Neural Habituation to Sensory Stimuli and Sustained Regulation across Time in Youth with Autism, with and without Sensory over-Responsivity

Background: As interest in sensory processing differences in autism has vastly increased, so too has interest in understanding the neurobiological bases of such differences. Our prior work showed that sensory over-responsivity (SOR) in autism is related to greater brain activity in amygdala and sensory cortices in response to mildly aversive sensory stimulation (Green at al., 2013, 2015). Here, we extended our investigation of neural responsivity to sensory stimuli by demonstrating that patterns of brain response to sensory stimuli differ across time, brain region, and SOR severity. Additionally, we examined how changes in prefrontal-amygdala connectivity across a period of sensory exposure differs according to SOR phenotype and contributes to interpretation of BOLD response.

Objectives: To extend the interpretation of brain response to sensory stimuli by examining 1) patterns of response (habituation) across different key brain regions over time in ASD youth with high versus low SOR and TD youth; and 2) how amygdala-prefrontal connectivity changes across sensory exposure in these three groups.

Methods: Participants were 42 children and adolescents with ASD and 27 TD matched controls, aged 8-17 years. ASD participants were grouped into high versus low SOR based on the median split of their parents’ ratings of SOR on the Short Sensory Profile (Dunn, 1999) and Sensory Over-Responsivity Inventory (Schoen et al. 2008). During fMRI, participants were presented with mildly aversive auditory (white noise) and tactile (scratchy sponge) stimulation. Stimuli were presented together for 6 blocks of 15-sec trials each. Parameter estimates of brain responses in key regions of interest (ROIs; i.e. amygdala, sensory cortices) were extracted for each block. A psychophysiological interaction analysis was used to examine how changes in amygdala connectivity from the first to second half of the sensory exposure varied as a function of SOR severity.

Results: ASD-high-SOR youth did not show differences in brain responses to the first block of sensory stimuli in any of the ROIs. However, examination of change in brain activity across the 6 blocks of sensory exposure revealed that ASD-high-SOR youth showed reduced habituation in amygdala and relevant sensory cortices, as well as reduced inhibition of irrelevant sensory cortices compared to TD and ASD-low-SOR youth. ASD-high-SOR and ASD-low-SOR youth showed distinct patterns of prefrontal-amygdala regulation.

Conclusions: Findings show that, across a period of sensory stimulation, ASD-high-SOR youth failed to sustain a) reduced habituation in sensory-relevant brain regions, b) reduced inhibition of irrelevant regions, and c) prefrontal downregulation of the amygdala. Taken together, these results indicate that sensory habituation in autism is an active, time-varying process dependent on sustained regulation across time, which may be a particular deficit in ASD-high-SOR youth. Thus, imaging studies that collapse brain responses across time will miss important group differences. Furthermore, ASD-low-SOR youth show increased prefrontal regulation compared to TD and ASD-high-SOR youth, suggesting that behavioral expression of SOR may depend on top-down mechanisms.