brain development does not end at birth, but continues into adolescence

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Postnatal Neural Development
brain development does not end at birth, but
continues into adolescence rapid postnatal
development occurs in first 2 years-- 80 total
weight characterized by increasing cortical
connectivity and glial development volume
increases in different regions of cortex are age
dependent dendritic spines increase during
first few months reach adult levels at
around 2 years number of synapses also reach a
max around 4-5 months, then decline slowly
through adolescence like cortical growth, the
number of synapses decrease in different
areas at different times during development
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Postnatal Neural Development
synaptic refinement also takes place at different
regions over time general patterns are present
early specific connections change myelination
also develops over time brainstem myelinates
earliest cerebellum next, then thalamus
cortex isn't fully myelinated until 30's
females myelinate earlier than males many
regions mature late because they require
sensory input only recently have scientists
begun mapping childhood development to brain
imaging
mouse sciatic nerve
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Postnatal Neural Development
basal ganglia and brainstem regions get more
drive from cortex around 3 months related to
loss of grasp reflex and gain of tonic neck
reflex SIDS may be related to increased
cortical inhibition of breathing reflex during
this time period vision is corellated with
anatomy as well smooth pursuit appears at 6-8
weeks cortical layers IV-VI project to MT
then visual acuity and alertness increase at 4
mo. linked to highest of synapses and
appearance of ocular dominance columns as well
as correctable amblyopia by forcing use of the
'lazy' eye
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Postnatal Neural Development
the two different visual streams (ie.
ventrolateral and dorsal streams) also form
connections at different times ventrolateral
stream involved in processing individual visual
pieces as a part of the whole, and then
integrating the parts to make a whole object
doesn't appear until about 4 months of age with
global/local processing at 6 mos. object
representations and visual rule learning
appear dorsal stream processes spatial info
and visual acuity ability to expect/predict a
visual cue appears at about 6 months and are
linked to parietal cortical maturation
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Postnatal Neural Development
infants have the rudiments of declarative memory
prefer looking at things they've seen before--
they remember them in monkeys, removing the
hippocampus before 3 wks disrupts ability recall
increases with time, paralleling development of
hippocampus through development of
spatial/relational memory at about 4-5
years facial recognition begins at birth
mother familiar faces recognized facial
expressions can be imitated is different than
adult cortical face recognition (may be a
precursor) initial recognition/imitation seems
to be a retino-collicular function linking
facial muscle to vision
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Postnatal Neural Development
ages 7-9 months sees emergence of fear as a
driving emotional force infants may become
fearful of unfamiliar faces infants do not
like being separated from their primary
caregiver younger infants can make the
discrimination, but do not show anxiety may be
linked to the maturation of the prefrontal cortex
connections to the limbic system,
particularly the amygdala and ventral
tegmentum visual 'search' matures as well 5-6
months, covering an object removes it from
consideration 7-8 months, will uncover an
object but not follow it to a new location
after even a few second delay suggests they can
maintain an image of where the object was in space
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Postnatal Neural Development
language acquisition seems to be primarily at the
cellular/synaptic level rather than the
connection level, making it very hard to
analyze initial phonemes and rapid initial
vocabulary may be related to the huge number
of synapses being formed during year 2 ability
to learn new languages may be tied to larger
number of synapses present during the first
decade, then lost from age 5- 15 years many
language skills can be recovered if brain
damage occurs in first decade of life doesn't
happen nearly as well for older
patients different aspects of language have
different critical periods
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Aging and Cognition
in elderly individuals, cognitive abilities vary
between individuals strongly suggests that
intellectual loss is not a required part of
aging studied in animals using a morris water
maze with young and old rats hippocampus and
medial temporal cortex mediates memory
formation young rats learn where the platform
is faster on average, suggesting a real
decline in ability during aging average results
are deceiving, though as old rats have a
broader range of scores, with 1/2 going below
the level of younger rats with others
having indisitinguishable times
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Aging and Cognition
hippocampus shows very specific age dependent
declines although amplitude of LTP is
unchanged, more or stronger stimuli are
required to generate LTP in old animals
secondly, potentiation decays more rapidly in
older animals, analagous to forgetting
information like LTP, LTD is also affected,
suggesting common molecular paths hippocampus
contains a 'place field' where pyramidal
neurons are most active when in a known
location location is dependent upon a set of
auditory/visual cues from memory in old rats,
place fields still exist, but can get
confused, substituting the wrong remembered
place for correct one
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Aging and Cognition
using stereology, scientists have shown that
neuronal number does NOT change significantly
in young vs old rats overall or relate to
learning in the hippocampus cortical input to
the hippocampus through the perforant path is
reduced during aging i.e. connectivity rather
than is compromised cortical synapses onto
hippocampal pyramidal cells are reduced (as
seen in other areas) synaptic number also
corellates with the age- dependent cognitive
loss in the hippocampus
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Aging and Cognition
'executive function' is found in the prefrontal
cortex (ie. lobotomy) certain processing
functions change, including order and source of
info memory of particular locations for short
term is found in prefrontal parts aged monkeys
do not remember which treat location was used
even after only a few seconds of seeing them
hippocampal memory is used for longer time
periods delayed response defecits in aged humans
mimic prefrontal damage different aspects of
age-related declines are independent ie.
