those parts of the
nervous system that controls their action (Hiscock & Kinsbourne, 1995). Therefore,
balanced activity is of singular selective advantage for the motor system. To have a
balanced bisymmetric organism and motor system, one must have a balanced and
bisymmetric nervous system. Likewise, to have effective goal directed movement, the
brain must integrate the sensory-motor loop with other brain functions that help motivate
and direct movement as well as provide fuel and oxygen for that movement. The more
goal directed the movement, the more integration is required, and the greater the
requirement for stimulus processing to support the increasing size of the nervous
system which is devoted primarily to sensory-motor functions. Any deviation from
bisymmetry of the motor system results in an imbalance that may result in improper
integration of brain function and over time creates an ever-increasing imbalance.

It has been shown that an increase in arousal or activation of one hemisphere (usually
contributed by the stimulus) is typically accompanied by an inhibition of arousal in the
opposite hemisphere, mediated at least partly by reciprocal inhibitory connections
through the brainstem (Liederman, 1995). Recent literature also states that when one
hemisphere is maintained at a high level of arousal for an extended period, the result is
an activation imbalance and the underutilized hemisphere becomes refractory
(Liederman, 1995). At the spinal cord level, especially in midline spinal muscles,
increased activation, or tone, over one side will be associated with the inhibition of
contralateral muscles, which will alter feedback through the cerebellum and thalamus to
the cerebrum resulting in an imbalance of activation of these structures. In the
periphery, the balance of muscle tone can be imbalanced not only from left to right but
also in the anterior and posterior direction. In the motor system, the midline postural
muscles of the spine and the ocular-motor muscles are primarily controlled reflexively
by the medial zone of the cerebellum or spino-cerebellum. This process is mediated by
the vestibular nuclei and the fastigial nuclei. These muscles have both decussating and
non-decussating controlling efferent pathways so that there exists bilateral innervation
or control. In normal situations therefore, these muscles should be equally balanced.
However, activation of muscles on one side is usually coupled with inhibition of
antagonist muscles on the other side. Decreased activation of the spino-cerebellum will
normally result in decreased activation and coordination of the spinal and ocular-motor
musculature.

Learning-disabled children quite often are seen to have poor postural tone, and ocular-
deficiencies especially saccadic hyper- or hypo-metria (Leisman, 1976a). In infants,
delays in the ability to roll over, head lift, and crawl may be a result of midline postural
muscle tone deficiencies or hypotonia. In older children, the spinal muscles must be
able to react as shunt stabilizers that are needed to create a stable base before spurt
muscle activity of the extremities, therefore apparent weakness of extremity muscles
may be due to failure of the spinal muscles to provide stability for extremity movement.
Persistent tonic neck reflexes that have been noted in hyperactive and learning disabled
children may be due to decreased activation of the cerebellum. Poor spinal muscle tone
may lead to early fatigue of these muscles and may result in muscle pain, neck pain,
and headaches in children. These children are also known to often sit in unusual
postures, shift position, and may this be the cause of fidgety behavior. In an effort to
compensate for their instability, they may hook their legs in their chairs.

In the extremities, muscles are innervated in an anterior and posterior distribution. This
distribution of anterior compartment and posterior compartment control becomes
reversed in the lower extremities during embryologic development so that in the upper
extremities the anterior compartment muscles are neurologically the same as the
posterior compartment muscles in the lower extremity. Voluntary motor activity is
continually controlled contralaterally by the corticospinal and rubrospinal tracts. Muscle
tone is regulated ipsilaterally by the reticulospinal tract and this regulation involves all
muscles ipsilaterally, which includes midline spinal or postural muscles as well as
anterior and posterior compartment muscles. However, the reticulospinal tract also
controls the normal balance of muscles so that anterior muscles of the upper extremity
and posterior muscles of lower extremity are slightly less activated or more inhibited in
relationship to their antagonist muscles. This ipsilateral increase of muscle tone as well
as balance of activation of anterior and posterior compartment balance is thought to be
a phylogenetic development in humans, which promotes an upright bipedal posture.

Reticulospinal output is under the direct control of descending neocortical activation

especially frontal lobe output. Therefore, asymmetric activation of the neocortex may
result in an imbalance of global motor tone as well as an imbalance of anterior and
posterior compartment muscle activation and inhibition. In the spinal or postural
muscles and ocular-motor muscles, this may result in an imbalance and in severe cases
in spinal muscles this may result in a scoliosis or curvature of the spine. It may also
result in a chronic head tilt to one side. In ocular-motor muscles, it may promote a
stabismus or lazy eye that can be aggravated by a chronic head tilt. Subjective clinical
reports often indicate that both strabismus and scoliosis are coincident, possibly a result
of asymmetric hemispheric or neocortical activation or arousal. Both conditions are
often associated with a history of learning disability (Rosner & Rosner, 1987;
Geschwind & Galaburda, 1985, Herman et al., 1985). In the extremities, this may result
in a fixed arm or leg on the side of decreased cortical activation or arousal. This results
in antagonist muscle weakness as well as decreased arm or leg swing on the side of
decreased cortical activation. This condition may also resemble or can be a form of
hemi-motor neglect ipsilaterally.

Motor distribution and development appear to also be asymmetrically distributed in the

cortex as observed by handedness. The left hemisphere appears to favor fine manual
movements, and favors control of distal muscles whereas the right appears to be
superior for control of proximal limb muscles and trunk musculature (Peters, 1995). The
outflow of the intermediate regions of the cerebellum is directed to muscles involved
with the distal portion of the limbs. The lateral region of the cerebellum is directed at
areas of the cortex and basal ganglia that are involved with planning and animation of
movement. There is thought to be an especially close relationship between the output
nuclei of the lateral cerebellum, the dentate nuclei, and the premotor and supplementary
cortices, which are directly implicated in the organization, planning, and modification of
motor activities (Allen et al., 1978; Halsband et al., 1993).

Basal ganglia dysfunction results in movement disorders of which we have described

two types, hyperkinetic and hypokinetic. Hyperkinetic disorders present with
increased motor activity and tone. Hyperactivity in children is often referred to as
childhood hyperkinetic disorder. Hypokinetic dysfunction is often seen as slowness of
movement or hypotonia. Frontal lobe motor dyspraxia dysfunction is seen in paratonia,
and neurological examination of hyperactive children suggests that they experience
more difficulties with coordination and more overflow movements than in control
children (Gillbery & Rasmussen, 1982; Gillberg et al., 1983; Shaywitz & Shaywitz, 1984;
Denkla et al., 1985). Studies that used various tests of motor coordination, such as
balancing, gesturing, copying, writing, maze tracing, and pursuit tracking reported more
difficulties on the part hyperactive children (Shaywitz & Shaywitz, 1984; Korkman &
Pesonen, 1994; Mariani & Barkley, 1997). Joe Sergeant and his associates performed
studies in which a range of task variables was manipulated to create differential
demands at different processing stages. They found that hyperactive children were
slower in responding and more variable in their response time (Sergeant & van der
Meere, 1990). They also found an event rate effect (van der Meere et al., 1989). In a
low event rate condition, the hyperactive children had a significantly longer reaction
time. This was thought to demonstrate a deficit at the motor adjustment stage, which
controlled the motor preparatory processes (Sanders, 1983).

It has also been noted that a conceptual model linking performance and hyperactivity
requires the consideration of factors related to energy supply. It has been suggested
that motor adjustment is optimized by preparatory processes. However, preparatory
processes could only be effectively maintained for short period requiring energy
resources of alertness or activation (Sanders, 1983; Meulenbroek & Van Galen 1988).
One hypothesis for this is that a low event rate, which causes a longer foreperiod, taxes
activation and therefore hyperactive children cannot maintain the activation and the
preparatory processes necessary. In contrast, it is postulated that a high event rate,
which has a shorter foreperiod, puts less demand on activation and therefore the
preparatory processes remain optimized (Leung & Connolly, 1998). This may explain
why in a high event rate condition, hyperactive children perform as well as controlled
children (van der Meere et al., 1992). It has been suggested therefore that hyperactive
children are primarily defective in energy resources, and a motor deficit is a secondary
consequence (Leung & Connolly, 1998). Therefore, checking for Metabolic factors
should be considered PRIMARY to effect frontal lobe function.

These results may be interpreted in the context of cerebral asymmetry. The right
hemisphere is favored for low temporal frequency movement therefore decreased
activation or arousal of the right hemisphere would result in a low event rate deficit and
fatigability, whereas the left hemisphere which favors high temporal frequency
movements would perform at normal levels. Barkley (1997) interpreted performance
impairments in complex motor coordination tasks, such as copying designs, writing,
maze tracing, and pursuit tracking, as indicative of a motor-control deficit, which, he
suggested, was a link to a more central deficit in behavioral inhibition. Behavioral
inhibition has been recognized as a core deficit associated with hyperactivity
(Pennington & Ozonoff, 1996; Barkley, 1997).

Much has been written about the role of the basal ganglia in motor and cognitive
functions (Alexander et al., 1986; DeLong, 1990; Alexander et al., 1990; Albin et al.,
1995; Graybiel, 1995; Brown et al., 1997; Feger, 1997). Five frontal-subcortical
pathways connect areas of the frontal lobe (supplementary motor area, frontal eye
fields, and the dorsolateral prefrontal, orbito-frontal, and anterior cingulate cortices) with
the striatum, globus pallidus and thalamus in functional systems, that mediate volitional
motor activity, saccadic eye movements, executive functions, social behavior, and
motivation (Alexander et al., 1986; Alexander & Crutcher, 1990; Mega & Cummings,
1995; Cummings, 1995). It has been suggested that normal basal ganglia function
comes from a proper balance between direct and indirect striatal output
pathways, and therefore abnormal imbalance or differential involvement of these
pathways can result in hyperkinesia or hypokinesia of the type seen in basal ganglia
disorders (DeLong, 1990; Albin et al., 1995; Alexander & Crutcher, 1990).

Litvan and colleagues (1998) found that patients with hyperkinetic disorders exhibited
predominantly hyperactive behaviors (e.g. Tourette’s agitation, ADHD, obsessive-
compulsive disorder, irritation, euphoria, or anxiety), and those patients with hypokinetic
motor activity, manifested hypoactive behaviors like apathy and possibly depression.
Injury of the caudate is thought to be responsible for neuropsychiatric symptoms that
include depression, mania, apathy, disinhibition, obsessive-compulsive-disorder (OCD),
defects in planning and sequencing, attention, and free recall (Salloway & Cummings
1994). Lesions of the globus pallidus can cause OCD, Tourette’s, apathy, irritability,
mania, and amnesia. Lesions in the medial caudate (and projecting to the orbito-frontal
cortex) can produce apathy and depression. Inferior lesions can produce disinhibited
behavior, with dorsolateral lesions of the caudate (and projecting to the dorsolateral
prefrontal cortex) being associated with decreased ability in executing executive
functions. Bilateral caudate dysfunction is thought to be involved in most patients with
mania (Alexander et al., 1994). With basal ganglia disorders then, we can see an
increase in motor activity, such as tremors, motor and vocal tics, uncontrolled
movement, or motor overflow, collectively known as hyperkinetic disorders. These
appear to correlate with hyperactive behaviors. In contrast, hypokinetic disorders
characterized by slowness or decreased motor output as in Parkinson's disease appear
to correlate with hypoactive behaviors.

Regarding motor activity and hemispheric asymmetry, it has been shown that the right
hemisphere has a somatotopic representation for sensory input for both right and left
sides of the body, as well as an attention control function for both sides of space. The
left hemisphere, however, is thought to have a similar pattern for the control of motor
activity and intention. Whereas the right hemisphere controls motor activity and intention
for only the contralateral side of the body, the left hemisphere appears to have control
over the right (contralateral) and left (ipsilateral) side of the body for motor activity and
intention. This was seen as early as 1905 when Liepmann reviewed results of 89
patients tested for signs of apraxia with unilateral hemiplegia. He found that right brain-
injured patients had normal right hand function while their left hand was paralyzed,
approximately half of the left brain-damaged patients showed signs of severe apraxia or
dyspraxia when trying to function with their left hands while their right hands were
paralyzed. The conclusion was that an intact left hemisphere was not only
necessary for normal function of right-sided movements, but it was also
important for the normal function of intentional actions on the left side. It
appeared that the left hemisphere played an executive role in voluntary motor
function for the entire body both left and right side (Liepmann, 1900; Harrington &
Haaland, 1991).

Interestingly dopamine, which is thought to regulate movement and is intimately

involved with mood and motivation, is asymmetrically distributed favoring the left
hemisphere. Decreased dopamine activity has been implicated in attention deficit
hyperactive disorder as well as a number of basal ganglia disorders including both
hyperkinetic and hypokinetic. Dopaminergic brain innervation arises from neurons
located in the mesencephalon forming two subsystems. In the cortex, there is extensive
dopamine innervation in the prefrontal, premotor, and motor areas and a relatively
sparse innervation in posterior regions. It appears that in general there is a preferential
innervation in motor versus sensory cortices and association areas versus primary
sensory areas (Fallon & Loughlin, 1987). Therefore, it is assumed that dopamine is
involved in higher integrative cerebral functions and in the regulation of cortical output
activity especially in motor control (Wittling, 1995) with conclusions based on anatomic
studies and confirmed by findings from lesion and pharmacological studies (Clark et al.,
1987). These studies show that the integrity of dopaminergic pathways is crucial for the
selection and operation of appropriate motor responses and for the coordination of
motor with sensory input.

Volkow and colleagues (2000) studied brain scans of 30 healthy males and females
spanning many adult ages. The brain scans measure dopamine, which they think
regulates human behavior including movement, working memory, and the
experience of pleasure and reward. They found a direct relationship between
depleted stores of dopamine and a decline on tests that measure motor and cognitive
abilities. In another study Glick, Ross and Hough (1982) examined neurotransmitter
concentrations in the left and right sides of various brain regions collected by Rossor
and colleagues (1980) in postmortem studies of 14 normal human subjects. Results
showed that dopamine content is significantly higher in the left globus pallidus than in
the right globus pallidus. Wittling (1995) states, "Neurotransmitters such as dopamine,
being more intimately involved in the control of motor behavior and higher integrative
functions, obviously favor the left side of the human brain, whose leading role in the
control of these functions is undisputed.”

Recent studies have described the first direct evidence that dopamine triggers the major
symptoms of schizophrenia, including psychosis. Nora Volkow (cf. Vastag, 2001)) was
recently quoted as saying “schizophrenia is caused by a very significant disruption of
the dopamine system." The area of the brain thought to be targeted by the disease is
the striatum, which is rich in dopamine. In schizophrenic patients, findings in visual half-
field tasks seem to provide evidence of a left hemisphere dysfunction (Bruder, 1995). In
studies of identical twins where one of the twins develops schizophrenia, it has been
noted that in comparing the movements of the two as children that the twin who
develops schizophrenia demonstrates motor deficiencies or jerky movements as
compared to the unaffected twin (Torrey et al., 1994). Abnormalities in dopaminergic
neurotransmission have been implicated in a number of neurologic and psychiatric
disorders including schizophrenia, attention deficit hyperactivity disorder (ADHD),
Tourette’s syndrome (TS), autism, alcoholism, drug addiction, and Parkinson's disease
(Cummings, 1990; Young & Penny, 1984; Bunzow et al., 1988; Cummings et al., 1991).
In each of the different conditions, it has been noted that a large percentage of
individuals have motor difficulty.

Ayers (1972) noted that learning disabled, autistic, and children with ADHD had motor
problems as a prominent feature. She thought that this was primarily a result of poor
sensory integration especially from the inner ear vestibular system; this is probably
because the majority of motor symptoms could best be described as cerebellar
symptoms. Ayers referred to this problem as developmental dyspraxia and she is
quoted as saying, "Developmental dyspraxia is one of the most common manifestations
of sensory integrative dysfunction in children with learning disorders or minimal brain
dysfunction." Ayers discussed five aspects of movements and movement disorders that
were disrupted in learning disabled children:

1) smooth control of movement such as picking up a pin,

2) postural reactions such as rolling over or balancing on one foot,
3) patterns of movement that are programmed into the central nervous system (e.g.
crawling or walking,
4) specific motor skills, (e.g. writing the alphabet), and
5) motor planning.

Ayers felt that developmental dyspraxia is a brain dysfunction that decreases the
organization of tactile, vestibular, and proprioceptive sensations and interferes with
motor planning. Motor planning is primarily performed by the cerebellum in connection
with the frontal lobe. The cerebellum is also the brain region that processes tactile,
vestibular, and proprioceptive sensations. Children with autism, ADHD, and patients
with schizophrenia have all been shown to have structural changes and atrophy
of the cerebellum (Fatemi et al., 2002, Harris et al., 1999; Keller et al., 2003). Some of
these patients have been shown to have smaller areas of the cerebellum, basal
ganglia, and frontal lobes than those not affected.

A subset of autism is PDD, pervasive developmental disorder. Autism is characterized

by an inability of relating to other people. The autistic child is often described as being in
its own world. Speech or communications is often limited and, if they learn to speak, it
has been noted that their speech lacks prosody, or intonation. In addition, autistic
children may have emotional problems; sometimes they may show too much emotion
and other times there appears to be no emotion at all. It is estimated that autism is a
disorder of the brain and behavior that affects 5 out of 10,000 children (Wing & Potter,
2002). Autistic children appear healthy but may stare into space for hours, throw
tantrums, show no interest in people, and perform perseverative or repetitive activities,
like head banging, they may also have their attention drawn to small details and they
may have difficulty inhibiting or stopping their actions.

Recently it has been reported that autistic children have subtle abnormalities in body
movements or motor activity that can allow diagnosis as early as three months of age.
Teitelbaum and colleagues (1998) described their findings obtained by examining
videotapes of babies that were later diagnosed with autism. The infants apparently
showed specific motor deficiencies, which included difficulty rolling over, sitting up,
crawling, and walking. It is thought that examining motor symptoms may also help
diagnose other developmental disorders like, schizophrenia or attention deficit disorder.
Anne Donnellon, of the University of Wisconsin at Madison, was quoted by the NY
Times (New York Times, 1/19/99) as saying, "Teitebaum's work is important because it
reflects a reality about autism that has been missed. We tend to think that it is a
problem with the mind. Now that we are really beginning to see how the brain works we
know that the mind is embodied. Body is part of the mind and there's no way to
separate." Teitebaum, in the same article, commented that he got the idea of looking at
autism as a movement disorder partly because of his work with brain damaged
organisms. As they recover, he said, they go through predictable stages that reflect
fundamental aspects of brain organization. Because human babies also pass through
predictable stages of development, he theorized that deficits in the brain might show up
in early movements. He notes that none of the autistic babies learned to roll over as
normal children did. In addition, unlike normal infants who usually learn to sit up at 6
months, autistic infants fall over easily falling to one side "like a log" and failing to break
their falls with their hands. Abnormalities are also seen in crawling and every autistic
child shows some degree of asymmetry in walking.

Glen Doman (Thomas, 1969; Doman, 1974) has noted in his subjective clinical
observations, that brain injured children, often are unable to crawl or walk. He thought
similarly that children go through predictable stages of recovery from injury. He thought
that if a child missed a stage of recovery that child would have difficulty
progressing beyond that point. He felt there were different stages of crawling that a
child needed to go through before they could walk. If children did not progress from
crawling to walking, their brains and nervous systems would not develop
normally. Left unanswered by this approach is whether the problem arises first in the
cerebellum or whether it starts as a motor problem. In addition, we do not know whether
the motor problem causes the difficulty in development and with the associated
symptoms or whether it a dysfunction of the cerebellum or sub-cortical motor regions
that causes the problem.

In infants, it is known that the cortex is not completely developed, especially the
frontal and prefrontal lobes, which are thought to assist in the control of motor
planning. In infancy, the control of movement is centered at the subcortical level,
especially in the cerebellum (Trevarthen & Aitken, 2001). The cerebellum receives
information from the motor system, the spino-cerebellum, or vermis. The lateral
cerebellum is thought to be involved with higher cognitive function and is
especially connected to the prefrontal cortex. The lateral cerebellum, or cerebro-
cerebellum, receives most of its input from the cerebrum. Therefore, examining
the cerebellum may give us an idea as to which problem is the primary. If the
vermis shows an abnormality, lack of development, or atrophy, it is more likely
that the motor system is at fault and the developmental lag starts with failure of
development of the vermis or its presynaptic connections. If the vermis alone is
smaller, then we can think that the problem arose principally after the
development of the lateral cerebellum, but initiated by a dysfunction of the motor
system. If the lateral cerebellum is affected, then either it can be the result of an
intrinsic problem, or an inadequacy of stimulation from the frontal lobe to the
lateral cerebellum.

In regard to ADHD, imaging studies over the past decade have indicated which brain
regions might malfunction in patients with the condition and that may account for the
symptoms. This work suggests that involvement includes the prefrontal cortex, part of
the cerebellum, and areas of the basal ganglia. In a study in 1996, Castellanos and his
colleagues found. Castellanos' group also found that the vermis region of the
cerebellum is that the right prefrontal cortex, the caudate nucleus, and globus
pallidus are significantly smaller in children with ADHD . Patients with
schizophrenia and autism have also shown structural changes of the cerebellum
(Cahn et al., 2002; Ojeda et al., 2002; Deshmukh et al., 2002). It has been noted that
several arguments support the cerebellum as a site of pathological or abnormal function
in schizophrenia. Traditional neuroscience however, still considers the cerebellum
exclusively associated with control of motor and ocular-motor functions. This is thought
to arise from research on human cerebellar function on patients with cerebellar lesions
where motor and ocular-motor signs are the most pronounced clinical finding (Martin &
Albers, 1995). Previously motor and ocular-motor abnormalities known to be present in
schizophrenia have been ascribed to basal ganglia, limbic and neocortical dysfunction
(Martin & Albers, 1995). Blueler (1911) noted gait abnormalities in schizophrenia
patients. He especially noted the irregular space and timing of their steps. Another
unpublished study observed 16 schizophrenic patients at psychiatric University Hospital
Zurich appear to show movement abnormalities. It was postulated that the clinical
pattern of these patients may correlate to Blueler's observations and that these clinical
findings may be blamed on a dysfunction of the anterior vermis of the cerebellum (Victor
et al., 1959; Dichgens & Diemer, 1984).

Various visual-motor abnormalities especially of saccadic and smooth pursuit eye

movements have been noted in schizophrenia, and an increase of dysmetric, mostly
hypometric, saccades are a consistent finding in schizophrenia (Leven et al., 1981;
Schmid-Burge et al., 1982). Saccadic dysmetria is thought to be characteristic of
lesions in the dorsal cerebellar vermis; hypermetric saccades are thought to
result when lesions involve larger areas of the dorsal vermis and fastigial nucleus
(Zee, 1984). A postmortem study (Weinberger et al., 1980) showed that an abnormally
small anterior cerebellar vermis was significantly more frequent in brains of
schizophrenics as compared to normal controls. Furthermore, the cerebellar cortices
showed Purkinje cell losses of different degrees and thinning of the granular and
molecular layers of the cerebellar vermis. It has also been reported in another study,
which reported a loss of Purkinje cells and granule cells in schizophrenia, mainly in
patients with catatonic schizophrenia, as well as patients with epilepsy and psychosis
(Stevens, 1982). Reyes and Gordon (1981) used light microscopy to analyze the brains
of eight schizophrenic patients. They also found a decreased number of Purkinje cells
per unit line length of Purkinje cell layer in chronic schizophrenia as well as an over
development (surface density) of the Purkinje cell layer.

Computerized tomography imaging studies (CT) also showed structural changes in the
cerebellum in schizophrenic patients. CT scans in nine of 60 schizophrenic patients
showed cerebellar atrophy (Weinberger et al., 1979). Another CT study suggested
pathology, mostly atrophy of the cerebellar vermis in a large percentage of
schizophrenic patients (Heath et al., 1979). Lippman and associates (1982) showed
abnormal cerebellar dimensions on CT scans in 30 percent (17 percent abnormal
vermis) of schizophrenic patients. Another study showed enlarged fourth ventricles and
decreased vermis width in chronic schizophrenic patients (Dewan et al., 1983). Sandyk
and colleagues (1991), in a CT study, found vermal cerebellar atrophy in 10 of 23
chronic schizophrenic patients. Data published by Rossi and associates (1993) shows a
gender difference in the vermis. MRI imaging shows male schizophrenics have
significantly smaller anterior vermal areas than female as compared to normal controls.

It is interesting to note that male children are three times as likely to develop ADHD
as girls (Barkley, 1997). PET scans of the frontal lobe in a group of medicated chronic
schizophrenics (Volkow et al., 1992) show decreased cerebellar metabolism that was
independent of metabolic activity in the basal ganglia. Psychiatric disorders have been
noted in various cases of cerebellar pathology (Heath et al., 1979; Kutty & Prendes
1981; Hamilton et al., 1983). Neuropsychiatric disorders especially dementia has been
seen with cerebellar degeneration (Schmahmann, 1991). Autistic symptoms have been
shown in Joubert syndrome an autosomal recessive disorder that has partial or
complete agenesis of the cerebellar vermis (Joubert et al., 1969; Holroyd et al., 1991).
Neuropathologic studies have shown loss of Purkinje cells and less frequently granule
cells in the neo-cerebellar cortex. Cell loss was also found in the deep cerebellar nuclei
in autistic individuals. The anterior cerebellum and vermis were also involved to a lesser
extent (Bauman, 1991; Courchesne, 1991) in affective psychosis but are still associated
with cerebellar atrophy. One study of patients with bipolar disorders showed vermis
atrophy (Lippman et al., 1982) and Nasrallah and colleagues (1981; 1982) found
cerebellar atrophy in a large percentage of patients with mania.

Alcohol abuse shows typical cerebellar atrophy, cerebellar lesions due to alcohol toxicity
are seen with anterior vermis atrophy (Victor et al., 1959). It is known that the
cerebellum is anatomically connected with areas of the brain that are not primarily
involved in motor functions (Leiner et al., 1991). Although for the past hundred years,
the cerebellum has been regarded as a motor organ (Brooks, 1984), the cerebellum
receives input from every sensory system (P. Brodal, 1978; 1981) and is known to be
activated by tactile stimulation without the requirement for movement (Fox et al., 1985).
The cerebellum is not considered a sensory organ as deciphering whether nervous
structures have a sensory or motor function is difficult since motor behavior is guided by
ongoing sensory acquisition of object information and the accuracy, coordination, and
smoothness of motor behavior depends on continuous updated sensory data (Gad et
al., 1996).

In regard to non-motor control, the same dependence on sensory input probably exists.
Neuroanatomic and electrophysiologic studies show that the cerebellum is part of a
neural system that includes the thalamus, basal ganglia, and frontal lobes (Thatch,
1980). In addition, PET studies have shown a strong correlation between metabolic
rates of the cerebellum and frontal cortex (Janck et al., 1988). Ascending projections
from the cerebellum to the hippocampus-amygdaloid complex arise primarily from the
fastigial nucleus, are bilaterally arranged, and are mono- and polysynaptic (Heath &
Harper, 1974; Newman & Reza 1979). It is thought that it is through the polysynaptic
connections that the projections reach the limbic system via the ventral tegmental area
(AlO) of the mesencephalon (Snider et al., 1975; 1976). The paleo-cerebellum-limbic
projections, which are the pathways from the anterior vermis and fastigial nucleus to
several areas of the limbic system, have been shown to modulate sensory input to the
hippocampus (Newman & Reza 1979) and also shorten or stop seizure discharge
produced by electrical stimulation of the amygdala and hippocampus (Maiti & Snider,
1975). It has been shown that this is a bilateral descending hippocampal-cerebellar
projection system ending mostly in the vermian portions of the cerebellum (Newman &
Reza 1979). Purkinje cells project from the cerebellar cortex by GABA and inhibit
neurons of the deep cerebellar nuclei of the cerebellum (Ito, 1976). According to studies
on intra-nuclear collateral neurons of the deep nuclei, these neurons most likely use
glutamate as a transmitter and mediate excitation of mesencephalic dopaminergic
neurons (Snider, 1975; Snider et al., 1976; Audinot et al., 1992), thereby increasing
mesolimbic and mesocortical activity. In addition, noradrenergic and serotonergic
projections as well as cholinergic pathways from the fastigial nucleus to the septal
region (Paul et al., 1973) may mediate non-motor functions of the cerebellum (Martin &
Albers, 1995).

It has been shown that the dopamine D3 receptor is expressed not only in limbic
structures but also has been noted in Purkinje cells of the cerebellar lobules IX and X
(archi-cerebellum) in rat brain. It is therefore thought that the same neuronal substrates
may be involved in motor control as well as in cognition and emotion. Structural
changes in other areas as the medial temporal lobe in schizophrenic patients are called
neuro-developmental disorders (Roberts, 1991). It has been postulated that the same
may be the case in vermal pathology in schizophrenia. The embryologic development of
the neo-cerebellum and the paleocerebellum, that is, essentially the anterior vermis,
differs in regard to neuronal tissue timing and migration (Larsell & Jansen, 1972; Altman
& Bayer, 1985). This developmental difference may offer a partial explanation of the
preferential involvement of the anterior vermis and it may also reflect the different input
that comes arrives in that area which promotes development. Findings suggest that a
decrease in anterior vermal areas of schizophrenics is specific to males (Rossi et al.,
1993). Increased activity of the fastigial nucleus because of decreased inhibition by
vermian GABAminergic Purkinje cells is in agreement with the dopamine hypothesis of
schizophrenia (Synder, 1976). The excitatory, possibly glutaminergic projections of the
fastigial nucleus to dopaminergic neurons in the mesencephalon are disinhibited and
therefore lead to elevated dopamine concentrations in the forebrain (Snider & Snider,
1979). In addition, the fastigial nucleus has been shown to modulate and project
through serotonergic, noradrenergic, and cholinergic pathways, which are thought to be
involved in the neurochemistry of schizophrenia (Tandon & Greden, 1989; Lieberman
& Koreen 1993) as well as depression, and other psychiatric symptoms. It has
further been reported that electrical stimulation of the cerebellum with the use of
cerebellar surface pacemaker stimulation for intractable behavioral disorders results in
at least minimal improvement in the majority of their chronic schizophrenics and also in
the smaller groups of patients with depression (Heath et al., 1980).

The hypothesis that dyslexia has a cerebellar-vestibular (C-V) foundation was first
reported by Frank and Levinson (1973). In their study, of 115 dyslexic children 97
percent showed what the investigators thought to be clear-cut neurologic signs of C-V
dysfunction. The reported C-V signs included positive Rhomberg, difficulty in tandem
walking, articulatory speech disorders, dysdiadokokensis (medical term for an inability
to perform rapid, alternating movements), hypotonia, and various dysmetric or dyspraxic
symptoms, pass pointing during finger to nose, heel to toe, writing, drawing as well as
ocular fixation, and tests for scanning (Dow & Mociegye, 1958). In addition, it was
reported that 90 percent of the dyslexic sample tested with electronystagmography
evidenced vestibular abnormalities (Frank & Levinson, 1973). It was further reported
that C-V related mechanisms thought to be responsible for each of the various
symptoms were examined neuropsychologically (Levinson, 1980; 1984). These finding
were seen as proof that dyslexia and learning disabilities reflected a single disorder and
were thought to share a common group of C-V determining mechanisms and symptom
combinations.

Ayers (1972) has reported a beneficial result of sensory integration or vestibular

stimulation training of learning disabled persons. Also positive responses in reading,
writing and concentration were reported for learning disabled individuals subjected to
ocular-motor fixation, scanning, and perceptual motor exercises thought to cause CV
stimulation (Hilliwell & Solan, 1972; (Pierce, 1977; Flay et al., 1984). In addition, a
reduction in academic failure has been noted for a large sample of culturally
disadvantaged first graders who were given physical education emphasizing exercises
requiring C-V control (Kohen-Raz, 1986). It has also been noted that vestibular-
determined postural training in deaf toddlers who exhibited gross motor and cognitive
retardation became normal when their deficient or reduced labyrinthine function was
stimulated (Kaga et al., 1981). Furthermore, Levinson (1990) performed neurological
and optokinetic measures of cerebellar and vestibular function on learning disabled
subjects and controls. He reported that a substantial majority of learning disabled (82-90
percent) showed ADD- like symptoms. Levinson thought that since learning disabled
sub-samples with or without attention deficit disorder (ADD) showed similar coexisting
symptoms and CV signs, it was probable that learning disabilities and ADD were a
reflection of the same underlying CV determinants. In studies using PET scans of 25
hyperactive adults compared to a control group Zametkin and Ernst (1999) found that
there was less overall activity in the brains of hyperactive adults, especially in the
premotor cortex and superior prefrontal cortex. The frontal lobes regulate goal directed
behaviors, a hierarchy of reflexive movements, cross-temporal contingencies, approach
and avoidance behaviors, response inhibition, and perseverations (Chatterjie, 1998a;
1998b). Furthermore, the prefrontal cortices regulate goal-accomplishing movements
(Luria, 1966). Along with the basal ganglia and cerebellum, these structures regulate
primary motor output (Chatterjee, 1998a; 1998b).

