Developmental Psychobiology - 2009 - Domellöf - Atypical Functional Lateralization in Children With Fetal Alcohol Syndrome

Erik Domellöf1,2
Louise Rönnqvist1
Maurice Titran3
Atypical Functional
Rana Esseily4 Lateralization in Children
Jacqueline Fagard4
1
Department of Psychology With Fetal Alcohol Syndrome
Umeå University
SE-901 87 Umeå, Sweden
E-mail: [email protected] ABSTRACT: In order to explore effects of prenatal alcohol exposure on functional
2 lateralization, item tasks measuring preferences of hand, foot, eye, and ear were
Kolbäcken Child Rehabilitation Centre
administered to a sample of 23 children diagnosed with fetal alcohol syndrome
Umeå, Sweden
(FAS) compared with typically developing (TD) children. In addition, a dichotic
3
Centre Hospitalier de Roubaix (CAMSP) listening task was administered to a subsample of 11 children with FAS and a TD
Roubaix, France group of comparable age, sex and handedness. The children with FAS were
characterized by increased nonright-handedness compared with TD children. No
4
Laboratoire Psychologie de la Perception differences were evident for preferential use of foot, eye, or ear. Moreover, children
(CNRS UMR 8158) with FAS displayed more right ear extinctions during dichotic listening relative to
Université Paris Descartes, Paris, France TD children, indicating a lack of right ear advantage. The results add to findings of
decreased manual asymmetry and less left-lateralized speech perception in children
with developmental disorders, and are further discussed in relation to the high
incidence of callosal abnormalities in alcohol-exposed children. ß 2009 Wiley
Periodicals, Inc. Dev Psychobiol 51: 696–705, 2009.
Keywords: fetal alcohol syndrome; fetal alcohol effects; fetal alcohol spectrum
disorders; functional laterality; handedness; dichotic listening task;
prenatal alcohol; children
INTRODUCTION largely localized and lateralized to the left cerebral

hemisphere (Gazzaniga, 2005). The development of
It is well documented that humans, from the beginning of functional asymmetries may be susceptible to change
life, are characterized by several types of functional due to intrauterine environmental effects on early neural
asymmetries. During typical development, handedness development. Support for such a claim can be obtained
and language lateralization eventually constitute two of from the consistent finding of atypical functional
the most evident expressions. A consistent finding is a asymmetries in prematurely born individuals (Marlow,
strong right-handed preference for specific manual tasks Roberts, & Cooke, 1989; O’Callaghan, Burn, Mohay,
(about 90% in most populations), with a majority of Rogers, & Tudehope, 1993; Rönnqvist & Domellöf,
populations also tending to prefer the right foot, right 2006). Furthermore, atypical lateralization in prematurely
eye, and right ear (Porac & Coren, 1981). An equally born children has also been related to impaired cognitive
consistent finding is that primary language functions are performance up to school age (Bracewell & Marlow,
2002; O’Callaghan et al., 1993). Similar to a premature
birth, intrauterine alcohol exposure is associated with an
Received 2 April 2009; Accepted 5 August 2009 increased likelihood of brain injury and subsequent
Correspondence to: E. Domellöf neurodevelopmental problems later in life. The present
Contract grant sponsor: Swedish Council for Working Life and study aims to discern whether alterations in functional
Social Research
Contract grant number: 2006-1577 lateralization also may occur as a consequence of prenatal
Contract grant sponsor: Swedish Research Council exposure to alcohol.
Contract grant number: 421-2001-4589 Many studies have documented the devastating effects
Published online 18 September 2009 in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/dev.20404 of prenatal alcohol exposure on the developing brain (see
Spadoni, McGee, Fryer, & Riley, 2007, for a review). Fetal
ß 2009 Wiley Periodicals, Inc. alcohol syndrome (FAS) refers to a disorder of growth
10982302, 2009, 8, Downloaded from https://onlinelibrary.wiley.com/doi/10.1002/dev.20404 by JUAN PEDRO SANCHEZ NAVARRO - Universidad De Murcia , Wiley Online Library on [08/03/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License
Developmental Psychobiology Atypical Functional Lateralization in FAS 697
deficiencies, craniofacial abnormalities, and abnormal of nonright-handedness among children with develop-
central nervous system (CNS) function following intra- mental disorders may reflect a neurodevelopmental
uterine alcohol exposure (Jones & Smith, 1973). A wide disturbance of cerebral lateralization, it is still unclear
range of neurodevelopmental disorders has been docu- how such atypical lateralization arises following various
mented in children with FAS and other fetal alcohol types of early brain damage and its relation to other
spectrum disorders (FASD, an umbrella term for the full functional (dis)abilities.
