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

ABSTRACT: 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.

SUBMITTER: Stellmann JP

PROVIDER: S-EPMC7340166 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

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

Stellmann Jan-Patrick JP Maarouf Adil A Schulz Karl-Heinz KH Baquet Lisa L Pöttgen Jana J Patra Stefan S Penner Iris-Katharina IK Gellißen Susanne S Ketels Gesche G Besson Pierre P Ranjeva Jean-Philippe JP Guye Maxime M Nolte Guido G Engel Andreas K AK Audoin Bertrand B Heesen Christoph C Gold Stefan M SM

Frontiers in human neuroscience 20200630

<b>Objectives</b>: 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. <b>Methods</b>: We investigated functional and structural networks in patie ...[more]

PMID: 32714172

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Project description:IntroductionThere is an urgent need for remyelinating therapies that restore function in people with multiple sclerosis (pwMS). Aerobic exercise is a promising remyelinating strategy because it promotes remyelination in animal models both independently and synergistically with medications. Here, in this study, we present an innovative, randomised, single-blind, clinical trial designed to explore: the relationship between demyelination and mobility (part 1), and if 24 weeks of aerobic exercise promotes remyelination in pwMS (part 2).Methods and analysisSedentary participants (n=60; aged 18-64 years) with stable MS will undergo a baseline visit with the following outcomes to assess associations between demyelination and mobility (part 1): spinal cord demyelination (somatosensory-evoked potentials, SSEPs), mobility (6-Minute Timed Walk, Timed 25-Foot Walk, Timed Up and Go, 9-Hole Peg Test) and patient-reported outcomes (PROs). After baseline testing, participants with significantly prolonged SSEP latency will advance to the clinical exercise trial (part 2) and will be randomised 1:1 to active or control conditions for 24 weeks. The active condition will be aerobic stationary cycling three times per week with graded virtual supervision. The control condition will be monthly virtual MS symptom education groups (six sessions). SSEP latency (remyelination endpoint), mobility outcomes and PROs will be measured at 12 and 24 weeks in all clinical trial participants. A subset of 11 active and 11 control participants will undergo a brain MRI with quantitative T1 myelin water fraction at baseline and 24 weeks (exploratory remyelination endpoint).Ethics and disseminationEthical approval was obtained from the Oregon Health & Science University Institutional Review Board (#21045). Dissemination of findings will include peer-reviewed publications, conference presentations and media releases. The proposed study will inform the feasibility, study design and sample size for a fully powered clinical trial of aerobic exercise to promote remyelination in pwMS.Trial registration numberNCT04539002.

Dataset Information

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

Publications

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

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