Aerobic Exercise Induces Functional and Structural Reorganization of CNS Networks in Multiple Sclerosis: A Randomized Controlled Trial

Jan Patrick Stellmann*, Adil Maarouf, Karl Heinz Schulz, Lisa Baquet, Jana Pöttgen, Stefan Patra, Iris Katharina Penner, Susanne Gellißen, Gesche Ketels, Pierre Besson, Jean Philippe Ranjeva, Maxime Guye, Guido Nolte, Andreas K. Engel, Bertrand Audoin, Christoph Heesen, Stefan M. Gold

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Objectives: Evidence from animal studies suggests that aerobic exercise may promote neuroplasticity and could, therefore, provide therapeutic benefits for neurological diseases such as multiple sclerosis (MS). However, the effects of exercise in human CNS disorders on the topology of brain networks, which might serve as an outcome at the interface between biology and clinical performance, remain poorly understood. Methods: We investigated functional and structural networks in patients with relapsing-remitting MS in a clinical trial of standardized aerobic exercise. Fifty-seven patients were randomly assigned to moderate-intensity exercise for 3 months or a non-exercise control group. We reconstructed functional networks based on resting-state functional magnetic resonance imaging (MRI) and used probabilistic tractography on diffusion-weighted imaging data for structural networks. Results: At baseline, compared to 30 healthy controls, patients exhibited decreased structural connectivity that was most pronounced in hub regions of the brain. Vice versa, functional connectivity was increased in hubs. After 3 months, we observed hub independent increased functional connectivity in the exercise group while the control group presented a loss of functional hub connectivity. On a structural level, the control group remained unchanged, while the exercise group had also increased connectivity. Increased clustering of hubs indicates a better structural integration and internal connectivity at the top of the network hierarchy. Conclusion: Increased functional connectivity of hubs contrasts a loss of structural connectivity in relapsing-remitting MS. Under an exercise condition, a further hub independent increase of functional connectivity seems to translate in higher structural connectivity of the whole brain.

Original languageEnglish (US)
Article number255
JournalFrontiers in Human Neuroscience
StatePublished - Jun 30 2020
Externally publishedYes


  • CNS networks
  • exercise
  • multiple sclerosis
  • neuroplasticity
  • randomized controlled trial

ASJC Scopus subject areas

  • Neuropsychology and Physiological Psychology
  • Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Behavioral Neuroscience


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