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PSYCH 473 > Neurobiology and Connectivity in Autism > Flashcards

Neurobiology and Connectivity in Autism Flashcards

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1
Q

What are the prenatal risks for autism?

A

prenatal exposure to valproate (anti-epileptic), thalidomide (anti-emetic), misoprostol (abortifacient)

gestational diabetes

gestational bleeding

multiple birth

first-born compared with third or after

maternal or paternal immigration: marked increase in male children born in urban areas

folic acid: some say increases risk, some say decreases risk

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2
Q

What are the perinatal risks of autism?

A

prematurity

abnormal presentation: especially breech presentation

Caesarean section

neonatal hypoxia: baby has lost oxygen during birth

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3
Q

What are the neonatal risks of autism?

A

exposure to air pollution

prenatal or postnatal depression: antidepressant use during pregnancy

early social deprivation

severe sensory deprivation: congenital blindness, hearing impairment, impaired vision and hearing

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4
Q

What are the convergent mechanisms of autism risk?

A

individual risk factors may result from common underlying causes

epigenetics: parental age, immigration, delivery complications

stress: immigration, depression, delivery complications

hypoxia/immune activation: pre/peri-natal risks

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5
Q

What is cortical enlargement in autism?

A

macrocephaly by 2-3 years seen in ~20% of autistic children

relative increase in cortical white matter: frontal lobe, temporal lobes, limbic structures (especially amygdala)

structures implicated in social, motor, and communication functions

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6
Q

What are the three “compartments” of functional change in autism?

A

dorsal executive control system

ventral social-affective processing system

subcortical nodes

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7
Q

What are the structures involved in the dorsal executive control system?

A

anterior cingulate

dorsolateral prefrontal cortex

caudate

dorsal striatum

associate with restrictive, repetitive behaviors

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8
Q

What are the structures involved in the ventral social-affective processing system?

A

amygdala-hippocampus

fusiform gyrus

orbitofrontal cortex

associate with social-affective behaviors

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9
Q

What are the structures involved in the subcortical nodes?

A

thalamus

basal ganglia

engaged by both systems

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10
Q

What are the executive functions that are altered in autism?

A

cognitive flexibility

planning

pre-potent inhibition

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11
Q

What are the executive functions that are persevered in autism?

A

rote memory

interference inhibition

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12
Q

What are the alterations in function of the inhibition network in autism?

A

cingulate gyrus and insula uncoupled from frontal-parietal processes

effects proposed to occur through deficits in set-shifting

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13
Q

What is the support from lesion studies for the dorsal changes in autism?

A

damage to the frontal cortex interrupts executive function

emergence of perseverative and repetitive behaviors

insistence on sameness

impulsivity

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14
Q

What are the circuit changes in set-shifting changes in autism?

A

hypoactivation: dorsolateral prefrontal cortex, anterior cingulate gyrus, left intraparietal sulcus, thalamus, basal ganglia

correlates with clinical manifestation of restricted and repetitive behaviors: anterior cingulate gyrus, left intraparietal sulcus

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15
Q

What are the ventral changes in autism?

A

changes in regions involved in social perception and cognition

amygdala hypofunction suggested by post-mortem, structural, and functional imaging

increased activation of amygdala observed in response to viewing facial photographs: heightened emotional response to gaze fixation in autism

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16
Q

What are the changes to the fusiform gyrus in autism?

A

fusiform gyrus implicated in normal processing of social stimuli especially faces, and facial features

hypofunction of fusiform gyrus observed in autism

increased activation of fusiform gyrus in response to viewing facial photographs

17
Q

What are the specific changes in social perception observed in autism?

A

normal processing seen for place and object stimuli

further hypoactivity of social processing areas: superior temporal sulcus, occipital face area, right pulvinar colliculus, bilateral superior colliculus

failure to engage subcortical regions involved in face detection

18
Q

What are the orbitofrontal changes in autism?

A

bilateral damage to the orbitofrontal cortex yields social cognitive impairment, especially in judging intentions of others

functional changes observed in orbitofrontal cortex in social tasks in autism

19
Q

What is the connectivity model of autism?

A

autism is a syndrome associated with aberrant connections between networks of brain region as opposed to focal deficits

proposed disconnects between frontal lobe and temporal lobe multi-modal higher-order associations cortices

20
Q

What is the evidence for the change in connectivity seen in autism?

A

amygdalo-fusiform and hippocampo-fusiform pathways for a typical matched subject pair of an autism participant and control participant

no macrostructural changes in tracts observed (i.e. volume)

microstructural changes seen: decreased lateralization in ASD, decreased lateral diffusion (may be increased myelin, decreased fiber diameter) especially in right H-F

21
Q

What are the changes in connectivity in verbal processing in autism?

A

fMRI testing during language tasks showed altered activity in ASD

decreased bold signal in left inferior frontal gyrus (Broca’s area)

increased bold signal in left superior temporal gyrus (Wernicke’s area)

lower functional connectivity observed: synchronization and correlation of time series of activation was altered

22
Q

What are the changes in connectivity in executive processing?

A

similar cortical areas activated in tower-of-London task

synchronization (functional connectivity) between frontal and parietal areas was lower in ASD

corpus callosum observed to have smaller cross-sectional area

corpus callosum size correlated with fronto-parietal connectivity in ASD group

23
Q

What is the overall summary of underconnectivity in ASD?

A

sheer volume of studies, tasks, and observed changes makes a consensus hard to define

clear evidence for disconnect between frontal and parietal regions

correlations between frontal-parietal connectivity and disorder severity

24
Q

What is cortical underconnectivity reflective of in autism?

A

inefficiency in optimizing connections to achieve task performance

less coordination, less than optimal output

25
Q

What does cortical underconnectivity result from?

A

use of alternate cortical route (compensatory routines)

dysfunction of key brain areas

26
Q

What is cortical underconnectivity?

A

may explain social and communication impairments as resulting from poor connectivity in social cognition, language, and executive function areas of the brain

most fcMRI studies examine only high-function patients

27
Q

What is overconnectivity in autism?

A

cortical-subcortical regions

thalamocortical projections

extrastriate cortex

frontal and temporal regions

amygdala

parahippocampal gyri

posterior cingulate-temporal lobe-parahippocampal gyrus in resting state fcMRI

cerebello-thalamo-cortical networks

28
Q

What are the correlations with overconnectivity in autism?

A

high connectivity in the default mode network correlated with lower abilities in verbal and non-verbal tasks

high connectivity between posterior cingulate and parahippocampal gyrus associated with severe repetitive behaviors

high connectivity between anterior cingulate and frontal eye fields associated with restricted repetitive behaviors

29
Q

What are the implications of overconnectivity?

A

overconnectivity does not represent enhanced function

likely to represent hyper specialization

overabundant connectivity between “non-essential” regions may allow cross-talk resulting in increased noise in the system

overconnectivity may result from impaired synaptic pruning - necessary for network specialization in development

PSYCH 473 (14 decks)

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