Autism can be thought of as a disconnection syndrome, in which the normal interactions between areas of the cerebral cortex are disrupted. Information flows between cortical areas along a hierarchy. Of particular interest is the influence of cortical areas that are higher in the hierarchy on early stages of sensory processing. This hierarchy is referred to as top-down control. Such interactions facilitate our interpretation of our external environment, by segmenting visual scenes into objects and their backgrounds. They play a role in object recognition, and they provide the necessary selection of scene elements that are relevant to perceptual tasks as opposed to those that are irrelevant.

Epidemiological and clinical studies show that children with autism have a ten-fold higher risk of epilepsy compared with the general population. In addition, most mouse models of autism display spontaneous epileptic tendencies, altered brain activity or synaptic deficits. The disrupted genes in mouse models of autism include BCKDK, CNTNAP2, FMR1, SYN1, CDKL5 and SCN1A. Joseph Gleeson and his colleagues at the University of California, San Diego and The Rockefeller University are studying the genetic basis of the connection between autism and epilepsy in order to gain insight into the mechanisms of these diseases, which may point to more targeted therapies.

SHANK mutations and copy number variations (CNVs) — duplications or deletions of stretches of DNA — are linked to autism. Mammals have three SHANK genes, each encoding multiple variants of the SHANK protein expressed by different messenger RNAs. Several mouse SHANK knockouts have been described, but these mutants exhibit inconsistent — and often contradictory — patterns of defects at synapses, or neuronal junctions. Thus, mouse genetic studies have not produced a clear picture of how SHANK proteins regulate the formation or function of synapses. This is most likely due to overlapping functions of the SHANK protein variants.

New protein synthesis is essential for long-lasting memory, and the proteins ERK and mTOR, which regulate gene translation, have a crucial role in this process. Several monogenic syndromes associated with autism, notably fragile X syndrome and tuberous sclerosis complex (TSC), involve proteins that function in these translational regulatory pathways.

Folic acid is an essential vitamin, meaning that people must consume folic acid in the diet, as the body is unable to manufacture it on its own. Strong evidence shows that women who take supplemental folic acid at the time of conception are less likely to give birth to children with neural tube defects such as spina bifida. If folic acid plays a crucial role in early brain development, it may also impact the risk for autism.

Human genomes differ from one another in many respects. Some people harbor more or fewer than the typical number (two copies, one from each parent) of certain genome segments. These differences are known as copy number variations (CNVs). CNVs play an important role in determining the phenotype, or observable characteristics, of each individual.

Autism appears to be caused by aberrant synapses, or connections between brain cells. A leading hypothesis is that a generalized hyper-excitability in the brains of individuals with autism impairs cognitive functions and increases seizure susceptibility.

Immune system activity in the central nervous system (CNS) has been implicated in numerous neuroinflammatory diseases. Over the past decade, however, Jonathan Kipnis has found evidence that mice with immune deficiencies also exhibit cognitive impairments.

Children with autism have been shown to display an increased latency of auditory processing, as measured by the electroencephalography (EEG) response to a sound as well as differences in brain activity at rest.

Deficits in social behaviors are a core aspect of autism and can be quite debilitating. Despite significant advances in identifying genes associated with autism spectrum disorders, the neural circuits that mediate social behaviors remain obscure.