Functional Integration of the Neural Theory-of-Mind Network and Its Relations to Children's Social Communication and Functioning

Background: Theory of Mind (ToM) impairments may contribute to social communication and interaction deficits in autism spectrum disorder (ASD). Individuals with ASD show atypical neural activity and connectivity in the ToM network. Despite its relevance to understanding functional integration, few studies have evaluated effective connectivity of ToM circuitry, i.e., how different neural regions interact to support ToM reasoning versus other inferential processes, during childhood. Moreover, associations between effective connectivity and variation in social communication and interaction across typical (TD) and atypical child development remain unclear.

Objectives: This study aimed to (a) evaluate effective connectivity between key nodes of the ToM network, i.e., the precuneus and bilateral temporoparietal junction (rTPJ and lTPJ), and other brain regions during ToM versus non-ToM reasoning and (b) explore relations between these neural measures of functional integration and children’s social communication skills and everyday social functioning. We predicted that (a) TD children would demonstrate greater connectivity between ToM regions and other neural circuitry implicated in social cognition during ToM reasoning and (b) the strength of this functional coupling would be associated with individual variation in children’s social communication and functioning.

Methods: Participants were 32 TD children, ages 9-13. In the MRI scanner, participants completed a false belief task. In the experimental (ToM) condition, children listened to vignettes describing social scenarios and evaluated characters’ beliefs. In the control condition, they listened to non-social scenarios and made inferences about physical causality. Children also completed the Social Language Development Test, and parents completed the Social Skills Improvement System questionnaire.

Results: Generalized psychophysiological interaction (gPPI) analyses seeded in the precuneus, lTPJ, and rTPJ revealed distinct patterns of effective connectivity during ToM versus control conditions. Results were significant at a peak threshold of p<.001 with a cluster-wise false discovery rate correction (p<.05). The precuneus demonstrated greater connectivity with the left middle temporal gyrus (MTG), while the lTPJ showed enhanced connectivity with the bilateral superior temporal sulcus (STS). The rTPJ showed increased connectivity with several brain regions associated with social cognition, including the left dorsomedial prefrontal cortex (DMPC), pSTS/MTG, pre-supplementary motor area, and right cerebellum. Brain-behavior analyses revealed that greater coupling between the rTPJ and DMPFC showed a trend-level association with better social functioning (r_s=0.33, p=.078); diminished coupling between the precuneus and MTG was associated with better social communication, specifically using mental state inferences to explain others’ behavior (r_s=-0.41, p=.027).

Conclusions: Children demonstrated greater coupling of the rTPJ, lTPJ, and precuneus with a distributed set of neural regions implicated in social cognition during ToM relative to control conditions. Findings elucidate how key nodes of the ToM network interact with other regions to support mental state reasoning. Results also suggest that measures of effective connectivity during ToM index individual variation in children’s social communication and functioning. This work has important translational implications for studying social deficits in children with ASD. Exploring effective connectivity in atypical neurodevelopment could yield insight into disruptions in functional integration of the social brain. Moreover, effective connectivity measures may serve as potential metrics of heterogeneity in social development.