Response Dissociation in Hierarchical Cortical Circuits: a Unique Feature of Autism Spectrum Disorder

A prominent hypothesis regarding the pathophysiology of autism is that an increase in the balance between neural excitation and inhibition results in an increase in neural responses. However, previous reports of population-level response magnitude in individuals with autism have been inconsistent. Critically, network interactions have not been considered in previous neuroimaging studies of excitation and inhibition imbalance in autism. In particular, a defining characteristic of cortical organization is its hierarchical and interactive structure; sensory and cognitive systems are comprised of networks where later stages inherit and build upon the processing of earlier input stages, and also influence and shape earlier stages by top-down modulation. Here we used the well established connections of the human visual system to examine response magnitudes in a higher-order motion processing region [middle temporal area (MT+)] and its primary input region (V1). Simple visual stimuli were presented to adult individuals with autism spectrum disorders (ASD; = 24, mean age 23 years, 8 females) and neurotypical controls ( = 24, mean age 22, 8 females) during fMRI scanning. We discovered a strong dissociation of fMRI response magnitude between region MT+ and V1 in individuals with ASD: individuals with high MT+ responses had attenuated V1 responses. The magnitude of MT+ amplification and of V1 attenuation was associated with autism severity, appeared to result from amplified suppressive feedback from MT+ to V1, and was not present in neurotypical controls. Our results reveal the potential role of altered hierarchical network interactions in the pathophysiology of ASD. An imbalance between neural excitation and inhibition, resulting in increased neural responses, has been suggested as a pathophysiological pathway to autism, but direct evidence from humans is lacking. In the current study we consider the role of interactions between stages of sensory processing when testing increased neural responses in individuals with autism. We used the well known hierarchical structure of the visual motion pathway to demonstrate dissociation in the fMRI response magnitude between adjacent stages of processing in autism: responses are attenuated in a primary visual area but amplified in a subsequent higher-order area. This response dissociation appears to rely on enhanced suppressive feedback between regions and reveals a previously unknown cortical network alteration in autism.