Non-invasive brain stimulation to assess neurophysiologic underpinnings of lower limb motor impairment in multiple sclerosis

Background: Multiple sclerosis (MS) is a neuroinflammatory disease resulting in axonal demyelination and an amalgamation of symptoms which commonly result in decreased quality of life due to mobility dysfunction and limited participation in meaningful activities. New method: The use of non-invasive brain stimulation (NIBS) techniques, specifically transcranial magnetic and transcranial direct current stimulation, have been essential in understanding the pathophysiological decrements related to disease progression, particularly with regard to motor impairments. Although the research in this area has primarily focused on the upper extremities, new interest has arisen in understanding the neurophysiological underpinnings of lower limb impairment. Therefore, the purpose of this review is to: first, provide an overview of common NIBS techniques used to explore sensorimotor neurophysiology; second, summarize lower limb neuromuscular and mobility impairments typically observed in PwMS; third, review the current knowledge regarding interactions between TMS-assessed neurophysiology and lower limb impairments in PwMS; and fourth, provide recommendations for future NIBS studies based on current gaps in the literature. Results: PwMS exhibit reduced excitability and increased inhibitory neurophysiologic function which has been related to disease severity and lower limb motor impairments. Comparison with existing methods: Moreover, promising results indicate that the use of repetitive stimulation and transcranial direct current stimulation may prime neural adaptability and prove useful as a therapeutic tool in ameliorating lower limb impairments. Conclusions: While these studies are both informative and promising, additional studies are necessary to be conclusive. As such, studies assessing objective measures of lower limb impairments associated with neurophysiological adaptations need further evaluation.