Intrainsular White Matter Connectivity and Sensory Profiles in Children with and without Autism Spectrum Disorder

Background: Individuals with autism spectrum disorder (ASD) have impairments in social responsiveness as well as altered responsiveness to sensory stimuli.  While the relationship between these symptoms is not known, the insula is a region of interest given its involvement in processing both sensory and social stimuli (Craig, 2011).  The functional anatomy of the insula follows an anterior-posterior gradient, with various sensory representations along the length of the axis including social/affective touch in the most posterior region (Olausson et al., 2002) and oral sensory stimuli more anteriorly. The most anterior region of the insula functions as a salience detector, evaluating sensory stimuli for affective relevance and acting as a hub to link salient stimuli to large scale neural networks for attention (Menon and Uddin, 2010) . White matter connections between regions of the insula may therefore serve as a pathway for the emotional processing of sensory stimuli, and may be particularly relevant for understanding the link between sensory and social responsiveness in ASD.  Because of its importance for social development and its representation in the insula, the present study focused on the sense of touch.

Objectives: We sought to explore properties of white matter connectivity between the anterior and posterior insula and their associations with sensory profiles including measures of responsiveness to social touch in children with and without ASD.

Methods: 24 children with ASD and 20 children with typical development completed MRI scans and their parents completed questionnaires about sensory behaviors. Anterior and posterior insular seeds were defined using a parcellation generated on a standard template (Farb et al., 2013). Probabilistic tractography was used to generate white matter tracts between the seeds.  Fractional anisotropy (FA) and tract volumes normalized for total brain volume were calculated for each subject. Independent samples t-tests were conducted to explore group differences in FA and tract volume, and correlations were used to assess relations between tract characteristics and sensory profiles. 

Results: FA and relative tract volumes were both decreased in the ASD group compared to the typically developing group (FA: t (52)=-2.186, p=.033, volume: t(53)=-2.241, p=.029). Within the ASD group, decreased intrainsular FA was associated with aberrant response to social sensory stimuli across sensory modalities (r=-.531, p=.008). Decreased tract volume was associated with aberrant response to social touch (r=-.433, p=.034) and tactile hyporesponsiveness (r=-.417, p=.04). Increased tract volume was associated with unusual sensory interest in touch (r=.441, p=.03). There were no significant associations between FA or volume and sensory profiles within the TD group alone.

Conclusions: We noted differences in the intrainsular white matter microstructure between individuals with and without ASD. These results suggest smaller and less organized  tracts connecting the posterior sensory insular cortex to the anterior salience detector in individuals with ASD, and this disorganization is associated with altered responsiveness to social sensory stimuli, particularly touch.  This suggests that individuals with ASD may ascribe less salience to social touch stimuli, which may impact social function, given the primacy of touch in early social development.