Altered Coupling of Psychological Relaxation and Regional Volume of Brain Reward Areas in Multiple Sclerosis

Abstract

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.

Neural Processes of Psychological Stress and Relaxation Predict the Future Evolution of Quality of Life in Multiple Sclerosis

“…Thus, given the positive association between the activity of this network and the right superior frontal gyrus (bar graph lower panel Figure 5), this finding could suggest that protracted self-reference after cessation of stress is a factor related to future mood-related HRQoL aggravation in MS. This interpretation of an altered relaxation processing in MS would also be consistent with the results of our recent study showing that PwMS have difficulty in integrating peripheral stress signals into the perception of relaxation (51). Moreover, when additionally considering the high correlation between temporal differences in mood-related and overall HRQoL of r = 0.80 (which was the highest correlation among all pairs of [sub-] scales; refer to Supplementary Figure 2, right panel), these arguments might legitimately also be used to explain the link between the activity of this network and future aggravation in overall HRQoL because overall HRQoL assessed by HAQUAMS is particularly sensitive to mood-related HRQoL.…”

“…Thus, future studies addressing associations between neural correlates of psychological stress (or of other factors with neuropsychiatric importance) on one hand and QoL on the other should rely on a larger number of participants to facilitate analyses with higher statistical power. However, the fact that the brain areas contributing to HRQoLpredictive networks identified in this study (e.g., dmPFC, amygdala, vmPFC, anterior insula) are well in line with those found in other studies investigating stress or stress-related factors in MS (28,51) or independent of MS (48)(49)(50)54) suggests that the statistical power of our analyses does not fundamentally question the results obtained. Another possible limitation is confounding variables, such as Vitamin D (58), the gut microbiome (59), physical exercise (60), or sleep disturbances (61), which pose a challenge to any observational MS study given the heterogeneous set of factors considered to influence the disease.…”

The Role of Stress Perception and Coping with Stress and the Quality of Life Among Multiple Sclerosis Patients

“…We investigated whether perceived stress and emotion-related coping strategies may indicate a poor adjustment to MS. 65 Patients with MS appear unable to integrate peripheral stress signals into their perception of relaxation. 66 Blunted neural and psychological stress processing have a detrimental effect on the course of MS 45 and, consequently, can decrease quality of life.…”

Central stress processing, T-cell responsivity to stress hormones and disease severity in multiple sclerosis

“… 25 Specifically, insula is the key area for measuring, signalling, encoding and remembering affectively relevant internal bodily states (so-called ‘gut-feelings’ 57 ), a domain impaired in PwMS. 58 , 59 Thus, when considering frequent insula atrophy in PwMS 60 and their impaired ability to perceive and evaluate peripheral stress signals, 61 , 62 one might speculate that altered immunological and affective processes in multiple sclerosis might be connected via AI functioning.…”