Disrupted stimulus offset responses in autism spectrum disorder

  • Awarded: 2019
  • Award Type: Pilot
  • Award #: 647415

A decrease in cortical neural inhibition has been hypothesized to be a primary contributor to the neurobiological basis of autism spectrum disorder (ASD)1. Despite the prominence of this hypothesis, the current experimental evidence has either been indirect or has come from animal models with mixed results.

Scott Murray and colleagues at the University of Washington are testing a novel prediction of disrupted neural inhibition. Specifically, they predict that there will be a diminished or absent stimulus neural offset response in individuals with ASD. This prediction is motivated by a striking observation made in previous functional magnetic resonance imaging (fMRI) measurements in response to simple visual stimuli in adults with ASD compared to neurotypical individuals. Specifically, an fMRI undershoot to sensory stimulation (the fMRI response goes negative before returning to baseline) was measured in neurotypical individuals, as is typically observed in sensory fMRI experiments. However, the fMRI undershoot was virtually absent in a group of matched ASD participants2.

Recent findings that have simultaneously measured electroencephalography (EEG) and fMRI responses have demonstrated that the fMRI undershoot: 1) reflects neural responses, 2) correlates with the magnitude of EEG stimulus offset responses and 3) is tied to inhibitory processing3,4. Thus, the initial fMRI observation of a lack of an undershoot in the ASD population suggests disrupted neural inhibition that is specifically tied to removal of excitatory drive.

To test this hypothesis, Murray, in collaboration with Sara Jane Webb, proposes to measure EEG/ event-related potential (ERP) stimulus offset responses, the fMRI undershoot and psychophysical measures of visual sensitivity following stimulus removal in an adult population with ASD compared to matched neurotypical adults. Together, these experiments seek to establish a novel measure of altered neural inhibitory processing in ASD.


  1. Rubenstein J.L. and Merzenich M.M. Genes Brain Behav. 2, 255-267 (2003) PubMed
  2. Murray S. O. et al. Front. Hum. Neurosci. 14, 241(2020) PubMed
  3. Mullinger K. J. et al. Proc. Natl. Acad. Sci. 110, 13636-13641 (2013) PubMed
  4. Mullinger K. J. et al. Neuroimage 157, 388-399 (2017) PubMed
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