Late fMRI Response Components Are Altered in Autism Spectrum Disorder.

Scott O Murray,Tamar Kolodny,Jennifer Gerdts,Michael-Paul Schallmo,Raphael A Bernier

doi:10.3389/fnhum.2020.00241

Abstract

Disrupted cortical neural inhibition has been hypothesized to be a primary contributor to the pathophysiology of autism spectrum disorder (ASD). This hypothesis predicts that ASD will be associated with an increase in neural responses. We tested this prediction by comparing fMRI response magnitudes to simultaneous visual, auditory, and motor stimulation in ASD and neurotypical (NT) individuals. No increases in the initial transient response in any brain region were observed in ASD, suggesting that there is no increase in overall cortical neural excitability. Most notably, there were widespread fMRI magnitude increases in the ASD response following stimulation offset, approximately 6–8 s after the termination of sensory and motor stimulation. In some regions, the higher fMRI offset response in ASD could be attributed to a lack of an “undershoot”—an often observed feature of fMRI responses believed to reflect inhibitory processing. Offset response magnitude was associated with reaction times (RT) in the NT group and may explain an overall reduced RT in the ASD group. Overall, our results suggest that increases in neural responsiveness are present in ASD but are confined to specific components of the neural response, are particularly strong following stimulation offset, and are linked to differences in RT.

Highlights

Autism spectrum disorder (ASD) is a behaviorally-defined neurodevelopmental disorder that includes difficulties in social communication and interaction, restricted interests and repetitive behaviors, and altered sensory responses (American Psychiatric Association, 2013; Lord and Bishop, 2015)
We demonstrate a lack of an fMRI undershoot in individuals with autism spectrum disorder (ASD) which may be attributable to disrupted neural inhibition
Disrupted neural inhibition, which is thought to lead to an increase in neuroexcitability and an increase in neural noise (Rubenstein and Merzenich, 2003; Nelson and Valakh, 2015), is an often-cited potential neurophysiological mechanism for ASD (Fatemi et al, 2009; Coghlan et al, 2012; Ford and Crewther, 2016; Robertson et al, 2016)

Summary

INTRODUCTION

Autism spectrum disorder (ASD) is a behaviorally-defined neurodevelopmental disorder that includes difficulties in social communication and interaction, restricted interests and repetitive behaviors, and altered sensory responses (American Psychiatric Association, 2013; Lord and Bishop, 2015). Simultaneous spike-rate and fMRI measurements in monkeys have shown that stimulus-offset spike-rate suppression is related to the fMRI undershoot (Shmuel et al, 2006), strengthening the link between the fMRI undershoot and inhibitory processes This relationship between the fMRI undershoot and neural inhibition is of particular interest in ASD given the possible role of disrupted inhibition (Coghlan et al, 2012) and its potential impact on increasing neural noise (Leventhal et al, 2003). To evaluate changes in stimulus offset responses in ASD and to compare them to more typically measured transient responses, we used an experimental procedure that elicited neural responses simultaneously in multiple sensory areas and the motor system in young adults with ASD compared to neurotypical (NT) controls This dataset was used previously to characterize sustained responses and adaptation in ASD, primarily in the visual and auditory cortex (Millin et al, 2018). We demonstrate a lack of an fMRI undershoot in individuals with ASD which may be attributable to disrupted neural inhibition

Participants

RESULTS

DISCUSSION

ETHICS STATEMENT