Differential deactivation during mentalizing and classification of autism based on default mode network connectivity

Abstract

The default mode network (DMN) is a collection of brain areas found to be consistently deactivated during task performance. Previous neuroimaging studies of resting state have revealed reduced task-related deactivation of this network in autism. We investigated the DMN in 13 high-functioning adults with autism spectrum disorders (ASD) and 14 typically developing control participants during three fMRI studies (two language tasks and a Theory-of-Mind (ToM) task). Each study had separate blocks of fixation/resting baseline. The data from the task blocks and fixation blocks were collated to examine deactivation and functional connectivity. Deficits in the deactivation of the DMN in individuals with ASD were specific only to the ToM task, with no group differences in deactivation during the language tasks or a combined language and self-other discrimination task. During rest blocks following the ToM task, the ASD group showed less deactivation than the control group in a number of DMN regions, including medial prefrontal cortex (MPFC), anterior cingulate cortex, and posterior cingulate gyrus/precuneus. In addition, we found weaker functional connectivity of the MPFC in individuals with ASD compared to controls. Furthermore, we were able to reliably classify participants into ASD or typically developing control groups based on both the whole-brain and seed-based connectivity patterns with accuracy up to 96.3%. These findings indicate that deactivation and connectivity of the DMN were altered in individuals with ASD. In addition, these findings suggest that the deficits in DMN connectivity could be a neural signature that can be used for classifying an individual as belonging to the ASD group.

Figure 1. Regions of Interest showing greater deactivation for control participants compared to participants with ASD for the contrast of rest blocks>all tasks combined (language, self-referential langauge, and ToM) in the (A) bilateral STG (68, −22, 4; −52, −62, 26), (B) LMPFC (−2, 66, 10), and (C) bilateral DLPFC (−42, 40, 18; 28, 30, 48) (p<0.005, cluster-corrected at 110 voxels).

Figure 2. Brain areas showing greater deactivation for control participants compared to participants with ASD for the contrast of rest>ToM task in the LMPFC, LACC, LSFG, LSTG, DLPFC, and PCC/PrC (p<0.001 uncorrected, FDR cluster-corrected).

Figure 3. The averaged DMN connectivity map (p<0.001, cluster corrected).

Significant clusters shown are represented as z scores. (A) DMN map for the control group. (B) DMN map for the ASD group. (C) DMN map of regions with greater connectivity in control participatns than participants with ASD. (D) Overlap of the control and ASD connectivity maps.

Figure 4. Correlations of resting-state time courses in which classification was based between ROI and seed region in the left AG, that showed significant group difference (p = 0.05, with Bonferroni correction), for each of the participants.