Thalamocortical connectivity is associated with autism symptoms in high-functioning adults with autism and typically developing adults

Abstract

Alterations in sensorimotor functions are common in individuals with autism spectrum disorder (ASD). Such aberrations suggest the involvement of the thalamus due to its key role in modulating sensorimotor signaling in the cortex. Although previous research has linked atypical thalamocortical connectivity with ASD, investigations of this association in high-functioning adults with autism spectrum disorder (HFASD) are lacking. Here, for the first time, we investigated the resting-state functional connectivity of the thalamus, medial prefrontal, posterior cingulate, and left dorsolateral prefrontal cortices and its association with symptom severity in two matched cohorts of HFASD. The principal cohort consisted of 23 HFASD (mean[SD] 27.1[8.9] years, 39.1% female) and 20 age- and sex-matched typically developing controls (25.1[7.2] years, 30.0% female). The secondary cohort was a subset of the ABIDE database consisting of 58 HFASD (25.4[7.8] years, 37.9% female) and 51 typically developing controls (24.4[6.7] years, 39.2% female). Using seed-based connectivity analysis, between-group differences were revealed as hyperconnectivity in HFASD in the principal cohort between the right thalamus and bilateral precentral/postcentral gyri and between the right thalamus and the right superior parietal lobule. The former was associated with autism-spectrum quotient in a sex-specific manner, and was further validated in the secondary ABIDE cohort. Altogether, we present converging evidence for thalamocortical hyperconnectivity in HFASD that is associated with symptom severity. Our results fill an important knowledge gap regarding atypical thalamocortical connectivity in HFASD, previously only reported in younger cohorts.

Fig. 1. Voxels that were found to exhibit hyperconnectivity with the right thalamus.

Significant clusters found in the HFASD (orange) and ABIDE (blue) cohorts are colored by p-value. A Top - axial view, middle - coronal view, bottom - sagittal view, sliced from center to right. HFASD clusters are primarily localized in the left and right precentral gyri, left and right postcentral gyri, and right superior parietal lobule. ABIDE clusters are primarily localized in the right precentral and postcentral gyri, right insulae, and right and left cuneus. B Bar graphs depicting group differences in group-level GLM parameter estimates, taken as an average of all the voxels in a particular cluster for each subject. The two clusters in the right precentral and postcentral gyri (Table 3) were averaged together as one cluster. SPL = superior parietal lobule.

Fig. 2. Correlations of left precentral/postcentral gyri cluster with AQ.

Correlations by group (A), in males by group (B), and in females by group (C). Reported r values are Pearson’s correlation coefficients.