Neurobiology and Connectivity in Autism Flashcards
What are the prenatal risks for autism?
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
What are the perinatal risks of autism?
prematurity
abnormal presentation: especially breech presentation
Caesarean section
neonatal hypoxia: baby has lost oxygen during birth
What are the neonatal risks of autism?
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
What are the convergent mechanisms of autism risk?
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
What is cortical enlargement in autism?
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
What are the three “compartments” of functional change in autism?
dorsal executive control system
ventral social-affective processing system
subcortical nodes
What are the structures involved in the dorsal executive control system?
anterior cingulate
dorsolateral prefrontal cortex
caudate
dorsal striatum
associate with restrictive, repetitive behaviors
What are the structures involved in the ventral social-affective processing system?
amygdala-hippocampus
fusiform gyrus
orbitofrontal cortex
associate with social-affective behaviors
What are the structures involved in the subcortical nodes?
thalamus
basal ganglia
engaged by both systems
What are the executive functions that are altered in autism?
cognitive flexibility
planning
pre-potent inhibition
What are the executive functions that are persevered in autism?
rote memory
interference inhibition
What are the alterations in function of the inhibition network in autism?
cingulate gyrus and insula uncoupled from frontal-parietal processes
effects proposed to occur through deficits in set-shifting
What is the support from lesion studies for the dorsal changes in autism?
damage to the frontal cortex interrupts executive function
emergence of perseverative and repetitive behaviors
insistence on sameness
impulsivity
What are the circuit changes in set-shifting changes in autism?
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
What are the ventral changes in autism?
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
What are the changes to the fusiform gyrus in autism?
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
What are the specific changes in social perception observed in autism?
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
What are the orbitofrontal changes in autism?
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
What is the connectivity model of autism?
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
What is the evidence for the change in connectivity seen in autism?
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
What are the changes in connectivity in verbal processing in autism?
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
What are the changes in connectivity in executive processing?
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
What is the overall summary of underconnectivity in ASD?
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
What is cortical underconnectivity reflective of in autism?
inefficiency in optimizing connections to achieve task performance
less coordination, less than optimal output
What does cortical underconnectivity result from?
use of alternate cortical route (compensatory routines)
dysfunction of key brain areas
What is cortical underconnectivity?
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
What is overconnectivity in autism?
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
What are the correlations with overconnectivity in autism?
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
What are the implications of overconnectivity?
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
