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


  • M.A. Schulz
  • S. Hetzer
  • F. Eitel
  • S. Asseyer
  • L. Meyer-Arndt
  • T. Schmitz-Hübsch
  • J. Bellmann-Strobl
  • J.H. Cole
  • S.M. Gold
  • F. Paul
  • K. Ritter
  • M. Weygandt


  • iScience


  • iScience 26 (9): 107679


  • 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.