Neurobiology of Sensory Overresponsivity in Youth With Autism Spectrum Disorders

Abstract

IMPORTANCE More than half of youth with autism spectrum disorders (ASDs) have sensory overresponsivity (SOR), an extreme negative reaction to sensory stimuli. However, little is known about the neurobiological basis of SOR, and there are few effective treatments. Understanding whether SOR is due to an initial heightened sensory response or to deficits in regulating emotional reactions to stimuli has important implications for intervention.OBJECTIVE To determine differences in brain responses, habituation, and connectivity during exposure to mildly aversive sensory stimuli in youth with ASDs and SOR compared with youth with ASDs without SOR and compared with typically developing control subjects. DESIGN, SETTING, AND PARTICIPANTS Functional magnetic resonance imaging was used to examine brain responses and habituation to mildly aversive auditory and tactile stimuli in 19 high-functioning youths with ASDs and 19 age-and IQ-matched, typically developing youths (age range, 9-17 years). Brain activity was related to parents' ratings of children's SOR symptoms. Functional connectivity between the amygdala and orbitofrontal cortex was compared between ASDs subgroups with and without SOR and typically developing controls without SOR. The study dates were March 2012 through February 2014. MAIN OUTCOMES AND MEASURESRelative increases in blood oxygen level-dependent signal response across the whole brain and within the amygdala during exposure to sensory stimuli compared with fixation, as well as correlation between blood oxygen level-dependent signal change in the amygdala and orbitofrontal cortex. RESULTSThe mean age in both groups was 14 years and the majority in both groups (16 of 19 each) were male. Compared with neurotypical control participants, participants with ASDs displayed stronger activation in primary sensory cortices and the amygdala (P < .05, corrected). This activity was positively correlated with SOR symptoms after controlling for anxiety. The ASDs with SOR subgroup had decreased neural habituation to stimuli in sensory cortices and the amygdala compared with groups without SOR. Youth with ASDs without SOR showed a pattern of amygdala downregulation, with negative connectivity between the amygdala and orbitofrontal cortex (thresholded at z > 1.70, P < .05). CONCLUSIONS AND RELEVANCEResults demonstrate that youth with ASDs and SOR show sensorilimbic hyperresponsivity to mildly aversive tactile and auditory stimuli, particularly to multiple modalities presented simultaneously, and show that this hyperresponsivity is due to failure to habituate. In addition, findings suggest that a subset of youth with ASDs can regulate their responses through prefrontal downregulation of amygdala activity. Implications for intervention include minimizing exposure to multiple sensory modalities and building coping strategies for regulating emotional response to stimuli.

Salience Network Connectivity in Autism Is Related to Brain and Behavioral Markers of Sensory Overresponsivity

“…These individuals also show decreased neural habituation to sensory stimuli and lack prefrontal inhibition of the amygdala during exposure to sensory stimuli. 10 Taken together, these results suggest that SOR may be related to overattribution of salience to extraneous sensory information, as well as to an inability to down-regulate the brain’s responses to this information, thus leading to over-attention towards sensory information. Therefore, we hypothesized that within youth with ASD, individual differences in SOR would be related to extent of connectivity with the salience network, particularly that higher SOR would be related to greater connectivity within the salience network (i.e., with the amygdala), and between the salience network and areas related to primary sensory processing.…”

“…Recent neuroimaging research suggests that SOR may be related to an over-attribution of salience to extraneous sensory information. 9,10 Thus, in the present study we sought to examine how intrinsic connectivity in the salience network relates to SOR by integrating resting-state functional magnetic resonance imaging (fMRI), task-based fMRI, and behavioral data, to test the assumption that atypical functional connectivity in ASD is directly related to altered brain activity during information processing, as well as to provide insight into SOR, an important source of heterogeneity and impairment in ASD that has as yet received little attention.…”

“…2 Consistent with this hypothesis, the anterior insula has been found to be hypoactive in response to social cognition tasks in ASD but hyperactive in response to basic sensory information. 10,12 However, to date there is little research on how differences in brain network organization in ASD relate to within-group heterogeneity in brain function during information processing, and none to our knowledge has focused on the salience network.…”

Matrix metalloproteinase-9 deletion rescues auditory evoked potential habituation deficit in a mouse model of Fragile X Syndrome

“…Sensory processing deficits are commonly observed in ASD (Green et al, 2015), but the underlying cellular mechanisms remain unclear. Fragile X syndrome (FXS) is a leading known inherited form of ASD affecting ~1 in 4000 males and 1 in 8000 females (Sherman 2002).…”

Theory of Mind: Towards an Evolutionary Theory

“…Especially if presented simultaneously across several sensory modalities, which is often the case in face-to-face social intercourse, they may overload their processing capacity and lead to a cognitive and behavioral "shut-down." Studies have shown that this sensory overresponsivity (SOR) is predicated on a hyperactivity in areas related to primary sensory processing, emotional regulation, and response to threat (Green et al 2015). 37 A similar, but less pronounced, inhibitory role is played by the freeze reflex, which seems to be driven by GABAergic and cholinergic neurotransmission (Power and McGaugh 2002;Jhou 2005).…”