Brain development

Nature and nurture

 Outline

• Part 1: Brain development: A

macroscopic perspective
• Part 2: The development of the cerebral
cortex
• Part 3: Nature and nurture
 Part I
Brain development: A macroscopic
perspective
 Part I
Brain development: A macroscopic
perspective
See Chronology of Prenatal
Development
p. 110-111
3-4 Weeks
3-4 Weeks
Neural Groove
3-4 Weeks
Neural Groove

Neural Tube
3-4 Weeks
Neural Groove

Neural Tube

Neuroepitheliu
m
3-4 Weeks
Neural Groove

Neural Tube

Neuroepitheliu
m
Brain

Spinal Chord
5 to 6 Weeks
Nervous system begins to function
Hind-, mid-, and forebrain are now distinguishable
5 to 6 Weeks
5 to 6 Weeks
5 to 6 Weeks
Forebrain
5 to 6 Weeks
Forebrain

Telencephalon
5 to 6 Weeks
Forebrain

Telencephalon

Diencephalon
5 to 6 Weeks
Forebrain
5 to 6 Weeks
Forebrain

Midbrain
5 to 6 Weeks
Forebrain

Midbrain

Hindbrain
 •Neurons forming rapidly
•1000’s per minute

7 Weeks
 Division of the halves of the brain visible

14 Weeks
7 Weeks
 •Nerve cell generation complete
•Cortex beginning to wrinkle
•Myelinization

6 Months
14 Weeks
7 Weeks
 9 Months

5 Months
14 Weeks
7 Weeks
 Telencephalon: C-shaped growth
Cortex: Folding

9 Months

5 Months
14 Weeks
7 Weeks
 Telencephalon: C-shaped growth
Cortex: Folding

9 Months

5 Months
14 Weeks
7 Weeks
9 Months
9 Months
9 Months

Medulla

Hindbrain Pons

Cerebellum
9 Months

Medulla

Hindbrain Pons

Cerebellum
9 Months

Medulla

Hindbrain Pons

Cerebellum
9 Months

Medulla

Hindbrain Pons

Cerebellum
9 Months Controls respiration, digestion, circulation,
& fine motor control

Medulla

Hindbrain Pons

Cerebellum
9 Months

Midbrain
9 Months
Basic auditory and visual processing

Midbrain
9 Months

Thalamus
Diencephalon
Hypothalamus
9 Months
Sensory relay station
Long-term memory
Intersection of CNS and hormone system

Thalamus
Diencephalon
Hippocampus

Hypothalamus
9 Months

Telencephalon

2 Cerebral hemispheres

Forms a “cap” over inner

brain structures
9 Months

Cross-sectional view
9 Months

Cerebral
Hemispheres

Cross-sectional view
9 Months

Cerebral
Hemispheres

Thalamus

Hypothalamus

Cross-sectional view Hippocampus

9 Months As the telencephalon
develops, it connects both
with itself, and with
the diencephalon

Cross-sectional view
9 Months As the telencephalon
develops, it connects both
with itself, and with
the diencephalon

Corpus Callosum

Internal Capsule

Cross-sectional view
9 Months

Hippocampus
Telencephalon
9 Months Thin layer of cells covering
both hemispheres

Telencephalon Cortex
Cortex
High-level visual processing

Visual Cortex
Cortex Auditory & visual processing
Receptive language

Visual Cortex

Temporal Cortex
Cortex Sensory integration
Visual-motor processing

Visual Cortex

Temporal Cortex

Parietal Cortex
Cortex Higher-level cognition
Motor control
Expressive language

Visual Cortex

Temporal Cortex

Parietal Cortex

Frontal Cortex
Cortical Development

Begins prenatally

Continues into late

adolescence
II: The development of the
cerebral cortex
A microscopic view
 Development of the Cortex

• 2 types of cells:
• Neurons
• Glial cells
 Development of the Cortex

• 2 types of cells:
• Neurons
• Glial cells
 Development of the Cortex

• 2 types of cells: Dendrite

• Neurons
• Glial cells
 Development of the Cortex

• 2 types of cells: Dendrite

• Neurons Cell body
• Glial cells
 Development of the Cortex

• 2 types of cells: Dendrite

• Neurons Cell body
• Glial cells
Axon
 Development of the Cortex

• 2 types of cells: Dendrite

• Neurons Cell body
• Glial cells
Axon

Synapse
 Development of the Cortex

• 2 types of cells: Dendrite

• Neurons Cell body
• Glial cells
Axon

Synapse

Transmit information through the brain

 Development of the Cortex

• 2 types of cells:
• Neurons
• Glial cells
Outnumber neurons 10:1
Nourish, repair, & mylenate neurons
Crucial for development
 Development of the Cortex

