A neural substrate for sensory over-responsivity defined by exogenous and endogenous brain systems

Abstract Background Exogenous (outward-directed) and endogenous (inward-directed) neural systems are essential for cognition and behavior. However, how they are altered in neurodiverse (ND) children remains unanswered in part due to heterogeneity. Sensory over-responsivity (SOR), the most prevalent form of sensory processing disorder (SPD), serves as a quintessential paradigm for investigating the interaction between exogenous and endogenous brain networks given that both basic and higher-order sensory processing are substantially implicated in this condition. Methods Neurodiverse children ages 8–12 years old (n = 83; 30 females and 53 males) were directly assessed for SOR using a structured clinical evaluation, the Sensory Processing 3 Dimensions Assessment (SP3D:A), and underwent 3 Tesla MRI. 39 ND children presented with SOR (ND/SOR) and 44 ND children presented without SOR (ND/NO-SOR). Exogenous and endogenous functional connectivity networks (FCNs) were generated through independent component analysis and investigated with two local functional connectivity (FC) measures, fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo), as well as a long-range FC measure, dual regression (DR). Moreover, we examined FC in the context of behavioral regulation as assessed through the Behavioral Assessment System for Children, 3rd edition (BASC-3), categorizing children as “resilient” or “dysregulated” through latent profile analysis. Results In general, ND/SOR children exhibit reduced long-range exogenous FC. However, in terms of local FC, we find that ND/SOR children have reduced exogenous and elevated endogenous FC which is diametrically opposed to ND/NO-SOR children. Furthermore, this double dissociation is specific to ND children who are behaviorally resilient, while emotionally dysregulated ND children possess a distinct pattern. Conclusion Achieving optimal brain system connectivity—a balanced contrast—is influenced by sensory over-responsivity and essential for resilience.