variety of syndromes following maternal alcohol use) Following the early work of Kimura (1961, 1967),
including neuropsychological deficits, motor impair- verbal dichotic listening paradigms have been widely
ments, and long-term behavioral problems (see Koditu- used to obtain a behavioral measure of lateralized
wakku, 2007; Streissguth, 2007, for reviews). Indeed, FAS language function in healthy and pathological adults and
and associated disorders are today considered to be a main children. According to Kimura’s structural model (1961,
source of developmental impairment (Riley & McGee, 1967), there is typically a predominance of the contrala-
2005). Very little is known regarding functional lateral- teral auditory projections reflected as a right ear advantage
ization in FAS/FASD. Animal studies have shown less (REA) during dichotic listening. Weaker ipsilateral
side preference in paw use in both rat pups and adults projections are suppressed during dichotic listening,
following prenatal alcohol exposure (Moreland, La resulting in a direct transferring of the right ear signal to
Grange, & Montoya, 2002; Zimmerberg & Riley, 1988). the left hemisphere (dominant for speech processing) and
Some indications of deviations from typical right- a later report of the left ear signal (at first projected to the
handedness in prenatally alcohol-exposed human children right hemisphere) via the corpus callosum (CC). In the
have also been noted (Janzen, Nanson, & Block, 1995; attentional model (Kinsbourne, 1970), the REA is
Olsen, 1995), although not consistently (Roebuck- explained as a consequence of anticipatory activation of
Spencer, Mattson, Marion, Brown, & Riley, 2004; the left hemisphere in the presence of verbal stimuli, with
Roebuck, Mattson, & Riley, 2002). To our knowledge, a subsequent attentional auditory right-sided bias and thus
however, this is the first study to characterize sensory- faster processing of the right ear signal. The CC serves to
motor preferences and language lateralization in children equilibrate activation between the cerebral hemispheres,
with FAS and contrast them to typically developing (TD) affecting the magnitude of the REA. Notably, despite
children. fundamental differences between these major models,
An excess of nonright-handedness is a frequent finding both pinpoint the functional integrity of the CC as having
in research devoted to functional lateralization in an important role in dichotic listening performance (see
individuals with developmental disorders due to under- Westerhausen & Hugdahl, 2008, for a review).
lying neurological damage (Bishop, 1990). By means of Studies using dichotic listening paradigms in clinical
methodologies such as handedness questionnaires, item pediatric populations have reported various types of
tasks, and reaching tasks over the left-right hemifields, a deviations from typical language lateralization, including
decrease in manual asymmetry in terms of atypical and both left ear/right hemisphere dominance for speech
less consistent hand preference has been reported for perception (i.e., a left ear advantage, LEA) and exagger-
children with a variety of disorders, including Down and ated REA. Differences seem to be associated with the
Williams-Beuren syndromes (Gérard-Desplanches et al., nature of underlying neurological abnormalities. For
2006; Groen, Yasin, Laws, Barry, & Bishop, 2008), example, in a longitudinal study involving preschool
Fragile X (Cornish, Pigram, & Shaw, 1997), autism children with focal left or right hemisphere damage
(Cornish & McManus, 1996), and intellectual disability of (Chilosi et al., 2005), LEA was found to be related to
idiopathic origin (Leconte & Fagard, 2006). Some of these cortical–subcortical lesions of the left hemisphere. In this
studies have also reported less strongly developed study, left hemisphere damage/right hemisphere language
preferences for other sensory-motor modalities (Gérard- lateralization was also demonstrated to be associated with
Desplanches et al., 2006; Leconte & Fagard, 2006). delayed language development. Hugdahl et al. (2003)
Assuming handedness as an indicator of brain laterality, reported that structural abnormality of the left planum
the increase in nonright-sided preferences in children with temporale area in dyslexic children was related to a slight
developmental disorders could be interpreted as a reduction of right ear scores but not to a LEA. CC lesions
consequence of core brain abnormalities affecting hemi- have been observed to be related to an exaggerated REA in
spheric organization. Indeed, ‘‘pathological left-handed- head injured children (Benavidez et al., 1999). In a study
ness’’ and ambiguous (or mixed) handedness have been involving children with CC anomalies associated with
suggested as two neuropathological dominance subtypes spina bifida meningomyelocele (SBM), however, no
caused by early brain damage preventing the establish- exaggerated REA could be demonstrated but rather a
ment of typical manual dominance (Soper & Satz, 1984). slight LEA depending on regional CC agenesis and spinal
However, although it is plausible that the high prevalence lesion level (Hannay et al., 2008).
