The Developing Brain: Experience and Development

Charles A. Nelson Institute of Child Development Department of Pediatrics University of Minnesota

Human Brain Development Embryogenesis

• Following conception, zygote rapidly divides, forming ball of cells (blastocyst)

• About 1 week post conception, blastocyst divides into inner and outer layer

• Outer layer becomes cord, sac, placenta; inner becomes embryo

1 Embryo, Umbilical Cord, Amniotic Sac Embryogeneis, Con’t

Placenta • Between 1st and 2nd week post conception, embryo divides into 3 layers

embryo • Inner (endoderm) becomes organs, etc. • Middle (mesoderm) becomes muscle/skeletal Amniotic sac system • Outer (ectoderm) becomes outer coverings PLUS nervous system Umbilical cord

Neurulation Neural Tube Formation

• Days 18-24: – dorsal region of ectodermal layer of embryo thickens and forms neural plate – plate forms a groove, followed by formation of neural tube – tube closes at rostral and caudal ends – cells trapped inside tube form CNS; those outside tube form ANS.

2 Errors in Neurulation Spina Bifida

• Neural Tube Defects, including – Spina bifida (“open spine”) – Anencephaly (lack of cortex) – (next slides are graphic)

3 Anencephaly (note: there are multiple anomalies here in addition to anencephaly)

• Precursors to and supportive tissue (glia) form; this continues postnatally.

• Regarding neurogenesis of neurons, previously believed was complete at birth. Now know there is postnatal neurogenesis through at least middle age in dentate gyrus (region of hippocampus), and possibly in other areas.

Neurogenesis, Con’t Cell Migration

• Postnatal neurogenesis influenced by experience (positive = ↑new neurons and negative = ↓ new • Following neural tube closure, there is proliferation of neurons). a single layer of epithelial cells that line the tube.

• Recent report (Gould et al., Sept., 2001) suggests • Cells are connected to each other and in some these new cells are short-lived (substantial decline by cases, to radial glial fibers. 9 weeks). • Expansion occurs between layers, and neuroblasts climb onto fibers and migrate in radial direction. Nevertheless… • Cortex forms in inside-out pattern, with earliest of 6 • Believe new cells involved in learning and memory layers formed first, followed by each subsequent layer.

4 Cell Migration in Ferret Brain Errors in Cell Migration (Courtesy of Susan McConnell, Ph.D.)

• Schizophrenia (?)

• Agenesis of the corpus callosum

Migrating • Prematurity may be example of incomplete cell migration, depending on degree

5 The Preterm Brain Differentiation and Synaptogenesis (approximately 25 weeks gestation)

Temporal • Once cells reach target destination, following Lobe events may occur: Frontal Lobe – cell body develops or – cell dies

• If cell body develops: – processes (axons, dendrites) form – synapses form Note lack of gyri and sulci

6 Synaptogenesis

• massive overproduction of synapses

• Newborn brain has many more synapses than adult brain.

• Overproduction followed by retraction to adult numbers of synapses.

• In human, rate of retraction varies from brain area to brain area.

Overproduction of Synapses Retraction of Synapses:

• In visual cortex, is burst of synapses 3 – 4 postnatal months, with peak occurring 4 months. • In visual and auditory cortices, adult levels of • Primary auditory cortex (Heschl’s gyrus) follows synapses obtained in early childhood (2-6 similar timetable. years). • In area involved in receptive language (angular gyrus) and in area involved in language production (Broca’s area) there are slightly fewer synapses at 3 • In middle frontal gyrus, adult levels are not – 4 months than in primary auditory cortex reached until mid- to late adolescence. (i.e.,these areas lag slightly behind basic auditory areas). • In middle frontal gyrus maximum density not reached until 12 months.

7 Summary of Synaptogenesis

• Synapse overproduction occurs early in life, whereas synapses elimination occurs much later, and varies greatly by area (e.g., 6 years for visual cortex, 15+ years for prefrontal cortex).

Why Overproduce Synapses? Myelination

• captures experience, thereby • Myelin is lipid/protein substance pruning/cultivating synapses • In CNS, myelin produced by oligodendroglia • can be adaptive for the organism (period of • In ANS, myelin produced by Schwann cells opportunity) but • Myelin wraps itself around axon as form of • can also be maladaptive (period of insulation vulnerability), depending on of • Myelin speeds conduction velocity experience • “Plasticity cuts both ways” (J. McVicker Hunt)

8 Myelination During Prenatal and Myelination, Con’t Early Postnatal Period

• Myelination has implications for both serial • System: and parallel processing (e.g., multitasking). – motor roots followed by • Myelination occurs in “waves” beginning – sensory roots, followed by – somesthetic (touch) cortex, prenatally and ending in young adulthood – primary visual (seeing) and then (and in some regions, as “late” as middle – primary auditory (hearing) cortex. age). • First postnatal year: • Historically stained for myelin in postmortem – regions of brain stem, tissue; now use structural Magnetic – cerebellum and Resonance Imaging (MRI) and Diffusion – splenium of corpus callosum all begin Tensor Imaging (DTI). • By 1 year all regions of corpus callosum underway

