To assess the contribution of resting-state functional connectivity (RS-FC) changes of the default mode network (DMN), right fronto-parietal network (RFPN), left fronto-parietal network (LFPN), executive network (EN) and salience network (SLN) to Social Cognition in multiple sclerosis (MS) patients.

Impairment in Social Cognition has been showed in MS. Theory of mind (ToM), a proxy of Social Cognition, is the ability to understand and interpret another person's beliefs, intentions (cognitive ToM) and emotions (affective ToM). In particular, ToM impairment in MS has been related to focal gray matter atrophy and microstructural white matter damage. To date no studies have explored RS-FC changes related to social cognition in MS.

Forty-one relapsing remitting (RR) MS patients and 25 sex, age and education-matched healthy controls (HC) were evaluated by a neurological examination and tasks assessing cognitive (the ToM Pictures Sequencing Task) and affective (the Reading the Mind in the Eyes Task) ToM. All subjects underwent a 3T magnetic resonance imaging (MRI) protocol including structural and RS-fMRI (RS-fMRI) sequences. FC of the DMN, RFPN, LFPN, EN and SLN was evaluated by independent component analysis. Regional gray matter atrophy was assessed by voxel-based morphometry.

MS patients performed worse on ToM, compared to HC. In MS patients we found: positive association between DMN RS-FC in the right middle temporal gyrus and reciprocity score; negative association between DMN RS-FC in the PCC and first-order false-belief score; negative association between EN RS-FC in the cingulate gyrus and TMPS score; negative association between EN RS-FC in the cingulate gyrus and reciprocity score. All detected RS-FC changes did not co-localize with regional gray matter atrophy.

ToM in MS is associated to relevant RS-FC changes of DMN and EN. Further research is warranted to clarify the adaptive or maladaptive role of this FC changes in MS.