Hyper-upregulation of abnormally low neural response along the visual pathway in autism

Abstract

A unifying theme of numerous proposals of the pathophysiology of autism spectrum disorder (ASD) is that it results from a pervasive alteration in neural excitability. However, the various forms of evidence implicating neural excitability appear contradictory. On one hand, a well-known hypothesis is that ASD might reflect an increase in excitation/inhibition (E/I) balance and hyper-excitability of cortical circuits. However, other evidence from animal models has pointed to the opposite hypothesis – that ASD can be characterized by a reduction in E/I balance resulting from reduced excitability. It has recently been suggested that both perspectives – over- and under-excitability – can be reconciled in a framework that takes into account the propagation of information in neural circuits and homeostatic mechanisms that stabilize neural responses. We used the well-established hierarchical structure of human visual motion processing to test the hypothesis that there is abnormal coupling of responses between visual areas in individuals with ASD. We used fMRI to measure neural responses to moving gratings of varying contrast in early visual cortex (EVC) and in human MT complex (hMT+), a motion selective region in the lateral occipital lobe that receives direct input from EVC. Our findings demonstrate that, among neurotypical participants, neural response magnitudes correlate between these brain regions: individuals with relatively high responses in EVC also have high responses in hMT+. On the contrary, among individuals with autism, there is a negative relationship between the magnitude of contrast responses in EVC and the magnitude of response in hMT+. Specifically, participants with abnormally low responses in EVC exhibit abnormally high responses in hMT+. Interestingly, the degree of abnormality in the neural responses correlates with severity of clinical symptoms of ASD. Our findings may suggest that compensatory homeostatic processes are dysregulated along the visual pathway, over-enhancing signals as they propagate through the visual system.

Meeting abstract presented at VSS 2018