The goal directed movements regulated by the prefrontal cortex are complex and have
multiple sequences. Luria suggested that following frontal lobe damage, subordinate
reflexes are no longer integrated seamlessly into goal directed movements (Luria,
1966). Frontal damage or dysfunction produces two characteristic defects.

• First patients with frontal damage may have difficulty initiating movements
without guidance of explicit stimuli. Clinically these patients are passive and
apathetic, reminiscent of children with autism or depression.
• Second, these patients may have difficulties inhibiting responses to stimuli.
Clinically they are distractible and react randomly to environmental stimuli. This is
more typical with children with ADHD.

Many patients with frontal damage show features of both kinds of deficits (Heilman &
Watson, 1991). They do not know when to move or when not to move (Chatterjie,
1998). The difference is that the primary symptom probably lies in an asymmetric
dysfunction of the prefrontal region. Autistic children for example are thought to have
left brain deficits, which normally produce approach behavior, therefore with
decreased activation avoidance behaviors are exhibited. This would be seen as a lack
of ability to appropriately perform intentioned movement, disability in initiating
movement or of approach movement. Children with right brain deficits show decrease
in avoidance behavior, which is typical of right frontal lobe involvement. This decrease
in effective avoidance movement translates to increased approach movements, typical
of a hyperactive child.

The right brain also governs attention, and with deficits in response inhibition, the
child's ability to focus attention will likewise be deficient with an oftentimes seen
consequence of perseverative or repetitive movements, all typical of right brain deficits.
Right-brain involved children will demonstrate increased levels of approach movements
and repetition that they find difficult to stop, whereas with the intention- governing, left-
brain, those children with primary activation impairment in this hemisphere we observe
lack of initiative, motivation, or effective intentional movements. Depression, shyness,
and lack of initiative or motivation are typical of left-brain decrease in activation or
arousal. Increase activation or arousal on one side or the other produces the exact
opposite reaction in each hemisphere.

What seems to be demonstrated is an imbalance in the complimentarity of the right and

left hemispheres as well between the frontal and parietal lobes of the same hemisphere
and attendant subcortical structures. For instance, increase firing of the basal ganglia
and thalamus activating one hemisphere will produce hyperkinetic movements and
increased activation of that hemisphere. Decreased basal ganglia and thalamic firing
may produce hypokinetic movement and decreased firing of frontal areas on that side.
Depending on whether the decrease or increase is right or left frontal will
determine whether the child exhibits increase avoidance or approach
movements. Again, the frontal lobe controls goal directed movement and behavior.

An individual’s approach to environmental stimuli is an important aspect of goal-directed

behaviors. Dense interconnections between prefrontal cortices and somatosensory,
visual, and auditory cortices provide the neural substrate for integration of and
sensations (Barbas & Pandya, 1991). Based on monkey studies, it has been postulated
that inhibitory interactions between parietal and frontal cortices mediate the approach to
and avoidance of stimuli (Denny-Brown, 1958). Therefore, it is thought that individuals
can choose to approach or avoid environmental stimulation by modulating parietal and
frontal lobe activity (Chatterjie, 1998). A recent study of patients with frontal lobe
disease (Beversdorf & Heilman, 1998) compared motor dysfunction to cognitive
dysfunction using standard tests of frontal lobe cognitive function. This study compared
the motor and non-motor functions of the frontal lobe to see if there was a correlation
between the two. In the past the motor and non-motor function of the frontal lobe were
considered separate and therefore did not relate directly to one another. This study
suggests that there is a direct and equal relationship between motor and non-motor
deficits of the frontal lobe. Therefore, the degree of cognitive or behavioral dysfunction
correlates directly to an individual’s motor dysfunction. Therefore, it is postulated that in
patients with diffuse prefrontal dysfunction, the inability to inhibit simple movements to
simple external stimuli may correlate with the inability to inhibit complex social behaviors
in response to complex internal stimuli. If this correlation is accurate, then a motor
dysfunction could result in cognitive and emotional dysfunction and vice versa. This also
has powerful therapeutic implications because it should follow that improved sensory-
motor function should result in improved cognitive and behavioral function of the frontal
lobe.

Although sensory and motor symptoms may be consistent findings in children with all
types of emotional and learning problems, some children will express more cognitive or
academic problems. These children demonstrate more typically, what has become
known as a learning disability and most of them have difficulty in left hemisphere
functions of verbal skill, reading, math, and writing. As we start to understand the
asymmetric distribution of specific function in the brain, we realize that traditional
education paradigms and instruction mostly emphasizes left-brain activities. This is not
to say that the right brain is not needed; however, the three R's, the foundation of
education, are left-brain activities. Therefore, standard I-Q tests are also biased toward
testing left-brain function, whereas E-Q or emotional intelligence involves mostly right-
brain functions. It has been said that to be successful in school, a child needs good left-
brain function, but to be successful in life one needs the right. The left-brain focuses on
small details, facts, and local stimuli, whereas the right-brain examines the big picture -
global stimuli. In reality, the goal is bilaterally, active, integrative function between the
two hemispheres. We want to aspire to a brain that functions like Leonardo DaVinci’s, a
great scientist, inventor (left-brain), and artist (right-brain). Balance of activity is key and
in these children, we see symptoms similar to a disconnection syndrome in split-brain
patients. Although learning disabilities may arise secondary to right brain, attentional,
behavioral, or hyperkinetic activity, the more severe learning disabilities that affect
academic performance are typically lateralized to the left. We have reviewed their
function and location earlier and will now examine dysfunction in language, auditory
processing, dyslexia, dyscalculia, dyspraxia while writing (dysgraphia), autism or autistic
tendencies which tend to constitute the majority of the population of learning disabled
children.

There exists a specific group of children who exhibit noticeable deficiencies performing
tasks that require semantic-linguistic or visuo-spatial skills or both. Characteristics of
children with developmental learning disabilities have been well documented over the
last few decades and have often been compared to adult patients with known brain
lesions (Boliek & Obrzut, 1995). Observation of these children has been summarized by
Hynd and Willis (1988) to include a congenital form of learning disability, which appears
to affect more males than females. It has also been noted that in general these learning
disabilities do not respond to classroom education remediation. It has further been
hypothesized that these disabilities may be related to a neurodevelopment process
primarily affecting the left hemisphere (Baliek & Obrzut, 1995). Laterality hypotheses
have been promoted mostly based on studies of infants, children, and adults with known
lesion sites. Developmental dysfunction of the same brain areas as seen in acquired
disorders, may be the basis of learning disabilities (Dawson, 1988; Obrzut, 1981). It is
generally accepted that individuals with learning disabilities demonstrate abnormal
cerebral organization, which includes abnormal or weak patterns of hemispheric
specialization (Bryden, 1988 Corballis, 1983; Obrzut, 1988). It has been shown that
learning disabled children exhibit decreased performance on a number of tests thought
to measure perceptual laterality, and it has been shown that weak laterality has been
found across several modalities including auditory, visual, and tactile as well as two
combined modalities such as verbal-manual tasks. It has been proposed that these
children exhibit abnormal cerebral organization (Corballes, 1983; Obrzut, 1988). The
basic assumption is that abnormal structural development of the central nervous
system, developed prenatally or during early postnatal development, causes abnormal
cerebral organization and associated functional specialization that is necessary for
lateralized processing of language and non-language information. It is thought that
cortical and subcortical dysfunction develops from abnormal patterns of activation or
arousal (Obrzut, 1991), inter-and-intra¬hemispheric transmission deficits, or inadequate
resource allocation (Keshner, 1988). Decreased or abnormal patterns of activation or
arousal will result in a delay or dysfunction of cerebral structure and function that will
result in a number of functional problems that contribute to learning disability.

In considering degrees of asymmetry (Galaburda, 1995), one characteristic that differs

in brains of dyslexics is the degree to which the language area in the brain is
asymmetric. It seems that the magnitude of asymmetry may be as important as other
issues like specialization of the brain for language. With change in the size of the
asymmetry, there is significant change in the circuitry so that at some point the
functional abilities of the system change. Therefore, in developmental dyslexia lack or
reduction of asymmetry may be a crucial factor in explaining the differences in linguistic
capacity compared with normals.
In human brains, it must be remembered that the larger areas are normally in the left
hemisphere for most linguistic abilities and in the right hemisphere for visual-spatial
skills. The planum temporale, which contains several auditory association cortices on
the left side, is thought to be an important part of the language network of the left
hemisphere. A lesions affecting a significant percentage of the planum temporale,
usually on the left side in right-handed individuals, leads to Wernicke’s aphasia
(Galaburda, 1995). Heschl's gyrus, which is the anterior portion of the planum
temporale, and contains the primary auditory cortex, is reported to be asymmetric as
well. The left auditory cortex is usually more oblique less transverse than the right, also
the right Heschl's gyrus is doubled more often than the left (Radenmacher et al., 1993).
Absence of asymmetry therefore is thought to reveal a brain that appears to have two
left brains and no right, or at least functions that way (Witelson, 1977b; Leisman &
Ashkenazi, 1980, Leisman & Zenhausern, 1982). It is further thought that this finding
suggests that asymmetry is produced by developmental curtailment rather than
enhancement. Therefore, lack of appropriate development would be more likely to be
because of decreased stimulus on one side and not an increase in stimulation on the
other.

In the frontal lobe, the frontal operculum contains mostly areas 44 and 45 of Brodmann;
both of these cortices belong to the category of motor association cortex. Area 44 is an
inferior premotor cortex and area 45 an inferior prefrontal cortex. The prefrontal cortex is
considered more multimodal (cognitive) than the premotor cortex. However, lesions that
produce Broca's aphasia affect area 44 in isolation more times than area 45
(Galaburda, 1995). Studies of the inferior parietal lobe in normal humans show a larger
left area PG in 80 percent of the brains examined. Area PG which is the same as
Brodmann's area 39 is found mainly on the angular gyrus and is a prototypical high-
order association cortex. Area PG (Brodmann's area 39) is extremely multimodal and is
found in between cortices dealing with somesthetic, auditory, and visual functions.

Lesions of the angular gyrus are known to result in anomic aphasia, acquired reading
and writing disorders, and Gerstmann’s syndrome, which most likely result from
dysfunction in the majority of area PG. The same brains that were noted to have a left-
sided predominance of area PG also show a larger planum temporale and left area 44
(Eidelberg & Galaburda, 1984). This finding is thought to suggest that asymmetries in
one area may be correlated with asymmetries in another area as long as the areas are
functionally related (Galaburda, 1995). Functional imaging, including PET and regional
cerebral blood flow (rCBF), has been used to examine brain organization in learning
disabled individuals. One study using PET and a radioactive glucose tracer found that
during reading, dyslexic subjects show active bilateral participation of the insular cortex
(Gross-Glenn et al., 1986). Studies using rCBF have shown that recruitment of both left
and right, and central and posterior cortical regions were seen in dyslexic subjects
during reading of narrative text (Hynd et al., 1987; Huettmer et al., 1989).

Sally and Bennet Shaywitz the co-directors of the Yale Center for Learning and
Attention, (Shaywitz et al., 1998) asked volunteers to perform a hierarchy of tasks while
they imaged the brain to see which areas were active. They discovered that poor
readers, people with dyslexia have a "glitch” in the wiring of the brains pathway that is
used for reading. They note that although there is the popular belief that people with
dyslexia reverse letters that is not the essence of the disorder. In fact, dyslexia is
defined as a great difficulty in reading that is not explained by a lack of
intelligence. Reid Lyn, chief of child development and Behavioral Branch at the
National Institute of Child Health and Human Development stated that as many as one
in five American children have great difficulty reading. A study by the U.S. Department
of Education (3/99) stated that 70 percent of school children are not reading at school
level, 90 percent of minorities. The ability to read is thought to require the ability to
match letters with sounds that represent them. It also requires phonological awareness
or the ability to break words into their component sounds therefore it is thought that
people who are unable or have difficulty reading can't recover the sounds from speech.

Using a spectrum of tasks that involve going from letters to sounds to words the
Shaywitz and colleagues (1998) designed a hierarchal series of reading tasks and
asked 29 adults with dyslexia and 32 good readers to perform these tasks. While the
subjects performed these tasks, the researchers imaged their brains with functional
magnetic resonance imaging. They found that in normal readers, the involved pathway
starts with the primary visual cortex, and then the angular gyrus takes over. The final
area involved is the superior temporal gyrus or Wernicke's area, where it is thought
that the sounds of language are converted to words. Subjects with dyslexia are found to
barely use this reading pathway, instead another area of the brain lights up, the inferior
frontal gyrus or Broca's area, which is thought to pair words with units of sound.

Electrophysiological studies have been conducted as well on learning disabled

individuals. One study showed that bilateral temporal indices in spontaneous EEG were
indicated for a group of learning disabled children (Morris et al., 1989). Studies using
electrical activity mapping (BEAM) (Duffy et al., 1980; 1988) suggest that learning
disabled children have dysfunction in cortical language zones, and patterns of
disturbances may be related to specific subgroups of disabled readers. Another study
reported different visual evoked potentials to language stimuli by two groups of reading
disabled children. The results of this study suggest that one group has increased
occipital-parietal involvement and the other has increased occipital-temporal
involvement (Harter, 1991). Another study used event-related potentials (ERP's) to look
at hemisphere asymmetry for language, signal processing efficiency, hemisphericity,
and frontally based attentional control in good and poor adolescent readers. The results
suggest that hemisphericity differences account for reading skill level only in good
readers but that frontally generated attentional ERP account for reading skills among
poor readers, whereas good readers show the expected ERP asymmetries, the poor
readers do not. The authors therefore suggested that below some "crucial" reading
threshold, frontal attentional skill might be a better predictor of reading disability,
whereas above this threshold good reading is predicted by hemisphericity (Segalowitz
et al., 1992). What we see is that functional abnormalities that may result in reading and
learning disabilities are dependent on baseline arousal and activation, and hemispheric
dominance. Therefore, it is thought that these results support a neurobiological basis of
developmental learning disorders. It also leads to the conclusion, as stated by Bolick
and Obrzut (1995), "for a large subset of learning disabled children, atypical cerebral
organization and unusual patterns of laterality, attention and arousal may underlie
deficits in auditory and visual, language and non language information processing
abilities."

Attentional factors have been studied with dichotic listening tasks. In one study, it has
been shown that all groups of children demonstrate a right ear advantage except the
younger poor readers (Obrzut et al., 1992). The results also show that there is an
interaction among handedness, age and reading ability and auditory verbal dichotic
tasks. Younger and older poor readers shift attention in the directed left condition,
however younger poor readers shift attention in the directed right condition. The lack of
attentional shifting for left and right handed good readers is thought to support a
structural theory of lateralization whereas degree and direction of attention shifting for
left and right handed poor readers is suggestive of inter-hemispheric transfer difficulties
and atypical cerebral organization (Obrzut, 1991). Regardless of the particular model
one subscribes to, the results support the view that, in contrast to a fixed laterality
deficit, learning disabled children experience an attentional dysfunction which interferes
with left hemisphere language processing by over-engaging either hemisphere (Boliek
and Obrzut, 1995).

More than 100 years ago, the first reports of children with learning disabilities appeared
in the literature (Bastian, 1898; Hinshelwood 1900; Kussmaul, 1877; Morgan, 1896).
Most of the reports at the time tried to explain why an estimated three to six percent of
the school age population could not learn consistent with what would be expected
considering their intellectual ability and many attempts at instruction (Gaddes, 1985).
After reviewing the early reports, Hynd and Willis (1988) concluded that by 1905 the
literature supported: 1) reading disability (cognitive word blindness) could manifest in
children with normal ability, 2) male seemed to be more commonly affected than female
children, 3) although children may exhibit a number of different symptoms, they all
suffer a core deficit in reading acquisition, 4) normal classroom instruction does not
improve reading ability, 5) some reading problems seem to be genetic, and 6) the core
symptoms appear similar to those that are seen in adults with left temporal-parietal
lesions. It is now recognized that learning disabilities may be expressed in many
different areas including arithmetic, writing, spelling, etc. However, it is well accepted
that reading disabilities or dyslexia has been the area most researched (Hynd et al.,
1995). Research for years seemed to support the theory that there is a neurologic basis
for dyslexia. For example, research suggests that reading disabled children have an
increased incidence of electrophysiologic abnormalities (Duffy et al., 1980). Soft signs
are also more often found in reading disabled children (Peters et al., 1975) as well as a
greater frequency of left or mixed handedness (Bryden & Steenhuis, 1991). Studies also
found that children with learning disabilities performed more poorly than normal children
on any given task, cognitive or perceptual, however they did better than children with
brain damage (e.g. Reitan & Boll 1973). Therefore, these children were referred to as
suffering from minimal brain dysfunction because they appeared to function between
normal and known brain damaged levels.

Language

There is evidence in the literature that suggests that very young children as well as
infants are lateralized for language processing (Molfese, 1989). No one would argue
with the fact that in the majority, language is lateralized to the left hemisphere. Although
language abilities appear to develop over the course of human ontogeny, language
lateralization remains stable at least from middle childhood if not earlier in infant
development. Based on the work of Dejerine (1911), who thought that there was a left
lateralized "word center" in the area of the angular gyrus, and contributions of Broca,
Wernicke, and others, a complete neuro-linguistic model of language and reading been
created to have. This model suggests that first, visual stimuli are registered in the
occipital cortex, with associations made in the secondary visual cortex. This input is
then compared and contrasted with other sensory input from other modalities in the
area of the angular gyrus in the left hemisphere. Associations of linguistic-semantic
comprehension with input from the area of the angular gyrus involve the cortical region
of the left posterior- superior temporal region, including the planum temporale. This
process is thought to be completed when inter-hemispheric fibers connect these regions
with Broca's area in the left inferior frontal region. Research has examined anatomic or
structural differences in dyslexia or individuals with other language problems.
Rosenberger and Hier (1980) suggested that there was limited but interesting evidence
that symmetry or reversed symmetry may be associated with poor verbal-linguistic
ability that is commonly found in children with dyslexia. In four consecutive autopsy
cases, it was found that focal dysplasias clustered specifically in the left superior
temporal region by a ratio of 11:1 (Galaburda, 1985). Another study (Larsen et al.,
1990) found that when symmetry the planum temporale presents in dyslexia, individuals
exhibit phonological deficits. They concluded that a relationship appears to exist
between anatomic brain patterns and neuro-linguistic processes.

The balance of activity or arousal between the two hemispheres as well as

intrahemispheric transfer is essential for effective language. One study on split-brain
patients for example noted, "Occasionally the commissurotomized patient may become
so absorbed in a right hemisphere task that speech and left hemisphere functions are
temporally depressed to the extent that one questions whether consciousness may not
be shifted entirely to the working hemisphere" (Sperry, 1962). In fact, mutism after
collosal section may be one extreme example of an arousal imbalance that interrupts
performance (Suillivan & McKeever. 1985). In another study, akinesia and mutism were
found to be correlated with mixed hand dominance (Sussman et al., 1983). In another
study of two-stage surgery, mutism occurred only after the second stage, which
involved transection of the posterior part of the callosum. What especially points to an
arousal explanation for the mutism is that manipulating attention alleviated the speech
problem. Interestingly, when the patient palpated an object with the hand contralateral
to the hemisphere that controls speech, speech was improved (Sullivan & McKeever).
That using the non-dominant hand improves speech suggests that the description is a
result of arousal imbalance (Liederman, 1995).

It has been shown that inter-hemispheric connections are crucial for equilibrating
activation levels between two regions or synchronizing activity. The same process is
thought to occur within hemispheric cortico-cortical pathways, which also equilibrate and
synchronize function (Koch & Leisman, 1996; 2001; Leisman & Ashkenazi, 1980;
Leisman & Zenhausern, 1982, Leisman, 2002). One within hemisphere syndrome,
which is caused by damage of corticocortical fibers, is conduction aphasia. This
syndrome is thought to be a result of damage to the arcuate fascicules a cortico-cortical
pathway from Wernicke 's area to Broca 's area. It has been shown that a small lesion
that is confined to the arcuate fascicules is enough to produce conduction aphasia
(Tanabe et al., 1987). The primary symptom of conduction aphasia is the inability
to repeat what is heard, even though language production is relatively fluent and
without dysarthria and aural comprehension is fundamentally intact (Benson, 1979). The
inability to repeat what has just been said may be due to a situation-specific under-
activation of Broca's area by Wernicke's area (due to the lack of activation along the
arcuate fascicules) rather than to a lack of transfer itself (Lieberman, 1995). Under-
activation of Broca' s area in this type of situation has been confirmed by measures of
metabolic activity. One study found that during a naming task, patients with conduction
aphasia had less of an increase in Broca's area than normal individuals (Demeurisse &
Capon, 1991). Under conditions when the subject initiates their own speech, there is
enough activation of Broca's area to subserve fluent output. However, in conditions
when the patient’s speech is an attempt to echo, that which was just heard, Broca' s
area is not sufficiently activated by Wernicke's area to allow word-by-word repetition. In
this case, it could be concluded that these patients had lost explicit access to
information but retained access to it on both categorical and implicit levels. In this case,
arousal level is enough for more lower level perception, however the activation that
would normally be superimposed on Broca's area that is obviously necessary for explicit
access, is not enough to raise signal-to-noise ratio to reach the level of activation
needed.

Activation or arousal levels may be related to motor activity. There is evidence of a

temporal linkage between hand performance and language milestones; disruptions in
the course of development of manual asymmetry coincide with transitions between
stages of language development (Ramsay, 1985). "Cycles" in the development of
handedness have been blamed on fluctuations in the degree to which speech interferes
with the use of the dominant hand (Bates et al., 1986). This interference is thought to be
because of the close proximity of the two control areas in functional control space
(Kinsbourne & Hicks, 1978) within the same hemisphere. We see these effects early in
development, but early childhood is too early to reflect lateralized differences in the
cerebrum, but is reflective of the precursors of these lateralized processors. It has been
noted that due to the relative immaturity of the newborn’s cerebrum (Dobbing & Sands,
1973), these precursors are most likely represented at the level of the basal ganglia and
thalamus.

Recent research implicates the cerebellum as playing a major role in the development
and maintenance of speech as well as other higher cognitive and behavioral functions.
It is generally accepted that language abilities in humans are probably dependent on
some phylogenetically new areas of the cerebral cortex (Benson & Geschwind, 1968;
1970; Benson et al., 1973; Ojerman & Crentzfeldt, 1987; 1991). However, it is not
generally accepted that new areas of the cerebellum may be important as well. Along
with the evolution of the new association areas in the cerebral cortex, connections to
new areas in the lateral cerebellum can respond to linguistic signals received from the
posterior lobes of the cerebral cortex. These responses are then thought to be able to
be transmitted from the neo-cerebellum to Broca's language areas in the frontal lobe of
the cerebral cortex. It is thought therefore that the neo-cerebellum can act as a link
between the posterior and frontal language areas of the cerebral neocortex. The
cerebellum seems to be able to contribute not only to the motor processing of speech
but also to the cognitive processes that think of the words to be expressed (Leiner et al.,
1989). It is interesting to note that it was this very type of transfer of posterior to anterior
cerebral areas by the arcuate fascicules that was at fault in conduction aphasia.

It has also been noted that there are no motor deficits but rather a cognitive deficiency
possibly related to an arousal imbalance. One study designed to distinguish the motor
from the cognitive function of speech, was constituted by a subtraction technique. Each
individual was asked to perform a sequence of tasks, ranging from simple to complex,
where each successive task necessitates an additional word-processing requirement.
By subtracting the motor activation measured in the simple task from the activation in
the complex task it is possible to distinguish the areas that are activated during word
association (Peterson et al., 1989). Results show that the area of the cerebellum
activated during the cognitive process of word association is structurally separate from
the area activated during the motor process. In the motor task of speaking a word
activation occurs in the superior anterior lobe, near the areas that are activated by
movements of extra-ocular muscles and movements of digits. However, in cognitive
tasks, word-association activation occurs in an inferior-lateral area in the right
hemisphere of the cerebellum. It has been noted that the lateral cerebellar area can
send its output to Broca' s area in the frontal lobe of the neocortex (Leiner et al., 1991).
Brain scans confirm that the medial part of the cerebellum is activated during finger and
motor speech movements (Bellugi et al., 1990; Peterson et al., 1989), while the
cognitive language tasks activate a more lateral part (Peterson et al., 1989; Roland et
al., 1989). These results suggest that in normal human brains, the lateral areas of the
neo-cerebellum participate in the cognitive aspects of language and learning, while the
more midline or medial areas are involved in motor aspects of speech and gesture.

The cerebellum is involved in all human learning, motor and cognitive, as well as in
linguistic, and sensory and emotional aspects of behavior. It has been shown that when
the cerebellum is damaged, something of the fundamental learning process is lost, the
ability to improve performance with practice. In a study bu Fiery and colleagues (1990),
a lawyer who had a stroke that impaired a large area of the posterior cerebellum on the
right was tested by being asked to associate a word to its use. Initially, 60 percent of his
responses were incorrect compared to two percent for normal subjects. In addition, it
was noted that normally when individuals are given successive nouns in successive
trials, they become faster at finding verbs to associate with nouns. However, in this case
the lawyer did not show this kind of improvement. In following trials, normal subjects
decreased their reaction time by 27 percent, his reaction time decreased by only 8
percent. It was further noted that lack of improvement was also seen in his performance
on other cognitive tasks involving two types of memory. The first was declarative
memory, which is connected to learning facts and events and the second was
procedural memory, which involves the learning of skills also known as habit learning.
The lawyer was impaired on procedural memory tasks but not declarative memory. It is
well documented that the cerebellum is involved in motor learning (Lou & Bloedel, 1988;
Solomon et al., 1989). It has also been postulated among those that think that long-term
memory is localized in the brain that learning may be stored within the cerebellum or in
some other structure that is connected to the cerebellum (Ito, 1990; Lalonde & Botez,
1990).

The hippocampus is thought to be involved in long-term memory and is connected to

the cerebellum. Pathways from the anterior vermis and fastigial nucleus to several
areas of the limbic system have been shown to modify sensory input to the
hippocampus (Newman & Rezza, 1979). It seems that involvement of the cerebellum in
associative learning, not simply motor but cognitive as well, now seems unequivocal
(Bracke-Tolkmitt et al., 1989; Fiez et al., 1996; Roland et al., 1989). To review, the
cerebellum’s role in practice improvement as well as new learning especially of
procedural learning is probably a result of the effects of surround inhibition. In the
cerebellum, a stimulus enters the granular layer where granule cells then excite Purkinje
cells and at the same time, the granule cells excite the output neuron immediately below
the area of activation. Therefore, the more this area becomes excited or activated the
more the Purkinje cells inhibit that specific area associated with the movement or
activity. However, due to surround inhibition of basket and stellate cells, Purkinje cells
surrounding the area of activation are inhibited, decreasing the inhibition of the output
nuclei below that area, increasing signal-to-noise ratio and neuronal excitation, and
priming them to respond faster to the next stimulus. Repetitive movements or cognitive
tasks that activate the same neuronal areas of cerebellum and neocortex will become
more inhibited but other areas are brought closer to threshold ready to respond to the
new cognitive though or motor activity. Therefore, all new learning, which includes
relearning an activity after a stroke, is dependent on the cerebellum.

We would expect all children with learning disabilities to have a deficit of the cerebellum.
The right cerebellar hemisphere would be associated with left cerebrum and would
affect speech, language, arithmetic, reading, and other left-brain activities. Left
cerebellar hemisphere dysfunction would be associated with right cerebral dysfunction
of social learning and behavior. This description would be consistent with the findings of
Ayers (1972) and Levinson (1988; 1989; 1990) who both found cerebellar symptoms in
the majority of children with learning disabilities and behavioral disorders. The
cerebellum has also been shown to be involved in other cognitive functions as well as
disorders such as William's syndrome, autism and fragile X syndrome.

In children with William's syndrome who have good verbal skills it is thought that the
neo-cerebellum is normal in size, however in others who have difficulty with language
the neo-cerebellum is smaller (Jernigan & Bellugi, 1990). William's syndrome is a
unique form of retardation that affects cognitive abilities while retaining normal linguistic
abilities both semantic and syntactic (Rae et al., 1998). MRI studies show that the neo-
cerebellum of these individuals appears normal, whereas the paleo-cerebellum is
reduced and the forebrain is significantly reduced (Jernigan & Bellugi, 1990). MRI
studies of William's and Down’s syndrome brains report cerebral hypoplasia, alterations
in the size of the paleo-cerebellum and midline neo-cerebellum (vermis), as well as
decrease size of the posterior compared with the frontal cerebrum (Jernigan et al.,
1993). In Down’s syndrome, the reduction of volume is more dramatic in the
cerebellum and brainstem than in the cerebrum (Jernigan & Bellugi, 1990). The
difference between these two groups of patients is the fact that children with William's
syndrome retain their complex language abilities even with severe cognitive deficits.
These MRI results also raise a possibility that the midline cerebellum or vermis may be
more connected to the posterior cerebrum or dorsal cortex and the lateral cerebellum
may be more connected to the frontal cerebral or ventral cortex.

Phylogenetically the older paleo-cortex may be more connected to the evolutionary

older dorsal cortex, whereas the neo-cerebellum may have been created to have in line
with the ventral cortex or neocortex, which is the latest evolutionary development. The
ventral cortex is more associated with left-brain activities such as speech and language
functions. Autistic children on the other hand usually have significantly impaired
language as well as cognitive and behavioral development. MRI studies of these
children in contrast show that the neo-cerebellum is decreased in size (Courchesne et
al., 1987; 1988; Murakami & Courchesne, 1989). Other studies have reported structural
abnormalities in the cerebellum and brainstem of autistic patients (Bauman & Kemper,
1985; 1986; 1989 Gaffney, et al., 1988; 1987). Studies have also shown specific loss of
cerebellar nerve cells in autistic patients (Ritvo, 1986).

Studies have also been performed on patients with Fragile X Syndrome, the most
common form of mental retardation. These individuals have been shown to have a
significant decrease in the size of the neo-cerebellum similar to that found in autistic
children (Reiss et al., 1991; Reiss & Freund, 1990). It has been noted that males with
Fragile X Syndrome express some autistic behavior, such as deficits in social
interaction with peers, abnormalities in verbal and non-verbal communication,
stereotypical motor behavior, and unusual responses to sensory stimuli (Havlovicova et
al. 2002; Harvey & Kennedy, 2002; Jones & Szatmari, 2002).

Verbal IQ is primarily an assessment of left brain cognitive function, patients with

cerebellar lesions were tested on a wide range of intellectual and learning abilities to
see what effect the cerebellum had on intelligence (Scott et al., 2001; Cotterill, 2001;
Neau et al., 2000). In contrast to normal subjects similar in age and education, the
cerebellar patients were significantly impaired on all IQ measures and these deficits
were not attributable to motor impairments per se. The researchers found that the
decrease in IQ was not expected, that apparently the deficits had not been anticipated
even though after testing the deficits were large enough that they should have been
apparent (Scott et al., 2001; Cotterill, 2001; Neau et al., 2000). Previously it was not
thought that cerebellar deficits affected IQ, and cerebellar that cerebellar deficits are not
usually associated with gross intellectual impairments, tending instead to be subtle, and
therefore requiring subtle and detailed testing for detection. This may be the case with
motor symptoms as well; they may be subtle or specific to only one side, therefore
requiring experience, skill, and attention to subtle effects. It may be the case that
cerebellar and motor signs although significant, may often be overlooked or missed.

Studies have been performed using ideography and mental imagery. Ideography refers
to the performance of purely mental tasks, which are not influenced by ongoing
perception of sensory signals or by the control of movements, speech, or behavior
(Ingvar, 1991). Blood flow and metabolic change studies have shown activation of the
cerebellum during various mental tasks in normal individuals. These tasks include
mental arithmetic (silent counting) (Decety et al., 1990; Ingvar, 1991), mental simulation
of tennis playing and other motor ideation (without any actual motor activity) (Decety &
Ingvar, 1990; Decety et al., 1988), mental association of word with its use (Peterson et
al., 1989), as well as learning to recognize complex geometrical objects (Roland et al.,
1989). In another study, 12 patients with cerebellar atrophy (CA) and 12 normal
controls matched for age and education were required to solve the Tower of Hanoi
puzzle, a nine-problem task that requires cognitive planning (Grafman et al., 1992). CA
patients were shown to have difficulty solving the Tower of Hanoi task that could not be
accounted for by motor impairment, age, education level, level of dementia, depression,
visuomotor procedural learning, verbal memory, or verbal fluency. The results suggest
that failure of this task is based on the specific demands of cognitive planning. In
addition, CCA (pure cerebellar cortical atrophy) patients took significantly longer in pre-
movement planning time (with no increase in between move pause time) relative to the
control group. The authors note that in addition to CA patients, there is evidence that
patients with frontal lobe lesions or dysfunction due to subcortical disease also fail on
cognitive planning tasks similar to the Tower of Hanoi (Shallice 1982). An explanation
for failure on the tower-type tasks is that assembling a sequential series of events or
actions into a coherent behavioral unit is difficult for patients with frontal lobe injury
(Grafman, 1989), subcortical lesions (Grafman et al., 1990), and cerebellar lesions
(Daum et al., 1993). The authors speculate that cognitive planning may be seen as an
analogue of cognitive representation to complex motor procedures that require a series
of individual movements to function as a unitary sequence (Ito, 1990). Therefore, it may
be possible that the cerebellar-frontal axis functions in different ways depending on the
requirements of the specific task. For instance, initiating motor activity may depend on
frontal cortex and motor sequences may depend on the cerebellum for the timing of the
movements. However, cognitive sequences may depend on the prefrontal cortex
for the initiation of plans or sequential actions and on the cerebellum for the temporal
integration of events that make up the cognitive plan or action (Decety et al., 1990). The
conclusion of the authors is that deficits in cognitive planning suggest a functional link
between the cerebellum, basal ganglia, and frontal lobe concerning specific cognitive
processes (Grafman et al., 1992).