• 2 types of cells:
• Neurons
• Glial cells
Outnumber neurons 10:1
Nourish, repair, & myelinate neurons
Crucial for development
 Development of the Cortex

• 2 types of cells:
• Neurons
• Glial cells
Outnumber neurons 10:1
Nourish, repair, & myelinate neurons
Crucial for development
Eg. Oligodendroglia
 Development of the Cortex

• 2 types of cells:
• Neurons
• Glial cells
Outnumber neurons 10:1
Nourish, repair, & myelinate neurons
Crucial for development
 8 stages of cortical development
1. Neural proliferation
2. Neural migration
3. Neural differentiation
4. Axonal growth
5. Dendritic growth
6. Synaptogenesis
7. Myelination
8. Neuronal death
 1. Neural
proliferation
• Begins with neural tube
closure
 1. Neural
proliferation
• Begins with neural tube
closure
 1. Neural
proliferation
• Begins with neural tube
closure
• New cells born in
ventricular layer
 1. Neural
proliferation
• Begins with neural tube
closure
• New cells born in
ventricular layer
• 1 mother cell produces ≈
10,000 daughter cells
 1. Neural
proliferation
• Begins with neural tube
closure
• New cells born in
ventricular layer
• 1 mother cell produces ≈
10,000 daughter cells
• All neurons (100 billion in
total) are produced pre-
natally
 1. Neural
proliferation
• Begins with neural tube closure
• New cells born in ventricular
layer
• 1 mother cell produces ≈
10,000 daughter cells
• All neurons (100 billion in
total) are produced pre-natally
• Rate of proliferation extremely
high; thousands/minute
 2: Cellular
migration
• Non-dividing cells
migrate from
ventricular layer
 2: Cellular
migration
• Non-dividing cells
migrate from
ventricular layer
• Creates a radial inside-
out pattern of
development
 2: Cellular
migration
• Non-dividing cells
migrate from
ventricular layer
• Creates a radial inside-
out pattern of
development
• Importance of radial
glial cells
 2: Cellular
migration
• Non-dividing cells
migrate from
ventricular layer
• Creates a radial inside-
out pattern of
development
• Importance of radial
glial cells
 3. Cellular
differentiation
• Migrating cells
structurally and
functionally immature
 3. Cellular
differentiation
• Migrating cells
structurally and
functionally immature
• Once new cells reach
their destination,
particular genes are
turned growth of
axons, dendrites, and
synapses
 4. Axonal growth

• Growth occurs at a growth cone

 4. Axonal growth

• Growth occurs at a growth cone

Growth cone
 4. Axonal growth
• Growth occurs at a growth cone
• Axons have specific targets
• Targets often enormous distances away
• Some axons extend a distance that is 40,000
times the width of the cell body it is attached
to
• Finding targets ?  chemical & electrical
gradients, multiple branches
 5. Dendritic growth
• Usually begins after migration
• Slow
• Occurs at a growth cone
• Begins prenatally, but continues postnatally
• Overproduction of branches in development
and resultant pruning
• Remaining dendrites continue to branch and
lengthen
 6.
Synaptogenesis
• Takes place as dendrites
and axons grow
• Involves the linking
together of the billions of
neurons of the brain
 6.
Synaptogenesis
• Takes place as dendrites and
axons grow
• Involves the linking together
of the billions of neurons of
the brain
• 1 neuron makes up to 1000
synapses with other neurons
• Neurotransmitters and
receptors also required
 Overproliferation and pruning

• The number of synapses reaches a

maximum at about 2 years of age
• After this, pruning begins
• By 16, only half of the original synapses
remain
 7:
Myelinization
• The process whereby glial cells wrap
themselves around axons
 7:
Myelinization
• The process whereby glial cells wrap
themselves around axons
• Increases the speed of neural conduction
 7:
Myelinization
• The process whereby glial cells wrap
themselves around axons
• Increases the speed of conduction
• Begins before birth in primary motor and
sensory areas
• Continues into adolescence in certain
brain regions (e.g., frontal lobes)
 8: Neuronal death

