mechanism

Autism's symptoms result from maturation-related changes in various systems of thebrain. The behaviors appear to have multiple pathophysiologies. Autism appears to result from developmental factors that affect many or all functional brain systems, and to disturb the timing of brain development more than the final product. Neuroanatomical studies and the associations with teratogens strongly suggest thatautism's mechanism includes alteration of brain development soon after conception. Just after birth, the brain of an autistic child grows faster than usual, followed by normal or relatively slower growth in childhood. The early overgrowth seems to be most prominent in areas underlying the development of higher cognitive specialization.

• Disturbed neuronal migration during early gestation.

• Unbalanced excitatory–inhibitory networks. or by poorly regulated synthesis of synaptic protein. Disrupted synaptic development may also contribute toepilepsy, which may explain why the two conditions are associated.

Interactions between the immune system and the nervous system begin early during the embryonic stage of life, and successful neurodevelopment depends on a balanced immune response. It is possible that aberrant immune activity during critical periods of neurodevelopment is part of the mechanism of some forms of ASD. Although some abnormalities in the immune system have been found in specific subgroups of autistic individuals, it is not known whether these abnormalities are relevant to or secondary to autism's disease processes. As autoantibodies are found in conditions other than ASD, and are not always present in ASD, the relationship between immune disturbances and autism remains unclear and controversial.

Several neurotransmitter abnormalities have been detected in autism, notably increased blood levels of serotonin. Whether these cause structural or behavioral abnormalities is unclear. Also, some inborn errors of metabolism are associated withautism but probably account for less than 5% of cases. Several studies have tested this hypothesis by demonstrating structural abnormalities in MNS regions of individuals with ASD, delay in the activation in the core circuit for imitation in individuals with Asperger syndrome, and a correlation between reduced MNS activity and severity of the syndrome in children with ASD. However, individuals with autismalso have abnormal brain activation in many circuits outside the MNS and the MNS theory does not explain the normal performance of autistic children on imitation tasks that involve a goal or object.

ASD-related patterns of low function and aberrant activation in the brain differ depending on whether the brain is doing social or nonsocial tasks.

In autism there is evidence for reduced functional connectivity of the default network, a large-scale brain network involved in social and emotional processing, with intact connectivity of the task-positive network, used in sustained attention and goal-directed thinking. In people with autism the two networks are not negatively correlated in time, suggesting an imbalance in toggling between the two networks, possibly reflecting a disturbance of self-referential thought. A 2008 brain-imaging study found a specific pattern of signals in the cingulate cortex which differs in individuals with ASD.

The underconnectivity theory of autism hypothesizes that autism is marked by underfunctioning high-level neural connections and synchronization, along with an excess of low-level processes. Evidence for this theory has been found in functional neuroimaging studies on autistic individuals and by a brain wave study that suggested that adults with ASD have local overconnectivity in the cortex and weak functional connections between the frontal lobe and the rest of the cortex. Other evidence suggests the underconnectivity is mainly within each hemisphere of the cortex and that autism is a disorder of the association cortex.

From studies based on event-related potentials, transient changes to the brain'selectrical activity in response to stimuli, there is considerable evidence for differences in autistic individuals with respect to attention, orientiation to auditory and visual stimuli, novelty detection, language and face processing, and information storage; several studies have found a preference for non-social stimuli. For example, magnetoencephalography studies have found evidence in autistic children of delayed responses in the brain's processing of auditory signals.