Resting-state functional brain connectivity for human mentalizing: biobehavioral mechanisms of theory of mind in multiple sclerosis

Although neural hubs of mentalizing are acknowledged, the brain mechanisms underlying mentalizing deficit, characterizing different neurological conditions, are still a matter of debate. To investigate the neural underpinning of theory of mind (ToM) deficit in multiple sclerosis (MS), a region of interest (ROI)-based resting-state fMRI study was proposed. In total, 37 MS patients (23 females, mean age = 54.08 +/- 11.37 years, median Expanded Disability Status Scale = 6.00) underwent an MRI and a neuro-psychosocial examination and were compared with 20 sex-age-education matched healthy subjects. A neuroanatomical ToM model was constructed deriving 11 bilateral ROIs and then between and within-functional connectivity (FCs) were assessed to test for group differences. Correlation with psychosocial scores was also investigated. Lower ToM performance was registered for MS both in cognitive and affective ToM, significantly associated with processing speed. A disconnection between limbic-paralimbic network and prefrontal execution loops was observed. A trend of aberrant intrinsic connectivity in MS within the anterior cingulate cortex (ACC) was also reported. Finally, a correlation between cognitive ToM and intrinsic FC was detected in ACC and dorsal striatum, belonging to the limbic-paralimbic network, likely explaining the behavioral deficit in MS. The results suggest that aberrant intrinsic and extrinsic connectivity constitutes a crucial neural mechanism underlying ToM deficit in MS.