Memory is another important cognitive function that may be affected in learning disabled
individuals. One of the tasks that parents and teachers appear most concerned about is
reading comprehension. Reading comprehension is thought to rely heavily on working
memory, which is thought to be a function of the frontal lobe especially the left frontal
lobe. There are two major types of memory, explicit (declarative) memory, and implicit
(non-declarative or procedural) memory (Leisman & Koch, 2000). Explicit memory is
also known as conscious memory, which is asymmetrically localized in the left
hemisphere, whereas, implicit memory or subconscious (subliminal) memory is
lateralized to the right hemisphere (Hugdahl, 1995). The learning and therefore
retention of new information about an individual’s autobiographical history is supported
by medial temporal lobe structures and the midline diencephalon. It appears that
damage to these areas interferes with the ability to form new explicit memories. It has
been noted that damage to these regions also leads to problems in remembering events
in the years immediately prior to the injury, but apparently leaves intact the majority of
previous episode and semantic memories acquired during one’s life. These areas are
not storage sets of information in long-term memory. However, damage to areas of the
temporal lobe outside the hippocampus are thought to cause a loss of episodic
memories while the ability to acquire new ones may remain intact. It has been reported
by Gazzaniga and colleagues (1998) that brain injury leading to deficits of implicit
learning and memory affects some patients while explicit memory remains intact. This is
thought to affect the medial temporal lobe and midline diencephalon. It is further thought
that the left supramarginal gyrus and left premotor cortex relate to the phonological loop
of the working memory system. Studies involving PET scans, and transcranial magnetic
stimulation in humans and lower organisms show that the motor cortex is critical for
implicit procedural learning of movement patterns. Activation of the basal ganglia and
the putamen would be anticipated because patients with Huntington's disease have
been shown to have deficits in sequence-learning tasks. Because the supplementary
motor cortex is also activated during implicit learning, it is thought to be part of a
network of a cortical-subcortical motor loop, which regulates voluntary movement.

In contrast explicit learning and awareness of the sequences requires greater activation
in the right premotor cortex, the dorsolateral prefrontal cortex associated with working
memory, the anterior cingulate areas in the parietal cortex controlling voluntary
attention, and the lateral temporal cortical area thought to store explicit memories. The
dorsolateral prefrontal cortex is associated with working memory; the DLPFC also has
been shown to have strong connections from the basal ganglia and cerebellum via
projections to the thalamus (Middleton & Strick, 1994).

Emotional and Affective Symptoms

Whereas most of the traditional cognitive functions previously reviewed are related to a
superiority of the left hemisphere, we recognize that a right hemisphere dysfunction may
also result in a learning disability or cognitive dysfunction. In general, when it comes to
emotional, behavioral, or affective disorders the right hemisphere is generally
responsible. However, the interaction with the left hemisphere as well as the interaction
with limbic structures may make emotional problems less clear-cut than cognitive
problems. Davidson (1995) has stated, “emotion is a class of behavior that has invited
the consideration of its underlying biological substrates since the time it was first
studied. Probably more than any other class of behavior, emotion often involves frank
biological changes that are frequently perceptible to the person in whom the emotion
arises as well as to the observer (e.g. facial blood flow changes as in 'white with fear')."
Because of the type of observations, it has been noted that most of the early research
on the biologic substrates of emotion has been focused on the autonomic reactions and
the subcortical and limbic system structures thought to be responsible for those
changes. However, more recently it has become apparent that in humans especially,
the cerebral cortex plays an important role in aspects of emotional behavior and
experience (Kolb & Taylor, 1990). In this regard, the anterior cortical regions especially
appear to play a major role, through their dense anatomic reciprocal connections with
subcortical centers, limbic structures, and posterior cortical circuits in the control of
emotional behavior.
In humans, the anterior cortical zones are the areas of the brain, which have shown the
most dramatic growth in relative size over the course of phylogenetic development
compared with other brain regions (Luria, 1973) and are thought therefore to be critical
to unique human behavior and emotion. Initial research on cerebral laterality in affective
disorder concentrated on exploring the hypothesis of right hemisphere dysfunction in
these types of disorders (Gruyelier & Venables, 1974; Flor-Henry, 1976; Kronfol et al.,
1978; Yozawitz, 1979). These and other research reports are thought to show some
support for this theory, however it has become clear that to completely consider the full
range of laterality findings in affective disorders, we must consider right and left,
anterior-posterior, and cortical¬-subcortical interactions (Bruder, 1995). Much of the
research has focused on interaction of these areas with the anterior cortical region.
Asymmetries in anterior cortical function have been implicated in different forms of
emotional behavior. Even early on, research seemed to suggest that injury of the left
hemisphere would more likely produce a catastrophic-depressive reaction compared to
similar damage to the right hemisphere (Goldstein, 1939). Research by Robinson and
colleagues (1984) reported that damage specifically to the left frontal lobe appears to
produce depression. In addition, the closer the damage is to the frontal pole the more
severe the depression. In contrast, patients that develop mania following brain injury are
more likely to have damage to the right hemisphere than the left. This dichotomy will
form the foundation of much of the symptoms that we will explore.

There are children with and without learning disabilities who exhibit depressive or manic
type symptoms such as being withdrawn, sad, irritable, slow moving (hypokinetic type
motor activity) or aggressive, hyperactive, angry, impulsive, fidgety, lacking
concentration, repetitive or persistent, frustrated, anxious, or violent. Most of these
symptoms and others will be explained by anterior activation asymmetries and their
interaction with other cortical, sub-cortical, and limbic processes. The asymmetric
control of different emotional behaviors relates to evolutionary advantages that have
developed due to these asymmetries (Levy, 1972).

It is generally agreed that approach and withdrawal are basic motivations that are found
at any level of phylogeny (Davidson, 1995). In several papers, Davidson and colleagues
(Davidson, 1984; 1987; 1988; Davidson et al., 1990b; Davidson & Tomarken, 1989)
have suggested that the anterior regions of the left and right hemisphere are specialized
for approach and withdrawal behaviors respectively. The left frontal region has been
described by Luria (1973) as being an important center for intention, self-regulation, and
planning. These characteristics have also been described as "will" which is important to
approach behavior. It is further noted that during child development, a child will
approach or reach out to objects with the right hand more than the left (Young et al.,
1983). It is thought that right-handed reaching and positive emotions together are
manifestations of a brain region, which controls approach behavior, and the left frontal
region is thought to act as a "convergence zone" for this circuit (Damasio, 1989;
Davidson, 1992a, 1992b). Therefore as expected damage to the left frontal region
produces behavior, that can be recognized as a decrease in approach. These
individuals have been described as apathetic, exhibit loss of interest or pleasure in
people and things, and have difficulty initiating voluntary action or movement (intention).
Hypo-activation in this same area is expected to be associated with a decreased
threshold for the experience of sadness and depression and associated behavior.

In contrast, it is thought that the right anterior region is specialized for withdrawal.
Electrophysiological measurement of regional hemispheric activation suggests that the
right frontal and anterior temporal regions are specifically activated during withdrawal
related behaviors such as fear and disgust. In addition, it has been shown that baseline
tonic activation in these regions shows a superiority to respond with exaggerated
withdrawal related negative affect to appropriate emotional activators. These individuals
are said to be generally more "negative" individuals (Davidson, 1995). We can again
see that the level of arousal or activation is critical to the function. Although activation of
emotions is often transient in response to stimuli, individuals also have chronic baseline,
arousal, or activation of areas of the brain that can be measured. Chronic imbalances of
arousal, with one side activated higher or lower than the opposite hemisphere, can
create different consistent affects from one individual to the other. A child with low right
hemisphere baseline activity may have a different dispositional affect than a child with a
low left frontal baseline arousal level. Not only will their affect reflect the asymmetric
arousal imbalance but also their emotional response threshold to stimuli will be lower
than normal. The greater the imbalance the more dramatic the response may be. This
imbalance or altered level of arousal can be measured subjectively by testing
perceptual asymmetries and thresholds. Dichotic testing and visual field-testing are two
ways of examining perceptual levels, which reflect arousal, or activation levels. There is
evidence to suggest that differences in right handed individuals in dichotic ear
advantage (Hellige & Wong, 1983; Kim & Levine, 1992) and visual field advantages
(Levy et al., 1983; Kim et al., 1990; Luh et al., 1991) are reliable and are thought real
individual differences in the relative activation or utilization of the right and left
hemisphere (Bruder, 1995). It has been also suggested that between subjects variation
in perceptual asymmetry in right-handed adults are more related to task independent
differences in characteristic arousal asymmetry than to hemispheric specialization (Levy
et al., 1983). Using a free field chimeric faces test to measure characteristic perceptual
asymmetry, it was shown that about half of the variation of asymmetry scores on this
and other visual laterality tests could be attributed to a common factor called
characteristic perceptual asymmetry (Kim et al., 1990; Luh et al., 1991). In another
study it was found that about half of the between subjects variation in dichotic listening
asymmetry could be attributed to characteristic perceptual asymmetry and that both
modality- specific and modality-general components contribute to the observed
asymmetries (Kim & Levine, 1992). This may reflect alteration of specific and non-
specific thalamic pathways together that create the characteristic perceptual
asymmetry.

Expressing and perceiving emotion are thought to be different in their areas of control.
In this matter, some researchers think that the right hemisphere plays a more general
role in all emotion (Borad et al., 1986). Most of the research in this area is related to the
perception of emotional information where evidence suggests that the right posterior
cortical region is the primary area for the perception of all emotion, positive or negative.
It has also been suggested that anterior activation asymmetry acts to predispose a child
to respond most of the time to positive or negative affect in the presence of an actual
emotional stimuli. It has been noted that while baseline anterior asymmetry predicts the
threshold of reaction to an emotional challenge, it is not always related to an individuals
unprovoked state (Davidson & Fox, 1989; Tomarken et al., 1990; Wheeler et al., 1993).
The diagnosis of children with affective disorders appears to be increasing.

Depression and anxiety in children can be very similar to what adults experience.
Depression can result in deep sadness, loss of interest in friends, tiredness and
thoughts of hopelessness. One important sign of depression is when a child stops
participating in social activities, his grades fall, or he does not feel like going to school.
These signs can now be recognized as being attributable to lack of approach or
expression of withdrawal symptoms, which are most often related to decreased
activation of the left hemisphere. The left hemisphere also is superior for most
cognitive or academic activities, so we would also expect a decrease in grades. In
addition, the left hemisphere is important for a child's self motivation or "will." If a child
has a decrease in left hemisphere baseline activity, especially frontal activity, we can
expect that these accompanying symptoms. It was only a relatively short time ago when
depression was thought to be a disorder of middle-aged women. However, the literature
currently supports the view that for many, depression may actually have begun in
childhood or adolescence. Now it is becoming quite common to hear about children on
antidepressants, however scientific information about the safety and efficiency is only
now being studied.

It has been noted that long-term psychotherapy does not appear to benefit teenagers as
well as with adults and the older antidepressants are not as effective as they are for
adults (Bedi et al., 2000; Martin et al. 2000). Now it appears that there is greater
emphasis on SSRI’s or serotonin selective reuptake inhibitors. Serotonin,
norepinephrine, and dopamine have all been implicated in a variety of effective
disorders. Although serotonin and norepinephrine are asymmetrically distributed in the
right brain, they appear to be involved in left-brain disorders and depression.

There is a considerable body of research examining the potential role of serotonin in the
regulation of affective states, behavior, and psychopathologic disorders. It has been
postulated that serotonergic dysfunction may contribute to depressive disorder and
suicidal behavior (Arora & Meltzer, 1989a; 1989b; Asberg et al., 1987; Meltzer & Lowy,
1987). In postmortem studies, lower concentrations of 5-HT and 5-HIAA (5-
hydroxyendoliacetic acid), the major metabolite of 5-HT, have been reported in midbrain
Raphe nuclei of suicide victims as opposed to normal controls. Norepinephrine has also
been shown to favor the right hemisphere. Both neurotransmitters have been reported
to be mostly involved in up-regulation (norepinephrine) and down-regulation (serotonin)
of arousal, and also apparently having reciprocally inhibitory effects (Flor-Henry, 1986)
and are asymmetrically distributed favoring the right side of the brain. In addition, it is
possible that changes of this normal pattern are correlated with affective and behavioral
abnormalities. Even though serotonin and norepinephrine favor the right hemisphere,
when there is a decrease there may be a more substantial negative effect on the
opposite hemisphere. This seems to be because the right half of the brain has better
compensatory mechanisms to counterbalance a deficit (up-regulation of receptors).
Therefore, the left hemisphere cannot compensate as well as the right, and as a result
may be more affected as a result.

Previously, alterations of neurotransmitters were looked on as the primary cause of

depression and other affective disorders. New research has gone way beyond a purely
chemical evaluation and more to a functional neurological examination of dysfunction. A
recent article in Psychology Today (4/1/1999) comments on these changes in focus.
Masano writes that recent findings are "radically different from the conventional wisdom
on several counts. First, it overturns the widespread belief that depression is 'just' a
chemical imbalance. Yes, neurotransmitters like serotonin function abnormally in
depression-but so do many other things. Second it challenges the view that this disorder
is 'merely' from the neck up depression affects the heart and the bones too, and the
body's stress system." He goes on to state "The evidence that the adult brain is much
more plastic than anyone recognized, that experience and environmental changes to
the brain circuitry underlying emotion is still, as Rockefeller University neurobiologist
Bruce McEwen says taking scientists by surprise. The surprise is not just kicking off a
revolution in our understanding of depression. It will force a revised view of all human
behavior and the capacity for change."

Davidson is quoted as stating that based on new imaging techniques such as PET and
fMRI, "the idea that there is global derangement of the serotonin or norepinephrine
system is not sustainable in light of recent brain imaging data," he further states "what
distinguishes depressed from non-depressed individuals are patterns of regional brain
function, differences in specific circuits" (Psychology Today 4/99; Davidson et al., 1999).
We can imagine that if these newer ideas apply to adults, that it applies even more to
children whose brains are much more plastic and changeable. These new concepts
must also affect our approach to treatment, moving away from trying to manipulate
chemicals and more toward trying to improve the function of the brain. As Davidson
states (Psychology Today 4/99; Davidson et al., 1999), "non pharmacological
treatments may exert quite specific biological effects in being able to affect certain
select brain regions." He points out "the deficits in activation of the prefrontal cortex that
we and others have identified in depression may be something that can be changed
with cognitive therapy." The balance of activity between hemispheres is also a strong
focus of attention.

The New York Times commented on a rekindling of interest in how the left and right
sides of the human brain interact (NY Times 1/19/99; Pettigrew & Miller, 1998). At a
meeting of the Society for Neuroscience in November 1998, Jack Pettigrew, a
neuroscientist at the University in Brisbane, Australia proposed that people with manic
depression have a "sticky switch" somewhere in their brain. He thinks that normally
this switch allows either the left or the right hemisphere to be dominant during different
mental tasks, with the two sides constantly taking turns. He proposes that. Another
theory being proposed is that people with manic depression one hemisphere
becomes locked into a dominant position in periods of depression while the other
hemisphere is locked at all times of mania of Frederic Schiffer, a psychiatrist at
Harvard Medical School, who thinks that one hemisphere can be more immature than
the other can and that this imbalance leads to different mental disorders (Schiffer, 1996;
Schiffer et al., 1998). Schiffer has used special goggles to help individuals "talk" to each
half of the brain separately to help learn which half is less mature and to bring the two
hemispheres into harmony. It has been shown through experimentation that it is
possible to stimulate one hemisphere and inhibit the other so that the individual looks at
the world using only half of their brain at a time. Schiffer explains that when individuals
gaze to the far right and therefore activate the left-brain they do better on verbal
memory tasks, and when they look to the far left to engage the right brain they feel more
inertia and fatigue. In general, Schiffer found when patients look through the goggles
they report very specific feelings depending on which side of the brain was being
activated. In general, he found that depressed patients felt worse when the right side
was stimulated and patients with posttraumatic stress syndrome felt worse when the left
side was more active. This again points to an arousal or activation imbalance, which
would therefore involve subcortical areas that provide arousal.

Pettigrew & Miller (1998) found a treatment that may imply the cerebellum is involved.
He reported that the placement of ice water in one ear seems to “unstick” the switch. Ice
water in the ear is a part of a traditional neurologic test known as caloric testing. This
test activates the vestibular apparatus and can test the balance of activation of the
cerebellum by activity one side more than the other. This test has also been used on
astronauts to understand the mechanism of space sickness. Pettigrew indicated that, if
one places ice water into one ear the opposite brain hemisphere will become activated.
He further noted that cold water in the left ear activating the right hemisphere might
temporarily reduce the symptoms of mania. Depression may be reduced by placing
water in the right ear. This would clearly imply that stimulation of the ipsilateral
cerebellum and contralateral cerebrum has an effect on alleviating both mania and
depression. This indicates the importance of the subcortical structures in the role of
depression and other emotional disorders.

Watson and Heilman (1982) hypothesized that a left subcortical lesion would not induce
depression because it would not interrupt hemispheric processing of positive emotions
and therefore would not "release" the more negative right hemisphere. They felt that a
left subcortical lesion would affect the patients arousal level, resulting in unawareness
but not depression. However, several studies of unipolar depression have indicated
abnormal changes in blood flow and glucose utilization in subcortical structures like the
caudate nucleus (Baxter et al., 1985; Buchsbaum et al., 1986). Basal ganglia
dysfunction is thought to be related to depression in Parkinson's disease and
Huntington's chorea. Also left anterior subcortical lesions including the body and head of
the caudate and anterior limb of the internal capsule have been noted to be significantly
associated with major depression. The severity of the depression relates directly to the
distance of the lesion from the frontal pole (Starkstein et al., 1987). Also in Parkinson’s
patients with unilateral symptoms, depression was more common in those with primarily
right-sided as opposed to left-sided symptoms which is thought to be consistent with left
caudate lesions and greater depression (Starkstein et al., 1990).

It has also been shown that stroke patients who also exhibit major depression have
been shown to have more subcortical atrophy on CT scan than non-depressed stroke
patients (Starkstein & Robinson, 1988). In another study it was demonstrated that
secondary mania patients had lesions confined to right subcortical structures such as
the thalamus and anterior caudate. Contrary to the prediction in 1982 by Watson and
Heilman it appears that the subcortical structures play an important role in
depression and mania, and that arousal or activation levels are more critical to the
processing of emotions in the frontal cortex than previously thought. It is also thought
that changes in emotional behavior are not satisfactorily explained by release of
contralateral cortical regions (Sackheim et al., 1982). Instead it is now thought that
lateralized changes in emotional behavior can be better explained as a result from
release of ipsilateral subcortical centers with possibly a hierarchy of emotional control
(Tucker, 1981; Tucker & Frederick, 1989).

Studies that have carefully reviewed pathologic emotional outbursts in the absence of
brainstem lesions found that subcortical structures such as the basal ganglia and
internal capsule are involved in almost all cases studied (Poeck, 1969; Rinn, 1984).
Examining the effects of the location of the lesion on emotional behavior, it has been
proposed that lesions that include the frontal convexity, both dorso-lateral and dorso-
medial prefrontal areas, can be associated with slowness, indifference, apathy, and lack
of initiative. On the other hand, lesions of the orbito-frontal cortex appear to result in
disinhibition, lack of social constraint, hyperactivity, grandiose thinking, and euphoria
(Kleist, 1931; Blamer & Benson 1975). It has also been noted that secondary mania is
significantly associated with cortical para-limbic involvement, which includes both orbito-
frontal and basal temporal dysfunction, especially in the right hemisphere. Mania is
apparently more frequent for right as opposed to left subcortical lesions, which includes
the thalamus and basal ganglia (Starkstein et al., 1987; Starkstein & Robinson, 1988). It
has also been found that manic symptoms like euphoria, hyperactivity, and insomnia
could possibly be a result of interruption of the control exerted by the orbito-frontal
cortex over septal, hypothalamic, and mesencephalic regions (Starkstein & Robinson,
1989; Nauta, 1971). This suggests that mania may be a result if disinhibition of intact
subcortical centers due to cortical dysfunction or decrease activation. These results
would be consistent with lesion effects seen in rats with right but not left hemisphere
lesions, particularly lesions located in the frontal lobe that produced hyperactivity
(Robinson, 1979; Pearlson & Robinson, 1981).

Similar effects have been noted with orbito-frontal or anterior cingulate ablations
(Tucker & Derryberry, 1991). This would lead us to think that a decrease in right
prefrontal cortex increases approach behavior possibly because of decreased inhibition
of orbito-frontal, cingulate, and limbic structures, collectively observed as mania,
hyperactivity, and perseverative behavior. PET studies (Drevets et al., 1992) have
revealed increased blood flow in orbito-frontal cortex and parts of cingulate gyrus along
with decreased metabolism in temporal and parieto-occipital regions in primary
depressed patients. It has been postulated that in major depression the neurologic
systems responsible for the processing of sensory exteroceptive information are
inhibited in favor of pathways responsible for processing of internal information,
emotion, and negative thoughts, relying on limbic and para-limbic representations
(Nauta, 1971). Therefore it is thought that this imbalance of activity, with increased
activation of para-limbic, limbic, and neocortical areas during the experience of intense
emotional states, can be seen as a functional "release" or disinhibition of the limbic
areas responsible for emotional processing (Liotti & Tucker 1995).
Attention Deficit Hyperactivity Disorder

Since the 1940's, clinicians have applied various labels to children who are hyperactive
and inordinately inattentive and impulsive. These children have been though to have
minimal brain dysfunction, brain injured child syndrome, hyperkinetic reaction of
childhood, hyperactive child syndrome, and most recently attention deficit disorder.
Russell Barkley thinks that ADHD is not a disorder of attention per se, but rather a result
of developmental failure in the brain circuitry that underlies inhibition and self-control.
He thinks this loss of self-control impairs other important brain functions crucial for
maintaining attention, including the ability to defer immediate rewards for later, greater
gain (Barkley, Scientific American, September, 1998). Daniel Goleman (1995), the
author of Emotional Intelligence, thinks that this ability to delay gratification is the best
predictor of future success of a child. Studies estimate that between two and 9.5
percent of all school age children worldwide suffer from ADHD (Yeargin-Allsopp &
Boyle, 2002; Pary et al., 2002; Gottlieb, 2002). Barclay also notes that Joe Sergeant
(2000; Sergeant et al., 2002) of the University of Amsterdam has shown that children
with ADHD cannot inhibit their impulsive motor responses to sensory input. He also
states that other researchers have found that children with ADHD are less capable of
preparing motor responses in anticipation of events and are not sensitive to feedback
about errors made in those responses.

Imaging studies suggest involvement of the prefrontal cortex, cerebellum, and basal
ganglia. Castellanos and colleagues (1996) at the National Institute of Mental Health
have shown that particularly the right prefrontal cortex, the caudate, and globus
pallidus are significantly smaller than normal in children with ADHD. Castellanos’
group (1988) found that the vermis region of the cerebellum is also smaller in ADHD
children. The prefrontal cortex regulates goal directed behavior, a hierarchy of reflexive
movements, cross-temporal contingencies, approach and avoidance behaviors,
response inhibition, and perseveration (Chatterjee, 1998). In addition, the prefrontal
cortex regulates movements directed at accomplishing goals (Luria, 1966), and together
with the basal ganglia and cerebellum, they regulate primary motor output (Chatterjee,
1998).

The goal directed movements regulated by the prefrontal cortex are complex and have
multiple sequences. Luria thought that with frontal lobe injury or dysfunction these
reflexes are no longer smooth and integrated goal directed movements (Luria, 1966).
Instead, these movements he saw as fragments of the internal action. Coordinating
movements to achieve an intended goal requires their organization over time; therefore,
the prefrontal cortex is important in cross-temporal contingencies (Foster, 1989).
Patients with frontal lobe dysfunction may present with different symptoms depending
on whether dysfunctions include the right or left prefrontal cortex. Left prefrontal cortex
dysfunction produces difficulty in initiating movements without guidance of explicit
stimuli. Clinically patients are passive, apathetic, and depressed and symptoms include
lack of approach with increased avoidance behavior. Increased avoidance behavior with
withdrawal to touch as seen in some autistic children is also a result of decreased
activation of the left prefrontal cortex. Right prefrontal cortex dysfunction can result in
difficulty inhibiting responses to stimuli. These children are distractible and react
randomly to environmental stimuli, all typical of the attention deficit hyperactive disorder
child, and can be viewed as a decrease in avoidance and an increase in approach
behavior, normal for right prefrontal cortex function. Simple approach behaviors
exhibited may include simple movements approximating stimuli such as the group or
smart reflexes, or complex approach movements (Lhermitte, 1986) where they
inappropriately use whatever implements are within view. In addition, with the right
prefrontal cortex the child may exhibit perseverative behavior, or the inappropriate
repetition of movements over time. Perseverations may be simple or complex (Sandson
& Albert, 1984; Hotz & Helm-Estabrooks, 1995). The simplest form of perseveration is
the inability to stop a single movement or muscle contraction after it has been
completed. For instance, the child may not be able to relax his or her grip after shaking
someone’s hand. Another type of perseveration is the continuous repetition of a
coordinated movement. For instance, a child may be unable to stop drawing loops after
beginning a circular motion. A third type of perseveration is the repetition of a self-
contained act even when required to switch to a different movement. For example, a
child may continue to write their name even when told to write something else.
Therefore, we see that typically right prefrontal cortex dysfunction can cause the
inappropriate release of reflexive movements that vary in complexity, from a sustained
single contraction, to the repetition of coordinated movement. This can also be
considered hyperkinetic motor activity like dystonia, tremor, or tics typical of ADHD, or
Tourette’s syndrome. It can also involve the repetition of a coordinated movement or
repetition of a complex act typical of obsessive-compulsive disorder and sometimes
seen with autism or pervasive developmental disorder.

In children, these impulsive repetitive behaviors may in part be due to decreased ability
to inhibit limbic structures like the amygdala. This could arise because of decreased
activation or imbalance of arousal, or activation of the prefrontal areas, which processes
cognitive information and inhibits the limbic system. It may also be because of delay in
development of the prefrontal cortex. In some children, a lack of stimulation or arousal
may delay the development of the prefrontal cortex, which is the latest part of the
neocortex to develop.

Researchers at McLean Hospital and Harvard Medical School have conducted imaging
studies on children between the ages of 11 and 17. The study found that the younger
children process information using the amygdala, which controls aggression, fear,
anger, and other primitive emotions. However, older children process the same
information using the frontal cortex (Kilgore & Yurgelun-Todd, 2001; Yurgelun-Todd
et al., 2002). Deborah Yurgelun-Todd (WGBH, 2002) of McLean Hospital's brain
imaging center is quoted as stating, "If the physiology isn't complete, parents can't
expect their children to have responses that are the equivalent to adults." She went on
to comment that "we probably need to assume that they don't always understand what
they are learning and may not respond accordingly." (WGBH, 2002) The researchers
think that the frontal cortex is responsible for inhibiting "gut" or emotional responses or
emotions. This is thought to explain why children and adolescents seem so impetuous
or impulsive. Without activation of the frontal lobe, children cannot have fully developed
emotional responses. The researchers in Boston tested the developing brain in 16
healthy children and teenagers. They had the children perform two cognitive
neuropsychological tasks. One test presented the child with a number of faces
expressing fear. They were also asked to determine what emotion the face was
expressing. The second task involved adolescents who were asked to complete a
number of word-production procedures including counting and word fluency.

The brains of younger children show strong amygdala activation when they respond to
the faces. The magnitude of reaction, which is shown as an increase in blood flow, is
larger on the left. This is consistent with research that face recognition is a right brain
activity, however it is thought that the right amygdala is inhibited by the left frontal
cortex. As children get older, there is more frontal cortex activity and less amygdaloid
activity. In language-based activities, which always originate in the frontal lobe, the
activity in that same area increases with age. In the study children younger than 13 all
had difficulty determining what emotion they were looking at, "they are not correctly
discriminating facial affect, which could explain why their response to individuals may
seem inappropriate." (WGBH, 2002). Recognition of faces and recognition of emotions
are both right hemisphere activities. This study suggests a natural delay in development
of the right brain to emotional stimuli, which is processed in the emotional amygdala,
instead of the cognitive prefrontal cortex.

If a child has a below normal activation of the right brain we would expect this
process of development to be slowed and the amygdala to process more
information than normal for longer periods of time. This would explain the
impulsive behavior of children with ADHD; this may also explain why males are
more prone than females, because the male right frontal lobe grows larger than
females. Therefore, the male brain may be more susceptible to delays in right
frontal cortex development. This may also explain the lack of social development of
children with ADHD. It has been noted that we have become increasingly aware of the
relationship between learning disabilities and social skills development. It is thought
likely that children with learning and social deficits make up a group of children with
non-verbal learning disabilities (Semrud-Clikeman & Hynd, 1990). This disorder was
first described as the inability to process environmental cues including those used in
communication (e.g. gesture, facial expression, and vocal intonation). These children
often have difficulties in processing other (non-communicative) information such as
visual-spatial and certain types of arithmetic problems. Hynd and Semrud-Clikeman
(1989) have suggested thalamic dysfunction in regard to attention resources, which is
also consistent with others who suggest the role of the thalamic nuclei in visual-spatial
input and emotional expression (Kelly, 1985). It has been noted that this subtype of non-
verbal learning-disabled children warrants further study not only for research value but
also for advancing more affective differential interaction strategies (Boliek & Obrzut,
1995).

Cortical-Subcortical Circuits and Affective Disorders

In considering how cerebellar, thalamic or basal ganglionic dysfunction may lead to

depression or mania, it has been proposed that it is the result of the disruption of frontal
cortical function. The caudate is thought to share common pathways with frontal cortical
structures either directly or through the dorso-medial nucleus of the thalamus.
Alexander and colleagues (1986) described five functionally segregated parallel frontal
cortical-striatal-thalamic loops, both motor and non-motor with variable degrees of limbic
input. Part of the non-motor loop, a dorso-lateral prefrontal network would be used for
storage in working memory of spatial locations (Goldman-Rakic, 1987). A lateral orbito-
frontal circuit, proceeding from the orbito-frontal cortex to a specific area of the caudate
and globus pallidus would then project to the thalamus and the orbito-frontal cortex
again. This loop is thought to be responsible for learning and recognition tasks requiring
frequent shifts of set. This interpretation is thought to explain the pronounced
perseveration seen in orbito-frontal damage. In addition, there is an anterior cingulate
circuit, which includes the ventral striatum, nucleus accumbens, and medio-dorsal
nucleus of the thalamus. The hippocampus and entorhinal cortex also send information
in this loop integrating information from the para-limbic association cortex. It is thought
that the nucleus accumbens is a target of dopaminergic terminals from the
mesencephalic ventro-tegmental area (VTA).

Mayberry (1992) conducted PET studies of basal ganglia stroke patients. They found
that compared to euthymic patients, all of the patients with mood change showed hypo-
metabolism in the orbital-inferior frontal cortex, anterior temporal cortex, and cingulate
cortex. Of course the cerebellum could be considered a primary source of many of
these findings as well. Recent reports on human emotional behavior show that
disorders in control of affect can follow atrophy of the midline cerebellum (Gutzmann &
Kuhl, 1987). Lack of behavioral self-control, including episodic rage, is sometimes seen
as an early symptom of tumor of the paleo-cerebellum (Elliot, 1982). It has been
reported that after the surgical removal of a benign tumor, several weeks of explosive
behavior follow. The cerebellum is connected to the neocortex and the limbic system.
One route connects the cerebellum to the thalamus and the cerebral neo-cortex. The
other route connects the cerebellum to the hypothalamus and therefore to older
structures of the brain (Dietricks & Haines, 1989; Haines & Dietricks, 1987; Haines et
al., 1984; 1990). It is thought that the midline paleo-cerebellum is connected primarily to
the limbic system and limbic neo-cortex, whereas the lateral cerebellum is more
connected to the neo-cortex especially the prefrontal cortex. It has been noted that a
large percentage of children with learning disabilities and affective disorders like ADHD
present with motor deficits that are consistent with cerebellar and or basal ganglia
dysfunction.

