David Heeger, André Fenton and Robert Froemke of New York University, in collaboration with Marlene Behrmann of Carnegie Mellon University in Pittsburgh, are investigating the possibility that generic, brain-wide circuit malfunctions lie at the root of autism spectrum disorders. They posit that if we understood these malfunctions better, both diagnosis and intervention might be optimized.

Their research builds on the idea that that there is a fundamental organizing principle, called the ‘canonical circuit,’ for both the architecture and the function of the brain. Two features of autism suggest that canonical circuit dysfunction may underlie the developmental abnormalities in autism: hypersensitivity to sensory stimuli and a high prevalence of seizure activity.

Behrmann and Heeger previously found that brain activity in response to sensory stimulation (visual, auditory and tactile) — known as sensory-evoked activity — is unreliable in individuals with autism. This atypical neural profile may reflect a fundamental perturbation in brain function, which would affect a wide swath of brain regions and their concomitant behaviors.

The team plans to carry out two sets of experiments, one in people and the other in a mouse model of autism, to determine whether unreliable sensory-evoked activity is indeed a hallmark of autism. The researchers plan to study adults with autism to determine whether the unreliable neural response profile is a characteristic of autism.

They also plan to compare the neural activity of these individuals with that of adults with schizophrenia to test whether unreliable neural activity is specific to autism or a more general manifestation of neuropsychiatric disorders. In addition, they aim to correlate the reliability of sensory-evoked activity with behavioral and psychophysical measures of sensation and perception.

Finally, they aim to determine whether mice lacking the fragile X mental retardation protein (FMR1), a mouse model of autism, exhibit unreliable responses analogous to those found in people with autism, and to explore the effect of unreliable neural activity on brain development.