Similar neural pathways link psychological stress and brain-age in health and multiple sclerosis

iScience. 2023 Aug 18;26(9):107679. doi: 10.1016/j.isci.2023.107679. eCollection 2023 Sep 15.

Authors

Marc-Andre Schulz^{1

2

3}, Stefan Hetzer^{2

4}, Fabian Eitel^{1

2}, Susanna Asseyer^{5

6

7

8}, Lil Meyer-Arndt^{8

9

10}, Tanja Schmitz-Hübsch^{5

6

7

8}, Judith Bellmann-Strobl^{5

7

8}, James H Cole^{11

12}, Stefan M Gold^{13

14

15}, Friedemann Paul^{5

6

7

8}, Kerstin Ritter^{1

2}, Martin Weygandt^{5

6

7

8}

Affiliations

¹ 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.
² Bernstein Center for Computational Neuroscience, Berlin, Germany.
³ Department of Psychiatry, Psychotherapy, and Psychosomatics, Rheinisch-Westfälische Technische Hochschule (RWTH), Aachen University, Aachen, Germany.
⁴ 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.
⁵ Experimental and Clinical Research Center, A Cooperation Between the Max Delbrück Center for Molecular Medicine in the Helmholtz Association and Charité Universitätsmedizin Berlin, Berlin, Germany.
⁶ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Experimental and Clinical Research Center, Berlin, Germany.
⁷ Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany.
⁸ NeuroCure Clinical Research Center, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
⁹ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Neurology, Berlin, Germany.
¹⁰ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Regenerative Immunology and Aging, BIH Center for Regenerative Therapies, Berlin, Germany.
¹¹ Centre for Medical Image Computing, Department of Computer Science, University College London, London, UK.
¹² Dementia Research Centre, Institute of Neurology, University College London, London, UK.
¹³ Institute of Neuroimmunology and Multiple Sclerosis (INIMS), Center for Molecular Neurobiology Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
¹⁴ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Department of Psychiatry and Psychotherapy, Campus Benjamin Franklin, Berlin, Germany.
¹⁵ Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Medical Department, Section Psychosomatic Medicine, Berlin, Germany.

Abstract

Clinical and neuroscientific studies suggest a link between psychological stress and reduced brain health in health and neurological disease but it is unclear whether mediating pathways are similar. Consequently, we applied an arterial-spin-labeling MRI stress task in 42 healthy persons and 56 with multiple sclerosis, and investigated regional neural stress responses, associations between functional connectivity of stress-responsive regions and the brain-age prediction error, a highly sensitive machine learning brain health biomarker, and regional brain-age constituents in both groups. Stress responsivity did not differ between groups. Although elevated brain-age prediction errors indicated worse brain health in patients, anterior insula-occipital cortex (healthy persons: occipital pole; patients: fusiform gyrus) functional connectivity correlated with brain-age prediction errors in both groups. Finally, also gray matter contributed similarly to regional brain-age across groups. These findings might suggest a common stress-brain health pathway whose impact is amplified in multiple sclerosis by disease-specific vulnerability factors.

Keywords: Age; Machine learning; Neural networks; Neuroscience.