No Theory of Mind

Weak Central Coherence

Executive Dysfunction

Cortical Abnormalities

• Whole Brain is heavier than expected <12 years and lighter than expected in adults

• Structural Abnormalities– Mini-Column abnormalities

• a basic functional unit of the brain that organizes neurons in cortical space and are involved in sensory information processing

• Mini column is a core line of neurons ascend vertically between layers VI and II of the cortex

– Less GABA-ergic interneurons which are source of lateral inhibition

– More immature dendrite arborizations and synapses» Prefrontal and Orbitofrontal cortices» Temporal lobe- Visual and Auditory parasensory areas

Subcortical Abnormalities

• Limbic system (amygdala, hippocampus, and related structures)– Smaller and more immature neurons with

reduced dendrite arbors

• More pronounced abnormalites in the amygdala and then hippocampus– Often find larger amygdala volumes,

suggesting incomplete neuronal pruning– Often find smaller amygdala with age,

suggesting cell death

Role of Hippocampus

• Lesions to the hippocampus produce deficits in declarative memory

• It is more slow to mature

• It is suggested that disruptions to the this system could disrupt or distort acquisition and interpretation of information

• Smaller in autistic

Motor Abnormalities

• Cerebellum and brain stem have significant reduction in number of Purkinje neurons

• Cerebellum involved in visuo-spatial processing, emotional processing, and motor processes

Neurotransmitters in Autism

• Hypo-serotonin– 7 possible mechanism (this is for you to study)– Reducing serotonin results in increase in

stereotypical behaviors, but no change in social deficits.

– Treatment with SSRIs result in reduction of aggressive and ritualistic behaviors

– PET studies found decreased SER synthesis in cortex and thalamus of autistic individuals

Autism

• CMI superior to desipramine in reducing ratings of autistic symptoms of stereotype behaviors, ritualized behaviors, anger. Both TCAs equal and superior to placebo in reducing hyperactivity

• Haldoeridol (DA antagonist) superior to placebo in reducing steretypy and withdrawal

-combo with BTincreased effectiveness of language learning

• Beta blockers (NE system) decreased aggression and levels of arousal, however, need better studies

Structural Conclusions

• Abnormalities in neuronal alignment, elaboration, pruning, and selective elaboration of appropriate neurons in the cerebral cortex.

• Abnormalities of dendritic and axonal arborations in the limbic system

• Selective elimination of neurons in the cerebellum• Abnormalities suggest onset of abnormal brain

development during 2nd trimester of gestation• Selective core involvement of the amygdala and

entorhinal cortex may be involved in social deficits.

Amygdala: Functions

• Recognition of affective significance of stimuli

• Social stimulus-reward associations• Cross modal associations• Long term memory (especially related to

emotion)• Perception of body movements• Perception of gaze direction• Perception of emotion

Circuitry of Austim

• Cortical regions in the temporal lobe participate in perceiving socially relevant stimuli; Amygdala, right somatosensory cortex, orbitofrontal cortices and cingulate cortices participate in linking perception of these stimuli to motivation, emotion, and cognition.

Role of the Cortex

• Prefrontal Cortex and posterior superior temporal sulcus are involved in “mentalizing” which is lacking in Autistic patients

• PFC is found to actively modulate extinction of amygdala related aspects of memory

Role of the Amygdala in Autism

• PET and MRI Studies– Increase activity in normal subjects when

viewing happy, and fearful expression in contrast to viewing neutral faces. Not found in Autistic patients

– Autistic patients appear to not be able to differentiate between threatening and non-threatening stimulus

– Found smaller amygdala and hippocampus in autistic patients