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

Summary Clinical and neuroscientific studies suggest a link between psychological stress and reduced brain health - in healthy humans and patients with neurological disorders. However, it is unclear which neural pathways mediate between stress and brain health and whether these pathways are similar in health and disease. Here, we applied an Arterial-Spin-Labeling MRI stress task in 42 healthy persons and 56 with multiple sclerosis. We tested whether brain-predicted age differences (“brain-PAD”), a highly sensitive structural brain health biomarker derived from machine learning, mirror functional connectivity between stress-responsive regions. We found that regional neural stress responsivity did not differ between groups. Although elevated brain-PAD indicated worse brain health in patients, anterior insula-occipital functional connectivity correlated with brain-PAD in both groups. Grey matter variations contributed similarly to brain-PAD in both groups. These findings suggest a generic connection between stress and brain health whose impact is amplified in multiple sclerosis by disease-specific vulnerability factors.