• As many as 50% of neurons created in

the first 7 months of life die
• Structure of the brain is a product of
sculpting as much as growth
III: Nature and nurture in brain
development
 III: Nature versus nurture
• The adult brain consists of approximately 100
billion (surviving) neurons that make trillions
of synaptic links
• Functionally highly organized, supporting
various perceptual, cognitive and behavioural
processes
• Perhaps the most complex living system we
know
 Question
• Of all the information that is required to
assemble a brain, how much is stored in the
genes?
• Nature view: argues that most of the
information is stored in the genes
• Nurture view: brain is structurally and
functionally underspecified by the genes 
emerges probabilistically over the course of
development
 Nature View
• (1) Not much is left to chance
 Nature View
• (1) Not much is left to chance
• (2) Brain a collection of genetically-specified
modules
 Nature View
• (1) Not much is left to chance
• (2) Brain a collection of genetically-specified
modules
• (3) Each module processes a specific kind of
information & works independently of other
modules
 Nature View
• (1) Not much is left to chance
• (2) Brain a collection of genetically-specified
modules
• (3) Each module processes a specific kind of
information & works independently of other
modules
• (4) In evolution: modules get added to the
“collection”
 Nature View
• (1) Not much is left to chance
• (2)“The
Braingrammar
a collection of genetically-specified
genes would be stretches modules
of
• (3) Each module processes
DNA that code afor
specific kind of
proteins…
information
that guide,& attract,
works independently
or glue neuronsof other modules
together
into
• (4) In evolution: networks
modules that…to the “collection”
get added
• (5) Inare necessarygenes
development: to compute
that codethe
forsolution
modules are
expressedtoand
some grammatical
modules problem.”
develop according to these
instructions
 The nature view: Evidence
• Neurogenesis
• Neuroblasts give rise to a
limited number of
daughter cells
• Cells have a genetically
mediated memory that
allows them to remember
how many times they
have divided
 The nature view: Evidence
• Genetics and migration
• Mutant or “knock-out”
mice
 The nature view: Evidence
• Genetics and migration
• Mutant or “knock-out”
mice
• Cannot produce a class of
proteins called cell
adhesion molecules
(CAM’s)
• Migration is disrupted
because cells cannot attach
to and migrate along glia
 The nature view: Evidence
• Growth of dendrites
and axons
• Undeveloped neuron
needs to establish basic
“polarity:” which end
is which?
 The nature view: Evidence
• Growth of dendrites
and axons
• Undeveloped neuron
needs to establish basic
“polarity:” which end
is which?
• Involves specific
proteins
 The nature view: Evidence
• Growth of dendrites
and axons
• Undeveloped neuron
needs to establish basic
“polarity:” which end
is which?
• Involves specific
proteins
 The nature view: Evidence
• Growth of dendrites and
axons
• Undeveloped neuron needs
to establish basic
“polarity:” which end is
which?
• Involves specific proteins
• Axons: Affords a
sensitivity to chemical
signals emitted by targets
 The nature view: Evidence
• Growth of dendrites and
axons
• Undeveloped neuron needs
to establish basic
“polarity:” which end is
which?
• Involves specific proteins
• Axons: Affords a
sensitivity to chemical
signals emitted by targets
 The nature view: Evidence
• Formation of synapses
• Knock-out mice
 The nature view: Evidence
• Formation of synapses
• Knock-out mice
• Staggerer
• Neurons in the cerebellum make contact, but
receptor surface does not develop
• Thus, a single gene deletion can interfere with
the formation of synapses in the cerebellum
 The nature view: Evidence
• Cell death
• Cells seem to possess death genes
• When expressed, enzymes are produced that
effectively cut-up the DNA, and kill the cell
• Similar mechanism may control the timing of
neuronal death
 Nurture view
• (1) Brain organization is emergent and
probabilistic not pre-determined
• (2) Genes provide only a broad outline of the
ultimate structural and functional organization
of the brain
• (3) Organization emerges in development
through over-production of structure and
competition for survival
•Gerald Edelman: Neural Darwinism
•OverproliferationNurture view
of structures + sensory experience
produce Darwinian-like selection pressures in
development
• (1) Brain organization is emergent and
•Structures that prove useful in development win the
probabilistic not pre-determined
competition for survival
• (2)rest
•The Genes provide
are cast off only a broad outline of the
ultimate structural and functional organization
of the brain
• (3) Organization emerges in development
through over-production of structure and
competition for survival
The “nurture” view:
Evidence
• Does experience affect developing structures
and functions?
• Is the pruning of brain structures systematic?
• Do developing brain regions competitively
interact?
 The “nurture” view: Hubel &
Evidence Weisel
• Raised kittens but deprived them of visual
stimulation to both eyes (binocular
deprivation)
• No abnormality in the retina or thalamus
 The “nurture” view: Hubel &
Evidence Weisel
• Raised kittens but deprived them of visual stimulation
to both eyes (binocular deprivation)
• No abnormality in the retina or thalamus
• Gross abnormality in visual cortex
• Disrupted protein production caused fewer and shorter
dendrite to develop, as well as 70% fewer synapses
• Effects only occur early in development, but persist
into adulthood
• Example: Surgery on congenital cataracts in adult
humans
 The “nurture” view: Hubel &
Evidence Weisel
• Early monocular deprivation
• After restoring stimulation, vision in this eye is
severely impaired
 The “nurture” view: Hubel &
Evidence Weisel
• Early monocular deprivation
• After restoring stimulation, vision in this eye is
severely impaired
• One effect: Monocular deprivation disrupted
the establishment of ocular dominance
columns
The “nurture” view: Development of
mammalian
Evidence visual system
Adult structure