698 Domellöf et al. Developmental Psychobiology
In the present article, we report two studies examining located in Roubaix and Villeneuve d’Ascq (France), and
the effects of intrauterine exposure to alcohol on func- in Leers-Nord (Belgium), to participate in the study. One
tional asymmetries. Firstly, sensory-motor preferences in girl lacked a full FAS diagnosis and was diagnosed as
a sample of children with FAS are assessed. Secondly, FASD. All children were assessed for sensory-motor
using a dichotic listening paradigm, language lateraliza- preferences. The mean age of the children was 8 years
tion is explored in a subsample of these children. 8 months (range 5–17 years).
The aim of Study 1 was to learn whether damage to the The children had been diagnosed as FAS on the basis of
developing brain due to alcohol exposure in children with self-reported drinking patterns during pregnancy and/or
FAS is functionally manifested as deviations from typical documented history of maternal alcohol consumption
right-sided preferences compared with TD children. during pregnancy. They all showed the characteristic
Based on previous observations of less evident right- facial dysmorphologies, except for the girl with
sided hand use preference in prenatally alcohol-exposed FASD. Testing was carried out at their rehabilitation
children, and the consistent finding of increased nonright- center and parental consent was granted before observa-
handedness in children with neurodevelopmental disor- tion. The experiment was conducted in accordance with
ders, it was hypothesized that children with FAS would the ethical standards specified in the 1964 Declaration of
display a decrease in right-sided preferences, in particular Helsinki.
with regard to handedness. The FAS children were compared with 76 TD children,
Expanding the characterization of functional laterali- 43 males and 33 females. The TD children were obtained
zation in children with FAS, Study 2 aimed to explore if from a large group of comparison children recruited and
prenatal alcohol-exposure results in deviations from observed in their regular school after granted permission
typical dichotic listening asymmetry compared with TD from the parents. For the present study, informed consent
children. Structural abnormalities of the CC are fre- was sent to the parents of children within the targeted age
quently observed in children with FAS/FASD (e.g., range. All children for whom parents gave their consent
Bookstein, Sampson, Connor, & Streissguth, 2002; were kept, allowing the largest and most unselected
Bookstein et al., 2007), including relative white matter sample as possible. The mean age of the TD children was
reduction (Sowell et al., 2001). At the microstructural 9 years 5 months (range 5–17 years). An ANOVA showed
level, one study using diffusion tensor imaging (DTI) has no significant age difference between the FAS group and
reported affected white-matter integrity of the CC in the TD group, F(1, 23) ¼ .01, p ¼ .91. The percentage of
young adults with FAS in terms of less fractional males and females was the same in both groups (56%
anisotropy and higher diffusion coefficients compared males).
with controls (Ma et al., 2005). Furthermore, another
study observed regional brain metabolic alterations in Preference Assessment. A 15-item questionnaire
adolescents and young adults with FASD relative to (Fagard & Corroyer, 2003) was used for the assessment
controls, including altered metabolism of the CC of sensory-motor preferences. The questionnaire included
(Fagerlund et al., 2006). Well in keeping with these the hand used for writing and for manual activities in
findings, subtle functional deficits in interhemispheric general (preferred hand to: brush teeth, throw ball, use
transfer and bimanual coordination (i.e., tasks sensitive to remote control, use hammer, use sports racket, use hair
a functional CC) have been observed at the behavioral brush, use spoon, take napkin to clean face, play marbles,
level (Roebuck-Spencer et al., 2004; Roebuck et al., cut with scissors, unscrew a lid, wind up a wind-up toy,
2002). Given the particular vulnerability of the CC in open a can, press orange in juice press), kick a ball
FAS/FASD, and presuming that dichotic listening asym- (preferred foot), look through a telescope (preferred eye),
metry relies on the functional status of the CC, we listen behind a door and listen at a telephone receiver
expected the children with FAS in the present study to (preferred ear). For each manual item the child had a
demonstrate atypical auditory lateralization during choice between ‘‘right,’’ ‘‘left,’’ or ‘‘one or the other’’ (i.e.,
dichotic listening. no preference). The older children were asked to answer
the questions directly, whereas the younger ones were
asked to do the real action. Whenever a younger child
hesitated between both hands and showed no clear
STUDY 1: SENSORY-MOTOR PREFERENCES
preference for either hand, we coded the response as
‘‘no preference.’’ The frequency of ‘‘no preference’’
Methods
found was between 0% and 5% for most items, although
Participants. Twenty-three children diagnosed with slightly higher for two items (12% for ‘‘take napkin to
FAS, 13 males and 10 females, were recruited in three clean face’’ and 13% for ‘‘press orange in juice press’’). A
rehabilitation centers specialized for FAS children, hand laterality index (HLI) for the manual activities was
calculated for each child according to the following medium (d ¼ .43). Even when calculated for the right-
formula: HLI ¼ [(Right Left)/(Right þ Left þ No pref- handers for writing only, the HLI was significantly lower
erence)] 100]. Thus, the HLI varies between 100 (i.e., in the FAS group (HLI ¼ 61.2) than in the TD group
completely right-handed) and 100 (i.e., completely left- (HLI ¼ 83.4), F(1, 76) ¼ 10.6, p < .01. The effect is large
handed). (d ¼ .74). Based on the overall HLI, we categorized the
children as right-handers (HLI > 0) or left-handers
(HLI < 0). A Chi-square test showed that the percentage
Statistical Analyses. Statistical analyses were carried out
difference between the two groups reached significance,
using Statistica for Windows version 6.1 software. In
w2(1) ¼ 3.7, p ¼ .05, characterized by less right-handers
addition to ANOVA and Chi-square analyses, indicating
among the children with FAS (69.6%) than among the TD
whether the true (population) effect differs from zero, we
children (86.8%). Thus, not only is there a larger
also checked the effect size for each analysis using
frequency of left-handers in the FAS group, but the
Cohen’s formula (1977). At this descriptive level, we
right-handers are also less right-handed than in the TD
considered the observed effect to be small, medium, or
group.
