Lecture 9 - Neurodevelopmental Disorders Flashcards
What are the different stages of brain development ?
- Cell birth (neurogenesis)
- Cell migration
- Cell differentiation
- Cell maturation (dendrites & axons growth)
- Synaptogenesis
- Cell death (apoptosis) & synaptic pruning
- Myelogenesis
What are neural stem cells ?
Undifferentiated cells that develop into brain & spinal cord
When is neurogenesis largely complete ?
Around 4.5 months after conception
In which parts of the brain does neurogenesis continue into adulthood ?
- Olfactory bulb
- Hippocampus
- Striatum
From where do stem cells migrate to the developing parts of the brain ?
From neural tube/subventricular zone
How do cells ‘know’ where to migrate ?
Following road formed by radial cells
How long does migration continue after birth ?
Around 8 months
How do layers develop during cell migration ?
From the inside out
Into what types do migrated cells differentiate ?
Neurons or glia cells
When is cell differentiation essentially complete ?
At birth
What are the key processes involved in neural maturation ?
- Dendritic arborization (branching)
- Growth of dendritic spines
- Growth of dendrites, axons & synapses
When does neural maturation begin and how long does it continue ?
- Begins prenatally
- May continue into adulthood
What are the neurobiological processes underlying the critical period of plasticity ?
- Onset : inhibition-excitation balance & deprivation
- Duration : pruning, rewiring & environmental enrichment
- Closure : structural brakes, functional brakes epigenetics silence genes rewiring & attentional arousal
What are the key features of neural development in the adolescent brain ?
- Rapid synaptic pruning & growth of connections
- Especially in PFC
What neural changes occur during adolescence ?
- Differences in GM & WM volume
- Changes in levels of dopamine & GABA
What are some types of abnormal brain development ?
- Anencephaly
- Holoprosencephaly
- Lissencephaly
- Micropolygria
- Microencephaly
- Porencephaly
- Heterotopia
- Callosal agenesis
- Cerebellar agenesis
What’s brain plasticity ?
Nervous system’s potential for physical or chemical change that enhances its adaptability to environmental change & its ability to compensate for injury
What are epigenetic changes & can they be inherited ?
- Altered gene methylation & gene expression
- Can cross to subsequent generations
What internal factors influence brain development ?
- Hormones
- Injury
- Nutrients
- Microbiota
- Gestational stress
What external factors influence brain development ?
- Environment : exposure to complex vs impoverished environment
- Experiences : adverse childhood experiences
How does diet and nutrition affect brain development ?
- Gene expression (dry/rainy season)
- Gut microbiome (& immune function) : brain development, myelination, formation of blood-brain barrier
- Iron deficiency : anxiety, ADHD…
What are the effects of lead poisoning on brain development ?
- ADHD
- Autism
How does early visual deprivation affect vision ?
- Long-lasting impairment of vision after optical defects are corrected
- Amblyopia
How does socioeconomic status (SES) affect brain development ?
- High SES : exposure to more words , more one-on-one conversations, child-directed speech
- Low SES : associated with lower cortical volumes in frontal, temporal & parietal cortex
How does early auditory experience shape language development ?
- Shape brain’s ability to distinguish sounds of native language
Why does language often survive early left-hemisphere injury ?
Appropriation of language zone in R hemisphere
What often survives early left-hemisphere injury in the brain ?
Language
What is a possible consequence of the right hemisphere taking over language functions after early left-hemisphere injury ?
Impaired visuospatial orientation
What principle explains the greater recovery from brain lesions during infancy compared to adulthood ?
Kennard principle
How does the developmental stage of injury affect recovery from brain injury ?
Recovery depends on developmental stage :
- <1 year : large impairement
- 1-5 years : reorganization of brain function
- >5 years : little or no improvement
What factors influence recovery from brain injury ?
- Developmental stage of injury
- Location & extend of damage
- Age of assessment
- Type of behavior affected
- Sensory experience
- Hormones
- Neurotrophic factors
To what condition are linked temporal lobe & area TE damage ?
- Temporal lobe : autism
- Area TE : ADHD
What are the mechanisms involved in brain recovery after injury ?
- Changes in the organization of the remaining intact brain circuits
- Generation of new circuitry
- Generation of neurons & glia to replace at least some lost neurons
What are some examples of neurotrophic factors influencing brain recovery ?
- Tactile stimulation
- Complex housing
What is the incidence rate of neurodevelopmental disorders ?
17-25 %
What areas can neurodevelopmental disorders affect ?
- Motor behavior (cerebral palsy)
- General intellectual functioning
- Learning
- Attention (ADHD)
- Social behavior (autism)
- Communication
How are intellectual disabilities diagnosed ?
