Lecture Week Three: Neurodevelopment & degeneration Flashcards
What are the 3 key steps in Primary Neurulation?
- Neural Plate forms (approx 18 days of development)
- Subsequent formation of the neural groove and neural fold
- Connection of the neural folds forms the neural tube
In what week does the neural tube close?
4th week of development
What does the Neural Tube develop into?
The Central Nervous System
What happens during the 3rd week of development? (1)
Folding of the neural tube
What happens during the 4th week of development? (1)
Neural tube closes
What happens during the 5th week of development? (2)
- Neural tube folds
- Separate CNS areas are emerging
What happens during the 6-7th week of development? (2)
- Telencephalon (lobes of the brain) start to enlarge
- CNS structures continue to develop
What happens during the 8-12th week of development? (3)
- Neurons proliferate and migrate
- Cerebral cortex begins to form
- Cerebellar cortex begins to form
What happens during the 12-16th week of development? (2)
- Neurons proliferate and migrate
- Areas of the CNS develop more intricately
What happens during the 16-40th week of development? (3)
- Neuronal migration
- Myelination Begins
- Synapse formation
What malformations can occur in the 3rd week of development? (1)
Neural tube defects
What malformations can occur in the 4th week of development? (2)
- Neural tube defects
- Holoprosencephaly ( L/R hemispheres don’t divide)
What malformations can occur in the 5th week of development? (2)
- Holoprosencephaly ( L/R hemispheres don’t divide)
- Sacral cord abnormalities
What malformations can occur in the 6-7th week of development?
No major malformations should occur during this period
What malformations can occur in the 8-12th week of development? (1)
- Migration/proliferation abnormalities (e.g. abnormal gyri)
What malformations can occur in the 12-16th week of development? (1)
- Migration/proliferation abnormalities (e.g. abnormal gyri)
What malformations can occur in the 16-40th week of development? (1)
Haemorrhage (ruptured blood vessel) or other destructive events
What does congenital mean?
Congenital means an illness or abnormality that is present before and/or at birth
What is one of the most common congenital CNS malformations?
Spina Bifida (Meningomyelocele)
- occurs from incomplete folding of the neural tube, leaving the spinal cord exposed
- Symptoms vary depending on extent and location of opening
- effects 5000 people in Australia
- 85-90% also have hydrocephalus (accumulation of cerebrospinal fluid in the brain)
What is a Chiari Malformation and how does it link to Spina Bifida (Myelomeningocele)?
Chiari Malformation is when the base/back of the brain is forced down through the skull into the top of the spinal canal. Occurs because Spina Bifida can cause Hydrocephalus (Accumulation of CSF) which presses on the brain pushing it down and out through the base of the skull.
What are some symptoms of Spina Bifida Meningomyelocele?
- Incontinence (involuntary evacuation of bowel and bladder)
- Motor impairments including paraplegia
- Cognitive impairments (difficulties with language, memory, attention, executive function)
In terms of Spina Bifida, the outcomes and symptoms experienced depend on 3 things. What are they?
- Extent of CNS malformation
- Complications such as shunt revisions (needing to re-do a surgery to fix a non-functional shunt [tube placed in brain to drain excess CSF]) or infection
- Environmental enrichments and SES
What is considered low birth weight?
Less than <2,500 g
What is considered very low birth weight?>
Less than <1,500g
What is considered extremely low birth weight?
Less than <750 g
How many weeks is considered Preterm birth
Less than <37 weeks gestational age
How many weeks is considered Very Preterm birth?
Less than <32 weeks gestational age
How many weeks is considered Extremely Preterm birth?
Less than <29 weeks gestational age
What is normal weight and term for birth?
Normal weight = over > 2,500 g
Normal Term = around 40 weeks (no less than 37)
Babies with congenital neurological conditions (e.g. cerebral palsy) are often born ____term and/or have ____ birth weight
Preterm and low birth weight
What are the survival rates (%) for babies born in the following weight ranges?
