Theory of Mind network in Multiple Sclerosis: a double disconnection mechanism.

The relationship between cognitive and affective theory of mind (ToM), clinical variables, and brain tissue injury is still a subject of debate in multiple sclerosis (MS). By adopting a ToM Networks model, we investigated ToM performance, and brain imaging correlates in relapsing-remitting (RR) and progressive (Pr) MS. 16RR, 19Pr, and 21 healthy controls were assessed with both cognitive (CToM) and affective ToM (AToM) tests and neuropsychological tools and were evaluated with MRI. Cortical thickness, sub-cortical volumetry, and tract-based-spatial-statistics were analyzed. Our results reported a CToM deficit in Pr, correlated with attention. While no relation between gray matter and CToM was observed, a widespread correlation between CToM and normal-appearing white matter was found. In particular, we registered a significant positive correlation between CToM and fractional anisotropy in Superior and Inferior Longitudinal Fasciculus and right thalamic radiation tracts. Moreover, an inverse correlation between CToM and mean diffusivity of the right fronto-occipital fasciculus, bilateral superior longitudinal fasciculus, cortico-spinal, left uncinate, corpus callosum, and forceps minor tracts was also observed. This work highlighted a double disconnection mechanism in Pr MS affecting communication both (1) inside the ToM network and (2) between the ToM network and cognitive execution areas, likely explaining the deficit in cognitive ToM.