Background:Psychological stress can influence the severity of multiple sclerosis (MS), but little is known about neurobiological factors potentially counteracting these effects. Objective:To identify gray matter (GM) brain regions related to relaxation after stress exposure in persons with MS (PwMS). Methods:36 PwMS and 21 healthy controls (HCs) reported their feeling of relaxation during a mild stress task. These markers were related to regional GM volumes, heart rate, and depressive symptoms. Results:Relaxation was differentially linked to heart rate in both groups (t= 2.20,p= 0.017), i.e., both markers were only related in HCs. Relaxation was positively linked to depressive symptoms across all participants (t= 1.99,p= 0.045) although this link differed weakly between groups (t= 1.62,p= 0.108). Primarily, the volume in medial temporal gyrus was negatively linked to relaxation in PwMS (t= -5.55, p(family-wise-error(FWE)corrected)= 0.018). A group-specific coupling of relaxation and GM volume was found in ventromedial prefrontal cortex (VMPFC) (t= -4.89, p(FWE)= 0.039). Conclusion:PwMS appear unable to integrate peripheral stress signals into their perception of relaxation. Together with the group-specific coupling of relaxation and VMPFC volume, a key area of the brain reward system for valuation of affectively relevant stimuli, this finding suggests a clinically relevant misinterpretation of stress-related affective stimuli in MS.