large if Cohen’s d was less than .35, between .35 and .65,
No significant differences between the FAS group and
or more than .65, respectively (Corroyer & Rouanet,
the TD group were obtained for any of the other laterality
1994). All post hoc comparisons were made with LSD
measures (footedness, eyedness, and earedness). Chi-
Fisher test, and for all analyses the preset alpha level
square analyses with regard to crossed preferences
was .05.
revealed that the percentage of children with a crossed
hand-foot preference was close in the two groups (25% of
the children with FAS, 15.7% of the TD children; p ¼ .33).
Results and Discussion
A larger difference was obtained for the percentage of
As shown in Table 1, 30.4% of the children with FAS used children with a crossed hand-eye preference (50% of the
the left hand for writing. Although not significantly so, children with FAS, 27.9% of the TD children), although
this percentage is well above the 18.4% observed in the failing to reach significance (p ¼ .06).
TD group, which itself is rather high but not uncommon As hypothesized, Study 1 showed that, in general,
when testing small populations of children (Fagard & children with FAS displayed an atypical manual lateral-
Corroyer, 2003; see Fagard, Dellatolas, & De Agostini, ization in terms of an increased nonright-handedness
2004, for a review). compared with TD children. As judged by the obtained
As shown by ANOVA analysis, the HLI calculated effect sizes, ranging from medium to large, the differences
from the 15-item manual laterality test was significantly found between the FAS and TD children regarding hand
lower in the FAS group (HLI ¼ 29.1) than in the TD group preference can be considered reliable. The excess of
(HLI ¼ 59.7), F(1, 97) ¼ 4.6, p < .05. The effect is nonright-handedness in the children with FAS is in
Table 1. Sensory-Motor Preferences in Children With FAS Compared With Typically Developing (TD) Children
Parameters FAS TD
n 23 76
Sex M: 56.5%, F: 43.5% M: 56.4%, F: 43.6%
Mean age 8.8 years (2.8) 9.5 years (2.5)
HLI (total)* 29.1 (66.4) 59.7 (57.7)
HLI (right-handers)** 61.2 (36.1) 83.4 (20.5)
Left (%) No Pref. (%) Right (%) Left (%) No Pref. (%) Right (%)
Hand (writing) 30.4 69.6 18.4 81.6
Categorization from HLI* 30.4 69.6 13.2 86.8
Foot (kicking a ball) 20.0 80.0 8.4 5.6 85.9
Eye (looking through hole) 38.1 4.8 57.1 32.9 2.9 64.3
Ear (listening through door) 25.0 5.0 70.0 36.3 4.3 59.4
Ear (telephone) 27.8 5.5 66.7 21.7 10.2 68.1
n, number; M, male; F, female; HLI, hand laterality index.

Significant group differences are highlighted in bold and standard deviations are presented in parenthesis.
*p < .05.