Cortex

Thalamus

Eyes/Retinas
The “nurture” view: Development of
mammalian
Evidence visual system
Adult structure

Cortex

Thalamus

Eyes/Retinas
 The “nurture” view: Hubel &
Evidence Weisel
• Early monocular deprivation
• After restoring stimulation, vision in this eye is
severely impaired
• Sensory input competes for available cortex
• With input from one eye eliminated, no
competition
• Therefore, input from uncovered eye assumes
control of available visual cortex and disrupts the
establishment of ocular dominance columns
 The “nurture” view: Hubel &
Evidence Weisel
• Early monocular deprivation
• After restoring stimulation, vision in this eye is
severely impaired
• Sensory input competes for available cortex
• With input from one eye eliminated, no
Findings point to the importance of
competition
stimulation from the environment
• Therefore, input from uncovered eye assumes
control of available visual cortex and disrupts the
establishment of ocular dominance columns
 The “nurture” view: Kratz, Spear, &
Evidence Smith
• Early monocular deprivation
• After restoring stimulation, vision in this eye is
severely impaired

Hubel &
Weise
 The “nurture” view: Kratz, Spear, &
Evidence Smith
• Early monocular deprivation
• After restoring stimulation, vision in this eye is
severely impaired
• A second effect: Residual function of the
deprived eye competitively inhibited by strong
eye
 The “nurture” view: Kratz, Spear, &
Evidence Smith
• Early monocular deprivation
• After restoring stimulation, vision in this eye is
severely impaired
• A second effect: Residual function of the
deprived eye competitively inhibited by strong
eye
• Deprived one of experience and then removed
strong eye
 The “nurture” view: Kratz, Spear, &
Evidence Smith
• Early monocular deprivation
• After restoring stimulation, vision in this eye is
severely impaired
• A second effect: Residual function of the deprived
eye competitively inhibited by strong eye
• Deprived one of experience and then removed
strong eye
• Prior to surgery, stimulation of deprived eye
elicited activity in only 6% of cortical neurons
 The “nurture” view: Kratz, Spear, &
Evidence Smith
• Early monocular deprivation
• After restoring stimulation, vision in this eye is
severely impaired
• A second effect: Residual function of the deprived eye
competitively inhibited by strong eye
• Deprived one of experience and then removed strong
eye
• Prior to surgery, stimulation of deprived eye elicited
activity in only 6% of cortical neurons: After
surgery 31%
 The “nurture” view: Kratz, Spear, &
Evidence Smith
• Early monocular deprivation
• After restoring stimulation, vision in this eye is
severely impaired
• A second effect: Residual function of the deprived eye
competitively inhibited by normal eye
• Deprived Findings point to the
one of experience andimportance
then removed ofnormal
eye competitive interaction between
developing
• Prior to surgery, brain
stimulation regionseye elicited
of deprived
activity in only 6% of cortical neurons: After
surgery 31%
 Impoverish
The “nurture” view:
ed
Evidence
Environme
• Animal raised in impoverished environments
have brains that are 10 to 20% smallernts
than
animal raised in normal environments. Why?
 Impoverish
The “nurture” view:
ed
Evidence
Environme
• Animal raised in impoverished environments
have brains that are 10 to 20% smallernts
than
animal raised in normal environments. Why?
• Decreased glial cell density
• Fewer dendritic spines
• Fewer synapses
• Smaller synapses
 The “nurture” view:
Evidence
Sur
• Cortical surgery
• Severed connection between optic nerve and
the occipital cortex as well as the connection
between auditory nerve and auditory cortex
• Reconnected optic nerve to auditory cortex
• Animals developed functionally adequate
vision
 The “nurture” view:
Evidence
• Daphnia: A crustacean; easily cloned
• Simple nervous system consisting of several
hundred neurons
• Connection patterns can be studied directly
• Genetically identical individuals show
different patterns of neuronal connectivity
 Nurture view: Summary
• Order in the brain is not completely specified
by the genes
• Instead, structures and functions emerge
probabilistically in development through the
combined influence of initial over-production
of structure, neural competition, and
experience
 Conclusions
• Genes are a critical source of guidance for
brain development
• Nevertheless, there is abundant shaping and
fine-tuning of brain structure and function with
sensory-experience
 4: Studying human brain
development
• Structural and functional change
• How are these changes investigated & what is
known?
 4: Studying human brain
development
Structural change: Methods