Fear, Anger, and Violent Behavior

In extreme cases, some children with learning disabilities or emotional disorders may
exhibit extreme emotions of fear, anger, and violent behavior. Violent behavior has
seemed to increase significantly especially among adolescents and young teens. These
behaviors may reflect extreme cases of approach and avoidance, and failure of the
frontal cortex to develop to the degree necessary to inhibit primitive emotions of the
limbic system. Research has shown that interestingly, individuals with history of violent
behavior show similar decreased activity in the same area of the brain as children with
depression, or manic behaviors like ADHD, OCD, and Tourette’s syndrome. Many
children and teens who are committing violent crimes have been previously diagnosed
with affective disorders (Phillips, 2002; Loeber et al., 2002).

Fear and Anxiety

The amygdala appears to be the main area in control of fear and anger as well as other
emotions. This primitive fight or flight instinct is the extreme end of approach or
avoidance behavior. In childhood anxiety disorders, posttraumatic stress disorder, and
phobias, as well as hyperactivity, obsessive-compulsive disorder, and depression may
all suffer from a failure to regulate the amygdala response (Ramamurthi, 1988;
Kulisevsky et al., 2002; Durston et al., 2001; Heim & Nemeroff, 1999; Filipek et al.,
1997; Castellanos et al., 1996; Benarroch, 1992). A recent Harvard study has found that
in normal individuals the amygdala is not only involved in fear responses, but
also with rapidly assessing the emotional importance of a fearful stimulus.

For example, if we see a bear in the woods the amygdala will trigger memories, as well
as physiological responses. If the bear is in the zoo, the neo-cortex will consciously
process information and inhibit the amygdala overriding the responses. The amygdala
appears to be able to work on an implicit level to process potentially dangerous stimuli.
Paul Whalen, Scott Rauch, and colleagues at Massachusetts General Hospital recently
showed that fear responses can be activated implicitly. The researchers used an
approach suggestive of subliminal advertising while using functional MRI to image the
brain. They showed subjects photographs of fearful faces for 33 milliseconds followed
by a longer, masking exposure to expressionless faces for 167 milliseconds. The
subjects had no conscious memory of seeing the fearful faces, however imaging
showed that the amygdala lit up even during the brief flash of a fearful face, but not
afterward and not during the similarly brief flash of a happy face. "So it’s a very fast and
preferential way to get information" says Whalen "anxiety is about hyper-vigilance
and there is a vigilance system" (NY Times Magazine, February 28, 1999; Shin et al.,
2001; Rauch et al., 2001; 2000; 1998; Whalen et al., 1998a; 1998b; Bush et al., 1999).

There is also growing evidence that the amygdala is important for social situations.
Patients with Klüver-Bucy syndrome-type behavior, suffer temporal lobe lesions that
often include the amygdala. These patients often act inappropriately in social situations.
They are not emotionally expressive and tend to be hypersexual. They may also ingest
items such as tea bags and cigarette butts, not being able to recognize the difference
between edible and non-edible items. In addition, primates with lesions to this area
seem to be shunned by the rest of the group.

Nancy Etcoff (Aharon et al., 2001) has indicated that if the amygdala is disrupted
individuals may find it difficult to make judgments about the environment. Other
researchers have focused on the brains reward system. Hans Breiter and his
colleagues (Breiter et al., 1997; Breiter & Rosen, 1999) used cocaine as a reinforcer in
drug dependent patients. They found what they think to be the human reward circuit.
Breiter's team found that access of the nucleus accumbens, the area of the brain
thought to regulate euphoria, and the amygdala, rich in dopamine, were both activated.
Dopamine appears to be involved in regulating pleasure and reward. It was found that
the nucleus accumbens is activated not during the actual dose of cocaine, but during
the state of craving or wanting the drug that follows. It is thought that these circuits may
be involved in schizophrenia which is characterized by lack of motivation, and interest in
rewards or pleasure or lack of "will". Because of these circuits, it is thought that we can
experience, learn, and unconsciously commit to emotional memory many fearful
situations without ever being aware of what has triggered the racing heart and quick
pulse. In small children who are exposed to abuse or violence, the limbic connections
may become extremely strong and reinforced before the prefrontal cortex has
developed mechanisms to inhibit these responses. These connections may become so
powerful that they may subconsciously promote reactions in a child or later in
adulthood. Panic attacks for example may be a result of this type of early experience.

The implication of fear conditioning experiments in organisms is that we have a

separate memory of fearful stimulus, harbored in the amygdala, probably informed by
things we have heard or seen but do not consciously remember. In a PET study, Roy
Dolan (1999; 2002; Dolan & Fletcher, 1999; Dolan et al., 2000) of the Wellcome
Department of Cognitive Neurology at the institute of Neurology in London has shown
that in humans, a fear conditioning route bypasses the cognitive part of the brain.
Researchers think that anxiety disorders appear to be a uniquely human phenomenon,
because of the involvement of the prefrontal cortex. It has been stated by one
researcher (New York Times, February, 1999) "bang on the amygdala and you're
going to get panic attacks. Bang on the hippocampus and you are going to get
posttraumatic stress syndrome. You mess up the medial prefrontal cortex and
you are going to get much worrying, they are all within the same system."

Bergmann (1995) reviewed a PET study examining the neuroanatomy of posttraumatic

stress disorder (PTSD) symptoms (Rouch et al., 1996). In this study, subjects were
exposed to recordings of scripts describing the subject’s past personal experiences,
including the traumatic experiences thought to have caused the PTSD. The script driven
scans showed findings of increased activity in the right-sided limbic, para-limbic and
visual cortex. No significant changes were found in the hippocampus or thalamus.
Decreases in activity were found in the left frontal and middle temporal cortex.
Bergmann thinks that these results suggest that emotions associated with PTSD are
mediated by the limbic and para-limbic areas of the right hemisphere. The right-sided
brain activity is apparently consistent with literature supporting the preferential role of
the right hemisphere in anxiety, panic, and phobic disorders. Similar areas of the brain
may be involved in aggressive, socially inappropriate behavior.

One of the most disturbing trends in the U.S. is the increase of youth violence over the
past few years. Statistics show (Gore, 2000) that in 1995 more than 862,000 violent
crimes in schools were reported by students in nations public and private schools,
according to a survey by the U.S. Department of Justice and the U.S. Department of
Education referenced by Gore. Juvenile arrests for murder and non-negligent
manslaughter increased 90 percent from 1986-1995, according to statistics compiled by
the U.S Justice Department's Office of Juvenile Justice and Delinquency Prevention
(2000). Arrests for aggravated assault increased 78 percent. Access to firearms is
thought to have exacerbated the situation according to the Justice Department. From
1984 to 1994, for example juvenile homicides involving firearms nearly tripled, while
homicides by other methods remained the same. It was noted that guns were the
weapons of choice in every school attack in the previous 18 months. Violent crime
committed by girls including murder increased 34 percent between 1991-1995.
Aggravated assaults by girls increased 39 percent, 6 percent for boys. It has been noted
that warning signals are depression and a lack of empathy or feelings for others. Youth
violence has increased significantly in the past decade (Eron et al., 1994). The homicide
rate for young men in the United States is seven times that of Canada and eighteen
times that of the United Kingdom (Tedschi & Felson, 1994).

According to Berkowitz (1993; 1994), feelings of frustration and other negative affects
give rise to aggression. We know that negative emotions are generally lateralized to the
right hemisphere. Frustration does not lead immediately to aggression, but leads to
hostile feelings. Frustration is common among children with learning disabilities,
especially since many have above average intelligence, know they should be able to
learn in a formal educational setting, but cannot. Children with behavioral problems
experience the same types of frustrations; their inability to perceive the emotions of
others may lead to inappropriate behavior.

Hostility and anxiety are part of the fight or flight, approach, or avoidance responses
triggered by the amygdala in response to a perceived threat. Research indicates that
hostile feelings can be modified by environmental means. Adults who have grown up in
caring homes with a great deal of nurturance apparently do not show the same level of
aggression as those who experience little nurturance. In contrast, children who were
abused tend to be more aggressive (Dodge 1993; Widom, 1989a, 1989b).

It is no coincidence that in the United States as we see a decrease in cognitive skills as

witnessed by the decline in standardized test scores, we have also seen an increase in
behavioral and emotional problems among our children. The use of Ritalin has
increased 700 percent since 1990 (Connor, 2002), and 90 percent of the world-wide use
is in the U.S.A. Researchers at Case Western Reserve University recently (Song et al.,
1998) set out to find out if an adolescent psyche is influenced by violent behavior in his
environment. After studying over 3,700 children ages 14-19, they report that the link is
both "sticking and obvious," teens exposed to physical or violent trauma at home are
much more likely to be chronically angry and act violently themselves. Violence is rising
dramatically among teenagers: 17 percent of teenage boys in this study report having
tried to shoot someone during the past year.

Is there a neurophysiological explanation for this behavior? A report in New York

Newsday (April 14, 1998) may give some answers. In the first study of its kind,
neuroscientists used the latest imaging technology to look inside the brains of killers to
determine if their brains differ in some way. Adrian Raine (Raine et al., 1997; 1998a;
1998b), a clinical neuroscientist at the University of Southern California Los Angeles
who led the study, identified 38 murderers, and determined whether they suffered
physical or sexual abuse, severe family conflict or parental divorce. Of the murderers,
12 had suffered significant abuse, while the remaining 26 experienced minimal abuse or
none at all. The researchers used PET scans to compare those who had suffered
trauma as a child with those who had not, and with a group that had not committed
violence. Compared with the subjects who had suffered abuse and with non-violent
individuals the 26 murderers from relatively benign backgrounds averaged 5.7 percent
less activity in the medial prefrontal cortex. More significantly, they showed an average
of 14.2 percent less activity in a specific area of the medial prefrontal cortex and the
orbito-frontal cortex on the right hemisphere.

The medial prefrontal cortex has been shown to inhibit the limbic system. Raine
was quoted as commenting (New York Newsday, April 14 1998), "The prefrontal cortex
is a bit like a emergency brake on the deeper areas of the brain that are involved in
aggressive feelings." Research has shown that the right orbito-frontal cortex is
involved in fear conditioning, the subconscious association between antisocial behavior
and punishment that is thought to be the key to developing a "conscience." The deficit
shown in the study may leave an individual with “an emotionally blunted personality
lacking in conscience development." Raine and colleagues (1998a) wrote in reporting
their findings, "the fact that there is an identifiable biologic disposition suggests its not
how the child was raised, it’s that they had a biological dysfunction combined with a
situation that led to the violence." This may explain also, how children with good family
backgrounds and good education may still suffer from a learning disability or affective
disorder.

The orbito-frontal cortex especially on the right is also described as the neo-cortical
representation of the limbic system (Nauta, 1971). Damage or dysfunction has been
noted to lead to impairments in visual object learning in monkeys (Thorpe et al., 1983),
perseverative behavior (Ledoux, 1987; Dayderry & Tucker, 1992), mania, and
inappropriate social behavior (Starkstein et al., 1988). These types of symptoms are
characteristic of impulsive disorders, which include borderline personality disorder
and antisocial personality disorder, and have been grouped into a larger group of
"obsessive-compulsive spectrum disorders." Some of these include dissociative
disorders, tic disorders, personality disorders, "schizo-obsessive spectrum
disorders,” and a wide range of neurologic disorders including epilepsy, autism, and
several basal ganglia disorders like Tourette’s syndrome.

Overlap of Symptoms

Asperger’s syndrome, a condition that is generally considered a form of autism, has

shown a dramatic increase over the past few years. Asperger’s is often confused by
physicians with ADHD, non-verbal learning disorder, and obsessive-compulsive
disorder. Hans Asperger, the Viennese pediatrician who first described the condition in
1944 called his patients "little professors" who use words as their lifeline to the world.
Most Asperger’s patients have average intelligence or above, 80 percent of autistic
people by contrast suffer some degree of mental retardation. The most striking
characteristic of the syndrome is strong interest in arcane subjects. It has been noted
that some patients have shown obsessions with clocks, the Titanic, deep fat fryers, lists
on Congressional members, etc. The key point to the diagnosis is that their obsessive
behavior significantly impairs their social functioning. It is thought that children with the
condition are not able to grasp the non-verbal cues that underlie most interactions with
others but intelligent enough to understand and regret their deficits. Even though it was
first described by Asperger in 1944, it was not until 1994 that the syndrome was
included in the Diagnostic and Statistical Manual of Mental Disorders of the American
Psychiatric Association (DSM-IV), the latest version of the mental health professionals
guidebook. More recently, researchers have talked of an autistic spectrum with
Asperger’s being described as the spans "smart end." Asperger’s has been described
as autism's mirror image.

In cases of autism, the difficulties are primarily handled by the left hemisphere.
However, in Asperger’s it has been noted that the deficits are primarily in the right
hemisphere, because difficulty is with non-verbal skills, leading some to speculate the
syndrome may be some day known as right-brained autism. Autism is usually
diagnosed around age 3 but children with Asperger’s are not usually identified until they
start school and their lack of social skills stand out. These children have been noted to
have problems with motor skills and auditory processing. Their strengths are in
intelligence and verbal ability. Other symptoms include: a marked lack of interest in
other children, or a consistently inappropriate style of engaging others, difficulty
understanding other children's feelings and expressions, inability to understand teasing
or jokes, few facial or bodily gestures, speech that is pedantic in tone or vocabulary,
overreactions to minor changes in routine or environment, and precocious verbal skills,
and marked self absorption in subjects unusual for the child's age.

It should now be apparent that there is a tremendous overlap of symptoms and

similarity of the areas that produce these symptoms. It becomes understandable
why these disorders are now seen as being on a continuum. In fact, we see that
most children that are diagnosed with one problem often have a second or third
diagnosis, probably because the same areas are involved, the symptoms
produced are almost identical, and the neurotransmitters involved are the same.
This leads us to think they may all have a similar underlying cause, but slight
genetic variations may predispose one child to more of one type of symptom
versus another. Genetics combined with developmental plasticity and
environmental influences may be the only major difference between disorders
like ADHD, OCD, Tourette’s, autism and depression. The other factor, and
perhaps the most important one, is that most of these disorders can be simply
considered as right brain or left brain disorders, and can be isolated to a deficit
that is either ventral or dorsal. To illustrate this more fully, let us examine some of
the major syndromes and compare the symptoms and how they overlap.

A recent paper that examines the neurobiology of obsessive-compulsive disorder

(Stein, 1996) describes the condition as being characterized by recurrent intrusive
thoughts and repetitive ritualistic actions. The author notes that although symptoms
have long been considered symbolic expressions of unconscious issues, recent
research has supported a neurophysiologic cause. Obsessions are defined as recurrent
and persistent thoughts, impulses, or images, which the individual regards as intrusive
and inappropriate (American Psychiatric Association, 1994). Compulsions are
repetitive behaviors or mental acts (also known as perseverations), that the
individual feels compelled to perform in response to an obsession or according
to rules that must be followed rigidly (American Psychiatric Association, 1994). The
individual with OCD is usually aware that symptoms are excessive but notes that they
are unable to resist these repetitive thoughts and actions. Perseverations are
characteristic of right prefrontal cortex dysfunction and can be considered
hyperactive behavior or hyperkinetic behavior. This is similar to hyperactivity, repetitive
movements, or vocal tics. These disorders appear to respond to treatment with
serotonergic uptake inhibitors but appear not to respond to the noradrenergic tricyclic
antidepressants (Zohar & Insel, 1987). This differentiates OCD from depression,
which is thought to be due to a left prefrontal cortex deficit. It has been suggested
that the dopamine system may also mediate OCD symptoms (Stein, 1996). It has also
been noted that tics are common in OCD (Pitman et al., 1987) and that OCD symptoms
are frequent in patients with Tourette’s syndrome (Hollander et al., 1989). Recent
evidence suggests an important role for the basal ganglia in OCD. Patients with
Tourette’s syndrome (Hollander et al., 1989), Syndenhom's chorea (Swedo et al.,
1989), and Huntington's disease (Cummings & Cunningham, 1992) may have co-
morbid OCD (Stern, 1996). In addition, patients with OCD may have co-morbid tics
(Pitman et al., 1987) or increased neurological soft signs (Hollander et al., 1990)
suggestive of basal ganglia pathology. Finally it has been reported that both
structural and functional brain imaging studies have shown basal ganglia pathology
especially decreased caudate volume in OCD patients (Luxenberg et al., 1988;
Robinson et al., 1995). Patients with frontal lobe lesions sometimes present with OCD
symptoms and OCD patients may show evidence of frontal lobe impairment in
electrophysiological studies (Khanna, 1988). Also reported has been an MRI study that
found abnormalities in right frontal lobe (Garber et al., 1989). These results together
suggest that cortical-basal ganglia-thalamic-cortical circuits may play a significant role in
OCD symptoms (Stein, 1996).

In another review paper, the authors (Spencer et al., 1998) looked at the apparent
overlap between Tourette’s syndrome and ADHD. They note that Tourette’s
syndrome is a chronic neuropsychiatric condition commonly associated with social,
occupational, and academic dysfunctions (Erenberg et al., 1986; Stokes et al., 1991).
They also note that children with Tourette’s syndrome have often been found to have
high levels of co-morbidity with OCD and attention deficit/hyperactive disorder. They
conclude that their findings confirm previously noted associations between Tourette’s
syndrome and OCD, but also suggest that disruptive behavioral, mood, and anxiety
disorders as well as cognitive dysfunctions may be accounted for by comorbidity with
ADHD. However, they state that Tourette’s syndrome with ADHD is apparently more
severe than ADHD alone. Another study by Farone and colleagues (1998) notes that
there is comorbidity between ADHD and conduct disorder (CD) that has consistently
been reported in both clinical and epidemiological studies (Bierman et al., 1991). These
studies are just an example of the significant overlap of many childhood learning
disabilities and affective disorders that have been noted in the scientific literature.
Depressive disorders, manic disorders, generalized anxiety disorders, and psychotic
disorders are all more common following damage or dysfunction of one hemisphere
than the other. Left frontal and left basal ganglionic lesions lead to an increased
incidence of major depression, whereas right orbito-frontal, basal temporal, basal
ganglia and thalamic lesions are associated with manic symptoms. Anxiety
disorders without depression and psychotic disorders have also been shown to be
associated with right hemisphere lesions, especially posterior temporal and parietal
lesions. In addition, there are several studies in both humans and lower organisms that
have shown that right and left hemisphere lesions result in different affects on the
biogenic amines, especially serotonin and norepinephrine. It is thought that these
biochemical changes induced by specific brain lesions may mediate through
asymmetric brain pathways the clinical manifestation of these disorders (Robinson &
Downhill, 1995).

Bernard and colleagues provide elective summaries of the behavioral traits and
physiological characteristics of those with autistic spectrum disorder culled from the
literature of the past thirty years and presented in Tables 9.1 and 9.2 below.

TABLE 9.1 Summary Comparison of Physiological Abnormalities in ASD: Autism,

ADD, ADHD, and other Developmental Disorders (Adapted from: S. Bernard S.,
Enayati, A., Redwood, L., Roger, H., Binstock, T., and Bernard, S. ARC Research,
Cranford NJ, USA www.biometricdiagnostics.com/content/amp/content.php3)

Biochemistry Low sulfate levels (Alberti et al., 1999)

Low levels of glutathione; decreased ability of liver to
detoxify xenobiotics; abnormal glutathione peroxidase
activity in erythrocytes (Golse et al., 1978; Edelson & Cantor
1998a; 1998b)
Purine and pyrimidine metabolism errors lead to autistic
features (Gillberg, 1992; Page et al., 1997; Page & Moseley,
2002)
Mitochondrial dysfunction, especially in brain (Chugani et
al., 1999; Lombard, 1998)

Low Vitamin D levels

Immune System More likely to have allergies and asthma; familial presence
of autoimmune diseases, especially rheumatoid arthritis; IgA
deficiencies (Plioplys et al., 1989; Comi et al., 1999; Warren
et al., 1986; Gupta et al., 1996)
On-going immune response in CNS; brain/MBP
autoantibodies present (Connolly et al., 1999; Singh et al.,
1993)
Skewed immune-cell subset in the Th2 direction; decreased
responses to T-cell mitogens; reduced NK T-cell function;
increased IFNg & IL-12 (Plioplys, 1989; Warren et al., 1986;
1987; Gupta et al., 1996; Messahel et al., 1998; Gupta et
al., 1998; Singh, 1996)
CNS Structure Specific areas of brain pathology; many functions spared
(Dawson, 1996)
 Pathology in amygdala, hippocampus, basal ganglia,
cerebral cortex; damage to Purkinje and granule cells in
cerebellum; brainstem defects in some cases (Dawson,
1996; Courchesne et al., 1994a; 1994b; 1994c; Ritvo et al.,
1986; Hoon & Riess, 1992; Piven et al., 1990; Abell et al.,
1999; Aylward et al., 1999; Otsuka, 1999; Sears, 1999;
Hashimoto et al., 1995)
Neuronal disorganization; increased neuronal cell
replication, increased glial cells; depressed expression of
NCAMs (Bailey et al., 1996; Minshew, 1996; Plioplys et al.,
1990)
Progressive microcephaly and macrocephaly (Fombonne et
al., 1999)
Neuro-chemistry Decreased serotonin synthesis in children; abnormal
calcium metabolism (Chugani et al., 1999; Plioplys, 1989;
Leboyer et al., 1999)
Either high or low dopamine levels; positive response to
peroxidine, which lowers dopamine levels (Gillberg, 1992;
Gillberg & Svennerholm, 1987; Ernst et al., 1997)
Elevated norepinephrine and epinephrine (Gillberg,
1992)
Elevated glutamate and aspartate (Moreno et al., 1992;
Carlsson, 1998)
Cortical acetylcholine deficiency; reduced muscarinic
receptor binding in hippocampus (Perry et al., 2000)
Demyelination in brain (Singh et al., 1993)
Neurophysiology Abnormal EEGs, epileptiform activity, variable patterns,
including subtle, low amplitude seizure activities (Gillberg,
1992, Bailey et al., 1996; Lewine, 1999; Nass et al., 1998)
Abnormal vestibular nystagmus responses; loss of sense of
position in space (Goldberg et al., 2000; Ornitz et al., 1985)
Autonomic disturbance: unusual sweating, poor
circulation, elevated heart rate (Ornitz et al., 1985)

TABLE 9.2 Summary of Behavioral Traits

(Adapted from: S. Bernard S., Enayati, A., Redwood, L., Roger, H., Binstock, T., and Bernard, S. ARC
Research, Cranford NJ, USA www.biometricdiagnostics.com/content/amp/content.php3)

Psychiatric Social deficits, shyness, social withdrawal (American

Disturbances Psychiatric Association, 1994; Gillberg, 1992; Capps et al.,
1998; Tonge et al., 1999)
Repetitive, perseverative, stereotypic behaviors;
obsessive-compulsive tendencies (American Psychiatric
Association, 1994; Gillberg, 1992; Cesaroni & Garber, 1991;
 Roux et al., 1998; Howlin, 2000)
Depression/depressive traits, mood swings, flat affect;
impaired face recognition (Piven & Palmer, 1999; Plioplys,
1989; Klin et al., 1999; DeLong, 1999)
Anxiety; schizoid tendencies; irrational fears (Gillberg,
1992; Muris et al., 1998)
Irritability, aggression, temper tantrums (McDougle et al.,
1995; Jaselskis et al., 1992; Tsai, 1996)
Lacks eye contact; impaired visual fixation (HgP)/ problems
in joint attention (ASD) (Filipek et al., 1999; Dawson, 1996;
Baron-Cohen et al., 1992!)
Speech and Loss of speech, delayed language, failure to develop
Language speech (American Psychiatric Association, 1994; Gillberg,
Deficits 1992; Filipek et al., 1999; Prizant, 1996)
Dysarthria; articulation problems (Filipek et al., 1999)
Speech comprehension deficits (Filipek et al., 1999; Bailey
et al., 1996)
Verbalizing and word retrieval problems (HgP); echolalia,
word use and pragmatic errors (ASD) (American
Psychiatric Association, 1994; Filipek et al., 1999; Dawson,
1996)
Sensory Abnormal sensation in mouth and extremities (Gilberg,
Abnormalities 1992; Baranek, 1999)
Sound sensitivity; mild to profound hearing loss
(Gilberg, 1992; Rosenhall et al., 1999; Roux et al., 1998)
Abnormal touch sensations; touch aversion (Gilberg &
Coleman, 1992; Baranek, 1999)
Over-sensitivity to light; blurred vision (Gilberg, 1992;
O’Neill & Jones 1997)
Motor Disorders Flapping, myoclonal jerks, choreiform movements,
circling, rocking, toe walking, unusual postures (Gilberg,
1992; Filipek et al., 1999; Tsai, 1996; Cesaroni & Garber
1991)
Deficits in eye-hand coordination; limb apraxia; intention
tremors (HgP)/problems with intentional movement or
imitation (ASD) (Gilberg, 1992; Filipek et al., 1999; Dawson,
1996)
Abnormal gait and posture, clumsiness and
incoordination; difficulties sitting, lying, crawling, and
walking; problem on one side of body (Bailey et al., 1996;
Teitelbaum et al., 1998; Gilberg, 1999)
Cognitive Borderline intelligence, mental retardation - some cases
Impairments reversible (Gilberg, 1992; Filipek et al., 1999; Edelson et al.,
 1998)
Poor concentration, attention, response inhibition
(HgP)/shifting attention (ASD) (Bailey et al., 1996; Dawson,
1996; Rumsey, 1985)
Uneven performance on IQ subtests; verbal IQ higher than
performance IQ (Dawson, 1996)
Poor short term, verbal, and auditory memory (Dawson,
1996)
Poor visual and perceptual motor skills; impairment in
simple reaction time (HgP)/ lower performance on timed
tests (ASD) (Bailey et al., 1996; Grandin, 1995; Schuler,
1995)
Deficits in understanding abstract ideas & symbolism;
degeneration of higher mental powers
(HgP)/sequencing, planning & organizing (ASD);
difficulty carrying out complex commands (Bailey et al.,
1996; Filipek et al., 1999; Dawson, 1996; Rumsey, 1985)
Unusual Self injurious behavior, e.g. head banging (Filipek et al.,
Behaviors 1999; Gedye, 1992)
ADHD traits (Gilberg, 1992; Dawson, 1996; Kim et al., 2000)
Agitation, unprovoked crying, grimacing, staring spells
(Filipek et al., 1999; Gedye, 1992)
Sleep difficulties (Gilberg, 1992; Richdale, 1999; Wiggs &
Stores, 1998)
Physical Hyper- or hypotonia leading to scoliosis; abnormal
Disturbances reflexes; decreased muscle strength, especially upper
body; incontinence; problems chewing, swallowing
(Filipek et al., 1999; Teitelbaum et al., 1998; Church &
Coplan, 1995; Schuler, 1995)
Diarrhea; abdominal pain/discomfort, constipation,
"colitis" (Deufemia et al., 1996; Horvath & Perman, 2002;
Wakefield et al., 1998)
Anorexia; nausea (HgP)/vomiting (ASD); poor appetite
(HgP)/restricted diet (ASD) (Gilberg, 1992; Kanner, 1943)
Part II Treatment Protocols
After our review of brain function and how symptoms are produced with decreased
output both inhibitory and stimulatory, let us explore our approach to help correct the
imbalance. It really seems easy – the brain runs on fuel and activation so just increase
stimulation and provide the proper fuel. In practice, however, it is not quite that
straightforward. There are numerous ‘causes’ to the imbalance that NEED to be
addressed first before any stimulation can occur. Sources of inflammation NEED to be
uncovered, metabolic function MUST be balanced, any anemia’s MUST be addressed,
any toxicity MUST be cleared, nutritional deficiencies NEED to be handled and the
immune system MUST be balanced. The one thing I desire to do in this section is to
clearly express the HOPE available in successfully treating brain imbalances.

There is no “how to” manual, since individuality needs to be addressed, but correction
IS possible, for I myself, am living proof. I was suffered from dyslexia until I was in high
school, making it impossible to read a book or keep up with others in any classes
requiring reading. My discovery that I was not just a ‘slow reader’ was a revelation that
shaped my career. In our clinic, we utilize over 100 Brain-Based Therapies as well
Metabolic, Functional Endocrinology Therapy. The success I personally experienced,
now I desire to pass on to as many as possible!

Current Treatment Rationale

Current thinking is that only two options for treatment exist: one being medication which
makes up approximately 75 percent of recommendations and the other being
psychological or behavioral counseling which makes up the other 25 percent. Most
teachers, as well as clinicians are not aware of the options or the possible effectiveness
and scientific rationale for their use. In fact, many other alternative treatment options
have been available for decades that are effective and safe. Some of these options
have merit and will be examined here in the light of recent brain, behavioral,
pharmacological, biochemical, and genetic research.

Behavioral Intervention Strategies

Cognitive Behavioral Therapy

This form of therapy has been used on adults for many fears or phobias, anxiety
disorders, panic attacks, and post traumatic stress disorder. Developed in the 1960's by
psychiatrist Aaron Beck (1967, 1976), this form of therapy gradually allows those with
these disorders to talk about, physically approach, and ultimately experience the very
things that terrify them. It is thought that this particular form of therapy deliberately sets
up a program of repeated programmed self awareness exercises to rewire connections
in the brain and form helpful new memories, just as repetitive practicing of the piano
gradually creates a memory of motor skills. Common cognitive distortions without a
neurobehavioral disorder likely have value. Cognitive distortions are natural
consequences of using fast track defensive algorithms that are sensitive to threat. In
various contexts, especially those of threat, humans have evolved to think adaptively
rather than logically. Hence, cognitive distortions are not strictly errors in brain
functioning and it can be useful to inform patients that 'negative thinking' may be
dysfunctional but is a reflection of basic brain design and not personal irrationality. The
neuropathology underlying ADHD and neurobehavioral disorders in general most
consistently points to dysfunction in cortical-striatal pathways leading to inactivation, or
insufficient engagement, of frontal and prefrontal lobes. By implication, there may be
functional disconnection between the anterior and posterior higher cortical regions,
instead of a fixed dysfunction in either one. Given this premise, reconnection of these
systems via cognitive interventions constitutes a logical remedial approach in the
treatment of ADHD and neurobehavioral disorders through integrative cognitive and
neuropsychological interventions.

Related to neurobehavioral disorders, however, studies have shown that CBT is just as
effective as drugs in many instances (Hunter et al., 2002; Barlow et al., 2000; Ninan et
al., 2000; Hinshaw et al., 1984). We have discussed the involvement of the thalamus in
the manifestation of developmental neurobiologic abnormalities. Rosenberg and
colleagues (2000) had recently studied the pathophysiology of obsessive-compulsive
disorder treated by CBT. They had reported increased thalamic volume in treatment-
naive pediatric OCD patients versus case-matched healthy comparison subjects that
decreased to levels comparable to control subjects after effective paroxetine therapy.
No study prior to theirs had measured neuroanatomic changes in the thalamus of OCD
patients near illness onset before and after CBT. Volumetric magnetic resonance
imaging studies were conducted in 11 psychotropic drug-naive 8-17-year-old children
with OCD before and after 12 weeks of effective CBT monotherapy. They reported no
significant change in thalamic volume in OCD patients before and after cognitive
behavioral therapy suggesting that reduction in thalamic volume after paroxetine
therapy may be specific to paroxetine treatment and not the result of a general
treatment response or spontaneous improvement. However, recent research has
demonstrated that CBT for OCD can systematically modify cerebral metabolic activity in
a manner, which is significantly related to clinical outcome. There does exist a
substantial body of research supporting an involvement of neural circuitry connecting
the orbitofrontal cortex, cingulate gyrus, and basal ganglia in the expression of the
symptoms of OCD. Data has been reported (Schwartz, 1998) which expands upon
previous work demonstrating effects of CBT on functional interactions between limbic
cortex and the basal ganglia reflecting the interactive nature of the relationships
between cognitive choice, behavioral output and brain activity.
Cognitive behavioral therapy gradually stimulates the neocortex by increasingly having
the patients physically interact with their environment. We have seen that children
exposed to violence or neglect have similar symptoms as posttraumatic stress disorder,
where the amygdala and limbic system are overactive. In children, this results from a
delayed development of the prefrontal cortex and the amygdala remains the primary site
of emotionally based information processing. The rise of physical activity engages the
muscle and joint receptors and the cerebellum, which is the initiator of all human
learning, cognitive or social. The cerebellum also is the largest source of stimulation to
the thalamus and the prefrontal cortex as well as the basal ganglia. As the person
physically interacts with the environment, it induces the cerebellum to promote
developments of the prefrontal cortex, which then inhibits the amygdala and limbic
system, which reduces the fear and stress responses. The prefrontal cortex now allows
the individual to have perception that is more appropriate and awareness of the reaction
of others to their actions as they learn what is socially appropriate behavior. We also
think that the recall the painful memories at the same time helps to link these in time
and space or synchronize these memories with other areas, if the now more efficiently
functioning neocortex forms new associative cognitive patterns for the previously
inhibited emotions. The individual would be theoretically forming new memories that are
less disturbing than the previous associations.

