The Neural Mechanisms of Split-belt Treadmill Adaptation in People With Multiple Sclerosis

Colorado State University51 enrolled

Overview

Majority of people with multiple sclerosis experience difficulty with balance and mobility, leading to an increased risk of falls. The goal of this clinical trial is to learn about brain activity during walking adaptation in people with multiple sclerosis. Also, this clinical trial will test a form of nerve stimulation to see if it can improve walking performance. The main questions it aims to answer are: * What areas of the brain are the most active during walking adaptation? * Can nerve stimulation make walking adaptation more effective? Participants will walk on a treadmill where each leg will go a different speed which will create walking adaptation. At the same time, brain scans will occur. There will be two sessions of walking adaptation, one with nerve stimulation, and one without nerve stimulation. Researchers will compare people with multiple sclerosis to healthy young adults to see if there are differences in brain activity.

Most people with MS (PwMS) experience significant gait asymmetries between the two legs leading to an increased risk of falls and musculoskeletal injury. The objective of this study is to investigate the neural mechanisms of gait adaptation and the effects of transcutaneous electrical nerve stimulation (TENS) on adaptability during split-belt treadmill training in PwMS. Our hypothesis is that TENS will strengthen sensorimotor integration via amplified afferent signaling, thereby enhancing adaptation, and further improving gait symmetry chronically. Functional near-infrared spectroscopy (fNIRS) will be used during a split-belt treadmill training paradigm to assess cortical activation during gait adaptation. Additionally, the effect of split-belt treadmill training coupled with TENS on gait adaptability in PwMS will be tested with experimental and a sham TENS split-belt treadmill sessions. Cortical activation and the effect of TENS on gait adaptability will be compared between young neurotypical adults and PwMS to assess differences that can be attributed to multiple sclerosis.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Interventions

Split-belt TreadmillBEHAVIORAL

Split-belt treadmill training, where the speed of each leg is controlled independently has been shown to create gait adaptation where the coordination of each leg is altered, creating improved gait symmetry for people with walking impairments.

Transcutaneous Electrical Nerve Stimulation (TENS)DEVICE

TENS is a form of nerve stimulation that stimulates at a frequency below motor threshold, targeting activation of sensory receptors, such as muscle spindles. Electrodes that create this stimulation will be placed on the skin superficial to the muscle bellies of the tibialis anterior and rectus femoris.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 86 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * A diagnosis of relapsing remitting multiple sclerosis OR a neurotypical adult (ages 18-86) * Not experiencing an active relapse * Able to stand and walk without an assistive device * Able to walk for three tenths of a mile without stopping to rest Exclusion Criteria: * Unable to walk for three tenths of a mile without assistance * Musculoskeletal injury in past 6 months * Lower extremity surgery in past 6 months * Unable to abstain from medications that impair balance * Currently pregnant * History of traumatic brain injury * History of vestibular disease * History of any other balance impairment unrelated to multiple sclerosis

Outcomes

Primary Outcomes

Change in Cortical Activation

Cortical activation is measured using functional near-infrared spectroscopy (fNIRS) during split-belt treadmill walking. Hemodynamic responses are modeled using a general linear model (GLM) applied to the oxyhemoglobin (HbO) signal. The model includes regressors for distinct phases of walking, with the primary contrast comparing early adaptation (strides 6-30 after split-belt onset) to a baseline walking period. The outcome is defined as the difference in this HbO beta weight contrast with TENS ON compared to TENS OFF. Activation is averaged across all fNIRS channels to provide a whole-brain estimate of cortical activity. A larger value indicates a greater increase in activation from baseline walking to early adaptation. This was measured on both training session 1 and training session 2 to account for the crossover design (i.e. participants are receiving TENS on different days).

Time frame: Training session 1 (day 1), training session 2 (day 28)

Change in Adaptation Savings

Adaptation savings is defined as the difference in early adaptation performance between training session 1 (Day 1) and training session 2 (Day 28) during split-belt treadmill walking. Early adaptation is quantified using relative step length asymmetry (SLA), calculated from strides 6 to 30 following split-belt onset. SLA is computed from three-dimensional motion capture and force data as the difference between step lengths of the legs, normalized to total stride length: SLA = (Step Length\_fast - Step Length\_slow) / (Step Length\_fast + Step Length\_slow). This yields a unitless measure of asymmetry. The outcome measure is the difference in SLA between visits (training session 2 - training session 1). Larger values reflect faster adaptation at training session 2, consistent with retention of prior learning.

Time frame: Training session 1 (day 1), training session 2 (day 28)

Rate of Step Length Asymmetry Adaptation

Step length asymmetry during early adaptation, representing the rate of adaptation. Early adaptation is quantified using relative step length asymmetry (SLA), calculated from strides 6 to 30 following split-belt onset. SLA is computed from three-dimensional motion capture and force data as the difference between step lengths of the legs, normalized to total stride length: SLA = (Step Length\_fast - Step Length\_slow) / (Step Length\_fast + Step Length\_slow). This yields a unitless measure of asymmetry. The outcome measure is the difference in early adaptation SLA during TENS ON compared to TENS OFF. Values closer to zero reflect faster adaptation.This analysis was performed only on data from each participant's first visit to avoid known effects of increased adaptation rate (learning) during subsequent exposures.

Time frame: Training session 1 (day 1)