**p < .01.
agreement with findings of less consistent hand prefer- children for sensory-motor preferences and we could not
ence in previous research on behavioral laterality in ex- contact them a second time for various reasons (n ¼ 10).
prematurely born children (Marlow et al., 1989; O’Call- The 11 participating FAS children were compared with 14
aghan et al., 1993), and in children with developmental TD children observed in their regular school and selected
deviations due to early damage to the brain or innate so that the two groups would be equivalent for age, sex
genetic disorder (Cornish & McManus, 1996; Cornish ratio, and handedness. The TD group included ten males
et al., 1997; Gérard-Desplanches et al., 2006; Groen et al., (71.4%) and four females (mean age 8 years 7 months;
2008; Leconte & Fagard, 2006). range 4–16 years). The two groups were also equivalent
In a questionnaire study, Olsen (1995) noted a tendency for handedness in terms of writing hand (45% and 43%
for a higher frequency of left-handedness in 7- to 9-year- left-handers in the FAS group and the TD group,
old children exposed to moderate maternal alcohol respectively).
consumption during pregnancy. Two studies included
observations of handedness by a 7-item manual laterality Dichotic Listening Paradigm. A dichotic listening
test in children and adolescents with FAS or FASD paradigm using words as verbal stimulus pairs was
(Roebuck-Spencer et al., 2004; Roebuck et al., 2002). applied. The dichotic stimulus pairs were distributed
Using performance of five of seven items with the same through headphones connected to a laptop computer. Two
hand as an indicator of preference, both studies found that words (made up of two or three syllables) were presented
the great majority of the participants were right-handed simultaneously to the right and left ear of the child, who
and only a nonsignificant few were left-handed or showed was then asked to report what word she or he had heard.
a mixed preference. Considering these results, increased There were 24 trials (i.e., 24 pairs of words) given for each
left- or nonright-handedness does not seem to be a child. The words were chosen from a French database
consistent finding between previous studies. In part, this (‘‘Manulex’’) giving the frequency of words used in
may be explained by differences with respect to handed- reading books for children of different ages. The two
ness assessment procedures and diagnosis of the partic- words of each pair were matched for frequency. Twelve
ipating children (i.e., level of alcohol exposure in utero). pairs comprised monosyllabic words, whereas the other
According to the present results, a more specific analysis 12 comprised bisyllabic words. In each category (mono-
of manual preferences and higher doses of alcohol during and bisyllabic), half of the pairs comprised semantically
pregnancy (i.e., presumably underlying the full FAS related words (e.g., ‘‘chien–rat,’’ ‘‘dog’’ and ‘‘rat’’ in
diagnosis) may reveal more evident deviations from English) and the other half of the pairs comprised
typical right-handedness. The possibility of a manifes- nonsemantically related words (e.g., ‘‘poisson–chem-
tation of left- or nonright-handedness in prenatally ise,’’ ‘‘fish’’ and ‘‘shirt’’ in English). In addition, four pairs
alcohol-exposed children as reflecting a disturbed hemi- of words served for familiarization at the beginning of the
spheric organization associated with subtle neurotoxic session.
effects of alcohol to the developing brain has been Four lists, made of the same pairs, were used with a
suggested (London & Glick, 1988; Olsen, 1995; randomized order of presentation. The headphones were
Zimmerberg & Riley, 1988). The present findings support reversed after the first twelve pairs to ensure that a
this notion, but suggest that deviations in manual difference in ear advantage could not be due to the
preference in children with FAS are more prominently material. We counted the number of words which were
noted in a higher frequency of nonright-handedness than either not reported or reported with an error (e.g., ‘‘table’’
left-handedness. for ‘‘sable’’ in ‘‘chaise-sable,’’ or ‘‘chien’’ for ‘‘vache’’ in
‘‘singe-vache’’). For each child, a total number of
extinctions was calculated, defined as the total number
of words that the participant failed to perceive and repeat
STUDY 2: LANGUAGE LATERALIZATION
independent of the ear in which it was presented. To
analyze the ear advantage, we calculated a language
Methods
laterality index (LLI) from the difference between left-ear
Participants. Eleven of the 23 children with FAS and right-ear extinctions. When this index was positive,
participating in Study 1 also completed an assessment of the child was categorized as having a REA. When it was
language lateralization based on a dichotic listening task, negative, the child was categorized as having a LEA. For
eight males (72%) and three females (mean age 8 years an index of 0, there was no bias.
5 months; range 3–17 years). The 12 other children could
not participate in this assessment either because they Statistical Analyses. The same statistical analysis pro-
refused to cooperate (n ¼ 2), or because the dichotic cedure as for Study 1 was used. Any other test carried out
listening task was not devised at the time we first tested the is indicated in the subsequent text.
Results and Discussion different from zero by calculating a Student’s t-test for
matched samples between the observed values and
The FAS group and the TD group were matched for
theoretical values of zero. It proved significant,
handedness (writing). However, as for the larger cohort
t(13) ¼ 3.6, p < .01, and the effect is large (d ¼ 2). In
tested for handedness, ANOVA analysis signaled a
contrast, the mean LLI was negative for the FAS group,
significantly lower overall HLI of right-handers in the
and not significantly different from zero (see Fig. 2). As
FAS group (HLI ¼ 72.0) than in the TD group
shown in Table 2, the LLI tended to be more positive for
(HLI ¼ 95.5), F(1, 12) ¼ 9.0, p < .02. The effect is large
the right- than for the left-handers in the TD group.