hippocampus and prefrontal cortex functions
may be at different levels of function like
hippocampus, prefrontal aging corellates with
synapses, not neuron
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Aging and Cognition
while normal aging is not associated with general
cell loss, more specific regions can exhibit
cell number (as well as synaptic number)
deficits cholinergic neurons of the basal
forebrain are lost in Alzheimers as well as
during normal aging these neurons project to
amygdala, hippocampus, and neocortex other
losses, including dopamine neurons from the
midbrain and norepinephrine from locus
ceruleus are also present during aging
normal Alzheimer's
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Neuropathology
neuropsychiatric disease research is limited by
several factors 1) lack of universally
accepted criteria creates inconsistent results
2) different underlying causes can generate the
same behavioral deficit 3) problems with using
children as research subjects and
controls autism is a syndrome associated with
deficits in numerous faculties, including
social interaction, language, and repetitive,
stereotyped movements appears in infancy, and
becomes more pronounced by age 3 autism
covers a range of deficits and heterogeneous
severity levels
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Neuropathology
autistic individuals show varying degrees of
social isolation, stereotyped behaviors,
resistance to changes in routine, abnormal
responses to sensory stimuli, poor speech, and
inappropriate emotional responses covers a range
of severity, from Rainman to simply slow
development autism is characterized by
megalencephaly in occipital, parietal, and
temporal lobes and abnormalities in amygdala,
cingulate, hippocampus, and other limbic
structures fMRI results show reduced temporal
cortex and amygdala function in face
recognition autism is a complex genetic disease
if 1 zygotic twin is autistic, it is 50
likely the other will be as well
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Neuropathology
two genes responsible for DNA methylation and
gene regulation fragile X and Rett's Syndrome
cause mental retardation as well as social and
language disruptions similar to (but not as broad
as) autism dyslexia is a condition associated
with poor reading skill but linked to subtle
deficits in motor control and sensory
processing, particularly visual
system magnocellular pathways in visual system
are reduced, causing contrast sensitivity and
visual persistence deficiencies certain brain
asymmetries are also reduced but it is
difficult to separate out the cause of
dyslexia from compensation for dyslexia
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Neuropathology
Triplet repeat disorders (such as Huntington's
Disease) are regions of unstable DNA where
copy number of certain sequences increase over
generations-- genetically inherited, but not
identical to parents caused by the slippage of
DNA polymerase in the repeated areas generally
the repeats are small in most people (5-30
copies) but grow to hundreds or thousands of
copies in affected individuals spinocerebellar
ataxias (SCAs) are closely related clinically,
causing progressive loss of balance and
coordination SCAs are linked to expanded CAG
triplet repeats that add glutamates to
proteins and cause a gain of function mutation,
but function unknown
18-fluorodeoxyglucose PET
SCA-6 control
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Neuropathology
Schizophrenia is a split between the emotional
and intellectual spheres of brain
function 'positive' functions (ie. added
pathology) includes hallucinations, delusions,
and disorganized speech/behavior 'negative
functions' include reduced speech content,
reduced pleasure and/or ability to express
emotions, and reduced attention
span schizophrenia is related to abnormal
dopamine synapses in the brain antipsychotic
drugs affecting the disease either block
dopamine receptors or inhibit synaptic release
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Neuropathology
the simplistic model is that schizophrenia is
simply an excess of dopamine
signaling cause-and-effect is hard to show,
however are dopamine receptor increases due
to the reduced dopamine signaling after drug
taking or is that the cause of the
disease? alternatively, the cause could be
glutamatergic inactivity, which increases when
the inhibitory dopamine signal is
decreased cortical architecture and
connectivity is altered NMDARs are reduced
in cortex and may affect synaptic elimination
or dendritic pruning
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Neuropathology
because schizophrenia first occurs during
adolescence, it may be related to
developmental changes incorrect neuronal soma
locations found in the hippocampus and cortex
NMDARs mediate synaptic changes in cortex during
adolescence normal adolescent phospholipids
are more extreme in schizophrenia both
environmental and genetic factors play a role
in developing the disease a sorting test shows
schizophrenics are less able to recognize
changes in target order involves prefrontal-
limbic connections several 'risk factor'
genetic markers are more often found in
diseased indivdiuals compared to normals
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Neuropathology
dementia is a term for degenerative loss of
multiple cognitive domains over 50 different
forms have been identified all become
increasingly severe over time age of onset and
rate of loss vary, although most develop
slowly Alzheimer's disease is the most common
age related dementia characterized by
increasingly severe recent memory impairment
as the disease progresses, meanings and remote
memories deteriorate amyloid plaques and
neurofibrillary tangles are found in the
brains after Alzheimer's Ab is an incorrectly
processed protein which accumulates and kills
nearby cells/processes normal microtubule-associa
ted protein tau forms tangles inside neurons,
disrupting them
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Neuropathology
during memory impairment phases of Alzheimer's,
tangles and plaques form in entorhinal cortex
which drives the hippocampus entire perforant
path gets associated with tangles spreads as
more cortical systems are affected and
cognition degrades 3 mutations are associated
with an early onset of the disease all
affect Ab protein processing (presenilins
12) or protein itself all 3 are autosomal
dominant mutations Ab is on chromosome 21, and
Downs syndrome patients who live into their
40's always develop plaques