Wykes and colleagues (2002) at the Institute of Psychiatry in London had recently
performed an evaluation of the effects on the brain of cognitive behavioral therapy
(CBT) by means of functional magnetic resonance imaging (fMRI). The authors
examined the effects on brain activity as a result of engaging in cognitive behavioral
therapy. Three groups (patients receiving control therapy or cognitive behavioral
therapy and a healthy control group) were investigated in a repeated measures design
using the two-back test. Data obtained by fMRI and a broad assessment of executive
functioning was completed at baseline and post-treatment. Brain activation changes
were identified after accounting for possible task-correlated motion artifact. The fMRI
analyses indicate that the control group shows decreased activation but the two patient
groups show significant increases in activation over time. The patient group that
receives successful cognitive behavioral therapy has significantly increased brain
activation in regions associated with working memory, particularly the frontal cortical
areas. The results are the first ever indications that brain activation changes in a
seriously disabled group of patients with schizophrenia can be associated clearly with
psychological rather than pharmacological therapy.

Neural Cognition Therapy (NCT)

Neural Cognition Therapy (NCT) is a form of neuro-psychotherapy that utilizes neural

pathways, thought or memory patterns and acupuncture to correct patterns of behavior,
emotions and thought (both conscious and subconscious). Dr. Kevin Conners,
combining specific techniques of Applied Kinesiology, Psychology, Neurology and
Acupuncture, developed it for aiding his treatment of Brain-injured, PSTS, emotionally
abused, and other patients who ‘just seem stuck’ or at a ‘dead end’ in their current
approach.
NCT does exist and may be used as a distinct therapeutic technique though it is
best utilized in conjunction with Brain-Based Therapy (BBT). NCT is based on the
characteristics:

1. NCT is based on a Cognitive Model of Emotional Response. Neural Cognition

therapy is based on the idea that thoughts are ONE cause of our feelings and
behaviors. These thoughts may be real (true) or unreal (not true) and may be triggered
by circumstances, events, or other thoughts. The benefit of this fact is that we can
change the way we think to feel / act better even if the situation does not change.

2. NCT is based on a Neural Model of Emotional Response. Neural Cognition

therapy is also based on the idea that neural pathways are ANOTHER cause of our
feelings and behaviors. These neural pathways are specific neural connections created
over time by firing (stimulation) into cortical centers. To put it simply: A neural pathway
is created and strengthened through repetition triggered by circumstances, events, or
other thoughts. Every one of life’s experiences, whether real or imagined, was definitely
real in one’s mind! The strength of these neural connections and therefore the greater
chance they will be traveled upon rests on the frequency these were fired upon or the
intensity of emotional energy that accompanied it. The benefit of this fact is that we can
change the way we react to stimulus by changing the pathways being fired.

Let me give you two examples:

A) Jill considered herself a normal, happy teenager with loving parents. When she was
19, in her first year of college, she was invited to her first dorm party where two young
males molested her after she admittedly had ‘way too much to drink’. Her life went on,
she graduated with honors, landed a wonderful job and married a great guy. Since the
birth of their baby two years ago, Jill has been experiencing a barrage of physical
symptoms and her relationship with her husband has been rocky at best. Through
therapy, Jill has realized that the ‘incident’ in college is a major contributor to how she
now reacts to the opposite sex at her job and her inability to enjoy and relate to intimacy
with her spouse. One horrible incident of such high emotional content ‘burned’ several
associative pathways in Jill’s brain. Here are a few of the connections that may need to
be severed: Men = control; sex = pain; alcohol = loss; commotion = crying; in situations
out of my control = theft of self; dark rooms = constriction; and the list goes on, from the
smells in the room to the sounds in the background, indelibly engrained in Jill’s neural
pathways. When stimulated in completely unrelated instances, the same pathways fire
and similar reactions are experienced.

B) Andrew was a quiet man who lived alone. His past is not well remembered though
his medical history is splattered with diagnosis after diagnosis from MD’s and
psychologists. Years of therapy and modern mood enhancers have helped him cope
and fit in; Andrew considers himself a normal, well-adjusted 40 year old. At 12, Andrew
lost both his parents to a tragic car accident and he was shipped off to his alcoholic
grandmother who ‘never said a kind word’ and ‘nurture’ was not in her vocabulary.
Years of negative associations can be even more damaging than horrific instances.
Multitudes of neural pathways are ‘burned’ and negative, fearful, or highly charged
connections with seemingly gentle characters, events and circumstances develop giving
rise to psychoses, neuroses, phobias and addictions as well as organic physical
disease.

3. NCT treatment is much more “Time-Sensitive” then traditional therapy. Though

NCT treatment is still a process over time, Neural Cognition therapy is considered
among the most rapid in terms of results obtained. The average number of sessions
clients receive (across all types of problems and approaches to NCT) is only 20. Other
forms of therapy, like psychoanalysis, can take years. What enables NCT to be briefer
is its use of Kinesiology to pinpoint specific thought patterns as well as acupuncture
points to assist in altering pathways. NCT is time-limited in that we help clients
understand at the very beginning of the therapy process that there will be a point when
the formal therapy will end. The ending of the formal therapy is a decision made by the
client. Therefore, NCT is not an open-ended, never-ending process.

4. NCT uses the Socratic Method. In Neural Cognition therapy, we want to gain a
very good understanding of their clients' concerns. That's why we often ask a lot of
questions. We also encourage our clients to ask questions of themselves, like, "How do
I really know that those people are laughing at me?" "Could they be laughing about
something else?"

5. NCT is structured and directive following a specific Acupuncture pattern. In

Neural Cognition therapy, we have a specific agenda for each session. Individual
emotions, thoughts, or concepts are addressed during each session. NCT focuses on
the client's goals.

6. Homework is a central feature of NCT. If when you attempted to learn your

multiplication tables you spent only one hour per week studying them, you might still be
wondering what 2 X 2 equals. You very likely spent a great deal of time at home
studying math tables, maybe with flashcards. The same is the case with
psychotherapy. Goal achievement (if obtained) could take a very long time if all a
person did was only to think about the techniques and topics taught for one hour per
week. That's why with NCT, we assign specific homework assignments and encourage
our patients to practice the techniques learned.

Eye Movements as Reflective of Neurocognitive Processes

Employed in Behavioral Therapeutic Intervention

Our eyes usually move in brief motions called saccades. Between the saccades, they
focus on the objects that we see (Leisman, 1976a). Although our eyes move several
times per second, we perceive the world only during the brief movements of fixation
(Leisman, 1976a). In essence, we can think of our visual experience as a rapid
sequence of still life photographs. However, the fixations occur too rapidly for us to
notice the interval between the snapshots (Haber, 1978; Leisman, 1976a).
The saccadic eye movements, generated during a visual oddball task, of autistic
children, normal children, children with attention deficit hyperactivity disorder (ADHD),
and dyslexic children were examined to determine whether autistic children differed
from these other groups in saccadic frequency Kemner et al., 1998). Autistic children
made more saccades during the presentation of frequent stimuli (than normals and
ADDH children), and between stimulus presentations. In addition, unlike the normal and
dyslexic groups, their saccadic frequency did not depend on stimulus type. This
abnormal pattern of saccades may negatively influence the ability to attend to stimuli,
and thereby learning processes.

Goldberg and colleagues (2002) have recently employed ocular motor paradigms to
examine whether or not saccades are impaired in individuals with high functioning
autism HFA. They recorded eye movements in patients with HFA and in normal
adolescents on anti-saccade, memory-guided saccade MGS, predictive saccade, and
gap/overlap tasks. Compared with the normal subjects, patients with HFA had a
significantly higher percentage of directional errors on the anti-saccade task, a
significantly higher percentage of response suppression errors on a MGS task, and a
significantly lower percentage of predictive eye movements on a predictive saccade
task. They also showed longer latencies on a MGS task and for all conditions tested on
a gap/null/overlap task (fixation target extinguished before, simultaneously, or after the
new peripheral target appeared). When the latencies during the gap condition were
subtracted from the latencies in the overlap condition, there was no difference between
patients and normals. These authors conclude that abnormalities in ocular motor
function in patients with HFA provide evidence for the involvement of a number of brain
regions in HFA including the dorsolateral prefrontal cortex, the frontal eye fields, the
basal ganglia, and parietal lobes.

In attempting to explain further why gaze-shift impairment is part of the clinical picture in
neurobehavioral disorders of childhood including autism, we should recall that recent
imaging and clinical studies have challenged the concept that the functional role of the
cerebellum is exclusively in the motor domain. Townsend and associates at the
University of California-San Diego (1999) presented evidence of slowed covert orienting
of visual-spatial attention in patients with developmental cerebellar abnormality (at least
90 percent of all postmortem cases of autism reported to date have Purkinje neuron
loss), and in patients with cerebellar damage acquired from tumor or stroke. In spatial
cuing tasks, normal control subjects across a wide age range were able to orient
attention within 100 msec of an attention-directing cue. Patients with cerebellar damage
showed little evidence of having oriented attention after 100 msec but did show the
effects of attention orienting after 800-1200 msec. These effects were demonstrated in
a task in which results were independent of the motor response. In this task, smaller
cerebellar vermal lobules VI-VII (from magnetic resonance imaging) were associated
with greater attention-orienting deficits. Although eye movements may also be disrupted
in patients with cerebellar damage, abnormal gaze shifting cannot explain the timing
and nature of the attention-orienting deficits. These data is consistent with evidence
from organism models that suggest damage to the cerebellum disrupts both the spatial
encoding of a location for an attentional shift and the subsequent gaze shift. These data
are also consistent with a model of cerebellar function in which the cerebellum supports
a broad spectrum of brain systems involved in both non-motor and motor function.

Disturbances in the orbital prefrontal cortex and its ventral striatal target fields have
been identified in neuroimaging studies of obsessive-compulsive disorder (OCD). In
organism models and studies of patients with lesions to this brain circuitry, a selective
disturbance in the ability to suppress responses to irrelevant stimuli has been
demonstrated. Such a deficit in response suppression might underlie the apparent
inhibitory deficit suggested by the symptoms of OCD. Although OCD commonly
emerges during childhood or adolescence, few studies have examined psychotropic-
naive pediatric patients near the onset of illness to find the possible role of atypical
developmental processes in this disorder. Oculomotor tests were administered to 18
psychotropic medication-naive, non-depressed patients with OCD aged 8.8 to 16.9
years and 18 case-matched healthy comparison subjects to assess the following 3 well-
delineated aspects of prefrontal cortical function: the ability to suppress responses, the
volitional execution of delayed responses, and the anticipation of predictable events. A
significantly higher percentage of response suppression failures were observed in
patients with OCD, particularly in younger patients compared with their case-matched
controls. No significant differences between patients with OCD and controls were
observed on other prefrontal cortical functions. Severity of OCD symptoms was related
to response suppression deficits. A basic disturbance of behavioral inhibition in OCD
was detected that may underlie the repetitive symptomatic behavior that characterizes
the illness (Rosenberg et al., 1997).

Mostofsky and colleagues (2001a) assessed saccadic eye movements in boys with
Tourette’s syndrome with and without ADHD, comparing performance with that of an
age-matched group of male controls. Three different saccade tasks (prosaccades,
antisaccades, and memory-guided saccades) were used to examine functions
necessary for the planning and execution of eye movements, including motor response
preparation, response inhibition, and working memory. The study included 14 boys with
Tourette’s syndrome without ADHD, 11 boys with Tourette’s syndrome and ADHD, and
10 male controls. Mostofsky and associates found that the latency of prosaccades was
prolonged in boys with Tourette’s syndrome (both with and without ADHD) compared
with controls. Variability in prosaccade latency was greater in the groups of boys with
Tourette’s syndrome and ADHD compared with both the Tourette’s syndrome-only and
control groups. Response inhibition errors on both the antisaccade task (directional
errors) and memory-guided saccade task (anticipatory errors) were increased in boys
with Tourette’s syndrome and ADHD compared with those with Tourette’s syndrome-
only. There were no significant differences among the three groups in accuracy of
memory-guided saccades. Mostofsky’s oculomotor findings suggest that Tourette’s
syndrome is associated with delay in initiation of motor response as evidenced by
excessive latency on prosaccades. Signs of impaired response inhibition and variability
in motor response appear to be associated with the presence of ADHD.

Abnormalities of executive function are observed consistently in children with ADHD,

and it is hypothesized that these arise because of disruption to a behavioral inhibition
system. In examining contextual abnormalities of saccadic inhibition in children with
attention deficit hyperactivity disorder, Cairney and associates (2001). Executive and
inhibitory functions were compared between unmedicated and medicated children with
ADHD, age-matched healthy children and healthy adults. Executive functions were
measured using a test of spatial working memory shown previously to be sensitive to
ADHD and to stimulant medication. Inhibitory functions were measured using an ocular
motor paradigm that required individuals to use task context to control the release of
fixation. Context was set according to the probability that a target would appear at either
of the two locations. In one block, targets appeared on 80 percent of trials. In the other
block, targets appeared on 20 percent of trials. The ability to control the release of
fixation was inferred from the fixation-offset effect, or the difference in saccade latency
when the current fixation is offset 200 ms prior to the onset of the saccade target (gap
condition), compared with when there is no offset (overlap condition). Although the
healthy children made more errors on the spatial working memory task than the healthy
adults, there was no difference between the two groups in their ability to control fixation
using context. Both showed a larger fixation-offset effect when target probability was
low. The unmedicated ADHD group made more errors on the spatial working memory
test than the healthy children, although spatial working memory performance was
normal in the medicated ADHD group. However, both the unmedicated and medicated
ADHD groups were unable to modulate the fixation-offset effect according to context,
and this was due to their inability to voluntarily inhibit saccades when there was a low
target probability. These data suggest that the context-based modulation of fixation
release is not controlled by the same systems that control executive function.
Furthermore, deficits in executive function and inhibitory control appear independent in
children with ADHD with others (Gould et al., 2001;Mostofsky et al., 2001b; Castellanos
et al., 2000; Karatekin & Asarnow, 1998; 1999; Ross et al., 1994) having found similar
effects in both males and females.

Bergman (1995) speculates that the hippocampus and amygdala are involved in using
eye movements as a rehabilitation tool. He notes that it is thought that these two
structures are involved in much of the brains learning and remembering. Therefore
where the amygdala "retains the emotional flavor of memory, the hippocampus retains
the dry facts." He also notes that inhibition of the amygdala is thought to arise from the
left prefrontal cortex (Ledoux, 1986). It is noted that the prefrontal cortex is the area of
the brain responsible for working memory. Therefore, strong emotions that are
generated in the amygdala may create neural static, decreasing the ability of the
prefrontal cortex to maintain working memory (Selemon et al., 1995). Sensory
information from visual, auditory, olfactory areas bypasses the thalamus (indirect activity
with thalamus) are first sent to the thalamus and then monosynaptically to the
amygdala. A second pathway from the thalamus projects to the neocortex; this
arrangement allows the amygdala to react before the neocortex. The neocortex
processes the information through several brain circuits before it finally perceives and
responds (LeDoux, 1986). It has been suggested that eye gaze interventions
resynchronizes the activity of the two hemispheres, by way of the alternating stimulus
which may mimic the activity of the pacemaker function within the cortex that may be
suppressed. Bergman concludes "stated more specifically, eye movement retraining
gradually shifts the brain activity from amygdaline hyperactivity to activation of greater
neocortical function."
Eye movement training can be powerful but difficult to perform for many children with
learning or behavioral problems. Eye movement training that is more specific to the side
of the cerebellar or cerebral deficit has been clinically found to be more effective. As
children become more coordinated with their eye movements, there usually is
improvement in learning and behavior. A direct neurological connection exists between
the neck and extraocular muscles; weakness of neck muscles can be tested by
examining for weakness and fatigueability of eye muscles. It has been noted that many
children with neurobehavioral disorders have difficulty or cannot cross their eyes
(convergence) in the midline (Eden et al., 1994). The extra-ocular muscles are
analogous to midline postural muscles, with weakness in each reflecting a bilateral
limitation. The child may be able to adduct one eye and not the other, this usually
represents a unilateral weakness or neurological imbalance, and the weakness is often
found on the same side as a neocortical decrease in activation. Saccadic dysmetria
especially hypometria is more indicative of cerebellar deficit. Saccadic dysmetria with
the child looking up to the right or down and left is usually associated with right
cerebellar lesions, whereas up and left and down and right dysmetria is associated with
left cerebellar lesions. These findings need to be correlated with other signs and
symptoms. There are currently some interesting studies examining eye movement
intervention strategies in neurobehaviorally involved children using functional imaging
techniques that should reveal or confirm more specifically it effectiveness and
mechanism of function.

The Interactive Metronome (IM)

The Interactive Metronome (IM) is a brain based rehabilitation assessment and training
program developed to directly improve the processing abilities that affect attention,
motor planning, and sequencing. This, in turn, strengthens motor skills, including
mobility and gross motor function, and many fundamental cognitive capacities such as
planning, organizing, and language.

How does IM work?

The IM program provides a structured, goal-oriented training process that challenges
the patient to precisely match a computer generated beat. Participants are instructed to
synchronize various hand and foot exercises to a reference tone heard through
headphones. The patient attempts to match the rhythmic beat with repetitive motor
actions such as tapping his/her toes on a floor sensor mat or clapping while wearing an
IM glove with a palm trigger.
A patented audio or audio/visual guidance system provides immediate feedback. The
difference between the patient's performance and the computer generated beat is
measured in milliseconds. The score indicates timing accuracy.

Who can benefit?

Individuals with motor planning and sequencing problems, speech, and language
delays, motor an sensory disorders, learning deficits, and various cognitive and physical
difficulties may benefit from the IM program. Adult and pediatric patients who have
benefited from IM include those with:
* Sensory Integration Disorder
*Asbergers Syndrome
*Autism Spectrum Disorder
*ADD/ADHD
*Cerebral Palsy
ADHD Study
A double blind, placebo-controlled study of 9-12 year old boys diagnosed with ADHD
found those who completed the IM program showed significant patterns of improvement
in attention, coordination, and control of aggression/impulsitivity, reading and language
processing. This study was published in the American Journal of Occupational Therapy,
March 2001

Timing in Child Development Study

A correlation study of 585 children in the public school district found significant
correlations between IM score and academic performance in reading, mathematics,
language, science, social studies, and study skills. This suggests that timing and
rhythmicity play a foundational role in the cognitive processes underlying performance
in these academic areas. The results were published by the High/Scope Foundation, a
prestigious, non-profit educational research institution.
Today, there are more than 2,500 certified IM providers in over 1700 clinics, hospitals,
and universities throughout the US and Canada. Each day the list of providers
continues to grow. IM has recieved an abundance of media recognition including CBS
Early Show, CNN News, US News and World Report, as well as various segments that
have aired on hundreds of TV affiliates, radio stations, and national publications.

Light Therapy

Levitan and associates (1999) at the University of Toronto report that evidence exists
from clinical, epidemiological, and neuroimaging studies that ADHD and seasonal
affective disorder (SAD) have several features in common. They assessed SAD
symptoms in adults with ADHD. One hundred and fifteen individuals attending an adult
ADHD clinic in Toronto, Canada were asked to complete the Seasonal Pattern
Assessment Questionnaire. The rate of SAD in the overall clinic sample was estimated
at 19.1 percent, a prevalence rate significantly greater than rates reported in large
population surveys at similar latitudes.

Decreasing or increasing the amount of light, varying the color of light, or blocking out
light from certain fields of vision, have been used for many different conditions. These
conditions include forms of depression, anxiety, learning disabilities, and sleep
disorders, etc. One of the most recognized disorders that have been treated with the
use of light is seasonal affective disorder or SAD. In a recent New York City survey,
more than one third of responding adults reported at least mild winter malaise: 6 out of
100 reported severe depression (Caldwell, 1999). It is thought that SAD, as well as
other similar disorders are due to the affect that light has on regulating of biological or
circadian clocks.
The first experiments of biological clocks date back to 1911 and were conducted by Karl
Von Frisch, an Austrian zoologist. Von Frisch discovered that Minnows did not respond
to ambient light perceived through their eyes. Von Frisch thought that something deep
inside the brain itself could respond directly to light. He later traced this affect to the
minnows pineal gland, which we now know to be the source of melatonin. In the brain, a
recently discovered group of cells known as the supra-chiasmatic nucleus of the
hypothalamus or SCN is thought to be the basis of biological clocks (Honma et al.,
2002; Reppert & Schwartz, 1984). In mammals, it appears to be remarkably reliable.
Even when removed from an experimental organism and placed in a dish, it continues
to keep time on its own for approximately a day. The SCN is divided into two structures.
One is the right hemisphere and one is in the left, just below and behind the eyes. Each
part of the SCN is made up of approximately 10,000 densely packs neurons. Recent
research in mice suggests that mammals have a set of special photoreceptors in their
eyes, which react to light signals and carry them directly to the SCN. These
photoreceptors are thought to be different from the rods and cones used to perceive
light stimulating the retina. It is thought that light helps to reset the biological clocks.
Light in the morning is thought to set the clock ahead and in the evening, backwards.
Whether the running of these biological clocks is an innate quality of cells or a product
of some unseen force, like gravity, is not known. Nevertheless, disruption of light stimuli
can disrupt these clocks.

Many other areas of the brain are affected by light. We can recall our earlier discussion
of the intricacies of the development and function of the ventral and dorsal visual
systems and their role in cognitive perception and limbic system function. We recall that
the dorsal visual system is associated more with right hemisphere function, which is
involved in global or low frequency stimulation. The ventral visual system is associated
more with left hemisphere function, specific for a local visual function or higher
frequency stimulation. These systems are powerfully connected to cognitive and
emotional functions.

Modulating the frequency of the stimulus can change the firing rate of the thalamus and
the brain as a whole. However, different frequencies of the same stimulus may have
asymmetric affects on the brain. Modulating the frequency of stimulus also takes into
account the metabolic rate of brain cells. Interestingly, it has been noted that red, which
is a low frequency source, would be expected to slow down the neocortex and affect
more of the right brain, increasing sympathetic responses. Blue light would be expected
to speed up the firing rate of the neocortex, (thereby inhibiting sympathetic and exciting
parasympathetic responses) which also may be more specific to left brain and in fact,
has been shown to increase parasympathetic functions (Vel'khover & Elfimov, 1995). It
has also been noted that a pale light blue paint on the walls of schools appears to
decrease hyperactivity in children, where pale yellow on the walls of schools appears to
improve concentration and learning abilities.

Altering the balance of light or vision from one hemisphere to the other has also been
shown to have powerful psychological affects. Dr. Frederick Schiffer, a psychiatrist, has
found that using a pair of glasses that block vision to either the right or left hemispheres
can help alleviate anxiety or depression (Schiffer, 1997; 1998). Schiffer thinks that these
glasses that work to relieve anxiety and distresses is remarkable testimony to the link
between the eyes and the two sides of the brain and a variety of psychological
problems. Schiffer attempted a simple experiment on himself. When he covered one
eye and part of the other, he detected a slight difference in his clarity of thought. Schiffer
then made safety glasses that covered one eye completely and half of the other. He had
seventy patients suffering from severe anxiety wear the glasses and measured the
affect on a one to ten scale, by which anxiety is calculated. Sixty percent of those
patients had a 1-point difference (improvement on the scale) and 23 percent had a 2-
point difference. Schiffer also had the patients wear glasses that covered the other eye.
In interviews, 40 of the patients said they felt more anxiety when they wore the glasses.
A study of a control group of college students, who were not in therapy, also found
measurable changes in their feelings of anxiety and changes in brain wave patterns with
the glasses. Although no significant knowledge base at present exists in the application
of light to the remediation of neurobehavioral disorders of childhood, the existing theory
supports it further investigation Various forms of visual imagery have been found to help
improve intelligence, motor performance, and behavior. Guided imagery is one form of
visualization. Guided imagery has the subject create internal scenarios and mental
pictures that evoke positive physical responses. Imagery is reported to improve the
immune system (Gruzilier, 2002a), reduce stress (Gruzelier, 2002b), and slow heart rate
(Oishi et al., 2000)

Leiner and associates (1992) have noted that several studies of ideation or mental
imaging show significant blood flow changes to the cerebellum and frontal lobe. If
individuals imagine a motor act like playing tennis or a cognitive act like mental
calculation, both show significant increases in different areas of the cerebellum and
neocortex. On the other hand, it has been shown that those who imagine shooting a
basketball display as much improvement in that skill after a week as those who actually
physically practice shooting a basketball. This would lead us to think that whether
imagined or actually done, motor acts must activate similar area of the cerebellum that
create functional improvement in motor control.

In the last decade, there has been a dramatic increase in research effectively
integrating cognitive psychology, functional neuroimaging, and behavioral neurology.
This new work is typically conducting basic research into aspects of the human mind
and brain. Parsons (2001), in one study the authors employed object recognition,
mental motor imagery, and mental rotation paradigms, to clarify the nature of a cognitive
process, imagined spatial transformations used in shape recognition. Among other
implications of the study was that recognizing a hand's handedness or imagining one's
body movement depends on cerebrally lateralized sensory-motor structures and
deciding upon handedness depends on exact match shape confirmation. In a second
study, using cutaneous, tactile, and auditory pitch discrimination paradigms, it was
suggested that the cerebellum has non-motor sensory support functions upon which
optimally fine sensory discriminations depend. Mental imagery, the generation and
manipulation of mental representations in the absence of sensory stimulation, is a core
element of numerous cognitive processes. Numerous investigators have recently
investigated the cortical mechanisms underlying imagery and spatial analysis in the
visual domain using event-related functional magnetic resonance imaging during the
mental clock task (Formisano et al., 2002) and fMRI (Knauff et al., 2002). The time-
resolved analysis of cortical activation from auditory perception to motor response
reveals a sequential activation of the left and right posterior parietal cortex, suggesting
that these regions perform distinct functions in imagery tasks.

Knauff and colleagues found that in the absence of any correlated visual input,
reasoning activates an occipital-parietal-frontal network, including parts of the prefrontal
cortex (Brodmann's area, BA, 6, 9) and the cingulate gyrus (BA 32), the superior and
inferior parietal cortex (BA 7, 40), the precuneus (BA 7), and the visual association
cortex (BA 19). Because reasoners envisage and inspect spatially organized mental
models to solve deductive inference problems, we do have a basis for concluded that
imagery has the capacity for effecting change in brain state. In one of the view imaging
studies to date on clinical applications of imagery as a therapeutic tool, Marks and
associates (2000) investigated subjective imagery in obsessive-compulsive disorder
before and after exposure therapy using fMRI. A small randomized study was
performed, with controls for type and order of mental imagery and for treatment
condition (exposure therapy guided by a computer or by a therapist, or relaxation
guided by audio-tape). Before and after treatment, during fMRI scanning, patients
imagined previously rehearsed scenarios that evoked an urge to ritualize, non-OCD
anxiety, or a neutral state, and rated their discomfort during imagery. The method
evoked greater discomfort during OCD imagery and anxiety (non-OCD) imagery than
during neutral imagery. Discomfort was reduced by canceling imagery. Discomfort
during OCD imagery (but not during anxiety non-OCD imagery) fell after exposure
therapy but not after relaxation. The results showed differences between OCD and non-
OCD images and their change after successful treatment, and confirmed clinical
suggestions that canceling images reduced OCD discomfort.

Sound Therapy

Dr. Oliver Sacks, author of An Anthropologist on Mars (1995) and Awakenings (1973)
has written that music therapy is a tool is a tool of “great power” for Alzheimer’s and
Parkinson’s’s patients “because of its unique capacity to reorganize cerebral function
where it has been damaged.” “There’s an overlap in brain mechanisms in the neurons
used to process music, language, mathematics and abstract reasoning,” says Dr. Mark
Tramo, a neuroscientist at Harvard Medical School (cf. Tramo, 2001; Tramo &
Bharucha, 1991; Tramo et al., 2001; 2002; Patel et al., 1998). “We think a hand full of
neuronal codes is used by the brain, so exercising the brain through music strengthens
other cognitive skills. It’s a lot like saying if you exercise your body by running, you
enhance your ability not only to run but also to play soccer or basketball.”

Various techniques use sound and music as their primary mode of therapy. These
techniques have reportedly been affective for children with learning disabilities and
behavioral problems. There are those who think that sound and music can effects
dysfunction in the nervous system through both its calming and energizing affects on
the brain and CNS. As a clinical therapy it is reported to be used in hospitals, schools
and psychological treatment programs to reduce stress or lower blood pressure,
alleviate pain, overcome various learning disabilities, improve movement and balance,
and promote endurance and strength.

Campbell, author of the book The Mozart Effect, (1998), has researched the affect of
music and its therapeutic affect (Rauscher et al., 1993). He thinks that since
development of the first musical instruments between 43,000 – 82,000 years ago,
humans knew that music created special effects. He suggests that music in the form of
song and dance preceded speech in humans and was the first form of language. He
states that research has shown that two-thirds of the inner ear cilia (hair cells) resonate
only at the higher music frequency’s 13,000 – 20,000 hertz. To indicate that the
application of the so-called Mozart Effect is without controversy would be an
understatement especially considering there have been numerous reports of an inability
to replicate the effect (McCutcheon, 2000).

Hughes and Fino (2000) had performed a study reported in Clinical

Electroencephalography The goal of this study was to determine distinctive aspects of
Mozart music that may explain the Mozart Effect, specifically, the decrease in seizure
activity. As many as 81 musical selections of Mozart, but also 67 of J.C. Bach, 67 of
J.S. Bach, 39 of Chopin and 148 from 55 other composers were computer analyzed to
quantify the music in search of any distinctive aspect and later to determine the degree
to which a dominant periodicity could be found. Long-term periodicity (especially 10-60
sec, mean and median of 30 sec), was found often in Mozart music but also that of the
two Bachs, significantly more often than the other composers and was especially absent
in the control music that had no effect on epileptic activity in previous studies. Short-
term periodicities were not significantly different between Mozart and the Bachs vs. the
other composers. The conclusion is that one distinctive aspect of Mozart music is long-
term periodicity that may well resonate within the cerebral cortex and also may be
related to coding within the brain. Thompson and associates (2001) in reporting on the
Mozart effect in which they claim was made that people perform better on tests of
spatial abilities after listening to music composed by Mozart, examined whether the
Mozart Effect is a consequence of between-condition differences in arousal and mood.
Participants completed a test of spatial abilities after listening to music or sitting in
silence. The music was a Mozart sonata (a pleasant and energetic piece) for some
participants and an Albinoni adagio (a slow, sad piece) for others. These investigators
also measured enjoyment, arousal, and mood. Performance on the spatial task was
better following the music than the silence condition but only for participants who heard
Mozart. The two music selections also induced differential responding on the
enjoyment, arousal, and mood measures. Moreover, when such differences were held
constant by statistical means, the Mozart Effect disappeared. Thompson’s findings
provide compelling evidence that the Mozart Effect is an artifact of arousal and mood.
We are here less concerned about Mozart as a composer and more about the effects of
sound in effecting change in brain and cognitive function.

Thompson and Andrews (2000) in their paper provide an overview of the theoretical
underpinnings of the Tomatis Method, along with a commentary on other forms of
sound/music training and the need for research. A public debate was sparked over the
Mozart Effect. This debate has turned out to be unfortunate because the real story is
being missed. The real story starts with Alfred Tomatis. Dr. Tomatis was the first to
develop a technique using modified music to stimulate the rich interconnections
between the ear and the nervous system to integrate aspects of human development
and behavior. The originating theories behind the Tomatis Method are reviewed by
Thomson and Andrews to describe the ear's clear connection to the brain and the
nervous system. The neuropsychology of sound training describes how and what the
Tomatis Method affects. The 50 years of clinical experience and anecdotal evidence
amassed by Tomatis, shows that sound stimulation can provide a valuable remediation
and developmental training tool for individuals with neurobehavioral disorders.

In Norway, in the 1980’s, educators used music therapy for children with severe
physical and mental disabilities. They found that music reduced muscle contraction in
patients’ with severe spastic conditions, increased range of motion in their spines, arms,
hips, and legs. These effects would suggest effects not only on the neocortex, but the
brainstem reticular formation as well as the cerebellum. Since music has powerful
effects on the hair cells in the vestibular apparatus, it would also be expected to have
effects on the olivary complex and the cerebellum. This, in fact, may be its primary
effect.

Studies of Alzheimer’s patients show that there is a pathological involvement of the

visual (Mahoney et al., 1994), primary auditory path (Mahoney et al., 1994; Hinton et al.,
1986; Blanks et al., 1989), and olfactory (Esiri & Wilcock, 1984; Talmo et al., 1989). In a
study of auditory system degeneration associated with Alzheimer’s Disease (AD), Sinha
and associates (1993), demonstrated marked degenerative changed in the ventral
nucleus of the medial geniculate body, the central nucleus of the inferior colliculus, and
the primary auditory cortex in 9 AD patients matched with controls on neuropathological
examination. German and colleagues (1987), showed neurofibrillary degeneration in
several brainstem nuclei, other than the locus coeruleus and dorsal Raphe nucleus,
including a structure known as the pedunculo-pontine nucleus that forms part of the
reticular activating system. O’Mahony and colleagues (1994) studied patients with AD
and examined the primary auditory pathway using brainstem auditory evoked responses
and middle latency response. They concluded from their results, that dysfunction of the
primary auditory pathway in patients with mild to moderate AD supports the hypothesis
that impairment of auditory function and arousal are primary features of AD. In addition,
Singeta and associates (1993) has shown that the rate of improvement of the electro-
oculogram rapid eye movement frequency (a sensitive direct indicator of level of
arousal) (Amadeo & Shagass, 1963) is positively correlated with the rate of
improvement in the dementia scale score in treated patients with senile dementia. This
is suggests that intellectual dysfunction in dementia is partly the result of reduced
arousal. Therefore, music can increase arousal of the brain through primary auditory
pathways. This may improve intelligence and frontal lobe function in neurobehavioral
disorders of childhood. The cerebellum and thalamus may be responsible for the
majority of this brain arousal. The auditory effects of listening to music as well as the
motor effects of playing music can increase cerebellar, thalamic, and neocortical
function.

