Background Pairing a bout of high intensity exercise with motor task practice can enhance motor learning beyond task practice alone, which is thought, in part, to be facilitated by an exercise-related increase in brain-derived neurotrophic factor (BDNF). The purpose of the current study was to examine the effect of different exercise intensities on BDNF levels and motor learning while controlling for exercise-related energy expenditure. Methods Forty-eight young, healthy participants were assigned to one of three groups: high-intensity exercise [High], low-intensity exercise [Low], or quiet rest [Rest]. The duration of the exercise bouts were individually adjusted so that each participant expended 200 kilocalories regardless of exercise intensity. BDNF was measured before and after exercise or rest. After exercise or rest, all participants practiced a 3-dimensional motor learning task, which involved reach movements made to sequentially presented targets. Retention was tested after 24-hours. BDNF genotype was determined for each participant to explore its effects on BDNF and motor learning. Results All participants equally improved performance, indicated by a reduction in time to complete the task. However, the kinematic profile used to control the reach movement differed by group. The Rest group travelled the shortest distance between the targets, the High group had higher reach speed (peak velocity), and the Low group had earlier peak velocities. The rise in BDNF post-exercise was not significant, regardless of exercise intensity, and the change in BDNF was not associated with motor learning. The BDNF response to exercise did not differ by genotype. However, performance differed between those with the polymorphism (Met carriers) and those without (Val/Val). Compared to the Val/Val genotype, Met carriers had faster response times throughout task practice, which was supported by higher reach speeds and earlier peak velocities. Conclusion Results indicated that both low and high-intensity exercise can alter the kinematic approach used to complete a reach task, and these changes appear unrelated to a change in BDNF. In addition, the BDNF genotype did not influence BDNF concentration, but it did have an effect on motor performance of a sequential target reach task.
Mobility disability is one of the most widespread and impactful consequences of multiple sclerosis (MS). Disease modifying drugs (DMDs) may delay the progression of disability over time; however, there is minimal evidence supporting the efficacy of DMDs for reversing mobility disability or restoring ambulatory function in persons with MS. Areas covered: This review outlines symptomatic pharmacologic and non-pharmacologic therapeutic approaches that target mobility disability with the goal of restoring and improving walking function. First, the efficacy of dalfampridine, currently the only Food and Drug Administration approved symptomatic pharmacologic agent that improves walking in persons with MS is described. Next, a review of the efficacy of non-pharmacologic therapies for improving walking, including exercise training, physical therapy, and gait training is given. Last, guidance on future research on mobility in MS is provided by emphasizing the importance of combinatory treatment approaches that include multiple intervention modalities, as the best treatment plan likely involves a comprehensive, multidisciplinary approach. Expert commentary: There has been an increased effort to develop symptom-specific treatments in MS that directly target mobility disability; however, more research is needed to determine the efficacy of these rehabilitative strategies alone and together for improving walking in persons with MS.
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.
Multiple sclerosis (MS) is a heterogeneous disease, both in its pathology and symptomology. This poses a challenge for the medical management and rehabilitation of MS; however, physical activity and exercise training are rehabilitation approaches that have demonstrated beneficial effects on many of the burdensome consequences of MS such as mobility impairment and fatigue. Given the heterogeneous course of MS, it is possible that outcomes of physical activity and exercise training interventions demonstrate heterogeneity both in the magnitude and pattern of change, but there has been little focus on response heterogeneity with these interventions among persons with MS. In this narrative review, a search of the existing literature was performed to identify studies that reported individual participant data, which was used to describe the variability in the response to physical activity and exercise training interventions among persons with MS. Inter-individual variability seemingly occurs across outcomes and modalities, which underscores the consideration of factors that might influence response heterogeneity. Factors related to MS disease characteristics, nervous system damage, and the degree of MS-related disability might influence individual responsiveness. Large-scale studies that permit the examination of heterogeneity and its predictors will inform future research on the area of physical activity and exercise training in MS, and lead to the development of individually tailored rehabilitation approaches that will more effectively elicit change.
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