(d ¼ 1.73).
However, an ANOVA performed for both the FAS group
A two-way ANOVA for group and handedness
and the TD group on the LLI as a function of handedness
(writing) on the total number of extinctions showed a
did not prove significant. Thus, we calculated an ANOVA
significant group difference with regard to this variable,
on the LLI as a function of group (FAS vs. TD) while
F(1, 21) ¼ 16.0, p < .01. The effect is large (d ¼ 1.75). As
pooling right- and left-handers, revealing a significant
illustrated in Figure 1, the difference was caused by the
group effect, F(1, 23) ¼ 15.8, p < .001. The effect is large
children with FAS having a higher total number of
(d ¼ 1.65).
extinctions (M ¼ 15.8, SD ¼ 7.7) compared with the total
The percentage of REA children (with a positive LLI)
number observed for the TD children (M ¼ 5.8, SD ¼ 4.9).
was much higher in the TD group (92.9%) than in the FAS
There was no significant difference between right- and
group (36.4%). A Chi-square calculated to test the
left-handers, and no group by handedness interaction on
difference in the distribution of REA children, LEA
the total number of extinctions. The number of extinctions
children and children with no bias between the two groups
was high for both ears for the FAS group (see Tab. 2).
showed the difference to be significant, w2(2) ¼ 9.1,
There were more extinctions for the right ear than for the
p < .02. Since half of the verbal stimulus pairs comprised
left, although not significantly so. In contrast, as revealed
semantically related words and the other half of the pairs
by a t-test for matched samples, the number of extinctions
nonsemantically related words, we checked whether the
was significantly higher for the left than for the right ear in
extinctions occurred with the same frequency for the two
the TD group, t(13) ¼ 3.6, p < .01. The effect is large
kinds of pairs. There was no overall tendency to report less
(d ¼ 2). An ANOVA calculated for the number of
semantically or nonsemantically related words, we found
extinctions as a function of group for the two ears
no significant difference between the two ears in that
independently showed a significant effect for group for the
respect, and no evident difference between the FAS and
right ear only, F(1, 23) ¼ 19.3, p < .001. The effect is large
TD groups.
(d ¼ 1.8).
According to expectations, children with FAS gen-
The mean LLI, calculated as the number of extinctions
erally showed a deviant pattern of auditory lateralization
for the right ear subtracted from the number of extinctions
during dichotic listening relative to TD children of
for the left ear, was positive for the TD group, indicating a
comparable age, sex and handedness. Large effects were
REA. We checked whether the LLI was significantly
revealed for all comparative analyses, proving the differ-
ences in explored dichotic parameters between the FAS
and TD children to be quite evident. The children with
FAS displayed more difficulties in perceiving and
repeating words, those administered to the right ear in
particular, and thus failed to show the typical pattern of a
REA. A slight majority (6 of 11) of the FAS children
exhibited a LEA, and one of them showed no advantage of
either ear. The finding of an atypical dichotic listening
asymmetry per se is in keeping with most previous studies
on language lateralization in clinical pediatric populations
using this method. Thus, early brain damage as a
consequence of prenatal alcohol exposure seems to have
an impact on cerebral lateralization of speech perception.
More specifically, the present findings are similar to those
obtained by Hannay et al. (2008) for children with SBM
with an absent callosal splenium in showing a slight LEA
FIGURE 1 Total number of extinctions during dichotic independent of handedness. The increased number of
listening as a function of group. Error bars represent the standard extinctions was mainly for words presented to the right ear
deviation. n, number. in children with FAS, but they also to a large extent failed
Table 2. Language Lateralization in Children With FAS Compared With Typically Developing (TD) Children of Comparable
Age, Sex, and Handedness
Parameters FAS TD
n 11 14
Sex M: 72.7%, F: 27.3% M: 71.4%, F: 28.6%
Mean age 8.5 years (4.4) 8.7 years (3.4)
Hand (writing) Left: 45.4%, right: 54.6% Left: 42.9%, right: 57.1%
HLI (right-handers)* 72.0 (21.0) 95.5 (6.6)
HLI (left-handers) 64.1 (33.4) 37.9 (39.1)
Total n of extinctions (right-handers) 14.8 (8.7) 7.1 (5.0)
Total n of extinctions (left-handers) 17.0 (7.1) 4.0 (4.4)
n of extinctions (left ear) 7.0 (4.7) 4.2 (3.4)
n of extinctions (right ear)** 8.8 (5.6) 1.7 (1.8)
LLI** 1.8 (7) 2.5 (2.6)
LLI (right-handers) 2.2 (6.8) 3.4 (2.9)
LLI (left-handers) 1.4 (8.1) 1.3 (1.6)
Children with REA* 36.4% (n ¼ 4) 92.9% (n ¼ 13)
Children with LEA* 54.5% (n ¼ 6) 7.1% (n ¼ 1)
Children with no bias* 9.1% (n ¼ 1) 0% (n ¼ 0)
n, number; M, male; F, female; HLI, hand laterality index; LLI, language laterality index; REA, right ear advantage; LEA, left ear advantage.