A common intervention that has been employed with children with ADD, learning
disabilities, and central auditory processing, or CAP deficits involves attempts to
influence activity in the cerebellar-vestibular system (CVS) by auditory stimulation in
frequency ranges generating hyperacusis and discomfort. Ann Blood and colleagues
(Blood et al., 1999; Blood & Zatorre, 2001), at McGill University in Montreal, conducted
the first scientific studies on music’s emotional impact on the brain. They employed
positron emission tomography PET to examine cerebral blood flow (CBF) changes
related to affective responses to music. Ten volunteers were scanned while listening to
six versions of a novel musical passage varying systematically in degree of dissonance.
Reciprocal CBF covariations were observed in several distinct paralimbic and
neocortical regions as a function of dissonance and of perceived
pleasantness/unpleasantness. The findings suggest that music may recruit neural
mechanisms similar to those previously associated with pleasant/unpleasant emotional
states, but different from those underlying other components of music perception, and
other emotions such as fear. In a subsequent study, Blood’s group again employed PET
to study neural mechanisms underlying intensely pleasant emotional responses to
music. Cerebral blood flow changes were measured in response to subject-selected
music that elicited the highly pleasurable experience of "shivers-down-the-spine" or
"chills." Subjective reports of chills were accompanied by changes in heart rate,
electromyogram, and respiration. As intensity of these chills increased, cerebral blood
flow increases and decreases were observed in brain regions thought to be involved in
reward/motivation, emotion, and arousal, including ventral striatum, midbrain, amygdala,
orbitofrontal cortex, and ventral medial prefrontal cortex. These brain structures are
known to be active in response to other euphoria-inducing stimuli, such as food, sex,
and drugs of abuse. This finding links music with biologically relevant, survival-related
stimuli via their common recruitment of brain circuitry involved in pleasure and reward.

Others (Langheim et al., 2002; Bodner et al., 2001; Satoh et al., 2001; Schlaug, 2001;
Parsons, 2001; Riecker et al., 2000; Penhune et al., 1998) have observed significant
increase in the function of the cerebellum in studies that examine the neuroanatomy of
expert musicians as they listen to music. It has been known for sometime that children
develop an early appreciation for music. In the first year of life, children have been
shown to pay attention more acutely to stimuli with a harmonic structure, and it seems
that they learn music in the same way as language, with one note exponentially
acquiring new ones (Garat, 1993). In the past few years, researchers have begun to
map areas of the brain involved in performing music or while silently reading scores.
However, no previous studies have examined the emotions elicited during a musical
piece.

Blood and her colleagues at McGill, decided to target the emotional response to music,
by studying ten adults from ages 19-43, as they listened to musical notes that either
clashed or had a harmonic tone. They designed the experiment using a single melody
and adding on six versions from a very pleasant sounding piece to something that a
two-year-old would bang out on the piano. They measured blood flow in the brain during
these experiences to see if they would find a difference. According to Blood, the
discordant notes triggered activity in the parahippocampal gyrus, an area near the
temporal lobe that plays an important role in processing sensory memory. When the
music was pleasing to the subjects, the investigators found significant activity in the
lower region of the frontal lobe. Responses were primarily found on the right side of the
brain. This activation is thought by Blood and colleagues as an indication of the
emotional responses to music. These brain regions were also different from the region
activated when musicians read a score, or were asked to pick out mistakes in musical
pieces. In 1992, researchers at the Montreal Neurological Institute published the first
study using PET to identify areas of the brain active during musical tasks. The late
Justine Sergent and her colleagues studied musicians as they read scores or
performed, and found many areas of the brain were involved in converting the written
score into finger movement.

Lawrence Parsons and his colleagues (reviewed in Parsons, 2001), advancing

Sergent’s studies, found that specific tasks called upon during the musical experience
rely on different areas of the brain. In one study, subjects were eight right-handed
faculty conductors. The conductors were instructed to focus on errors in melody,
harmony, or rhythm in a Bach Choral. The errors appeared one to every two beats and
the musicians were instructed to take notice but not to perform any motor responses.
Each task was shown to produce very different patterns of brain activity. Melody
activated both the left and right hemispheres in the temporal lobe, while harmony and
rhythm triggered activity more in the left hemisphere. Harmony did not activate the
temporal lobe at all. Each of the tasks also activated right fusiform gyrus. This same
area in the left hemisphere has been linked to visual processing of words. Researchers
suspect that the right fusiform gyrus may have evolved to regulate information on
musical notes and passages. It has been noted that stroke patients who have lost
language function may be able to gain some verbal improvement, by singing words,
which Parsons’ thinks may be facilitated by this region of the brain. Listening for errors
in harmony, melody, and rhythm also activate the cerebellum even though the
conductors were not moving, indicating the cerebellum’s involvement in cognition.

Schlaug (2001), of Beth Israel Deaconess Medical Center in Boston, reported that
skilled male musicians he studied have larger cerebella than average. He employed CT
scans to compare 32 right-handed male musicians with 24 right-handed men with no
musical training. Schlaug and his colleagues (1995) have previously reported that male
musicians have larger corpus callosa and a larger primary motor cortices in the frontal
lobe. They have not found similar differences in the cerebellar volumes between male
musicians and non-musicians. Other studies have shown functional brain changes in
individuals who have mastered certain skills or suffered brain damage; this is the fist
study that has identified structural changes in the brain that are associated with a
learned skill. This indicates that the cerebellum is involved in both motor and cognitive
function and in the processing and the production of music.

An interesting parallel exists between brain changes associated with the acquisition of a
musical skill (Schlaug, 2001) and languages acquisition (Leiner et al., 1992). Leiner and
associates have noted that the lateral areas of the cerebellum are activated during the
cognitive aspects of speech production, whereas, the medial cerebellar cortex is
activated during the motor function of speech. If music were indeed the first form of
human language, then we would expect to find a parallel between music and language
processing in the cerebellum, thalamus, and frontal lobe. It is also interesting to note
that musicians have been found to demonstrate structural changes in the cerebellum,
frontal lobe (motor cortex), and the corpus callosum. Since the cerebellum is thought to
act as an association cortex external to the neocortex, especially between the dorsal
and ventral language areas, it may assist in integrating function of the hemispheres.
This being the case, we may expect to see an enlargement in the corpus callosum
associated with hemispheric integration. Since both the corpus callosum and the
cerebellum may be involved in the temporal synchronization of multiple areas, this may
be the reason for the observed enlargement.

This may also explain the results of a recent study by Chan and her colleagues (1998)
and others (Patel et al., 1998), that indicate that children who spend a few years
learning to play a musical instrument, also develop better verbal skills compared with
those who never studied music. These findings seem to be consistent with the brain
scans that have shown the left planum temporale to be larger in musicians than in
individuals without extensive training in instrumental music. Chan and associates
studied 60 female college students from the University of Hong Kong, of whom 30 had
at least 6 years of training with western musical instruments before the age of twelve
and the other 30 had no formal training. The students were tested for verbal memory by
attempts to remember lists of words. The researchers stated, “We found that adults with
music training learn significantly more words than those without any music training.”
However, they found adults with and without music training were not significantly
different in their ability to remember visual images such as words written on paper.

According to one neuroscientist, Evan Balaban, “There has been a long tradition of
researchers trying to segregate speech and muscle in the brain. There is now evidence
from several studies that they (music and speech), may have more to do with each
other than was previously thought.” If musically trained individuals had structural
changes (the planum) as well as functional language changes that non-musicians do
not have, the main differences in ability between them would be the motor acts
associated with playing music and possibly the breathing associated with wind
instruments (Patel & Balaban 2001a; 2001b). Both of these differences in ability and the
functional changes associated with them can be attributed to the effects of the
cerebellum. This would also demonstrate that motor activities have a carry-over effect
on cognitive function of the frontal lobe, such as in the case of verbal memory.

Musically trained brains respond to randomly heard musical tones in fundamentally

different ways than those who are untrained. This effect is apparently more pronounced
among those who take music lessons before the age of six. Recent studies suggest
(Pascual-Leone, 2001; Pantev et al., 1998; 2001; Schlaug, 2001) that when a piano
tone is played, either more neurons are activated or the neurons are responding in a
more synchronized fashion. No change occurs in those without musical training. In one
study, German researchers asked 20 musicians from a local conservatory were asked
to watch a cartoon, while either pure non-musical tones or piano tunes were presented.
They measured electrical activity in the brain during the activity. A control group of non-
musicians heard the same tones. The results of this study conducted by Christo Pantev
and colleagues at the University of Münster found that musically trained brains showed
about 25 percent more activity than non-musicians. What was also interesting is that the
effect was observed only when piano tones were presented to musicians. Pure tones,
which are not musical, had no apparent effect. In addition, those who began lessons
before their sixth birthday seemed to have the strongest response. It was also noted
that the brains of musicians respond differently to piano tones, (Pantev et al., 1998).

Penhune, Zattore, and Evans (1998), at Montreal Neurological Institute reported that
there exists a difference in brain activities measured by PET scans in musicians with
perfect pitch (the ability to hear a tone and name it) compared to those with relative
pitch (the ability to recognize the difference between a major and a minor note). The
recorded activity differences were noted in the left frontal cortex in those with perfect
pitch. When those with relative pitch were asked to choose between a major and minor
note, this region in the frontal lobe also became active. The authors concluded that
those with perfect pitch were processing the information more efficiently. The left frontal
lobe is the motor speech area, shown to be connected with activation of the right
cerebellum. With this recent increase in research showing the effects of music on the
brain, music as therapy has gained wider acceptance in more mainstream centers.

Olfactory Stimulation Therapy

The sense of smell can be used as a powerful stimulus to the brain. A number of recent
investigations have suggested a significant role for olfactory stimulation in the alteration
of cognition, mood, and social behavior. These orthodox investigations have a common,
if uneasy, relationship with the holistic practice of so-called aromatherapy. In children
and adults, various studies have shown improvement in learning abilities and emotional
disturbances, as well as affects on blood pressure and stress responses. One study
using peppermint oil has shown improvement in cognitive function on children as
compared to controls (Soussignan et al., 1995). In their study Soussignan and
associates examined the facial responsiveness of ten mutic children with pervasive
developmental disorder (PDD) and ten normal children matched for sex and
chronological age who were all covertly videotaped while presented with a set of odors
contrasted in hedonic valence. Hedonic ratings of the stimuli were obtained from both
the group of normal subjects and a panel of adults. Two methods were used to measure
facial responses in the same subjects. The first method consisted in an analysis of facial
movements with the Facial Action Coding System. Results show that PDD and normal
subjects displayed distinct action units in response to unpleasant odors. PDD subjects
typically displayed muscular actions indexing negative experience, while normal
subjects showed more smiles. With the second method, odor-elicited facial behavior
was rated by a panel of observers, who were asked to judge whether the subjects were
exposed a pleasant, neutral, or unpleasant smell. The facial responses to unpleasant
odors were classified more accurately in PDD than in normal subjects. These findings
suggest a functional ability to sense the hedonics attached to odors, but a deficit of
socialization of hedonic facial displays in developmentally disordered subjects.

Murphy Barkley and Bush (2001) examined 105 young adults with attention deficit-
hyperactivity disorder (ADHD) who were compared with a control group of 64 normals
on 14 measures of executive function and olfactory identification. The ADHD group
performed significantly worse on 11 measures with no Group X Sex interaction, contrary
to the findings of Ceccarelli and colleagues (2002) in rats. No differences were found in
the ADHD group as a function of ADHD subtype or comorbid oppositional defiant
disorder. After IQ was controlled, some group differences in verbal working memory,
attention, and odor identification were no longer significant, whereas those in inhibition,
interference control, nonverbal working memory, and other facets of attention remained
so. The deficits in olfactory identification seen in neurobehavioral disorders in part can
serve as a basis for therapeutic intervention in this modality as well as others.

Further support for the use of olfactory stimulation as part of an overall intervention
strategy in neurobehavioral disorders of childhood comes from the study of Levy and
colleagues (1999) who noted that memory for odors induces brain activation as
measured by functional MRI. fMRI brain scans were obtained in 21 normal male and
female subjects and in two patients with hyposmia or diminished sense of smell in
response to the imagination of odors of banana and peppermint and to the actual smells
of the corresponding odors of amyl acetate and menthone, respectively. In normal
subjects, brain activation in response to imagination of odors was significantly less than
that in response to the actual smell of these odors, and activation following imagination
of banana odor was significantly greater in men than in women, for the actual smell of
the odor of amyl acetate. The ratio of brain activation by imagination of banana to
activation by actual amyl acetate odor was about twice as high in women as in men.
Before treatment, in patients with hyposmia, brain activation in response to odor
imagination was greater than after presentation of the actual odor itself. After treatment,
in patients with hyposmia in whom smell acuity returned to or toward normal, brain
activation in response to odor imagination was not significantly different quantitatively
from that before treatment; however, brain activation in response to the actual odor was
significantly greater than that in response to imagination of the corresponding odor.
Brain regions activated by both odor imagination and actual corresponding odor were
similar and consistent with regions known to respond to odors. Their study indicates that
(a) odors can be imagined and similar brain regions are activated by both imagined and
corresponding actual odors; (b) imagination of odors elicits quantitatively less brain
activation than do actual smells of corresponding odors in normal subjects; (c) absolute
brain activation in men by odor imagination is greater than in women for some odors,
but on a relative basis, the ratio for odor imagination to actual smell in women is twice
that in men; (d) odor imagination, once the odor has been experienced, is present,
recallable, and capable of inducing a relatively constant degree of brain activation even
in the absence of the ability to recognize an actual corresponding odor.

Henkin and Levy (2001) looked further at the nature of the lateralization of brain
activation to imagination and smell of odors also using fMRI finding a left hemispheric
localization of pleasant and right hemispheric localization of unpleasant odors. fMRI
brain scans were obtained in 24 normal subjects in response to imagination of banana
and peppermint odors and in response to smell of corresponding odors of amyl acetate
and menthone, respectively, and of pyridine. The results indicated that in normal
subjects, activation generally occurs in the direction of left (L) to right (R) brain
hemisphere in response to banana and peppermint odor imagination and to smell of
corresponding odors of amyl acetate and menthone. There are no overall hemispheric
differences for pyridine odor. Localization of all lateralized responses indicates that
anterior frontal and temporal cortices are brain regions most involved with imagination
and smell of odors. Imagination and smell of odors perceived as pleasant generally
activate the dominant or L to R brain hemisphere. Smell of odors perceived as
unpleasant generally activates the contralateral or R to L brain hemisphere. According
to these authors, predominant L to R hemispheric differences in brain activation in
normal subjects occur in the order amyl acetate > menthone > pyridine, consistent with
the hypothesis that pleasant odors are more appreciated in left hemisphere and
unpleasant odors more in right hemisphere. Anterior frontal and temporal cortex regions
previously found activated by imagination and smell of odors accounted for most
hemispheric differences.

Detox Therapy

Here's something rather rotten from the State of Denmark. Its government yesterday
unveiled official research showing that two-year-old children are at risk from a
bewildering array of gender-bending chemicals in such everyday items as waterproof
clothes, rubber boots, bed linen, food, nappies, sunscreen lotion and moisturizing
cream.
The 326-page report, published by the environment protection agency, is the latest
piece in an increasingly alarming jigsaw. A picture is emerging of ubiquitous chemical
contamination driving down sperm counts and feminizing male children all over the
developed world. And anti-pollution measures and regulations are falling far short of
getting to grips with it.

Sperm counts are falling so fast that young men are less fertile than their fathers and
produce only a third as much, proportionately, as hamsters. And gender-bending
chemicals are increasingly being blamed for the mystery of the "lost boys": babies who
should normally be male who have been born as girls instead.
The Danish government set out to find out how much contamination from gender-
bending chemicals a two-year-old child was exposed to every day. It concluded that a
child could be "at critical risk" from just a few exposures to high levels of the
substances, such as from rubber clogs, and imperiled by the amount it absorbed from
sources ranging from food to sunscreens.

The results build on earlier studies showing that British children have higher levels of
gender-bending chemicals in their blood than their parents or grandparents. Indeed
WWF (formerly the World Wildlife Fund), which commissioned the older research,
warned that the chemicals were so widespread that "there is very little, if anything,
individuals can do to prevent contamination of themselves and their families." Prominent
among them are dioxins, PVC, flame retardants, phthalates (extensively used to soften
plastics) and the now largely banned PCBs, one and a half million tons of which were
used in countless products from paints to electrical equipment.

Young boys, like those in the Danish study, could end up producing less sperm and
developing feminized behavior. Research at Rotterdam's Erasmus University found that
boys whose mothers were exposed to PCBs and dioxins were more likely to play with
dolls and tea sets and dress up in female clothes.
And it is in the womb that babies are most vulnerable; a study of umbilical cords from
British mothers found that every one contained hazardous chemicals. Scientists at the
University of Rochester in New York discovered that boys born to women exposed to
phthalates had smaller penises and other feminization of the genitals.

The contamination may also offer a clue to a mysterious shift in the sex of babies.
Normally 106 boys are born for every 100 girls: it is thought to be nature's way of
making up for the fact that men were more likely to be killed hunting or in conflict. But
the proportion of females is rising, so much so that some 250,000 babies who
statistically should have been boys have ended up as girls in Japan and the United
States alone. In Britain, the discrepancy amounts to thousands of babies a year.

A Canadian Indian community living on ancestral lands at the eastern tip of Lake Huron,
hemmed in by one of the biggest agglomerations of chemical factories on earth, gives
birth to twice as many girls as boys. It's the same around Seveso in Italy, contaminated
with dioxins from a notorious accident in the 1970s, and among Russian pesticide
workers. And there's more evidence from places as far apart as Israel and Taiwan,
Brazil and the Arctic.

Yet gender-benders are largely exempt from new EU regulations controlling hazardous
chemicals. Britain, then under Tony Blair's premiership, was largely responsible for this
– restricting their inclusion in the first draft of the legislation, and then causing even what
was included to be watered down. Confidential documents show that it did so after
pressure from George W Bush's administration, which protested that US exports "could
be impacted".

Now the Danish government is planning to lobby to have the rules toughened up. It is
particularly concerned by other studies which show that gender-bending chemicals
acting together have far worse effects than the expected sum of their individual impacts.
It wants this to be reflected in the regulations, citing its discovery of the many sources to
which the two-year-olds are exposed – modern slings and arrows, as it were, of
outrageous fortune.

Integrated Sensory-Motor Intervention Strategies in Brain Based Therapy

According to practitioners, Occupational Therapy is a health profession concerned with

improving a person’s occupational performance. In a pediatric setting, the Occupational
Therapist deals with children whose occupations are usually players, preschoolers, or
students. The Occupational Therapist evaluates a child’s performance in relation to
what is developmentally expected for that age group. If there is a discrepancy between
developmental expectations and functional ability, the OT looks a variety of perceptual
and neuromuscular factors, which influence function.

A. Jean Ayres is credited with having first identified sensory integrative dysfunction,
which is defined as an irregularity or disorder in brain function that makes it difficult to
integrate sensory input effectively. It is thought that sensory integrated dysfunction may
be present in motor, learning, social, emotional, speech, language, or attention
disorders. Ayres thought that proprioceptive input is extremely important to the function
of the sensory system and the brain as a whole. She identified gravity as an important
input to the central nervous system because of its constancy of input. She thought that
the primary source of this proprioceptive and gravitational input was from the vestibular
apparatus of the inner ear and the vestibular system. She called this the cerebellar
vestibular system. She thought that this system was a primary force in brain
development. This was insightful considering the paucity of research to then support her
theories of the development and function of the brain. Her observations and results
were impressive enough that now Occupational Therapy with its developmental early
intervention focus is universally adopted.

The vestibular apparatus and its receptors do not vary their sensitivity or influence the
brain directly. The balance and sensitivity of the apparatus is set by the function of the
cerebellum and the function of the cerebellum is a product of the service of four major
pathways: (1) the visual system, (2) the proprioceptive system from muscles and joints,
especially the cervical spine, (3) the vestibular system, and (4) the cerebral cortex.
Since the cerebral cortex is just forming in a developing child and the vestibular and
visual systems are relatively constant, the proprioceptive system is by far the most
important to the cerebellum and its effects on the thalamus and the neocortex.

Ayres observed that children with learning and neurobehavioral problems exhibit what
she termed sensory defensiveness. It was thought that this sensory defensiveness was
the result of an over-activation of our protective senses. It was noticed that some
children had decreased responses to sensory stimuli and some appeared to have
increased sensitivity to sensory input. We now have a better way of understanding and
explaining these observations and realize that both are the product of decreased
sensory input to the cerebellum, thalamus, and neocortex. The cerebellum has two
halves as does the cerebrum. These two halves must be balanced in their activation. If
they are not, the hemisphere with decreased activity may initially be less sensitive to
incoming sensory stimuli with an increased threshold of activation because the neurons
are less active. However, over time, this decreased activation causes the cells to shift
closer to threshold as a compensatory mechanism. This makes the child more sensitive
to stimuli that affect the dysfunctional half of the cerebellum. Tactile, proprioceptive,
extraocular, and vestibular input indeed results in over-firing of the cerebellum. The
child will experience lower threshold to touch, movement of the head, neck, or body
expressed as motion sickness, disordered eye movements, or visual perceptual
disturbances. Cerebral activity associated with cognition or emotion also can make the
cerebellum fire aberrantly and the cells, which have less endurance or fatigue-ability to
this input, may cause these cells to produce free radicals and result in oxidative stress
injury to these same cells (Forster et al., 1996; Joseph et al., 1998). In the basal ganglia
this may produce hyperkinetic and/or hypokinetic behavior through the same process. In
the cerebrum, we recognize this as epilepsy, epileptiform activity, or spontaneous firing
of neurons (Joseph et al., 1998; 1999; Heim et al., 2000).

Ayres (1972) observed the symptoms of this process and describes several types of
sensory defensiveness.
 • Tactile defensiveness: Children with tactile defensiveness avoid letting others
touch them and would rather touch others. They frequently fuss or resist hair
washing or cutting. They may act as if their life is being threatened when being
bathed or having clothes changed. These children are often irritated by some
types of clothes, clothing labels, or new clothes. They may dislike being close to
others or avoid crowds. They can be agitated by people accidentally bumping
into them. They often do not like to get their hands or feet dirty. They may seem
unnecessarily rough to people. Some may bump or crash into things on purpose
as a way of seeking sensation or seen under responsiveness to certain
sensations or pain.

• Oral defensiveness: Some children dislike or avoid certain textures or types of

foods. They may be over or under sensitive to spicy or hot foods, avoid putting
objects in their mouth and/or intensely dislike teeth brushing or face washing.
Sometimes have a variety of feeding problems since infancy.

• Gravitational insecurity: This appears to be an irrational fear of change in

position or movement. These children are often fearful of having their feet leave
the ground or having their head tip backwards.

• Postural insecurity: This is a fear and avoidance of certain movement activities

due to poor postural mechanisms.

• Visual defensiveness: This may involve an over sensitivity to light and visual
distractibility. With this problem, children may avoid going outside in certain light
and/or need to wear hats or sunglasses to block out light. They may startle more
easily and/or overt their eyes or seem to avoid eye contact.

• Auditory defensiveness: This reflects an over sensitivity to certain sounds and

may involve irritable or fearful responses to noises like vacuum cleaners, motors,
fire alarms, etc. Children sometimes make excessive amounts of noise to block
out sounds (cf. Zentner & Kagan, 1996). Other symptoms can include unusual
sensitivity to taste and/or smell (cf. preceding section).

When we understand how the cerebellum functions and how it affects the thalamus and
cerebral cortex, we will then be able to explain more fully all of the symptoms of autistic
spectrum disorders as a primary deficit or imbalance of cerebellar-cortical activation.
We remember that the primary output of the cerebellar cortical cells or Purkinje cells is
inhibitory to the cerebellar output nuclei. The cerebellum also controls motor
coordination, balance, postural stability, and extraocular eye movements. It also
activates the thalamus, which relays all sensory input to the cerebrum. Decreased
activation of the cerebellum results in its dysfunction even though it may be more
sensitive to input and may cause decreased stability of thalamus and cerebrum, even
though the overall level of stimulation is decreased. This decreased threshold or
increased signal-to-noise ratio may cause the cells to fire prematurely; therefore they
may reach oxidative stress earlier. This increased sensitivity is a product of decreased
activation and is perceived as unpleasant by the child. This explains why a child with
the same problem can present differently with one being over-reactive to certain
stimuli and another being under-reactive. The underlying problem is the same, a lack
of the central nervous system being properly activated. The same lack of stimulation
can produce hyperkinetic behavior, while another may present with hypokinetic
behavior.

Ayres devised a number of ways of treating these problems of sensory defensiveness.

In Brain Based Therapy (BBT), the approach to treatment primarily involves vestibular,
proprioceptive, and tactile stimulation along with behavior modification techniques.
Examples of some of these treatments for particular problems are:

• Tactile defensiveness: BBT treatment approaches include applying rapid and

firm pressure touch to arms, hands, back, legs, and feet with a non-scratching
brush with many bristles. The brushes recommended are specific plastic surgical
scrub brushes. This is followed by gentle joint compression to the shoulders,
elbows, wrists, hips, knees, ankles and sometimes fingers and feet. This
treatment is recommended because the results are effective for short periods.
Therapists note that if these procedures are applied consistently over time, the
defensiveness is permanently reduced or even eliminated. Deep pressure touch,
compression, or traction to the joints and heavy muscle action together is a
special combination to reduce or eliminate sensory defensiveness. (Summation
of sensation that is neurologically experienced in a short period over a large body
space).

• Oral defensiveness: BBT treatment of applying heavy pressure across the roof
of the mouth and giving input to the temporo-mandibular joint. Oral motor
activities are also used that involve biting or resistive sucking use with a knot on
the end, fruit roll-ups, beef jerky, etc. to bite and pull on. Therapists use small
straws, sports bottles, plastic tubes, etc. for sucking as well as mouth toys that
involve sucking and blowing.

• Gravitational and postural insecurity: in which treatment includes jumping on

bouncing surfaces, trampolines, bed mattresses, or on the floor with jarring
action, jumping and crashing into piles of pillows or beanbag chairs, bouncing
while sitting on an inflated ball, play wrestling, swinging on suspended tire inner
tubes, “frog” sling swings, wet hammocks, platform swings, and “bungee” cords.
Climbing and crawling over an under large pillows, beanbag chairs, jungle gyms,
rocks, trees, up stairs, on hands and knees through obstacle courses made of
furniture, balance activities, walking on a balance beam, rocker and wobble
boards, fine motor coordination, handwriting, and peg board drawing.

A significant number of outcome studies have indicated the effectiveness of this approach to treatment
along with support of Ayers (1972) concept of sensory defensiveness (Baranek & Berkson, 1994;
Baranek et al., 1997; Humphries et al., 1997; Sakamoto, 1994; Case-Smith, 1991; Royeen, 1985; Hamill,
1984; Larson, 1982; Ayres & Tickle, 1980). In general though, OT techniques do not utilize a specific
approach based on asymmetric hemispheric function or deficits.
The Effects of Physical Exercise on Cognitive Performance

If there is one activity that seems to be the “magic bullet” against almost every disease
or disorders, it is exercise, especially aerobic exercise. It seems almost every day a new
study shows exercise to reduce the risk and severity of a new disease from cancer to
the common cold to depression, exercise seems to be the one thing that prevents or
cures them all. There have been many theories proposed as to why exercise has such
dramatic health benefits. Some think it is because of its affect on heart and
cardiovascular system. Some think because of its affect on the endocrine system, while
others think it affects the immune system. The fact is that it affects all of these systems
but aerobic exercise most impact the efficient functioning of the central nervous system.
When one modality affects all of the systems of the body, it must be because of a
primary affect on the brain. As we have seen, autonomic, immune, endocrine, cognitive,
emotional, and sensory systems are all asymmetrically distributed in the brain. Exercise
therefore must have a generalized affect on all brain functions. As we know, the primary
source of activation of the brain is through the motor system, therefore, high frequency
low intensity activity of the motor system will have powerful affects on the global
activation, arousal, and attention of the cerebellum, thalamus, basal ganglia and
cerebrum. Aerobic exercise affects all muscles of the body including the involuntary
postural antigravity muscles, as well as the voluntary muscles of the extremities and
trunk. It also increases the efficiency of the cardiovascular system to deliver blood and
oxygen to the brain, and increases the capacity of the lungs to take in oxygen. We
would expect, therefore, that exercise would be helpful in improving a child’s ability to
learn and control behavior and to focus attention. Lack of physical activity would be
expected to cause the opposite affect.

Researchers at the Salk Institute for Biological Studies in La Jolla, CA, demonstrated
that mice that regularly exercise on running wheels had twice the number of new brain
cells compared to sedentary mice. One of the study’s authors, Fred Gage, has said that,
“More people in my lab have started running since we found this result.” The studies
published in the Proceedings of the National Academy of Sciences and in Nature,
Neuroscience (Van Praag et al., 1999a; 1999b) are remarkable in several ways.
Gauge’s Lab demonstrated that humans along with mice and non-human primates do
grow new brain cells after birth. In a previous study, the Salk researchers had found that
those mice who had “enriched environment” with a tunnel, toys and an exercise wheel
grew more cells than those in regular lab cages (Kempermann & Gage, 1999; van
Praag et al., 2000). What’s more, in the area of new brain cell growth, the hippocampus
is associated with learning and memory. Researchers thought that it might not just be
running per se, but exercise in general that causes the growth of new brain cells. Does
growing more brain cells mean the running mice are necessarily smarter? Van Praag
and Gauge have said it is reasonable to think so because previous studies on “enriched
environment” mice showed that they perform better on learning tasks. Exercise has
been shown to enhance cognitive function and to help stroke victims recover from brain
injury (Shepherd, 2001; Levy et al., 2001).

The type of exercise is important and the combination of physical activity and mental
focus or “purposeful” activity at the same time or close together, appears to yield the
greatest changes. Nudo and associates (1996) documented plastic changes in the
functional topography of primary motor cortex (M1) that are generated in motor skill
learning in the normal, intact primate. The investigators employed intra-cortical micro-
stimulation mapping techniques to derive detailed maps of the representation of
movements in the distal forelimb zone of M1 of squirrel monkeys, before and after
behavioral training on two different tasks that differentially encouraged specific sets of
forelimb movements. After training on a small-object retrieval task, which required
skilled use of the digits, their evoked-movement digit representations expanded,
whereas their evoked-movement wrist/forearm representational zones contracted.
These changes were progressive and reversible. In a second motor skill exercise, a
monkey pronated and supinated the forearm in a key (eyebolt)-turning task. In this case,
the representation of the forearm expanded, whereas the digit representational zones
contracted. Their results show that M1 is alterable by use throughout the life of an
organism. These studies also reveal that after digit training there was an areal
expansion of dual-response representations, that is, cortical sectors over which
stimulation produced movements about two or more joints. Movement combinations that
were used more frequently after training were selectively magnified in their cortical
representations. This close correspondence between changes in behavioral
performance and electrophysiologically defined motor representations indicates that a
neurophysiological correlate of a motor skill resides in M1 for at least several days after
acquisition. The finding that contracting muscles in the behavior come to be represented
together in the cortex argues that, as in sensory cortices, temporal correlations drive
emergent changes in distributed motor cortex representations.

Tantillo and associates (2002) had performed a study examining the effects of exercise
on children with ADHD evaluated by studying the rate of spontaneous eye blinks, the
acoustic startle eye blink response (ASER), and motor impersistence. The children
evaluated, both male and female, were between 8 and 12 years old all meeting the
DSM-III-R criteria for ADHD. All children in their study ceased methylphenidate
medication 24 hours before and during each of three daily conditions. After a maximal
treadmill walking test to determine cardio-respiratory fitness (VO(2peak)), each child
was randomly assigned to counterbalanced conditions of treadmill walking at an
intensity of 65-75 percent VO(2peak) or quiet rest. Responses were compared with a
matched group of control participants. Boys with ADHD had increased spontaneous
blink rate, decreased ASER latency, and decreased motor impersistence after maximal
exercise. Girls with ADHD had increased ASER amplitude and decreased ASER
latency after sub-maximal exercise. The author’s findings suggest an interaction
between sex and exercise intensity that is not explained by physical fitness, activity
history, or selected personality attributes. Their findings support the employment of
vigorous exercise programs as adjuvant in the management of the behavioral features
of ADHD.

