Subregion-specific thalamocortical functional connectivity, executive function, and social behavior in children with autism spectrum disorders

The thalamus has extensive cortical connections and is an integrative hub for cognitive functions governing social behavior. This study examined (1) associations between thalamocortical resting-state functional connectivity (RSFC) and social behavior in children and (2) how various executive function (EF) subdomains mediate the association between thalamocortical RSFC and social behavior. Children from the autism brain imaging data exchange (ABIDE) initiative with neuroimaging, behavioral, and demographic data were included in our study (age < 14, ASD; n = 207, typically developing; n = 259). Thalamocortical RSFC was examined for associations with social communication and interaction (SCI) scores (SRS; social responsiveness scale) using Spearman's rank-order correlation, first in ASD children and then in typically developing children. This was followed by a more granular analysis at the thalamic subregion level. We then examined the mediating roles of eight EF subdomains in ASD children (n = 139). Right thalamus-default mode network (DMN) RSFC was significantly associated with SCI scores in ASD children (ρ = 0.23, p_FDR = 0.012), primarily driven by the medial (ρ = 0.22, p_FDR = 0.013), ventral (ρ = 0.17, p_FDR = 0.036), and intralaminar (ρ = 0.17, p_FDR = 0.036) thalamic subregions. Cognitive flexibility (ACME = 0.13, p_unc = 0.016) and emotional control (ACME = 0.08, p_unc = 0.020) significantly mediated the association between right thalamus-DMN RSFC and SCI scores. This study provided novel insights into the association between thalamocortical RSFC and social behavior in ASD children at the thalamic subregion level, providing higher levels of precision in brain-behavior mapping. Cognitive flexibility and emotion regulation were highlighted as potential targets to ameliorate the downstream effects of altered thalamocortical connectivity to improve social outcomes in ASD children.