- 501-750g
- 751-1,000g
- 1,001 -1,250g
- 1,251-1,500g
- 501-750g = 55%
- 751-1,000g = 88%
- 1,001 -1,250g = 94%
- 1,251-1,500g = 96%
Between 1960 and 1983, how many times greater (x) were the survival rates of infants born with low birth weight?
x70 times greater
What are the 3 causes of CNS damage in infants with very low birth weight and very preterm births?
- Infection
- Insult (sudden disturbance in cerebral blood flow)
- Disruption to normal neurodevelopmental processes
What are the three main neuropathological changes that occur in VLBW VPTB babies with CNS damage?
- Enlarged ventricles
- Reduced white and gray matter
- Cortical malformations
What are the 4 factors that effect the LONG TERM outcomes of people born VLBW/VPTB?
- Birth weight and gestational age
- Medical complications
- Family environment
- Sex
Cognitive outcomes for Children with VLBW/VPTB are evident from early/middle/late life?
Early life
VLBW/VPTB effects the development of which three categories?
- Motor development
- Language
- Attention
Cognitive outcomes for children with VLBW/VPTB are most severe in those who also have _____ complications
Neonatal complications: complications that develop after or during the birthing process
Do children with VLBW/VPTB have difficulties that persist throughout adulthood, or just childhood?
Through adulthood as well.
What were IQ ranges like for children born in these 3 weight categories?
- <750g
- 750-1,499 g
- Full-term (1,500 +)
- <750g had the highest rate of IQ scores for both the 70-84 range and <70 range (compared to other weight classes)
- Full Term babies had the highest % in the 100-114 IQ range
- 750-1,499g group peaked at IQ range of 85-99, but were also the only group to have children in the >130 IQ range as well
What two neuropsychological factors are most impacted on by VLBW of <750g?
- Executive functioning (significantly impacted)
2. Visual-motor (majorly impacted, but less so than EF)
What is one of the most major neurological developments to happen after birth?
The development of the Superior Longitudinal Fasciculus
Levels of SLF (superior longitudinal fasciculus) development correlate with performance on what cognitive measures? (3)
- Attention
- Executive Functioning
- Language
What are Critical Periods?
Critical Periods: Stages within development where neurons have a heightened capacity for adaptation. Certain exposures to environmental experiences must happen at this stage in order to ensure normal development
What is the difference between critical periods and sensitive periods?
Critical Period: strict time frame where experience to certain environmental stimuli provides information that is essential for normal development and permanently alters performance (missed = abnormal/no development)
Sensitive Period: a limited but gradual time frame during development where the effect of certain environmental experience is especially strong on brain function. (missed = normal/slow development but not as advanced as others)
What evidence did the 2005 Kuhl study provide that shows early speech perception influences later language development? (3)
- Vowel discrimination at 6 months old predicts language skills at 2 years old
- Event-related potential (brain voltage response) to speech in newborns predicts language ability in 3-8 year old children
- Children with language disorders (e.g. reading disabilities, specific language impairment) often have impaired speech perception
What is an example of a critical period surrounding the development of language?
Critical Period: Phonetic (speech sounds)
Lack of exposure to phonemes during this period leads to irreversibly reduced language development. Case example of Genie (13 yr old, language skills of a 1 yr old, never developed language skills past childhood level despite training)
Is language proficiency developed during a critical or a sensitive periods of development?
Critical period. It must be developed before 7 years of age. Critical period for language proficiency involves developing:
- Grammar
- Syntax
- Phonetics
What is dementia?
Dementia is a general term used to describe a chronic and substantial decline in two or more areas of cognitive function
What are 3 key features/trends of dementia?
- Most dementias are progressive
- often caused by neurological disorders (50% of ND cause some form of dementia)
- Incidence rate increases with age (at age 85, incident rate becomes 1 in 4)
What is normal aging?
Involves slight cognitive decline after a certain age, which tends to be specific rather than generalised. Occurs in all people, even in the absence of disease or illness.
What can normal aging declines be confused for?
Can be confused with early stages of dementia (MCI) and other neurological diseases
Aging affects our ____ capacities, while sparing our ____ knowledge
Aging affects our FLUID capacities (motor and memory), while sparing our CRYSTALLIZED knowledge (knowledge and understanding)
What 3 factors affect when cognitive deterioration can be seen to start?