Significant group differences are highlighted in bold and standard deviations are presented in parenthesis.
*p < .05.
**p < .01.
to perceive words presented to the left ear. This pattern GENERAL DISCUSSION
does not suggest a greater involvement of the right
hemisphere for speech processing, but rather a reduced In the two presented studies on functional asymmetries in
lateralization in children with FAS as a consequence of children with FAS, we found evidence for increased
alcohol-induced prenatal brain damage. nonright-handedness and reduced or reversed (LEA)
dichotic listening asymmetry compared with TD children.
The respective findings are largely in keeping with
previous studies showing altered functional lateralization
in children with developmental disorders, and support the
assumption of atypical functional laterality as reflecting
an altered hemispheric organization due to early brain
injury.
In theorizing more specifically what underlying neural
anomalies may be associated with the findings of atypical
functional asymmetries in FAS, the present work is
hampered by the lack of brain imaging data. On a
speculative note, however, there are reasons to suggest
that the functional integrity of the CC may be implicated.
CC anomalies in humans have been found to result in a
changed organization of a wide range of lateralized
functions due to disrupted interhemispheric transfer
(Gazzaniga, 2000). In this context, the CC has been
suggested having an important role in coordination of
motor planning and control, with a bearing on both
bimanual and unimanual performance, and in auditory
FIGURE 2 Mean language laterality index for dichotic interhemispheric transfer. Furthermore, magnetic reso-
listening as a function of group. Error bars represent the standard nance imaging (MRI) studies have repeatedly found
deviation. LLI, language laterality index. Note: A positive LLI abnormalities in CC regions in children exposed prena-
indicates a right ear advantage (REA), a negative LLI indicates a tally to alcohol (Bookstein et al., 2002, 2007; Sowell et al.,
left ear advantage (LEA), and a zero LLI indicates no bias. 2001). Even in the absence of significant morphometric
differences, DTI and magnetic resonance spectroscopy anomalies as a consequence (Benavidez et al., 1999;
(MRS) studies have reported abnormal development of Hannay et al., 2008; Plessen et al., 2007). Such findings
white matter and altered metabolism in the CC in young are in keeping with both Kimura’s (1961, 1967)
adults with FAS/FASD, possibly associated with neuro- structural model and Kinsbourne’s (1970) attentional
behavioral deficits due to disrupted connectivity (Fager- model in suggesting that compromised functional integ-
lund et al., 2006; Ma et al., 2005). rity of the CC has an impact on dichotic listening
The finding of less evident handedness as opposed to performance. In the present study, the number of
increased left-handedness in children with FAS is extinctions for the right ear in children with FAS was
generally compatible with the ‘‘increased randomness markedly reduced compared with the TD children,
hypothesis’’ for children with developmental disorders indicating an evident deviation from typical auditory
suggested by Bishop (1990; see also Groen et al., 2008). lateralization. The number of extinctions for the left ear
Could callosal dysfunction play a role in such increased was also high in the children with FAS, similar to findings
randomness with regard to hand preference in children of reduced correct left ear responses in individuals with
prenatally exposed to alcohol? An evident excess of CC damage (Westerhausen & Hugdahl, 2008). It should
nonright-handedness is yet to be established in research be noted that, in the present study, the dichotic listening
devoted to infants and young children with agenesis of the paradigm was administered in a nonforced condition.
CC (ACC), although some deviations from a typical Thus, no conditions were presented with specific
development of manual asymmetry have been noted instruction to focus on either the right (‘‘forced-right’’)
(Moutard et al., 2003; Sacco, Moutard, & Fagard, 2006). or left (‘‘forced left’’) ear stimulus as a measure of
Increased nonright-handedness has also been confirmed modulating effects of attention and executive functions on
in older individuals with partial or total ACC (Sauerwein auditory lateralization (Hugdahl & Andersson, 1986).
