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The effects of gait training combined with 4 mA cerebellar transcranial direct current stimulation in people with multiple sclerosis
Dissertation   Open access

The effects of gait training combined with 4 mA cerebellar transcranial direct current stimulation in people with multiple sclerosis

Alexandra Courtney Fietsam
University of Iowa
Doctor of Philosophy (PhD), University of Iowa
Summer 2023
DOI: 10.25820/etd.007048
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Abstract

People with MS (PwMS) experience various motor and/or sensory symptoms as areas of demyelination and lesions may present throughout the central nervous system. However, mobility impairments, particularly walking dysfunction are continually reported to be the most life-altering consequences of the disease. Unfortunately, most pharmacological interventions for PwMS aim to decrease demyelination and lesion progression and fail to effectively improve symptoms, such as gait impairments, and/or have significant side effects. Therefore, many PwMS choose to not take medications and instead rely on lifestyle interventions. However, recommendations for this approach have not been established. Transcranial direct current stimulation (tDCS) is thought to alter cortical excitability and has been used previously to improve MS-related symptoms, with variable results. However, no studies have assessed whether tDCS can effectively alter leg muscle activation. Moreover, most previous studies have used tDCS intensities ≤ 2 mA, despite evidence that higher intensities may be warranted in PwMS. Therefore, in Chapter 2, a case series was performed to evaluate the effects of a single sessions of 3 mA and Sham tDCS over the motor cortex (M1) on leg muscle glucose uptake during walking in PwMS using positron emission tomography (PET) with the glucose analog [18F] fluorodeoxyglucose (FDG). The results demonstrated various alterations in glucose uptake and glucose uptake asymmetries in individual muscles and muscle groups, with the greatest changes in subjects who were not physically active. These results suggest that physical activity levels may be important to consider in tDCS studies in PwMS as regularly exercising may be sufficient to improve or maintain motor performance. The results of Chapter 2 were in line with the tDCS literature, showing variable results between subjects. It is still unclear which tDCS parameters are most effective to increase motor performance in PwMS, particularly stimulation intensity and target brain region. Specifically, the use of higher intensities (≥ 2 mA) may be warranted to in PwMS due to demonstrated cerebral hypometabolism and decreased neuronal conduction velocity. Moreover, the cerebellum may be an important brain region to target due to its vital role in gait and balance, but only a few studies have explored this possibility. Additionally, while the pilot studies in Chapter 2 evaluated the effects of a single session of tDCS, multiple sessions may be necessary to induce lasting improvements in MS-related symptoms. Lastly, pairing tDCS with task-specific exercise (e.g., gait training) interventions may be important to improve mobility in PwMS. Therefore, in Chapter 3, the effects of 9 sessions of either 4 mA or Sham tDCS over the cerebellum combined with treadmill-based gait training on walking and balance performance as well as fatigue and quality of life were assessed. In addition, alterations in brain and leg muscle glucose uptake were evaluated via PET/FDG as a potential underlying mechanism of improvements. The results demonstrated improvements in walking performance, minimal alterations in balance performance, and no change in quality of life. Importantly, the effects of the gait training on functional outcomes were not amplified by tDCS. However, although there were no differences at post-testing, the 4 mA tDCS group did report an increase in perceived fatigability at the 2-week follow-up, while the Sham group showed a decrease in perceived fatigability at the 4-week follow-up. Lastly, there were few alterations in brain and leg glucose uptake, with no differences demonstrated between the groups. The contrasting results of Chapters 2 and 3 may be due to the different tDCS parameters used, particularly the stimulation site (i.e., motor cortex vs. cerebellum) or because Chapter 2 assessed individual differences after active and Sham stimulation while Chapter 3 evaluated group differences (i.e., active vs. Sham groups). Overall, these data suggest that gait-specific exercise interventions may improve walking performance in PwMS. However, these improvements may not result in alterations in other MS-related symptoms, including balance deficits, fatigue, and quality of life. Moreover, tDCS may improve brain and leg glucose metabolism in individual PwMS, particularly those with higher levels of disability and low levels of physical activity, but this technique may not be effective at the group level for PwMS due to high levels of variability in disability status. In conclusion, these data demonstrate the variability of tDCS interventions on functional outcomes and, therefore, provides insight to why various interventions may be necessary to improve MS symptoms, particularly across the disability spectrum. However, the results of these studies demonstrate that engaging in physical activity may effectively improve or maintain motor performance in PwMS. Specifically, gait training may be an important intervention to improve mobility in PwMS. However, it is unclear if tDCS, particularly placed over the cerebellum, can significantly amplify the effects of exercise interventions, potentially due to the variability in both MS-related disability and tDCS outcomes.
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