- Genetics
- Environmental factors
- Extent of compensatory strategies used to overcome weaknesses
Why has research on aging been so inconsistent? (4)
• Design differences (cross sectional vs longitudinal);
• Participant selection criteria (few criteria vs very stringent);
• Lack of study of the “oldest old” i.e. >85 yrs (much more
difficult!);
• Individual differences.
Is functional deterioration due to just cell loss?
No, not just due to cell loss
Volume loss and atrophy may reflect …… (4)
- Decline in neuron numbers
- Neuron shrinkage
- Synapse loss
- White matter loss
For individuals over the age of 50, what % of brain weight is lost every decade?
2% less each decade
What are the two main changes that occur during atrophy?
Enlarged ventricles and smaller neural structures
Volume loss is most consistent in the ____ regions of the brain
Prefrontal regions (e.g. DLPFC)
Which cortical regions are least impacted on by age-related neuronal loss?
Parietal lobe, unimodal visual areas, temporal lobe
By age 80, MRI’s show a ___% loss of grey matter, and a ____% loss of white matter
MRI results show a 12-14% loss of grey matter and 25% loss of white matter
After what age does the loss of Hippocampus volume accelerate?
55 years of age and over
Volume loss is apparent in aging for what 3 structures of the brain?
- Hippocampus
- Nuclei of the basal ganglia
- Anterior cingulate cortex
Volumetric brain imaging often shows
thin ____ _____, enlarged ____ and _____, and a reduced _____ lobe
width as we age.
Volumetric brain imaging often shows
thin cortical gyri, enlarged sulci and ventricles, and a reduced temporal lobe width as we age.
Is neuronal loss due to aging specific or generalised? Give an example
Specific. It only occurs in some subcortical (below the cortex) structures and only occurs to specific types of neurons.
Example: Loss of Cholinergic neurons occurs in the basal forebrain, locus coeruleus, and the dorsal raphe nucleus
What are the Cholinergic systems in the human brain?
Cholinergic systems: Two major pathways: basal-forebrain cholinergic neurons, {including the nucleus basalis and medial septal nucleus} and pedunculopontine–lateral dorsal tegmental neurons. Other cholinergic neurons include striatal interneurons, cranial-nerve nuclei, vestibular nuclei, and spinal-cord preganglionic and motoneurons. A group of cholinergic neurons in the thalamic paracentral nucleus project to the striatum and visual cortex. There is also the habenula–interpeduncular pathway.
Apart from cell loss and volume reduction, aging includes what other 4 consequences/events occur?
◦ Reduced dendritic branching (potential to affect the quality and efficiency of neuronal transmission)
◦ Reduced concentrations of neurotransmitters, like dopamine (motor and executive functions) and acetylcholine (learning and memory).
◦ Accumulation of senile plaques,
neurofibrillary tangles and amyloid;
◦ Arteriolar walls thicken and cerebral blood flow decreases
In the Wu 2008 study, what activity caused ageing mice to have enhanced dendritic branching?
Treadmill running
Does cerebral blood flow increase or decrease in old age?
Decrease
Does the hippocampus change in any way as part of the aging process?
While its structure is preserved physiologically, its functional organisation is changed during normal aging.
Effects of ____________ decay much more rapidly in the elderly, and is associated with rapid forgetting.
Effects of LONG-TERM POTENTIATION decay much more rapidly in the elderly, and is associated with rapid forgetting.
Neuronal loss that occurs in the entorhinal cortex (olfactory and limbic systems) may be secondary to ______ cell loss or functional deterioration
Neuronal loss that occurs in the entorhinal cortex (olfactory and limbic systems) may be secondary to HIPPOCAMPAL cell loss or functional deterioration
Cell loss in the entorhinal limbic system results in the ______ becoming disconnected from the _____ regions
Cell loss in the entorhinal limbic system results in the HIPPOCAMPUS becoming disconnected from the FRONTAL regions
Neurodegenerative disorders / neurological problems are COMMON / UNCOMMON / or RARE in individuals >80yrs (AD, PD, stroke, etc
Common
What are two big issues of using common measures of cognitive function?