Magnetic resonance imaging

 4: Studying human brain
development
Structural change: Methods

• T1-weighted image
• Segmentation
• Measure thickness
or volume in various
regions
 4: Studying human brain
development
Structural change: What do we know?

• Total volume increases

• White matter increases

Girls Boys

Giedd et al, Nature Neuroscience, 1999

 4: Studying human brain
development
Structural change: What do we know?

• Total volume increases

• White matter increases
• Grey matter increases
and decreases
• Heterochronic change

Girls Boys Giedd et al, Nature Neuroscience, 1999

 4: Studying human brain
development
Structural change: What do we know?

• Total volume increases

• White matter increases
• Grey matter increases
and decreases
• Heterochronic change

Growth Shrinkage

Sowell, J Neuroscience, 2005

 4: Studying human brain
development
Functional change: Methods – ERP’s

• Evoked response potentials

• Scalp-measured voltages
• Many trials averaged
• Waveforms
 4: Studying human brain
development
Functional change: Methods – ERP’s

• Advantages
• Use with infants
• Inexpensive
• Relatively non-invasive
• Excellent temporal resolution
• Disadvantages
• Poor spatial resolution
 4: Studying human brain
development
Functional change: What do we know?

• N170 greater for inverted faces

• Faces special
• Development?
• 12-month-olds show N170 effect
• 6-month-olds do not

de Haan et al, J Cog Neuroscience, 2002

 4: Studying human brain
development
Functional change: What do we know?

• N170 greater for inverted faces

• Faces
ERP’s can reveal special
important changes in brain
• Development?
functioning in infancy and
• 12-month-olds
early childhood. show N170 effect
• 6-month-olds do not

de Haan et al, J Cog Neuroscience, 2002

 4: Studying human brain
development
Functional change: Methods -- fMRI

• T2*-weighted image
• Blood-oxygenation
dependent response
(BOLD)
 4: Studying human brain
development
Functional change: Methods -- fMRI

• T2*-weighted image
• Blood-oxygenation
dependent response
(BOLD)
• Eg. Block design

Time
 4: Studying human brain
development
Functional change: Methods -- fMRI

• Advantages
• Excellent spatial resolution
• Disadvantages
• Expensive
• Motion sensitive
• Limited viability with very young children
 4: Studying human brain
development
Functional change: What do we know?

shape
12-year-olds & adults
color

Switch Repeat Switch Repeat

18s 36s 18s 36s 18s 36s 18s 36s 18s

Time

Morton & Ansari, 2007

 4: Studying human brain
development
Functional change: What do we know?

All participants

Switch > Repeat

• Frontal cortex
• Parietal cortex

Morton & Ansari, 2007

 4: Studying human brain
development
Functional change: What do we know?

0.5 Switch Repeat

0.45
0.4
0.35
0.3
0.25

Age x Trial Type interaction reveals

0.2
0.15

development changes
0.1
0.05
0
Children Adults

R Parietal cortex
Switch > Repeat
Only adults
Morton & Ansari, 2007
 4: Studying human brain
development
Functional change: What do we know?

• Challenges
• What does an Age x TrialType interaction reveal?
 4: Studying human brain
development
Functional change: What do we know?

• Challenges
• What does an Age x TrialType interaction reveal?
• Need to consider behavioral performance
• If perform similarly, could suggest developmental
change
• If perform differently, possible that differences in
brain activity reflect difference in performance not
age
 Brain Development Conclusions
• (1) Brain changes throughout development
both structurally and functionally
• (2) Developmental changes occur through and
interaction of genes and experience.