Underconnectivity between voice-selective cortex and reward circuitry in children with autism

Abstract

Individuals with autism spectrum disorders (ASDs) often show insensitivity to the human voice, a deficit that is thought to play a key role in communication deficits in this population. The social motivation theory of ASD predicts that impaired function of reward and emotional systems impedes children with ASD from actively engaging with speech. Here we explore this theory by investigating distributed brain systems underlying human voice perception in children with ASD. Using resting-state functional MRI data acquired from 20 children with ASD and 19 age- and intelligence quotient-matched typically developing children, we examined intrinsic functional connectivity of voice-selective bilateral posterior superior temporal sulcus (pSTS). Children with ASD showed a striking pattern of underconnectivity between left-hemisphere pSTS and distributed nodes of the dopaminergic reward pathway, including bilateral ventral tegmental areas and nucleus accumbens, left-hemisphere insula, orbitofrontal cortex, and ventromedial prefrontal cortex. Children with ASD also showed underconnectivity between right-hemisphere pSTS, a region known for processing speech prosody, and the orbitofrontal cortex and amygdala, brain regions critical for emotion-related associative learning. The degree of underconnectivity between voice-selective cortex and reward pathways predicted symptom severity for communication deficits in children with ASD. Our results suggest that weak connectivity of voice-selective cortex and brain structures involved in reward and emotion may impair the ability of children with ASD to experience speech as a pleasurable stimulus, thereby impacting language and social skill development in this population. Our study provides support for the social motivation theory of ASD.

Keywords: auditory cortex; nucleus accumbens.

Fig. 1.

Within-group functional connectivity results for left- and right-hemisphere voice-selective cortex. (Left) TD children and children with ASD showed significant connectivity between left-hemisphere pSTS and a distributed cortical network. The seed region used in this analysis was a 6-mm sphere centered at the Montreal Neurological Institute (MNI) coordinates [−63, −42, 9] (23). (Right) In contrast to TD children, right-hemisphere pSTS connectivity is sparse for children with ASD and is restricted primarily to superior temporal cortex. The seed used in this analysis was a 6-mm sphere centered at MNI coordinates [57, −31, 5] (23). Images are thresholded at P < 0.000001 for voxel height and an extent of 100 voxels. aMTG, anterior middle temporal gyrus; BA 45, Brodmann area 45 (pars triangularis); FG, fusiform gyrus; pSTG, posterior superior temporal gyrus; OP, occipital pole; PT, planum temporale; Thal, thalamus.

Fig. 2.

Between-group functional connectivity results for left-hemisphere voice-selective cortex. Group differences for the TD>ASD contrast indicated ASD underconnectivity between left-hemisphere pSTS and structures of the reward network, including the VTA, nucleus accumbens (NAc), insula, and OFC. No voxels showed significant connectivity for the ASD>TD contrast. The seed used in this analysis was a 6-mm sphere centered in left-hemisphere pSTS at MNI coordinates [−63, −42, 9] (23). Images are thresholded at P < 0.01 for voxel height and an extent of 100 voxels. Mean connectivity differences between TD children and children with ASD are plotted in the bar graphs for six left-hemisphere and four right-hemisphere regions (error bars represent SEM). SFG, superior frontal gyrus; SMA, supplementary motor area.

Fig. 3.

Between-group functional connectivity results for right-hemisphere voice-selective cortex. Group differences for the TD>ASD contrast indicated ASD underconnectivity between right-hemisphere pSTS and an array of cortical regions. No voxels showed significant connectivity for the ASD>TD contrast. The seed used in this analysis was a 6-mm sphere centered at MNI coordinates [57, −31, 5] (23). Images are thresholded at P < 0.01 for voxel height and an extent of 100 voxels. Mean connectivity differences between TD children and children with ASD are plotted in the bar graphs for four left-hemisphere and three right-hemisphere regions (error bars represent SEM). Ent, entorhinal cortex; Hipp, hippocampus; mSTS, mid-superior temporal sulcus; SFG, superior frontal gyrus; SMA, supplementary motor area.

Fig. 4.

Voice-selective pSTS connections entered into regression models for brain-behavior analyses. Functional connectivity between bilateral pSTS and the distributed reward circuit, including VTA, NAc, OFC, and anterior insula, as well as the amygdala, predicted communication subtests of the ADOS (R² = 0.713, P = 0.008) and ADI (R² = 0.740, P = 0.003) in children with ASD. Because of the narrow range of clinical symptom scores, logistic regression was performed, and scatter plots are not depicted for the ADOS and ADI measures.