- Don’t take into account the normal declines in vision, hearing, and motor skills that occurs with aging
- They are based on data from younger individuals, not very accurate data for individuals ages 60 and over.
What 6 major faculties decline with aging?
- bodily function (motor speed, gait and balance)
- speed of information processing
- certain attention functions
- executive function (e.g. shifting set)
- visuospatial abilities
- memory (mainly recall)
What is the major faculty that is not affected by aging?
Language functions
What is Bradykinesia?
Slowness in motor execution and function
Is slowed reaction time in aging individuals due to the slowing of peripheral nerve conduction?
No
What 3 dysfunctions can combine to cause age-related disturbances in gait and balance?
- Sensory dysfunction
- Motor dysfunction
- Extrapyramidal (involuntary/automatic muscle control) dysfunction
Is gait dysfunction in the elderly treatable or untreatable?
Treatable
Age-related cognitive deficits become most apparent under what conditions?
Conditions of high cognitive load
Aging populations show consistent deficits in the performance of ____ tasks
timed tasks. E.d. Digit symbol
What type of attention only tends to decline after the age of 80?
Sustained attention
What type of attention remains fairly intact with increasing age?
Selective attention
What type of attention shows deficits in aging populations when exposed to highly complex tasks? What might cause this?
Divided attention. Might be due to reduced cognitive resources.
Most attention studies on aging individuals are confounded by impairments in….
Impairments in primary perceptual abilities
Assessments of executive functioning in aging individuals that contain tasks involving _____ ______ and __________ show age-related deficits (65+ years)
Assessments of executive functioning in aging individuals that contain tasks involving CONCEPT FORMATION and SET-SHIFTING show age-related deficits (65+ years)
How is visuospatial ability affected by aging?
Performance on visuospatial (both perceptual and constructional) tasks declines with age
What visuospatial ability tasks are hard for the elderly? (compared to younger participants)
- WAIS Block Design
- Object Assembly tasks
- Figure drawing
- Recognising incomplete or embedded figures
- Matching patterns
What type of memory is not affected by aging?
Implicit memory
What types of memory are most affected by aging? (2)
Explicit memory and working memory
What types of memory are only minimally/moderately affected by aging
Sensory memory (including iconic) and short-term memory
In terms of long-term memory, how are the following 3 sub-categories of memory affected by aging?
- Episodic memory
- Semantic memory
- Retention of ‘old’ memories
- Episodic memory: Declines after 60 yrs (or earlier)
- Semantic memory: Only shows declines for newly acquired memories
- Retention of ‘old’ memories: Unaffected
What have studies shown about memory deterioration and brain activation in aging people?
elderly people show different patterns of
prefrontal activation associated with semantic encoding and explicit
retrieval from LTM.
List the elements of language that
- Improve with age (1)
- Preserve with age (3)
- Decline with age (1)
- Improve: Vocabulary
- Preserve: phonology, lexical decisions, syntactic knowledge
- Decline: Naming objects (mild agnosia)
What is agnosia?
inability to interpret sensations and hence to recognize things (e.g. people, objects, sounds, shapes, smells…)
Slower ___________ and Reduced ___________ has been shown to account for some of the variance in cognitive performance of the elderly.
Slower processing speed and reduced cognitive resources has been shown to account for some of the variance in cognitive performance of the elderly.
What is the most comprehensive theory of the aging brain to date?
the theory of Functional Plasticity (greenwood 2007).
What are the three key ideas of brain aging included in the 2007 Functional Plasticity hypothesis?
- Cortical areas shrink with age, but also show increases in task-related activation as we age.
- Atrophy within cortical regions drives strategic changes, and subsequently a functional reorganisation (i.e., plasticity)
- The brain may be able to rewire itself to help it keep up on day to day tasks.
What is the most commonly seen way to compensate for age-related declines?
The recruitment of additional brain areas to complete a task.
What is an example of a cognitive task that requires large amounts of additional brain region recruitment in the elderly in order to be completed (compared to young controls)
Verbal working memory tasks