Elliot and associates (1994) examined the effects of antecedent exercise conditions on
maladaptive and stereotypic behaviors in 6 adults with both autism and moderate to
profound mental retardation. The behaviors were observed in a controlled environment
before and after exercise and non-exercise conditions. From the original group of
participants, 2 were selected subsequently to participate in aerobic exercise
immediately before performing a community-integrated vocational task. Only antecedent
aerobic exercise significantly reduced maladaptive and stereotypic behaviors in the
controlled setting. Neither of the less vigorous antecedent conditions did. When aerobic
exercise preceded the vocational task, similar reductions were observed. There were
individual differences in response to antecedent exercise. These authors note that the
use of antecedent aerobic exercise to reduce maladaptive and stereotypic behaviors of
adults with both autism and mental retardation is supported.

Similar results were reported by Rosenthal-Malek and Mitchell (1997) in an investigation

of the reduction self-stimulatory behaviors adolescents with autism after vigorous
exercise. Celiberti and colleagues (1997) in a detailed case study of an autistic boy also
examined the differential and temporal effects of two levels of antecedent exercise
(walking versus jogging) on his self-stimulatory behavior. The exercise conditions were
applied immediately before periods of academic programming. Maladaptive self-
stimulatory behaviors were separately tracked, enabling identification of behaviors that
were more susceptible to change (e.g., physical self-stimulation and "out of seat"
behavior) versus those that were more resistant (e.g., visual self-stimulation).
Examination of temporal effects indicated a decrease in physical self-stimulation and
"out of seat" behavior, but only for the jogging condition. In addition, sharp reductions in
these behaviors were observed immediately following the jogging intervention and
gradually increased but did not return to baseline levels over a 40 minute period.

We now know that exercise has benefits for overall health as well as for cognitive
function. Recent studies using organism models have been directed towards
understanding the neurobiological bases of these benefits. It is now clear that
voluntary exercise can increase levels of brain-derived neurotrophic factor
(BDNF) and other growth factors stimulate neurogenesis, increase resistance to
brain insult, and improve learning and mental performance. Recently, high-density
oligonucleotide microarray analysis has demonstrated that, in addition to increasing
levels of BDNF, exercise mobilizes gene expression profiles that would be predicted to
benefit brain plasticity processes. Thus, exercise can provide a simple means to
maintain brain function and promote brain plasticity (Cotman & Berchtold, 2002).

Lieberman and colleagues (2002) reporting in the American Journal of Clinical Nutrition
note that the brain requires a continuous supply of glucose to function adequately.
During aerobic exercise, peripheral glucose requirements increase and carbohydrate
supplementation improves physical performance. The brain's utilization of glucose also
increases during aerobic exercise. However, the effects of energy supplementation on
cognitive function during sustained aerobic exercise are not well characterized. The
investigators examined the effects of energy supplementation, as liquid carbohydrate,
on cognitive function during sustained aerobic activity. Young, healthy men were
randomly assigned to 1 of 3 treatment groups. The groups received a 6 percent (by vol)
carbohydrate (35.1 kJ/kg), 12 percent (by vol) carbohydrate (70.2 kJ/kg), or placebo
beverage in 6 isovolumic doses, and all groups consumed two meals (3200 kJ). Over
the 10-hour study, the subjects performed physically demanding tasks, including a 19.3-
km road march and two 4.8-km runs, interspersed with rest and other activities. These
investigators found that vigilance consistently improved with supplemental
carbohydrates in a dose-related manner; the 12 percent carbohydrate group performed
the best and the placebo group, the worst. Mood-questionnaire results corroborated the
results from the monitors; the subjects who received carbohydrates reported less
confusion, and greater vigor than did those who received the placebo. Supplemental
carbohydrate beverages enhance vigilance and mood during sustained physical activity
and interspersed rest. In addition, ambulatory monitoring devices can continuously
assess the effects of nutritional factors on cognition as individuals conduct their daily
activities or participate in experiments. These approaches have not been employed in
studying neurobiological involved children.

In an interesting study reported in the Journal of Physiology, London by Thornton and

associates (2001) at the Laboratory of Physiology at Oxford University, Positron
Emission Tomography (PET) was used to identify the neuroanatomical correlates
underlying 'central command' during imagination of exercise under hypnosis, in order to
uncouple central command from peripheral feedback. Three cognitive conditions were
used: imagination of freewheeling downhill on a bicycle (no change in heart rate, HR, or
ventilation, V(I)), imagination of exercise, cycling uphill (increased HR by 12 percent and
V(I) by 30 percent of the actual exercise response), or volitionally driven
hyperventilation to match that achieved in the second condition (no change in HR). The
researchers found significant activations in the right dorso-lateral prefrontal cortex,
supplementary motor areas (SMA), the right premotor area (PMA), supero-lateral
sensorimotor areas, thalamus, and bilaterally in the cerebellum. In the second condition,
significant activations were present in the SMA and in lateral sensorimotor cortical
areas. The SMA/PMA, dorso-lateral prefrontal cortex, and the cerebellum are
concerned with volitional motor control, including that of the respiratory muscles. The
neuroanatomical areas activated suggest that a significant component of the respiratory
response to 'exercise', in the absence of both movement feedback and an increase in
CO2 production, can be generated by what appears to be a behavioral response.

Lardon and Polich (1996) examined the electrophysiologic effects of physical exercise
by comparing groups of individuals who engage in regular intensive physical exercise
(12 + h/week) to control subjects (2 + h/week). Electroencephalographic (EEG) activity
was recorded under eyes open/closed conditions to assess baseline differences
between these groups. Spectral power was less for the exercise compared to the
control group in the delta band, but greater in all other bands. Mean band frequency
was higher for the exercise compared to controls in the delta, theta, and beta bands.
Some differences in scalp distribution for power and frequency between the exercise
and control groups were found. The findings suggest that physical exercise substantially
affects resting EEG and again supports the effects of exercise on brain function.

Repatterning Exercise (Cross Crawl)

Humans are contralateral beings in reference to their neurological organization. The

automatic sequencing of upright muscle movement (walking and running) is meant to be
always coordinated the same way. That is the right arm goes forward, the left leg will do
the same and when the left arm goes forward, the right leg will do the same. This is
what is meant by a contralateral (cross pattern) neurological organization.

These are learned processes. They start to be learned by crawling on the ground as an
infant. They are further developed by learning to walk and run, and by various games
that children play. The complex patterns of which are stored in the nerve messaging
patterns of the cerebral cortex, the cerebellum and spinal and peripheral nerves. These
manage the switch on - switch off co-ordination of the muscles of locomotion, posture
and corrective activity to maintain balance.

When you start new exercise patterns, what the nervous system does is it builds new
connections. Nerves are NOT inanimate wires that transfer electrochemical signals.
They are alive and they form new connections.

As you exercise more, you create and grow a stronger series of connections. They
become more active with use. In fact if you don't use nerves, and they don't get a
minimal amount of stimulus, they die. This brings home the old saying "if you don't use
it you lose it". The bit you lose is the nerve that activates the tissue. If the nerve dies
off then the body part connected to that nerve either won't work well or if enough nerves
die off, it won't work at all.

There is another saying. "The more you use it the more you get it back".

This is the reason why athletes, swimmers, musicians, gymnasts spend so much time
"practicing". What they are doing is ensuring they have the most nerve connections and
function around the skills that they want to perform at their peak. We can all switch on
more control and more function too. We do this by exercising. In this case we would do
it with the "Cross Crawl Marching". With a cross crawl patterning, we rebuild and reset
nerve function and we regain stability. However, under certain circumstances, usually
following some sort of trauma, this instantaneous contralateral synchronization
becomes confused, (right leg forward with right arm forward). This results in
neurological disorganization, which results in poor co-ordination, balance, liability to
subluxate the spine and pelvic joints.

Consequences

Let us say your body gets a shock to the system. This can instantaneously results in a
disorganization of the nerve impulses. It is important to understand that this can affect
both the motor impulses, going from the brain to the body directing it to work in a
certain way and the sensory impulses, going from the body to the brain, providing
feedback monitoring as to how the body is performing. The nerves are working, but not
as co-operating members of your body’s team.

Cross Crawl Marching is one of the easiest ways to activate your brain and nervous
system to give it the proper motor and sensory stimuli it needs to take control of your
bodily functions to either prevent or to rehabilitate problems. This exercise should only
be done to an EARLY fatigue stage. Meaning that at the first sign that your muscles are
tired, stop the exercise. A "march" is considered to be the raising of one arm and
opposite leg. Perform the exercise as follows:

March in place, lifting an arm and the opposite leg as high as possible TOGETHER.
Speed is not as important as full range of motion. In fact the slower this exercise is
performed the greater the control necessary and the greater the benefits. The more
range of motion you achieve, the more stimulus your brain receives and the greater the
incentive the brain has to establish its new pattern. Again, stop at early signs of fatigue.
Ideally, you should perform between 200-500 marches a day. If you manage to do the
exercise very slowly, do 200 marches. Otherwise do the 500. The slower you do this
exercise the greater the level of balance and control that you need to acquire and the
greater the benefits to you as you master the exercise.

Structural Correction

Traditionally the view has been that there is a separation between motor skills and
cognitive ability. However, the same pathways and same global increase activation of
the areas involved with motor skill also underlie the areas that form the foundation of
cognitive ability. However, the brain is activity dependent, therefore even though the
potential to learn is enhanced through motor training, if a specific cognitive skill is not
trained, it will not adequately develop. In an interview with Steven Keele (Keele & Ivry,
1990; Keele & Posner, 1968; Keele et al., 1985; 1988), who is associated with the
Psychology Department at the University of Oregon and whose research has helped
bring the study of motor control into the mainstream of cognitive psychology, addresses
this question. When he is asked why the topic of motor control does not get discussed
much in textbooks of cognitive psychology he states, “The basic neglect may derive
from the implicit but faulty assumptions that psychologists have about motor control.
They often think that motor control is an add-on something beyond cognition itself…” He
continues, “…some scientists view the learning or control of a series of actions as being
relatively primitive compared to such notable human achievements as declarative
memory, the ability to reason, or language.” He goes on to relate that, “Almost 50 years
ago the great neuropsychologist, Carl Lashley, pointed out a remarkable fact about
human skill that should disabuse one of the notions that motor control and motor skill
are less “human” than other remarkable capacities of our species. Humans speak, they
type, they sign, they write each and intricate motor skill. In the domain of music people
play the fiddle, may dance to it and they may sing or hum along. People build cabinets,
knit, and blow fine glassware. These diverse motor activities are beyond the realm of
other organisms and suggest that motor capabilities are related to other intellectual
capabilities. Indeed some psychologists such as Jerome Bruner have suggested that
even human language capability is an outgrowth of capabilities involved to create new
motor sequences.”

“Extensive evidence suggests that knowledge is acquired as a result of extensive

practice, thousands of hours of highly dedicated practice is key in separating the most
successful people in various motor and non-motor skill domains from the rest of us. This
perspective grew initially out of analysis of chess expertise, but also has been found to
apply to muscle performance and basketball.” Keele concluded, “…The surprising idea
that stands out in the expertise literature is that the extraordinary motor capabilities of
humans are best understood as an extension of their extraordinary cognitive abilities.”
When we examine “geniuses” through out history, we can see that artists and
sculptors like da Vinci and Michelangelo, musicians like Bach and Mozart, were
geniuses not only in their cognitive ability but also in their motor skill as well, to
paint or play music.”

The question is, does the constant practice of developing a motor skill like painting, or
playing an instrument creates the cognitive genius or visa-versa? Motor skills develop
first. We know motor skills develop first in a child but if they focus on the motor skill to
the exclusion of all else, then they will not perform well in other areas of life. However, if
motor skill is used as a tool to develop brain areas, and then academic and social
pursuits are diligently taught, the child will learn those activities better and faster. The
key is balance and in an otherwise normal child who is behind, and in a child who is
developmentally delayed, the fastest and most effective way to increase the rate of
development of their brain function may be through motor activity and motor
development. If there is a delay in motor skill development, then there will be a
subsequent delay in their cognitive and emotional development as well.

Therapists think that hyperactive children often have persistent tonic neck reflexes.
This is a normal reflex present in young children and they think that if this reflex persists
in older children, it is not only a sign of poor neurological organization, but makes it
difficult and uncomfortable for the child to sit normally. BBT’s note that many children
who are hyperactive are also fidgety, sit in unusual postures, especially a slumped
posture or hook their feet under the chair for support. They may tend to stand when
eating or doing homework and they may experience fatigue of their neck and postural
muscles, which becomes painful and affects the child’s ability to concentrate. Brain
Based Therapists have designed a series of crawling exercises and claim that these
intervention techniques are effective in alleviating the ADD symptoms and improve
academic performance and behavior. These techniques emphasize the importance of
the motor system to effect the neurological development of a child’s brain and a
subsequent improvement in learning and behavior. While the theory does not take into
the cerebellum, differential hemispheric activation, and their effects on developing brain
function into consideration, the theory does emphasize the role of postural muscles in
the manifestation of the observed symptoms. Most children with learning disability and
ADD do have poor postural tone, indicative of cerebellar, thalamic and frontal lobe
dysfunction. Therefore, any activity emphasizing proximal and postural coordination will
increase feedback to these brain regions. These activities may be more significant to
right brain development and therefore would be expected to improve symptoms of right
brain deficit, including hyperactivity, Anxiety, ADHD, ADD, and behavioral problems.

The use of spinal manipulation for purposes of promoting health and curing disease
dates back almost as far as recorded history to the Greeks and Egyptians. The primary
effect of spinal manipulation is on the brain and nervous system. Another premise of D.
D. Palmer (B.J. Palmer, 1906) was that the main conduit or path to affect the brain is
the musculoskeletal system, especially the spine, and especially the upper cervical
spine. In addition, we now see based on a preponderance of scientific information that
this observation is indeed correct. The majority of all sensory input arises from
somatosensory receptors of the musculoskeletal system and the largest percentage of
that amount comes from the receptors of the spinal muscles and joints located in the
upper cervical spine receptors (Leisman, 1976a). Through the ability of these spinal
receptors and based on their upright orientation and transduction of gravitational forces
into electrochemical impulses that constantly bombard the brain by way of the dorsal
column and spino-cerebellar and non-specific thalamic pathways, they provide the
baseline activation or arousal on which, in part, other brain activity is based. Through
specific pathways, the same somatosensory receptors can affect specific cortical areas
that are involved with higher functions of perception, cognition, and emotional behavior,
especially in the frontal lobe.

However, with manifestation of symptoms, especially musculoskeletal symptoms, which

make up the vast majority of health complaints of humans, they are primarily symptoms
of neurological dysfunction and are best treated by affecting the nervous system
directly. This can be achieved by use of spinal manipulation, joint mobilization, exercise,
and by stimulating the brain through a variety of environmental stimuli, such as sound,
light, heat, cold, odors, tactile sensation, and cognitive activities, as indicated earlier in
the chapter. Virtually all those with neurobehavioral disorders of childhood also
demonstrate dysfunction of their motor-sensory system. Either this dysfunction of the
motor-sensory system may in fact be a primary cause of the brain dysfunction or the
brain dysfunction may be the primary cause of the motor-sensory dysfunction. Either
way, the motor-sensory systems, which include the postural muscles and joints of the
spine and neck, are dysfunctional.

Therefore, no matter what the primary source, an intervention strategy for the motor-
sensory dysfunction ought to result in an improvement of brain function and vice versa.
This is especially true in the frontal lobe where we have seen that both motor and non-
motor functions can be measured and a dysfunction of one is reflective of an equal
dysfunction of the other. Therefore, an improvement of frontal lobe motor function
associated with an improvement in a child’s motor function capacities, such as muscle
tone, coordination, mobility, strength, and endurance, should also be reflective of an
improvement in non-motor functions of the frontal lobe such as cognitive, emotional,
and behavioral. By directing and including diagnosis and treatment of musculoskeletal
system function, we develop tools of measuring and affecting central nervous system
status.

An example of the relationship between musculoskeletal complaints relating to higher

brain function has been presented in a recent article in Spine (Luoto et al., 1999). In this
paper, the authors examine the mechanisms explaining the association between lower
back pain and deficits in information processing. Low back trouble, chronic pain in
general and depression has been associated with impaired cognitive functions and slow
reaction times. It is known that the preferred hand performs significantly better than the
non-preferred hand in motor tasks. The authors hypothesize that chronic low back pain
hampers the functioning of short-term memory in a way that leads the preferred hand to
loose its advantage over the non-preferred hand, but that the advantage would be
restored during rehabilitation. Reaction times for the preferred and non-preferred upper
limbs were tested in 61 healthy control and 68 low back pain patients. A multi way
analysis of covariance was used to examine the group, handedness, and rehabilitation
effects on reaction time. A significant interaction among group, handedness, and
rehabilitation was found. At the beginning, the reaction times for the preferred hand
were faster among the control subjects, but not among the patients with low back pain.
After the rehabilitation, the preferred hand was faster among both the control subjects
and the patients with low back trouble. During the rehabilitation, back pain,
psychological distress, and general disability decreased significantly among the patients
with chronic low back trouble. The results support the hypothesis that chronic low back
pain and disability impedes the functioning of short-term memory, resulting in decreased
speed of information processing among patients with chronic low back symptoms.

Recent studies (Blake et al., 2002; Byl & McKenzie, 2000; Byl & Melnick, 1997; Byl et
al., 1996; 1997) report on a theory that suggests that a dysfunction in the way of the
brain receives and processes information from the body, may trigger so called writer’s
and musician’s cramps. Researchers at The University of California and San Francisco
School of Medicine say that the debilitating disorder also called focal dystonia of the
hands stems from pushing the brain past its ability to learn quick repetitive movements.
When the brain signals become “jumbled” these researchers think the muscles spasm
and stiffen. Nancy Byl, Professor Physical Therapy, and Michael Merzenich, Professor
of Otolaryngology, based their studies on previous research that explains the
mechanism of how messages are wired to the brain. Studies explain how tactile
receptors or nerves upon the skin speed signals to an area of the brain called sensory
maps, which undergo rewiring or plasticity with each learning experience. Researchers
read these maps and identify zones that correspond to individual fingers and parts of
the fingertips.

According to ongoing studies conducted by Byl, Merzenich, and colleagues on monkeys

first published in 1996, rapid repetitive movements result in degeneration of the brain’s
sensory map that leads to muscle spasm and impaired muscle tone. They suggest that
during successive movements, the brain is forced to process too numerous sensations
and muscle commands. This gives rise to faulty movements they say that causes
fingers and hands to spasm. Standard therapy is used to treat focal dystonia including
anti-Parkinson’s drugs, muscle relaxants, and injections of botulinuium toxin (Botox) to
weaken problematic muscles. The authors feel that this treatment approach may be
inappropriate. Instead, they suggest retraining therapy that consists of exercises to help
patients fine-tune their tactile senses. This should, they think, help diffuse overloaded
sensory maps so they can discriminate sensations better.

Byl noted that after 12 weeks of retraining therapy (BBT), 14 of 16 patients with severe
focal dystonia of the hand who were not helped by standard therapies reported
improvement in function and were able to return to work. A brain scan taken on one of
the patients showed that the sensory maps appeared more neatly arranged. Although
many think that there are primary biomechanical factors that produce repetitive strain
type injuries, Byl thinks that focal dystonia of the hand is more likely to occur if a person
is exposed to biomechanical risk factors like a high level of repetitive movements and
small fingers spread. She maintains that a significant factor focal dystonia is a
disorganization of the sensory maps adding that Botox and other treatments simply
“quiet symptoms.” She further states, “The nervous system is responsive to repetitive
behaviors but we have always assumed that those modifications of the nervous system
from repetitive movements would have a positive outcome, that it would make one
smarter and be able to test more accurately. But what we are saying is we have
identified a dysfunctional reorganization of the sensory brain that seems to be
associated with the disability disorder negative outcome.” Focal dystonia, as described
by Byl and associates, can be considered a primary dysfunction in the motor system,
including the basal ganglia, thalamus, cerebellum, and frontal lobe. Focal dystonia or
hypokinetic behaviors may be isolated to the sensory-motor cortices. Lower back and
neck pain are also oftentimes considered repetitive strain injuries and the same
mechanism may apply. Hypermobility of the spinal joints may also produce improper
repetitive sensory input that may rewire sensory maps to produce fatigue-ability or
oxidative stress to brain cells. This may result in a focal dystonia of the spinal muscles
with effects on the sensory- motor cortices. These painful muscle spasms either may be
a product of the central nervous system irregular activation or may also result in
abnormal repetitive feedback to the cortex.

Kelly and his colleagues (2000) had employed a mental rotation reaction-time paradigm
to measure the effects of upper cervical manual spine adjustments on cortical
processing. Thirty-six subjects with clinical evidence of upper cervical joint dysfunction
participated in the study. Subjects in the experimental group received a high-velocity,
low-amplitude upper cervical adjustment. A non-intervention group was used to control
for improvement in the mental rotation task because of practice effects. Reaction time
was measured for randomly varying angular orientations of an object appearing as
either normal or mirror-reversed on a computer screen. The average decrease in mental
rotation reaction time for the experimental group was 98 ms, a 14.9 percent
improvement, whereas the average decrease in mental rotation reaction time for the
control group was 58 ms, an 8 percent improvement. The difference scores after the
intervention time were significantly greater for the experimental group compared with
the control group. The results demonstrate significant improvement in a complex
reaction-time task after an upper cervical adjustment providing support for the notion
that upper cervical spinal manipulation may affect cortical processing.

Carrick (1997) attempted to ascertain whether manipulation of the cervical spine is

associated with changes in brain function. He employed physiological cortical maps
reflecting brain activity before and after manual manipulation of the cervical spine in 500
subjects. Subjects were divided into six groups and each subject underwent
manipulation of the second cervical segment. Blinded examiners obtained reproducible
pre- and post-manipulative cortical maps. Brain activity was demonstrated by
reproducible circumferential measurements of cortical hemispheric blind-spot maps
before and after manipulation of the second cervical motion segment. Carrick found
that manipulation of the cervical spine on the side of an enlarged cortical map is
associated with significantly increased contralateral cortical activity. Manipulation
of the cervical spine on the side opposite an enlarged cortical map is associated with
decreased cortical activity with strong statistical significance. Manipulation of the
cervical spine was specific for changes in only one cortical hemisphere. Carrick
concluded that accurate reproducible maps of cortical responses could be used to
measure the neurological consequences of spinal joint manipulation. As cervical
manipulation activates specific neurological pathways, manipulation of the cervical
spine may be associated with an increase or a decrease in brain function depending
upon the side of the manipulation and the cortical hemisphericity of a patient. Carrick’s
essential point is that there exists an asymmetric distribution of the visual field loss and
cerebral dysfunction. He also shows that specific manipulation of the cervical spine on
the side opposite of the functional cortical deficit specifically increases the function of
that hemisphere of the brain. He also shows manipulation of the same side can
increase the dysfunction. This study therefore supports the notion spinal manipulation
may be effective in facilitating the restoration of aspects of brain function, but that it can
be specifically directed toward one hemisphere or the other.

In the context of the forgoing discussion, attempts to evaluate manual and manipulative
therapies in the treatment of children with ADHD have been performed (Giesen et al.,
1989). Investigators evaluated the effectiveness of the treatment for reducing activity
levels of hyperactive children by these intervention strategies. Data collection included
independent evaluations of behavior using unique wristwatch type devices to
mechanically measure activity while the children completed tasks simulating
schoolwork. Further evaluations included electrodermal tests to measure autonomic
nervous system activity. Clinical evaluations to measure improvement in spinal
biomechanics were also completed. Placebo care was given prior to intervention. Five
of seven children showed improvement in mean behavioral scores from placebo care to
treatment. Four of the seven showed improvement in arousal levels, and the
improvement in the group as a whole was highly significant. Agreement between tests
was also high in this study. For all seven children, three of the four principal tests used
to detect improvement agreed either positively or negatively (parent ratings of activity,
motion recorder scores, electrodermal measures, and X-rays of spinal distortions).
While the behavioral improvement taken alone can only be considered suggestive, the
strong interest agreement can be taken as support for the efficacy of this intervention
strategy.
Diet:

Although we live in affluent countries, our children, as we have shown, are suffering
from malnutrition and lack of environmental stimuli, and adequate physical activity and
the average child’s diet deficient in basic nutrition. Children are getting fatter and eating
more, but are still deficient in the proper nutrients that they need for their brains to
develop and function optimally. Another factor is that if the brain is not functioning or
activated properly, the neurological regulation of the digestive system, the ability to
secrete acids with which to break down food, the ability to absorb food and nutrients, as
well as the circulation to the intestines and brain, are all decreased. Therefore, even
with proper diet or even dietary supplementation, a child may be undernourished, as the
brain requires both fuel and stimulation. Without fuel or wit too much stimulation the
brain will dysfunction. Without stimulation, the body cannot break down and absorb food
and fuel; both the body and brain work together.
A low calorie diet is not good for the development of the child, pre or post-natally. On
the other hand, a high calorie diet, especially combined with physical inactivity,
produces obesity, decrease in both dopamine and dopamine receptors (Popa et al.,
1988), and both cognitive (Rodin et al., 1977) and motor dysfunction (Maffeis et al.,
1997; Petrolini et al., 1995). Small decreases or restriction of caloric intake appears to
work best on the brain. Caloric restriction experiments on primates and other organisms
have extended their life span by up to 50 percent (Ingram et al., 2001; Greenberg &
Boozer, 2000). Ray Walford has conducted a number of studies on caloric restriction.
His studies indicate that slight caloric restriction prevented the decline of dopamine
receptors in the brain cells of organisms. In another study, Walford showed that function
of dendrites of brain cells was also improved by caloric restriction. The caloric restriction
that Walford recommended is not extreme, it is reported that optimal caloric intake is
from 1,500 to 2,000 calories a date, which is about 500 to 1,000 calories less than most
men eat (Walford et al., 1995). Therefore, slight modifications in diet can have
demonstrable changes in learning disabilities and behavioral problems and overall brain
development and function.

Laura Stevens (Stevens et al., 1995; Burgess et al., 2000) has studied biochemical
factors affecting children with ADHD. She notes that as children use about 45 raw
materials (vitamins, minerals, amino acids, essential fatty acids, water and
carbohydrates) to make thousands of other chemicals that make up their bodies and
brains, if they do not take in the right nutrients and in the appropriate amounts, their
bodies and brains cannot develop and function properly. She notes that in computerized
three-day records for 100 children in her ADHD study, she determined that sugary
drinks frequently replace milk at meals, fruits and vegetables are scarce, and sugar and
fatty snacks replace healthy foods. Many children were found to be taking in much less
than the recommended dietary allowances of several nutrients, calcium, magnesium,
iron and zinc and vitamins B-6 and C. She recommends some basic principles that she
has found to be effective. The first principle is variety. Different fruits, vegetables,
grains, meats, fish, etc. helps to guarantee that a child will get all of the nutrients they
need for proper brain function.

The basic food pyramid can NOT be used as a guide for what a child should eat every
day. At the bottom of the food pyramid are breads, cereal, rice, and pasta. Sensitivities
to these things, especially GLUTEN is common and testing for this is an absolute must
before dietary changes are made. At the top of the pyramid are fats, oils, and sweets.
Sweets and certain fats should be used sparingly and should be picked carefully. Efforts
should be taken to reduce “bad fats.” These consist of saturated and hydrogenated, and
partially hydrogenated fats. On the other hand, “good fats,” which are a source of
essential fatty acids, should be included every day in a child’s diet and have been found
to be missing in most children with ASD. Essential fatty acids (good fats) are extremely
important for proper brain function. They are necessary to be consumed in a child’s diet
because the body does not produce these important nutrients. Rich sources of
essentially fatty acids can be found in raw nuts, walnuts, and fish oils, beans, flax,
coconut oil, olive oil and cold water fish.
A child should have at least five servings of fruits and vegetables daily. Also, included
should be two to three servings of lean meat and poultry, fish, eggs, dry beans and raw
nuts. If a child is sensitive or intolerant of milk and dairy products (which should only be
consumed if they are raw/unpasteurized), they will need a calcium supplement.

Based on reports from caregivers, case studies, and observation of patients with
schizophrenia and children with severe behavioral disorders, Dohan hypothesized
(Dohan et al., 1969; 1984; Dohan, 1966a; 1966b; 1969; 1970; 1979; 1980a; 1980b;
1988) that gluten and dairy foods might worsen these behaviors. He noted that in
many cases, a restricted diet could lead to significant improvement or recovery from
these disorders. For several years, the biochemical explanation for this phenomenon
remained unclear. However, several other studies seemed to bear out this observation,
and in 1981, using more advanced laboratory technology, Karl Reichelt found and
reported (Reichelt et al., 1981) abnormal peptides in the urine of schizophrenics and
autistics. Peptides are pieces of proteins that are not completely broken down into
individual amino acids. Reichelt has observed that these peptides, which are 4 or 5 or 6
amino acids long, have sequences that match those of opioid peptides (casomorphin
and gliadomorphin). The known dietary sources of these opiate peptides are casein
(from milk) and gliadin or gluten (from cereal grains). He has since conducted several
studies examining this finding (Knivsberg et al., 2002; 2001; Pedersen et al., 1999;
Reichelt et al., 1996; Seim & Reichelt, 1995), as have several other researchers
(Garvey, 2002; Buckley, 1998), including Paul Shattock (Whiteley & Shattock, 2002) in
England. The best evidence for this correlation lies in the many case reports of
improvement or recovery of children with ASD on this diet.

O'Banion and associates (1978) examined the effect of particular foods on levels of
hyperactivity, uncontrolled laughter, and disruptive behaviors were studied in an 8-year-
old autistic boy. The floor of the child's room was taped off into six equal-sized
rectangles to measure general activity level. Frequency data were recorded on
screaming, biting, scratching, and object throwing. A time-sample technique was used
to record data on laughing. Data were gathered during four phases. During an initial 4-
day period, the child was fed a normal American diet. A 6-day fasting period followed,
during which time only spring water was allowed. The third phase lasted 18 days and
involved the presentation of individual foods. During the final phase of the study, the
child was given only foods that had not provoked a reaction in the third phase. Results
showed that foods such as wheat, corn, tomatoes, sugar, mushrooms, and dairy
products were instrumental in producing behavioral disorders with this child.

Lucarelli and colleagues (1995) also examined the hypothesis that food peptides might
be able to determine toxic effects at the level of the central nervous system by
interacting with neurotransmitters. They note, as have others, that a worsening of
neurological symptoms can be demonstrated in autistic patients after the consumption
of milk and wheat. These investigators examined the effects of a cow's milk free diet (or
other foods which gave a positive result after a skin test) in 36 autistic patients. They
looked for immunological signs of food allergy in autistic patients on a free-choice diet.
They noticed a significant marked improvement in the behavioral symptoms of patients
after a period of 8 weeks on an elimination diet and found high levels of IgA antigen
specific antibodies for casein, lactalbumin and beta-lactoglobulin and IgG and IgM for
casein. The levels of these antibodies were significantly higher than those of a control
group, which consisted of 20 healthy children. Their results supported the hypothesis
that a relationship exists between food allergy and infantile autism. Reichelt’s group
(Knisbserg et al., 2001) performed dietary intervention applied to 15 subjects with
autistic syndromes. Pathological urine patterns and increased levels of peptides were
found in their twenty-four-hour urine samples. The peptides, some of which are probably
derived from gluten and casein, were thought to have a negative pharmacological effect
on attention, brain maturation, social interaction, and learning. Dietary intervention was
reported to significantly reduce the autistic symptoms.

Knivsberg and associates (2002) have noted that in autistic spectrum disorders, urinary
peptide abnormalities, derived from gluten, gliadin, and casein exist. They reflect
processes with opioid effect. These investigators evaluated the effects of gluten and
casein-free diet for children with autistic syndromes and urinary peptide abnormalities.
Randomly selected diet and control groups with 10 children in each group participated
with the study lasting one year. The development for the group of children on diet was
significantly better than for the controls. In a review, this same group of researchers
(Knivsberg et al., 2001) has noted that since the 1980’s various studies on dietary
intervention have been published. The scientific studies include both groups of
participants as well as single cases, and beneficial results are reported in all, but one
study. While some studies are based on urinary peptide abnormalities, others are not.
The reported results are, however, identical; reduction of autistic behavior increases
social and communicative skills and autistic traits reappear after the diet has been
broken.

Nutritional therapies are varied. There are dietary changes, nutritional supplements,
herbal medicines, and homeopathy that are the most commonly used and accepted
forms of therapy for children and adults. It is important that proper testing be done to
determine the individual’s specific source of inflammation.