& Lassonde, 1994), indicating a role of the CC in the Including forced conditions in the study of speech
development of hand preference. A recent pilot study perception asymmetries in children with FAS could add
explored visuo-manual performance in children with FAS important information with regard to presumed CC
by kinematic analysis of goal-directed arm-hand move- dysfunction and whether REA may be modified by such
ments and performance on the Purdue Pegboard test with ‘‘top-down’’ instructions in these children.
both right and left hand (Domellöf, Fagard, & Rönnqvist, In conclusion, although based on a limited number of
2008). Preliminary findings indicate deficits in goal- participants, the outcomes of the present study clearly
directed arm-hand movements and bimanual perform- indicate an atypical functional lateralization as a con-
ance, presumably supported by a functional CC (Gaz- sequence of intrauterine exposure to alcohol. However,
zaniga, 2000). It is also evident from the results that the further research on side-specific behavior in relation to
children with FAS displayed no side differences with prenatal alcohol exposure is warranted to corroborate and
regard to either kinematic parameters or number of extend the present findings. Such future efforts would
inserted pegs. Relating to the latter, one previous study has optimally include larger and more coherent study groups,
noted a similar lack of side differences in terms of number and access to complete background data. With regard to
of inserted pegs during peg board performance in the latter, all participating children with FAS in the present
preschool children with FAS (Janzen et al., 1995). study showed signs of intellectual problems, but we only
Furthermore, an impact of prenatal alcohol exposure on had record of confirmed general cognitive deficits for four
the development of the CC in rats has been associated with of them. Groen et al. (2008) found an association between
atypical paw preference (Moreland et al., 2002). Taken weaker or less steady hand preference and reduced
together, these outcomes are in line with a proposed role of language and memory ability in children with Down
underlying callosal dysfunction in the present findings of syndrome. It would be of interest to learn whether a
decreased manual asymmetry in children with FAS. similar relationship exists between the present observa-
As shown by the present findings related to dichotic tions of decreased functional asymmetries in children
listening, the children with FAS also displayed reduced with FAS and language impairment from the perspective
asymmetry for speech processing. The overall index for of hemispheric specialization. Finally, the addition of
language lateralization indicates a lack of REA and rather brain imaging techniques such as MRI and DTI to the
a tendency for LEA in these children. A similar decrease investigation is needed to further the understanding of
in REA for speech perception has been reported in functional lateralization following intrauterine alcohol
individuals with ACC (Di Stefano, Salvadori, Fiaschi, & exposure in relation to the integrity of brain regions such
Viti, 1998; Sacco, 2009; Sacco, Moutard, & Fagard, in as the CC at macro- and microstructural level. Following
preparation). Deviations from the typical REA pattern these recommendations could prove to be of both
have further been observed in children with developmen- theoretical and clinical value. Increased knowledge of
tal disorders or focal brain injury with CC lesions or functional asymmetries in children within the fetal
alcohol spectrum would promote the understanding of Corroyer, D., & Rouanet, H. (1994). Sur l’importance des effets
how lateralized behavior may relate to hemispheric et ses indicateurs dans l’analyse statistique des donnees [On
organization, regional dysmorphologies of the brain, the importance of effect size and indicators of effect size in
and developmental problems characterizing these disor- the statistical analysis of data]. Annee Psychologique, 94,
607–623.
ders. Such knowledge could also demonstrate to be of
Di Stefano, M., Salvadori, C., Fiaschi, E., & Viti, M. (1998).
benefit in the important work of finding characteristic Speech lateralisation in callosal agenesis assessed by the
markers for FAS/FASD at the behavioral and neurofunc- dichotic fused words test. Laterality, 3, 131–142.
tional level. Domellöf, E., Fagard, J., & Rönnqvist, L. (2008). Kinematic
measurement of goal-directed arm movements in children
with fetal alcohol syndrome: A preliminary study. Devel-
NOTES opmental Medicine & Child Neurology, 50 (Suppl. 114),
31–32.
This study was supported by grants from the Swedish Council for Fagard, J., & Corroyer, D. (2003). Using a continuous index of
Working Life and Social Research (2006-1577) to the first author laterality to determine how laterality is related to interhemi-
and the Swedish Research Council (421-2001-4589) to spheric transfer and bimanual coordination in children.
the second author. We thank the children and their families for Developmental Psychobiology, 43, 44–56.
taking part in this study. Fagard, J., Dellatolas, G., & De Agostini, M. (2004). Origine de
la latéralité manuelle. In: J. Fagard (Ed.), Droitiers/Gauchers:
Des asymétries dans tous les sens (pp. 155–164). Marseille:
Solal.
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Developmental Psychobiology - 2009 - Domellöf - Atypical Functional Lateralization in Children With Fetal Alcohol Syndrome

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Erik Domellöf1,2

INTRODUCTION largely localized and lateralized to the left cerebral

n, number; M, male; F, female; HLI, hand laterality index.

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