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

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

JOURNAL=Frontiers in Human Neuroscience

VOLUME=14

YEAR=2020

URL=https://www.frontiersin.org/journals/human-neuroscience/articles/10.3389/fnhum.2020.00255

DOI=10.3389/fnhum.2020.00255

ISSN=1662-5161

ABSTRACT=<p><bold>Objectives</bold>: 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.</p><p><bold>Methods</bold>: 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.</p><p><bold>Results</bold>: 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.</p><p><bold>Conclusion</bold>: 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.</p>