Sensory Seeking and Salience Network Functional Connectivity in Females and Males with Autism Spectrum Disorder

Background: Individuals with an autism spectrum disorder (ASD) are significantly more likely to experience atypical sensory sensitivities and seeking behaviors compared to their typically developing (TD) peers (Liss et al., 2006). Prior work in our lab has found that sensory over-responsivity (SOR) in autism is related to atypical resting-state functional connectivity in the salience network (SN), an intrinsic brain network thought to be related to where the brain directs attention (Green et al., 2016). However, most studies examining the neurological basis of sensory processing have been done with primarily male samples, so little is known about how ASD females process sensory information. Additionally, little is known about the neurobiological basis of sensory seeking (compared to SOR) though we hypothesize that seeking is also related to atypical attribution of salience to sensory stimuli.

Objectives: To examine SN functional connectivity underlying sensory seeking in males and females with ASD and to determine whether atypical seeking-related connectivity confers resilience in the form of better executive functioning.

Methods: The relationship between sensory seeking and SN functional connectivity was compared between ASD males and females in two samples of youth aged 7-18 years. In Study 1, resting-state fMRI was conducted on 78 ASD (43F) and 103 TD (55F) participants. The anterior insula (AI), thought to be the hub of the SN (Seeley, 2007), was used as the seed in whole-brain analyses. Seeking behaviors, determined through self-report on the Short Sensory Profile (SSP; Dunn, 1999), were correlated with AI connectivity. Because youth with ASD have been shown to be poor reporters of their own internal sensations (Shalom, 2006), we replicated the analysis in a second sample of 44 ASD (11F) and 31 TD (10F) participants that had parent reports of sensory seeking on the SSP. Whole-brain analyses were thresholded at Z>2.3 and corrected for multiple comparisons at p<.05 for both studies. Executive functioning was measured with the BRIEF (Gioia et al., 2000).

Results: In both studies, there were no sex differences in seeking. In Study 1, ASD females with more abnormal sensory seeking behaviors showed greater AI connectivity with medial prefrontal cortex (mPFC) compared to their male counterparts. In Study 2, sensory seeking related to greater positive connectivity between the SN and mPFC across males and females with ASD. Better executive functioning was correlated with both more sensory seeking and greater SN connectivity with mPFC in both males and females.

Conclusions: Sensory seeking may potentially be used as a regulatory mechanism for ASD adolescents, as shown through correlations with prefrontal connectivity and executive functioning. This process appears to only have sex group differences when sensory seeking behaviors are self-reported, perhaps providing insight into the ways males and females with autism are able to report on their internal states. Results of mediation analysis will be discussed to determine whether seeking might mediate the relation between medial prefrontal connectivity and executive functioning.