Myelination During Childhood to Adolescent Period

Developmental Event Timeline Overview of Developmental Event Neuralation 18-24 prenatal days Cells differentiate into one of three layers: endoderm, mesoderm and ectoderm, which • Through pre-adolescent period, observe then form the various organs in the body. The neural tube (from which the CNS is derived) develops from the ectoderm cells; the neural crest (from which the ANS is derived) lies between the ectodermal wall and increase in gray matter volume (more the neural tube. Neuronal Migration 6-24 prenatal weeks Neurons migrate at the ventricular zone along radial glial cells to the . dendtritic spines?) and decrease in white; this The Neurons migrate in an inside-out manner, with later generations of cells migrating through previously developed cells. reverses in adolescence, with decrease in The cortex develops into 6 layers Synaptogenesis 3rd trimester - Neurons migrate into the cortical plate and extend apical and basilar dendrites. adolescence Chemical signals guide the developing dendrites toward their final location, where gray and increase in white (retraction of synapses are formed with projections from subcortical structures. These connections are strengthened through neuronal activity, and connections with very synapses, increase in connectivity?). little activity are pruned. Postnatal Neurogenesis Birth - Adulthood The development of new cells in several brain regions, including: - dentate gyrus of the hippocampus – Changes of note: parietal, temporal, and - olfactory bulb - possibly cingulate gyrus; regions of parietal cortex occipital lobes show relatively little change, Myelination 3rd trimester – middle Neurons are enclosed in a myelin sheath, resulting in an increased speed of action whereas frontal lobe show large changes. age potentials. Gyrification 3rd trimester – adulthood The smooth tissue of the brain folds to form gyri and sulci.

Structural Development of the Birth – late adulthood The prefrontal cortex is the last structure to undergo gyrification during uterine life. Prefrontal Cortex The synaptic density reaches its peak at 12 months, however, myelination of this structure continues into adulthood Neurochemical Development Uterine life - All major neurotransmitter systems undergo initial development during uterine life and are of the Prefrontal Cortex adolescence present at birth. Although it is not well studied in humans, it is thought that most neurotransmitter systems do not reach full maturity until adulthood.

9 Neural Plasticity: Two Types of Plasticity Some General Principles and Terms (from William Greenough )

Experience-expectant • Development based the expectation that appropriate • Recovery of Function: cortical function environments will provide information needed to returned following injury (e.g., return of select appropriate subsets of synaptic connections. language following stroke) Common to all members of the species (examples: visual development; language; initial formation of • Sparing: lack of loss in performance following attachment) brain damage (e.g., no impairment in Experience-dependent language despite a perinatal stroke that • Unique to each individual, it most likely involves destroys left frontal cortex). active formation of new synaptic connections throughout the life span based on each person’s • Neuronal Plasticity: hypothesized to underlie interaction with his/her environment (example: recovery of function. learning; quality of attachment?).

Examples of Developmental Plasticity Examples of Developmental Plasticity, Con't

• The development of normal vision depends • Prenatal exposure to teratogens alters brain on access to normal visual input during a development sensitive period of development. • Prenatal exposure to stress can cause longlasting neurobehavioral deficits in rats and monkeys • Similarly, correcting certain visual impairments (e.g., strabismus) must occur during this sensitive period.

• Development of speech perception depends on exposure to normal speech sounds during a sensitive period of development.

10 Conclusions about Examples of Developmental Plasticity, Con't Developmental Plasticity

• Memory circuits are reorganized following • Collectively, in most cases perinatal injury to the hippocampus, resulting in sensory/perceptual development, and spared semantic memory (but impaired episodic possibly some aspects of cognitive and memory). linguistic development, proceed normally if such systems are “set” correctly during a • Focal brain lesions in in language-related areas sensitive period of development. that occur pre- or perinatally appear to have little effect on language. • But also: quality of environmental input following this influences the quality and • Correcting some language learning disorders can trajectory of subsequent development. occur late in childhood with appropriate and -based intensive intervention.

Examples of Adult Plasticity

• Long history of housing rats (generally adult rats) in complex environments (Donald Hebb; Marian Diamond)

• Generally, such rearing leads to – Better performance on rat “IQ” tests – more neural connections, and a thicker cortical expanse in general

11 Examples of Adult Plasticity, Con’t Examples of Adult Plasticity, Con’t

Motor and Somatosensory Systems Motor and Somoatosensory Systems, Con’t • Effects of deaffrentation: Silver Spring monkeys • Reorganization of somatosensory cortex in showed reorganization of somatosensory cortex years after limb deaffrentation. stringed instrument players • Effects of amputations on human: Areas in the brain • Neural representation of 1st vs. 2nd language representing amputated limb show reorganization by depending on neighboring area (e.g. forearm & face) – Age of acquisition • Effects of abnormal sensory input: fMRI studies reveal that visual cortex is activated when blind – Degree of mastery Braille readers read Braille.

Conclusions about Plasticity Conclusions about Plasticity, Con’t

• Collectively, reorganization of neural • Conversely, motor and somatosensory pathways is possible well beyond infancy and systems can be modified for much of the life early childhood span (with some constraints).

• Development in most sensory systems • Studies of deprivation suggest positive, early depends on experience occurring during a caregiving experiences are important in sensitive period (generally first few years of regulating normal emotional life) development…but effectiveness of some interventions support the concept of plasticity.

12 Conclusions about Plasticity, Con’t Conclusions about Plasticity, Con’t

• Collectively, the likelihood of a given • Not clear what aspects of cognitive behavioral system exhibiting plasticity seems development require experience at particular to depend on whether the system being (e.g., sensitive) points in time challenged is one … – that has had the right early experience to “set” it – whose function is somehow essential to the infant early in life (e.g., ability to see)

Conclusions about Plasticity, Con’t Take-Home Messages

… • We should re-think the concept of “critical” • that depends on neural circuits whose periods. elaboration requires exposure to particular • We should recognize that some behavioral types of experience during a sensitive period and brain systems are formed earlier than of time, and finally others. • Some experiences are going to be more • that requires continual challenges and/or important at particular points in time than maintenance thereafter. others.

13 Video Chapter Complete

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