Hyperconnectivity of the Right Posterior Temporo-Parietal Junction Predicts Social Deficits in High-Functioning Boys with Autism

Background: Autism is characterized by impaired social cognition, which may be underpinned by systems-level atypical neural connectivity. The posterior right temporo-parietal junction (pRTPJ) is a key region involving in representing other’s mental states. In neurotypical individuals, the pRTPJ exhibits intrinsic functional connectivity (iFC) with areas associated with social cognition (e.g., the default mode network, DMN). Atypical activation at pRTPJ during mentalizing in individuals with autism has been shown, however the iFC of the pRTPJ remains underexplored.  

Objectives: We test whether boys with autism show altered resting-state iFC of the pRTPJ. We further test whether atypical iFC of pRTPJ is associated with social deficits in autism.

Methods: Resting-state fMRI (3-Tesla Siemens Tim Trio system, 6-minute scan with eyes closed, TR=2sec) was collected in 46 boys with autism and 44 typically developing (TD) boys. Participants exhibiting greater than 4 time points of excessive in-scanner head motion of frame-wise displacement >1mm were excluded from analyses. The final sample included 40 boys with autism (aged 9-17 years, mean age=12.38±2.17; mean PIQ=105.60±16.06), and 42 age- and performance IQ-matched TD boys (mean age=11.64±2.71; mean PIQ=111.29±13.45). Data were preprocessed using the Data Processing Assistant for Resting-State fMRI (DPARSF) toolbox based on SPM8, without regressing out mean global signals. Motion artifact was corrected by nuisance regression against 24-autoregressive motion parameters at an individual level, together with individual mean frame-wise displacement included as a covariate in the group-level analysis. Seed-based approach was used to investigate iFC (i.e., Pearson’s correlation between time-series) of the pRTPJ. General linear model was used to analyze between-group differences in iFC, cluster-wise FWE-corrected at p<0.05, with a cluster-forming voxel-level threshold of p<0.01. Pearson’s correlations between atypical iFC (seed-peak atypical coordinate pairs) in the autism group and social difficulties measured by the Chinese version of the ADI-R and Social Responsiveness Scale (SRS) were calculated, corrected for multiple comparisons at FDR q<0.05 (an FDR q between 0.05-0.1 was considered trend-level significant).  

Results: TD boys demonstrated a resting-state pRTPJ iFC pattern comparable to the known spatial involvement of the DMN, which was not reliably observed in boys with autism. Boys with autism showed pRTPJ hyperconnectivity relative to TD boys in a right-hemispheric cluster (9693 mm³) involving the lingual gyrus (LG), fusiform gyrus (FG), and middle occipital gyrus (MOG), each with a group-difference peak. There was no increased connectivity of the pRTPJ in TD boys compared to boys with autism. There were significant positive correlations between the pRTPJ-right MOG connectivity and total SRS score (r=0.36, q=0.048), and the ‘social communication’ (r=0.38, q=0.045) and ‘social emotion’ (r=0.38, q=0.045) subscores of the Chinese SRS. pRTPJ connectivity with other two subregions showed trends of positive correlations with the same Chinese SRS scores (r=0.23-0.29, q=0.083-0.091). There was a positive correlation between social reciprocity deficits on the ADI-R and pRTPJ-right FG connectivity (r=0.34, q=0.051).

Conclusions: We found resting-state hyperconnectivity between pRTPJ and right occipito-temporal regions in high-functioning boys with autism, which was correlated with their social deficits. This indicates that atypical connectivity of the pRTPJ may be integral to the atypical neurobiology of autism.