How is the brain's response to stress related to disability in people with multiple sclerosis?

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The study aimed to evaluate the link between stress-induced neural activity measured with functional MRI (fMRI) and disease severity in people with multiple sclerosis (MS). Previous prospective clinical studies support an association between psychological stress and MS disease severity, and peripheral stress systems are frequently dysregulated in MS. However, the exact relationship between neurobiological stress systems and MS symptoms remains unknown.

The researchers used an Arterial-Spin–Labeling fMRI stress paradigm in 36 MS patients and 21 healthy controls. They measured brain activity during a mental arithmetic task whose frequency adapted to performance and that included performance feedback, then examined associations between this activity and disease severity measures.

Across all participants, stress increased heart rate, perceived stress, and neural activity in visual, cerebellar, and insular cortex areas compared with rest. None of these responses was related to cognitive load, measured as task frequency. Although patients had lower task performance and cognitive load than controls, stress responses did not differ between the groups.

Among patients, greater insula activity during stress relative to rest was associated with less impairment of pyramidal and cerebral functions. Cerebellar activation was negatively associated with gray matter (GM) atrophy—that is, positively associated with GM volume. This relationship was also observed in overlapping areas in healthy controls. Cognitive load did not contribute to these associations.

The researchers concluded that the paradigm induced psychological stress independently of cognitive load and that stress-induced brain activity reflects clinical disability in MS. The association between stress-induced activity and GM volume in overlapping areas in patients and healthy controls suggests that MS alone cannot explain this relationship.

The work was supported by the German Research Foundation, grant WE 5967/2-1 to Martin Weygandt. The funder had no influence on study design; data collection, analysis, or interpretation; report writing; or the decision to submit the article for publication.

Disclosures: Dr. Meyer-Arndt, Dr. Weygandt, Dr. Behrens, Dr. Wakonig, Dr. Brandt, Dr. Hetzer, Dr. Haynes, and Dr. Paul reported nothing to disclose. Dr. Bellmann-Strobl reported speaking honoraria from TEVA, unrelated to this work. Dr. Ritter reported research support from Philips Research, unrelated to this work. Dr. Scheel disclosed a patent for manufacturing computed tomography imaging phantoms using 3D printing technology and research support from the Federal Ministry of Economics and Technology, unrelated to the present work. Dr. Gold reported honoraria from Mylan GmbH, unrelated to this work, and research support from GAIA Group and Biogen Idec.