Essential Fatty Acids

Farooqu and Horrocks (2001) reporting in the Journal of Molecular Neuroscience, state
that plasmalogens are glycerol-phospholipids of neural membranes, rate-limiting
enzymes, are in the peroxisomes and are induced by docosahexaenoic acid (DHA). The
authors suggest that deficiencies of DHA and plasmalogens occur in peroxisomal
disorders, like Alzheimer's disease, depression, and ADHD, The authors claim that this
situation may be responsible for abnormal signal transduction associated with learning
disability, cognitive deficit, and visual dysfunction. These abnormalities in the signal-
transduction process can be partially corrected by supplementation with a diet enriched
with DHA or essential fatty acids.

The symptoms of essential fatty acid deficiencies include:

• Excessive thirst
 • Frequent urination

• Dry skin

• Dry hair

• Dandruff

• Soft and brittle nails

• Small hard little white bumps on the backs of the arms, elbows or thighs.

There are two essential fatty acids relevant to our discussion: linolenic acid, an omega-6
fatty acid and alpha-linolenic acid, an omega-3 fatty acid. These are the precursor
molecules for making long chain fatty acids such as dihommo-gamma-linolenic acid
(DGLA), arachadonic acid, eccosapentaenoic acid (EPA) and docosahexaenoic acid
(DHA). Omega-6 and Omega-3 fatty acids are essential because they help make up the
cell membrane around every cell including brain cells. The balance of these essential
fatty acids helps to determine the fluidity of the membrane and the ability of molecules
to enter and exit the cell. This balance also affects the ability of molecules to bind to
receptors in the membrane. These long chain fatty acids are also critical because the
body converts them to prostaglandins and other important molecules that help cells
communicate with each other. Arachadonic and DHA are more concentrated in the
brain and retina than in other cells. They therefore play a crucial role in brain and
nervous system function. Studies have suggested that approximately 40 percent of boys
with ADHD have significantly lower levels of omega-3 and 6 fatty acids than controls
with normal behavior (Mitchell et al., 1987). However, boys with ADHD have few
symptoms of fatty acid deficiencies and have blood levels comparable to boys in the
control group. It is thought that the reason for lower levels could include lower dietary
intake or a metabolic block in the omega-3 and 6 fatty acid pathways.

Ways to increase intake of essential fatty acids, especially omega-3, is to use cold
process cod liver oils or olive oils for homemade salad dressing. These oils can be
included into spaghetti sauce, soup, etc. or used to make a pasta salad; also baking
with them is good. Frying with these oils should be avoided because the molecules do
not sustain their structure with high heat and oxygen so use coconut oil in frying at
higher temperatures. Flaxseed oil is a more concentrated source of omega-6 and 9 fatty
acids and therefore should be avoided. Beans are also a good source of essential fatty
acids, especially navy and kidney. Tofu is soy and should be avoided. Cold water fish,
like salmon, tuna, mackerel, and sardines are an excellent source of omega-3 fatty
acids.
Food Allergies and Behavior:

Well-designed studies reported in the late 1980’s and early 1990’s have reported that
food sensitivities are indeed a major factor for many children with ADHD (Egger, 1985;
Kaplan et al., 1989; Carter, 1993; Boris, 1994; Rowe & Rowe, 1994; Breaky, 1997). It is
possible that a brain dysfunction, especially right brain deficit, will alter the body’s
immune response making it over responsive. It may also alter the environment of
the intestinal tract, which may create a sensitivity or allergic response to certain foods
and environmental allergies. There has been extensive research examining the brain-
intestinal connection. It is fairly well documented that the GALT or gut associated
lymphoid tissue is associated with an individual’s absorption and immune
responsiveness. It is also thought that in various individuals who may be overly
sensitive, have specific nutritional deficiencies, or who may suffer from poor brain
regulation, may demonstrate a dysfunctional GALT. The gastrointestinal system, as a
result, becomes less efficient at filtering allergens and larger molecules that may be
associated with allergic responses. Infection may more easily pass across the stomach
lining and enter the blood stream. Therefore, sensitivity may be secondary to the
decreased activation or stimulation of motor or other sensory input (Uhlig et al., 1997;
Anderson, 1995). It is also possible that the decreased parasympathetic activation
associated with higher-level neocortical activity and development may be deficient and
therefore, inhibition of the sympathetic control mechanisms are decreased (Anderson et
al., 2000; Girardi et al., 1995; Mikkelsen et al., 1981). This is associated with decreased
blood flow to the gut, which may make the gut tissue break down, may eventually
produce injury to the gut tissue, such as ulcers, but will also reduce the ability to absorb
food and nutrients from the gut itself. It also will decrease the parasympathetic system’s
ability to appropriately secrete acid, to breakdown foods effectively, and may reduce
some of the peristaltic activity in muscle contraction. These sensitivities may decrease
with therapy or exercise, but nonetheless, these food allergies and sensitivities are
important factors to consider.

• Pale sallow complexion

• Puffiness, dark circles under eyes

• Recurrent stomachaches, constipation or soiling

• Headaches including migraines

• Leg and muscle aches

• Bed wetting

• Chronic stuffy, itchy, running noses

• Recurrent ear infections

• Fatigue

• Mental sluggishness, “spaciness” or inability to concentrate.

The most common foods and additives that cause reactions are:
 • Gluten (Gliadin and Lectin)

• Artificial colors and flavors

• Chocolate

• Sugar

• Casein - Milk and milk products

• Eggs

• Corn

• Legumes (peas, beans, peanuts and soy).

A child may be sensitive to more than one of these as well as other foods. Any food the
child craves is suspect. The only definitive way to test a child for food sensitivity is to do
stool testing through Enterolabs.

TH1 and TH2 Balancing

There are 2 parts of your immune system, the TH1 and TH2 response. When a person is Auto-
Immune, one of these systems is “hyper-firing” or Dominant. Balancing this system goes far in
reducing a patient’s symptoms:
TH2 TH1

These SHOULD be
Balanced!
TH1 or TH2

TH1 Dominance TH2 Dominance

There are specific dietary changes and supplements that can help and hinder the above response:
NOTE: ALL AI cases need Vitamin D, Glutathione, and Omega 3 fish oils +

Things that stimulate the TH1 response: (Take these if you are TH2 Dominant)
Echinacea
Garlic
Vitamin C
Immune stimulants
Licorice root (Glycyrrhiza)
Astragalus
Beta-glucan mushroom
Maitake mushroom (Grifola frondosa)
Lemon Balm (Melissa officinalis)
Things that stimulate the TH2 response: (Take these if you are TH1 Dominant)
Caffeine
Green Tea
Grape Seed Extract
Herbal barks (Cramp Bark, Pine Bark, White Willow Bark)
Lycopene
Resveratrol
Pycnogenol

Therefore, if a patient is TH1 Dominant, they should AVOID TH1 Stimulants and TAKE
TH2 Stimulants

Sugar and Artificial Sweeteners:

If one thinks that a child is sensitive to sugar, then one might attempt a no sugar diet for
a couple of months. A no sugar diet avoids sugar, corn syrup, fructose, dextrose, honey,
and maple syrup. The child’s symptoms may increase for the first few days without
sugar. Then reintroduce sugar and observe their behavior before and after. Even if a
child were not sensitive to sugar one would want to keep their consumption of sugar
low. Foods that are high in sugar are usually low in important essential nutrients, as well
as usually contain artificial colors and flavors, chocolate, and saturated, hydrogenated
and partially hydrogenated fats. In addition, if a child eats a large amount of sugar
containing foods, this reduces their intake of high-density nutritious foods. Some
suggestions to help avoid sugar in the diet: substitute all – fruit juices, fruit drinks or
punches, with 100 percent unsweetened orange, grape, grapefruit or tomato juice. One
should choose frozen and canned unsweetened fruits and pure fruit juices as well as
fresh fruits for desserts and use small amounts of all fruit jams. A nutritious breakfast
should include high protein food (eggs, homemade sausage, fresh fruit, gluten-free
cereal or bread and raw milk). Most western children start the day with sugary cereal.
Not only are these products high in sugar content, they also contain artificial colors and
preservatives, which can all cause adverse reactions.

Artificial Sweeteners:

Some children with ADHD have serious reactions to the artificial sweetener aspartame
(Equal, Nutrataste or Nutrasweet). It is as good as eating poison for anyone! A parent
can make their own soda by using club soda with concentrated unsweetened juices.
Another note on aspartame is that aspartate is a precursor to the most powerful
excitatory neurotransmitter in the brain, glutamate. It is thought by some that by
ingesting aspartame the breakdown into aspartate may be associated with an over
production of this type of neurotransmitter which could produce over-excitation or even
excito-toxicity of the nervous system. Saccharin and acesulfame are other popular
artificial sweeteners that are chemically different from aspartame. A child may tolerate
small amounts of these, although some children have mild intestinal distress or diarrhea
from too much. In general, artificial sweeteners should be avoided.

Yeast Sensitivities:

Candida albicans is a common and usually harmless yeast that normally lives in the
intestinal and urinary tracts in humans. It usually does not produce difficulty in a healthy
child with a properly functioning brain and immune system. However, a child who has
chronic infection, which may be associated with decreased function of the left
hemisphere and in turn associated with immune responsiveness (Clow et al., 2003;
Flannery & Liederman, 1995; Phillips et al., 1995; Rich &, McKeever, 1990) may expose
the child to many rounds of antibiotics. The chronic use of antibiotics provides a less
than optimum environment for both bacteria normally present and necessary for
effective digestion and mutant forms of the bacteria. Normal bacteria not only aid in
digestion, but also create a certain pH of the intestine that helps suppress the growth of
yeast. When the bacteria are suppressed, the yeast can grow unchecked and Candida
albicans is therefore thought to play a role in a number of health problems. These
include recurrent infection, fatigue, irritability, hyperactivity, and other neurological
symptoms, like short attention span, “spaciness,” and depression. It is also possible that
some of these symptoms will also reflect a decrease in brain activation, especially of the
left hemisphere that may be the prime cause of or be associated with other diseases or
disorders co-existing with the yeast infection.

Inferential data of the likelihood of yeast infection can be obtained by determining

whether a child received four or more prescriptions for antibiotics in the preceding year;
whether the child had been on a prolonged course of antibiotics for a four week period
or longer; whether the presenting symptoms (not the infection) worsened after treatment
with antibiotics; whether the child craves sugar, and if the child complains or appears to
have persistent digestive problems, including gas, bloating, and constipation or
diarrhea. Several simple treatments can be used to treat a child’s yeast problem. Avoid
foods that promote the growth of yeast, such as sugar, honey, corn syrup, maple syrup,
etc.

Other possible interventions include:

• Anti-fungal medications that can be cautiously prescribed. Nystatin powder

seems to be a safe prescription anti-fungal medication that kills yeast in the
intestines. However, Nystatin in tablet form also contains food dyes, as many pills
and vitamins do, which can cause a reaction in children that are sensitive. In addition,
the liquid suspensions, like many liquid prescriptions and over-the-counter
medications, contain sugar leaving only one choice for children that are sensitive to
dyes and sugars and that are the powered form of Nystatin. However, this has a
slightly unpleasant taste, so it may be advisable to prepare the medication in clear
gels and tablets and place the powder in the tablets if a child is able to swallow pills.
A child’s symptoms may also worsen in the first few days.
 • Foods that contain yeast should be avoided because it is thought that some
children may be allergic or sensitive to yeast. These foods would include breads,
dried fruit, and cheese.

• One of the best ways to treat yeast problems besides continuing the use of
antibiotics and increasing brain activation, especially left brain stimulation therapies,
is to restore the natural bacterial environment by reintroducing the symbiotic bacteria.
This can be ingested in the forms of lactobacillus acidophilus and planterum.

• Many infections that children experience are viral, few are bacterial. Recent
studies have indicated that antibiotic abuse is rampant among physicians, with an
estimated 50,000 prescriptions for antibiotics being unnecessarily written in one year.
A large percentage of these are for otitis media infections that are often viral. Not
only does this unnecessary medication promote yeast infection, it creates stronger
antibiotic resistance to mutant bacteria.

Specific Supplementation

Although supplements are generally not viewed as being medication, they are
reportedly effective and necessary in most children with autistic spectrum disorders.
Their use should be viewed in much the same way as the use of medication. This
means that although a child may benefit from these treatments, most of the time, like
medication, these supplements and remedies are treating the symptoms and not the
root causes of the problem. If a child’s body and nervous system are functioning and
developing properly and the child receives a sufficient and nutritious diet, the child
should not require the use of supplements, herbs, or homeopathic remedies. The most
important factor in brain development is natural environmental stimulation. When the
child is deprived of such stimulation, the brain does not develop and function adequately
and it will not adequately regulate the breakdown and absorption of food. Even if the
diet is proper, the child may ultimately be deficient in various vitamins and minerals
simply due to the relative absence of such in our food supply.

In some cases, a child may have a genetic predisposition to a certain mineral or vitamin
deficiency and therefore that individual child may require supplementation to
compensate for the inherited decrease in production, absorption, or inability to produce
the relevant substances on their own. In these cases, the deficiencies may exacerbate
the symptoms and even create additional symptoms. In this case, nutritional
supplementation may be helpful to compensate for the inability of the body to absorb
these nutrient forms from the diet or to produce them themselves. When this is properly
prescribed and monitored, it may be anywhere from a mild to dramatic effect in
alleviating the symptoms that a child has and improve learning ability and behavior. This
may lead some to conclude that nutrition deficiency therefore is the primary cause of the
symptoms and supplementing the diet is the cure. However, if after a course of
supplementation, which is then discontinued, symptoms return, then the root problem is
probably related to something else and nutritional intervention is palliative. The
treatment can be continued, but the search and therapy for the underlying cause must
be continued.

Many who use nutrition as a therapy are quick to criticize the use of medication
because it is not “natural” and is riskier than the use of vitamins, minerals, or
herbs. This may be true, but the philosophy of giving a child a pill or a powder to
cure a problem can be as damaging if it takes the focus off the root problem,
which is likely decreased physical activity, combined with poor nutrition, and
inadequate environmental stimulation.

The maintenance of health by ensuring a proper balance of nutrients, vitamins,

minerals, and amino acids in the body as an organized modality of intervention is an
emerging clinical science. Extensive research in recent years has shown the far
reaching impact of various nutrients, including vitamin C, vitamin B-6, vitamin B-12,
magnesium, calcium and others, have specificity for brain and neuronal growth and for
nervous system function. Nutrients and supplements that have been shown, under
controlled circumstances, to enhance brain function and cognitive abilities and improve
behavior include:

• Vitamin A – a powerful antioxidant, which helps to protect the membranes of

brain cells, which can be damaged by oxidative stress and free radical production. It
also aids circulation. It should be taken with beta carotene, another source of vitamin
A. For most children a daily dose would be approximately 10,000 units.

• B Vitamins – a group of vitamins essential for neuronal growth and stability. The
four B vitamins that are most essential for brain function are B-12, B-6, B-1 and folic
acid. B-12 deficiency is thought to result in cognitive defects or learning difficulties,
poor memory, a decrease in reasoning skills, as well as behavioral symptoms. A
deficiency of B-12 is 300 percent more common in individuals who do not take
vitamin supplements. A daily dose of B-12 is anywhere between 100 to 1,000 mg,
depending on age and size of the child. B-6 is thought to aid in converting blood
sugar into glucose, which is the brain’s only fuel. It also protects blood vessels. B-6
improves memory and is thought to boost the efficiency of the immune system. For
children, an appropriate dose is approximately 50 to 80 mg daily. B-1 (thiamine) is
important for metabolic processes in the brain and peripheral nervous system. It is
also a powerful antioxidant and it improves the ability of B-6 and vitamin E to destroy
free radicals. B-1 deficiency can result in behavior and memory impairment and is
implicated in Korsokoff’s psychosis. A daily dose is 50 to 80 mg is considered
appropriate. Vitamin B-3 (niacin) is used to manufacture neurotransmitters, convert
carbohydrates to glucose, and lower cholesterol level. It also appears to have a
calming effect in children because it is thought to increase the effects of the inhibitory
neurotransmitter GABA. Niacin can cause a mild flushing and burning sensation of
the skin, however another form of B-3, niacinamide, does not. A daily dosage is 100
mg is considered appropriate. Vitamin B-5 (pantothenic acid) is thought to be crucial
to the synthesis of neurotransmitter acetylcholine, implicated in memory and the
efficient function of the autonomic nervous system. B-5 also assists in forming a
protective sheath around the spinal cord. A severe deficiency of B-5 can produce
paralysis and certainly motor symptoms. A daily dose is 100 mg is considered
appropriate. Folic acid has been noted to be helpful in decreasing depression, even
in low doses, and in improving cerebral circulation. Behavioral and emotional
symptoms appear to be significantly higher in people with low folic acid levels. Folic
acid is particularly helpful at breaking down chemical homocysteine, which is toxic to
brain cells and nervous tissue. A daily dose is 400 mg is recommended.

• Vitamin C is so important to brain function that its levels in the brain are almost
15 times higher than they are outside the brain. Vitamin C is thought to be the most
powerful of all the antioxidants. It also enhances the antioxidant effect of other
nutrients, especially vitamin E. Vitamin C is important in the manufacture of several
neurotransmitters including acetylcholine, dopamine, and norepinephrine, all thought
to be deficient in children with ADHD. Vitamin C also improves the responses of the
immune system and arterial function. This vitamin should be taken twice a day; the
dose is 500 mg each. Vitamin E is thought to be a powerful antioxidant and therefore
protects brain cells from damage from oxidative stress and free radicals. Therefore, it
not only can help prevent brain dysfunction, but can promote and improve neuronal
development and function. Studies have shown that vitamin E, when taken with
selenium can improve mood and cognitive function in people. Vitamin E also
improves immune function. A daily dose is 400 i.u. and because vitamin E is fat
soluble, it can accumulate to toxic levels.

• Calcium supplements are essential when a child dislikes green vegetables or is

sensitive to dairy. Calcium may also have a calming effect on behavior. The dosage
is 500 mg of calcium lactate from a vegetable source. Too much calcium can
decrease the absorption of other minerals.

• Magnesium is thought to aid in the metabolism of neurons. Magnesium is also a

powerful antioxidant that increases the effect of vitamin E. If a child is hyperactive,
irritable, has difficulty sleeping, muscle twitching, and wets the bed, magnesium may
be helpful. Magnesium is an important co-factor in a multitude of chemical reactions
in the body. Refined foods are often deficient in magnesium content. Good food
sources are whole grains, nuts, seeds, seafood, fresh vegetables, and fruits.
Magnesium supplements may improve a child’s behavior and decrease allergies.
Magnesium has a calming effect on many children with ADHD. Two recent studies
suggested (Kozielec, 1997 and Starobrat-Hermalin, 1997) that magnesium deficiency
is common in children with ADHD and that supplementation with magnesium “200
mg a day” resulted in significant decreases in hyperactivity. Magnesium chloride and
magnesium citrate are two well-absorbed forms. Dosage 200 to 600 mg a day is
appropriate.

• Zinc is also an essential mineral that works as a cofactor in many of the body’s
metabolic pathways. Zinc is thought to play a particularly important role in brain
 metabolism. It is considered part of an antioxidant “chain reaction” that destroys free
radicals. It also increases the strength and stability of neurons protecting them from
damage. If a child has a loss of appetite, slow growth, and white spots on their
fingernails, they may have a zinc deficiency. Good food sources include eggs, liver,
shellfish, wheat germ, beef, dark meat, turkey, nuts and seeds. Taking 10 mg of zinc
together with a multi-mineral supplement for two months may improve behavior. Too
much zinc can decrease the absorption of other vital minerals.

• Selenium is thought to be the most powerful antioxidant mineral. It is especially

effective in preventing the oxidation of fats. This is particularly important in the brain,
since approximately 60 percent of the brain is composed of fat. Selenium also aids
the immune system and is thought to improve circulation. Selenium has been shown
to produce an anti-anxiety effect in some individuals. Selenium content is reduced in
refined foods. Good food sources are seafood, liver, and meat. Grains are a good
source only if they are grown in selenium rich soils. Dosage should be 100 mCg in a
preparation of sodium selenate. This dosage should not be exceeded as selenium
may be toxic in large amounts.

In an exceedingly ambitious attempt to enroll parents of autistic children in evaluating

treatment intervention strategies, Table 11.2 below presents the results of parent’s
behavioral ratings of drug and diet interventions including both the benefits and adverse
effects. These ratings have been collected from 1967 to the present and represent the
responses of 21,500 parents who have completed questionnaires for the Autism
Research Institute, albeit under non-controlled conditions. For the purposes of Table
11.2, the parents responses are given on a six-point scale which had been combined
into three categories: “made worse” (ratings 1 and 2), “no effect” (ratings 3 and 4), and
“made better” (ratings 5 and 6). The “Better-Worse” column gives the number of
children who “Got Better” for each one who “Got Worse.” There are three sections:
Drugs, Biomedical/Non-Drug/Supplements, and Special Diets.

TABLE 11.2: Autism Research Institute Parent Ratings of Behavioral Effects of

Biomedical Treatment Interventions (1967-2003)

Got No Got
No. of
Worse Effect Better Better:Worse
Cases(B)
(%)(A) (%) (%)
BIOMEDICAL/NON-DRUG/SUPPLEMENTS
Vitamin A 2 59 39 22:1 334
Calcium(D) 2 62 35 14:1 988
Cod Liver Oil 3 51 46 14:1 411
Colostrum 6 58 37 6.7:1 163
 Detox.(Chelation) 3 28 70 27:1 116
Digestive Enzymes 4 44 52 14:1 314
Di-methyl-glycine
7 51 42 5.9:1 4547
(DMG)
Fatty Acids 4 44 51 12:1 299
5 HTP 11 55 35 3.3:1 66
Folic Acid 4 55 41 11:1 1100
Food Allergy
4 37 59 14:1 290
Treatment
Magnesium 6 65 29 5.2:1 288
Melatonin(E) 10 33 57 5.9:1 302
Pepcid 9 61 30 3.2:1 64
SAMe 25 46 29 1.1:1 28
St. Johns Wort 11 67 22 2.0:1 46
Tri-methyl-glycine
14 42 44 3.1:1 182
(TMG)
Transfer Factor 18 51 31 1.7:1 39
Vitamin B3 5 55 41 9.0:1 487
Vitamin B6 alone 7 64 29 4.1:1 590
Vitamin B6 &
4 49 46 11.1:1 5079
Magnesium
Vitamin C 2 59 39 16:1 1306
Zinc 3 55 43 17:1 835
SPECIAL DIETS
Candida Diet 3 45 52 18:1 605
Feingold Diet 2 47 51 23:1 645
Gluten-/Casein-Free
4 33 64 18:1 724
Diet
Removed Chocolate 1 50 49 36:1 1491
Removed Eggs 2 61 37 21:1 882
Removed Milk
2 51 48 30:1 4950
Products/Dairy
Removed Sugar 2 51 47 24:1 3392
 Removed Wheat 2 53 46 26:1 2701
Rotation Diet 2 50 47 20:1 678
DRUGS
Note: For seizure drugs: The first line shows the drug’s behavioral effects; the
second line shows the drug's effects on seizures.
Aderall 39 28 34 0.9:1 285
Amphetamine 47 28 25 0.5:1 1174
Anafranil 31 37 31 1.0:1 351
Antibiotics 30 59 11 0.4:1 1617
Antifungals(C):
7 42 51 7.2:1 185
Diflucan
Antifungals(C):
5 48 47 10:1 727
Nystatin
Atarax 26 53 21 0.8:1 443
Benadryl 24 51 25 1.1:1 2512
Beta Blocker 18 49 33 1.8:1 236
Buspar 26 45 30 1.2:1 281
Chloral Hydrate 41 37 22 0.5:1 375
Clonidine 21 31 48 2.2:1 1090
Clozapine 44 39 16 0.4:1 79
Cogentin 19 53 28 1.4:1 149
Cylert 45 35 21 0.5:1 580
Deanol 15 55 29 1.9:1 195
Depakene: Behavior 25 43 32 1.3:1 871
Depakene: Seizures 12 30 57 4.6:1 569
Desipramine 38 25 38 1.0:1 61
Dilantin: Behavior 28 48 24 0.9:1 1049
Dilantin: Seizures 14 36 51 3.8:1 377
Felbatol 26 45 29 1.1:1 38
Fenfluramine 21 51 28 1.4:1 453
Halcion 37 30 33 0.9:1 43
Haldol 37 27 35 0.9:1 1119
 IVIG 13 45 42 3.2:1 31
Klonapin: Behavior 28 33 38 1.4:1 156
Klonapin: Seizures 38 50 12 0.3:1 26
Lithium 27 42 31 1.1:1 384
Luvox 28 36 37 1.3:1 120
Mellaril 28 38 33 1.2:1 2023
Mysoline: Behavior 44 40 15 0.3:1 131
Mysoline: Seizures 19 58 23 1.2:1 57
Naltrexone 22 46 32 1.5:1 200
Paxil 27 28 45 1.7:1 192
Phenergan 30 44 26 0.9:1 244
Phenobarbitol:
47 37 16 0.3:1 1052
Behavior
Phenobarbitol:
17 43 40 2.4:1 458
Seizures
Prolixin 34 34 33 1.0:1 83
Prozac 31 33 36 1.2:1 975
Risperidal 19 28 53 2.8:1 401
Ritalin 44 26 29 0.7:1 3540
Secretin:
8 43 49 6.2:1 217
Intravenous
Secretin:
12 47 41 3.6:1 78
Transdermal
Stelazine 28 44 27 1.0:1 415
Tegretol: Behavior 24 45 31 1.3:1 1345
Tegretol: Seizures 12 33 55 4.5:1 721
Thorazine 36 40 24 0.7:1 897
Tofranil 30 37 33 1.1:1 698
Valium 36 41 23 0.7:1 788
Zarontin: Behavior 34 43 22 0.7:1 129
Zarontin: Seizures 21 51 29 1.4:1 87
Zoloft 33 31 36 1.1:1 212
(A) “Worse” refers only to worse behavior. Drugs, but not nutrients, typically also cause physical problems
if used long-term.
(B) No. of cases is cumulative over several decades, so does not reflect current usage levels (e.g., Haldol
is now seldom used).
(C) Antifungal drugs are used only if autism is thought to be yeast-related.
(D) Calcium effects are not due to dairy-free diet; statistics are similar for milk drinkers and non-milk
drinkers.
(E) Caution: While melatonin can benefit sleep and behavior, its long-term effects on puberty are unknown

Pharmacotherapy and Autism

We have indicated throughout the work that neurobehavioral disorders have a

remarkable comorbidity with many disorders of childhood (Jensen et al., 1997; 1999).
As many as two-thirds of elementary school-aged children with ADHD referred for
clinical evaluation, have at least one other diagnosable psychiatric disorder. (Cantwell,
1996) Concomitant disorders include: conduct disorder (Klein et al., 1997; Rigs et al.,
1998) oppositional defiant disorder (Eiraldi et al., 1997), learning disorders, anxiety
disorders (Diamond et al., 1999), and mood disorders, especially depression (Garrison
et al., 1997). The genetic, neurochemical, and neurophysiological underpinnings have
been explained throughout the text for both ADHD and other neurobehavioral disorders
on the autistic spectrum. Its no wonder targeted drug intervention is not available. Table
11.2, while highly subjective, reports parents’ qualitative responses of symptom
reduction, over many years.

Clearly emerging, as subjectively effective for improving autistic symptoms are select
anticonvulsants, and for ADHD, stimulant drugs that improve behavior and learning
ability in 60 to 80 percent of correctly diagnosed children. The primary drugs employed
in treatment are methylphenidate, amphetamines, and pemoline, with buspirone, and
buporion (Welburtin) used in refractory cases. Of these, methylphenidate accounts for
90 percent of prescribed medication.

There are several reasons for the use of anti-epileptic drugs in autistic spectrum
disorders, including the high incidence of epilepsy in these individuals, the anecdotal
reports suggesting an improvement of communication and behavior in autistic subjects
with epileptic discharges, and the increased awareness that some disruptive behaviors
may be manifestations of an associated affective disorder. Martino and Tuchman (2001)
report a study on the current use of anti-epileptic drugs in the treatment of autism, and
on the association of affective disorders with epilepsy and autism. The evidence
supporting the hypothesis that there may be a subgroup of autistic children with
epilepsy and affective disorders that preferentially respond to anti-epileptic drugs is,
according to these authors preliminary. The authors note that evidence exists that
autism, epilepsy, and affective disorders commonly co-occur, and that they may share a
common neurochemical substrate, which is the common target of the psychotropic
mechanism of action of different anti-epileptic drugs. This may then explain the data
reported in Table 11.2. The authors summarize the literature on this topic and present
an overview in Table 11.3 below.
Table 11.3: Anti-epileptics in patients with autism and related conditions

(From Di Martino, A. and Tuchman, R.F. (2001). Antiepileptic drugs: Affective use in autism spectrum
disorders. Pediatric Neurology, 25,199-207.)

ADHD and autistics seem to have different responses to stimulant medication.

Stimulants such as amphetamines usually result in increases in activity, irritability,
explosiveness, and stereotypic behavior when administered to autistic patients. An
exception to this lack of effectiveness of stimulants is the moderate to high functioning
autistics who have ADHD-like symptoms. This type of patient does benefit from
stimulant medication.

In attempting to overview the literature on the clinical pharmacology of autism treatment,

we can group the findings into the categories of controlled studies of dopamine
antagonists, of 5-HT agonists, fenfluramine, and controlled studies of naltrexone
summarized in Tables 11.4-6.
Table 11.4 - Controlled studies of DA antagonists in autistics.

Study Dose (mg/d) Population Results

HLP 0.5-3.0
Autism
mg/d Improvement:
29 males, 11
Placebo Conners, CGI, Children's Rating
Anderson females
4 week x- Scale
et al 1984 2-7 yo
over Performance: on HLP @ level 20 IQ
mild-profound
i.e., PHP vs pts higher
MR
HPH
Improvement:
HLP 0.16- Conners (temper outbursts), CGI,
Autism
0.18 mg/kg/d Children's Rating Scale (trend)
35 males, 10
Placebo Cognition:
Anderson females
3 week x- HLP didn't facilitate or adversely
et al 1989 2-8 yo
over effect learning decrease in
borderline to
i.e., HPP vs hyperactivity, tantrums, withdrawal,
profound MR
PHP vs PPH & stereotypes increase in calm &
relatedness

The administration of conservative doses of haloperidol to autistic children results in significant decreases
in hyperactivity, negativism, and stereotypes and in some cases has been shown to facilitate learning. On
follow-up, haloperidol is therapeutically effective for up to 4-1/2 years and helped many autistic children
remain with their families as well as remain in educational programs without producing any adverse
effects on IQ. Although haloperidol appears to be useful in the treatment of autism, the utility of the drug is
limited by the risk of tardive dyskinesia. It would seem appropriate that future research with neuroleptics
in the treatment of autism be targeted at drugs that do not cause tardive dyskinesia such as clozapine or
more practically one of its congeners that does not cause bone marrow suppression or sedation.

Table 11.5: Controlled studies of 5-HT agonist, fenfluramine, in autistics.

Study Dose (mg/d) Population Results

placebo x 2
10 autistics decreased 5-HT by 62%
weeks
8 controls Conners - improvement in
August et al FFA 1.5 mg/kg/d
matched for hyperactivity, affect, &
1984 x 16 weeks
age & sex 5-13 distractibility
placebo x 2
yo No effect on WISC IQ score
weeks

FFA 2 mg/kg/d Autism Real Life Rating Scale:

(max=120 mg/d) 17 males, 3 no effect
Yarbrough
placebo females ADRs (65%) - agitation,
et al 1987
x-over x 15 wk 9-28 yo tenseness, insomnia &
each IQ = 12-51 withdrawal ADRs

decreased bE not significant

(low dose=?)
FFA 1.5 mg/kg/d Autism
3 responders
(max=60 mg/d) 8 males, 1
Ross et al decreased echolalia, motor
placebo females
1987 disturbances
x-over x 16 wk 3-12 yo
perseveration & increased
each IQ = 31-83
attention, social awareness
ADRs: lethargy, weight loss

7 completers
Autism
FFA 1.5 mg/kg/d decreased 5-HT by 58%
7 males, 2
Beeghly et placebo Conners & Real Life Rating
females
al 1987 x-over x 4 mo Scale no change
7-14 yo
each 2 responders (highest blood
IQ = 36-112
levels)

hyperactivity decreased
FFA (max=60 according to parents but not
Levinthal et
mg/d) vs PLB n=15 teachers
al 1993
over 62 weeks an equivocal response at
best
Fenfluramine, as indicated in Table 11.4, may beneficially affect autistic patients by its ability to decrease
CNS serotonin or beta-endorphin levels. However, the studies suggest that only a minority of patients
were benefited by the therapy. It seems that the too small a dose of the drug is being utilized. Thus future
studies and treatments should be aimed at using doses greater than 1.5-2.0 mg/kg/d.

Table 11.6: Controlled studies of naltrexone in autistics.

Study Dose (mg/d) Population Results

placebo x 2
weeks decreased 5-HT by 62%
10 autistics
FFA 1.5 Conners - improvement in
August et 8 controls
mg/kg/d x 16 hyperactivity, affect, &
al 1984 matched for age
weeks distractibility
& sex 5-13 yo
placebo x 2 No effect on WISC IQ score
weeks