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

Katharina Wakonig; Fabian Eitel; Kerstin Ritter; Stefan Hetzer; Tanja Schmitz-Hübsch; Judith Bellmann-Strobl; John-Dylan Haynes; Alexander U Brandt; Stefan M Gold; Friedemann Paul; Martin Weygandt

doi:10.3389/fneur.2020.568850

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

Front Neurol. 2020 Oct 6:11:568850. doi: 10.3389/fneur.2020.568850. eCollection 2020.

Authors

Katharina Wakonig¹, Fabian Eitel^{2

3}, Kerstin Ritter^{2

3}, Stefan Hetzer³, Tanja Schmitz-Hübsch^{1

4}, Judith Bellmann-Strobl^{1

4}, John-Dylan Haynes^{1

3

5}, Alexander U Brandt^{1

6}, Stefan M Gold^{7

8

9}, Friedemann Paul^{1

4

10}, Martin Weygandt^{1

4}

Affiliations

¹ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, NeuroCure Clinical Research Center, Berlin, Germany.
² Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health (BIH), Department of Psychiatry and Psychotherapy, Berlin, Germany.
³ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin Center for Advanced Neuroimaging, Berlin, Germany.
⁴ Max Delbrück Center for Molecular Medicine and Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Experimental and Clinical Research Center, Berlin, Germany.
⁵ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Bernstein Center for Computational Neuroscience, Berlin, Germany.
⁶ Department of Neurology, University of California, Irvine, CA, United States.
⁷ Institute of Neuroimmunology and Multiple Sclerosis (INIMS), University Medical Center Hamburg Eppendorf, Hamburg, Germany.
⁸ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy, Berlin, Germany.
⁹ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychosomatic Medicine, Berlin, Germany.
¹⁰ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neurology, Berlin, Germany.

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.

Keywords: autoimmunity; brain reward system; gray matter; multiple sclerosis; neuroinflammation; psychological relaxation; psychophysiological stress responses; ventromedial prefrontal cortex (vmPFC).