Systematic Review on Exercise Training as a Neuroplasticity-Inducing Behavior in Multiple Sclerosis

Abstract

Background. Exercise training is associated with functional improvements in persons with multiple sclerosis (MS), perhaps based on neuroplasticity. However, inferences regarding neuroplasticity require observations of exercise-related changes in the central nervous system that explain functional adaptations. This systematic review critically evaluated studies on exercise training, neuroimaging outcomes, and functional outcomes in MS based on consistency with a well-established conceptual model for characterizing exercise training as a possible neuroplasticity-inducing behavior in this population. Methods. We performed targeted and comprehensive searches of multiple databases for papers involving exercise training interventions on functional and neuroimaging outcomes in persons with MS. Acceptable study designs included randomized controlled trials, single-group pre/post designs, and quasi-experimental designs. Four independent reviewers extracted relevant data from each eligible paper on characteristics of participants, exercise interventions, neuroimaging outcomes, functional outcomes, pattern of study results, and potential risks of bias. Results. The literature search returned only 10 papers (involving 8 original interventions) that met eligibility criteria wherein inferences regarding neuroplasticity could be drawn, based on inclusion of neuroimaging and functional endpoints. Within those 10 papers, there is mixed evidence for exercise training as a neuroplasticity-inducing behavior in persons with MS. Conclusions. Such a paucity of evidence supporting exercise-induced neuroplasticity in MS is likely a product of a very small number of papers that do not sufficiently examine hypothesized mechanisms of action. Future research might consider examining specific neural changes that might result from exercise prescriptions that are specifically designed to induce certain functional changes among persons with MS.

A pilot randomized controlled trial of robotic exoskeleton-assisted exercise rehabilitation in multiple sclerosis

“…Consistent with our a priori hypotheses, those improvements in thalamocortical RSFC were moderately associated with improvements in functional mobility and CPS based on effect size estimates. Such a pattern of results provides preliminary evidence supporting REAER as a possible neuroplasticity-inducing behavior in persons with substantial MS mobility disability, whereby REAER-related improvements brain connectivity might explain downstream adaptations in motor and cognitive function (Sandroff et al, 2020). This is particularly exciting considering that REAER might represent an innovative approach for rehabilitating the highly prevalent and burdensome consequences of co-occurring mobility and cognitive disability in MS that may even be superior to the current standard-of-care.…”

“…In addition, our previous case-study reported that 4-weeks of RE-assisted ER (REAER) was associated with improved mobility as well as improved cognitive performance relative to CGT in 4 PwMS (Androwis et al, 2019). We further hypothesized that the aforementioned functional changes may have been attributable to adaptive neuroplasticity (Pascual-Leone, et al, 2005;Straudi, and Basaglia, 2017), whereby REAER might have changed brain functioning which led to improvements in both mobility and cognitive performance (Sandroff et al, 2020). As that study (Androwis et al, 2019) did not include neuroimaging outcomes, we speculated that such a neural mechanism might involve adaptations in thalamocortical resting-state functional connectivity (RSFC), given previous evidence of associations among increased thalamocortical RSFC, walking-based measures of cardiorespiratory fitness, and cognitive performance with 12-weeks of treadmill walking ER in 10 fully-ambulatory PwMS .…”

Physical activity may contribute to brain health in multiple sclerosis: An MR volumetric and spectroscopy study

“…Physical activity may improve brain function in pwMS 5,17,52 . Additional to studies in MS, 15 studies in other neurological conditions have demonstrated that physical activity was associated with structural benefits in the brain such as reducing brain region shrinking 53,54 .…”

“…Physical activity may improve brain function in pwMS. 5,17,52 Additional to studies in MS, 15 studies in other neurological conditions have demonstrated that physical activity was associated with structural benefits in the brain such as reducing brain region shrinking. 53,54 These findings develop regular physical activity as a disease-modifying treatment in MS. Several molecular pathways have been proposed as mediators of exercise benefit on brain function and structure.…”

“…To date, there are many approaches for treating and/or managing MS, and physical activity is recognized as potent stimulus for yielding beneficial effects among people with MS (pwMS) 3–7 . Regular physical activity and exercise may improve the physical capacity (endurance, strength, and balance) of pwMS 8,9 .…”