- Standardized IQ testing
- Neuropsychological evaluation
- Assessment of adaptative behaviors
Describe the characteristics of mild intellectual disability
- Emerge after during school years
- Slower development but able to function with minimal support
- Causes : head injury, stroke, infections
Describe the characteristics of moderate intellectual disability
- Major delays in development
- Able to understand speech & live in a supervised or group home
Describe the characteristics of severe intellectual disability
- Limited ability to communicate
- Physical limitations
- Need of constant care
- Causes : prenatal/congenital anomalies
What are some examples of intellectual disabilities ?
- Cerebral palsy
- Hydrocephalus
- Fragile X syndrome
- Fetal alcohol spectrum disorder
- Down syndrome
What are the different types of communication disorders ?
- Language disorder
- Speech sound disorder
- Childhood-onset speech disorder (sluttering)
- Social communication disorder
What are some specific neurodevelopmental disorders ?
- Reading disabilities
- Mathematical disabilities
- Developmental coordination disorder (clumsy child syndrome)
What are the symptoms of cerebral palsy ?
- Spasticity (involuntary muscle activity, limbs resist being moved)
- Athetosis (slow involuntary movements)
- Rigidity
- Ataxia (uncoordinated voluntary movements)
- Impairments in cognitive, emotional functioning (irritability, epilepsy, speech production
What causes cerebral palsy ?
- Blood clots
- Brain trauma during fetal development or birth (up to 5 years postnatal)
- Infections
- Traumatic brain injury
- Prematurity
- Oxygen depravation at birth
What are the underlying neural mechanisms of cerebral palsy ?
Lesions of corticospinal tracts, basal ganglia, brainstem, cerebellum
What is infant hydrocephalus & what causes it ?
- Hydrocephalus : condition involving accumulation of CSF in brain’s ventricles
- Causes : malformation, tumor or infection cause blockage of CSF (cerebral aqueduct, intraventricular foramen or 4th ventricle)
What are the symptoms of infant hydrocephalus ?
- Severe motor/mental disabilities
- Dementia
- Coma/death
What are the underlying neural mechanisms of infant hydrocephalus ?
- Damage to the cortex due to expansion
- Cortex can be stretched but not damaged
How is infant hydrocephalus treated ?
Draining the ventricles
What are the symptoms of fragile X-syndrome ?
- Low ears, high forehead
- Learning impairement, hyperactivity
- Boys > Girls
What causes fragile X-syndrome ?
- Genetic abnormality of the FMR1 gene
What are the treatments for fragile X-syndrome ?
- Glutamate antagonists or GABA agonists
- Gene replacement/reactivation (under investigation)
What are the symptoms of fetal alcohol spectrum disorder ?
- Physical malformations, facial features
- Intellectual impairements, hyperactivity, social problems
What causes fetal alcohol spectrum disorder ?
- Alcohol use (worst during first 3 months of pregnancy)
- Epigenetic changes in sperm of father due to alcohol use
What are the underlying neural mechanisms of fetal alcohol spectrum disorder ?
- General effects on cell division & maturation
- Epigenetic effects
- Small brains with abnormal gyri
- Misaligned cells in the cortex
What are the symptoms of autism spectrum disorders ?
- Impoverished social interaction, narrow play
- Insistence on “sameness” & routines
- Repeated & stereotypical body movements
- Inability to cope with new situations & habituate to ongoing events
- Subts facial anomalies
- Sometimes exceptional memory or mathematical abilities
What causes autism spectrum disorders ?
Several theories :
- Highly heritable & epigenetic factors, gene mutations (fragilex)
- Toxins, pollution, microbiome
- Bacterial/virus infections, vitamin deficiency
What are the underlying neural mechanisms of autism spectrum disorder ?
- Alterations in glutamate/GABA balance
- Alterations in somatosensory system, impairment in learning system
- Differential development of cingulate cortex
- Central brain stem/pons development
- Maturation of HOSA1 gene : brain stem & cerebellar development
What are the symptoms of ADHD ?
- Impulsivity, hyperactivity : excessive talking, running…
- Inattention : avoiding tasks, distractability…
- Creative, flexible & good at task-switching
What causes ADHD ?
Several theories :
- Brain damage
- Encephalitis (infection)
- Genetic
- Toxins
- Home/school environment
What are the underlying neural mechanisms of ADHD ?
- Delayed development of frontal cortex (self-regulation, inhibition)
- Dysfunction of motivational circuit (reward delay discounting)
- Reduced orbitofrontal GM
- Deficiencied of dopamine, noradrenaline & serotonin
- Dopamine dysregulation in basal ganglia & frontal cortex
What are the treatments for ADHD ?
- Methylphenidate & dexamphetamine
- Cognitive enhancer - stability/flexibility
