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 1000s 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: Neurons Glial cells
Dendrite

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. 2. 3. 4. 5. 6. 7. 8. Neural proliferation Neural migration Neural differentiation Axonal growth Dendritic growth Synaptogenesis Myelination 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 prenatally

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 prenatally Rate of proliferation

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

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 &

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

 Takes place as dendrites and axons grow Involves the linking together of the billions of neurons of the brain

6. Synaptogenes is

 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

6. Synaptogenes is

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 geneticallyspecified modules

Nature View
(1) Not much is left to chance (2) Brain a collection of geneticallyspecified 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 geneticallyspecified 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 The grammar genes of genetically (2) Brain a collectionwould be stretches of DNA that code specified modules for proteins that guide, attract, or glue neurons together (3) Each module processes a specific kind into networks that of information & works independently of are necessary to compute the solution other modules grammatical problem. to some (4) In evolution: modules get added to the collection (5) In development: genes that code for modules are expressed and modules

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 (CAMs) Migration is disrupted because cells cannot

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

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

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 Overproliferation of structures + sensory experience Nurture view produce Darwinian-like selection pressures in development organization is emergent and (1) Brain Structures that prove useful in development win the probabilistic not pre-determined competition for survival (2) Genes provide only a broad outline of The rest are cast off

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: Evidence

Hubel & Weisel

Raised kittens but deprived them of visual stimulation to both eyes (binocular deprivation) No abnormality in the retina or thalamus

The nurture view: Evidence

Hubel & 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

The nurture view: Evidence

Hubel & Weisel

Early monocular deprivation After restoring stimulation, vision in this eye is severely impaired

The nurture view: Evidence

Hubel & 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: Evidence

Adult structure

Development of mammalian visual system

Cortex

Thalamus

Eyes/Retinas

The nurture view: Evidence

Adult structure

Development of mammalian visual system

Cortex

Thalamus

Eyes/Retinas

The nurture view: Evidence

Hubel & 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

The nurture view: Evidence

Hubel & Weisel

Early monocular deprivation After restoring stimulation, vision in this eye is severely impaired Sensory input competes for available cortex Findings point to the importance of With input from one eye eliminated, no stimulation from the environment competition Therefore, input from uncovered eye assumes control of available visual cortex and disrupts the establishment of ocular

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: Evidence

Kratz, Spear, & 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

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

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 Findings point to the importance of normal competitive interaction between eye developing brain regions Deprived one of experience and then removed normal eye Prior to surgery, stimulation of deprived eye elicited activity in only 6% of cortical

Impoveris The nurture view: hed Evidence Environm Animal raised in impoverished ents environments have brains that are 10 to
20% smaller than animal raised in normal environments. Why?

Impoveris The nurture view: hed Evidence Environm Animal raised in impoverished ents environments have brains that are 10 to
20% smaller 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 overproduction 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 ERPs Evoked response potentials Scalp-measured voltages Many trials averaged Waveforms

4: Studying human brain development

Functional change: Methods ERPs 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 special ERPs can reveal 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 color 12-year-olds & adults

Switch
18s 36s 18s

Repeat
36s 18s

Switch
36s 18s

Repeat
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 0.45 0.4 0.35 0.3 0.25 Switch Repeat

Age x Trial Type interaction reveals development changes

0.2 0.1 0.15 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.