Falls are common in Veterans with multiple sclerosis (MS), and current rehabilitation approaches to reduce falls are inadequate. Protective step training (in which a person is exposed to repeated "slips") is a promising tool to reduce falls in older adults. However, whether this approach is effective in people with MS is unknown. Investigating the effect of promising therapies, such as protective step training, will enhance our ability to treat Veterans with MS who are at risk for falls. Therefore, we will assess whether people with MS improve postural control and reduce falls through protective step training. we will also determine whether cognitive ability or brain structure can predict who will improve most. These data will inform clinical treatment strategies in people with MS at risk for falls.

Current rehabilitation strategies to prevent falls in people with MS are inadequate. Protective step training is a novel and promising treatment in which people are exposed to repeated slips. This training aims to improve automatic postural control including quick, protective steps, which are a critical aspect of fall avoidance, and are delayed in people with MS. This therapy has been shown to prevent falls in healthy older adults. However, the effectiveness of perturbation training in Veterans with MS is unknown. Identifying effective methods of fall prevention in people with MS, such as perturbation training, can lead to fewer falls in this population.

People with MS often exhibit considerable variability in their "responsiveness" to rehabilitation. Said differently, improvement in performance through training is variable across individuals. The ability to predict responsiveness to treatment would be extremely beneficial for clinicians; improving the efficiency by which they provide care. Recent work suggests cognitive ability and structural brain connectivity may predict responsiveness to motor rehabilitation. However, the degree to which these characteristics predict responsiveness in people with MS is currently unknown.

Therefore, the overall goals of this project are to understand 1) whether people with MS can improve postural control and reduce falls through perturbation training, and 2) whether the investigators can predict (via cognitive testing and neuroimaging), who will benefit most from treatment. The investigators will achieve these goals through three specific aims. Aim 1: identify whether people with MS can improve protective stepping, a critical skill for fall prevention, through 2 weeks of protective step training. Aim 2: determine if cognitive capacity predicts postural improvement through training in people with MS. Aim 3: determine if brain structural connectivity predicts postural improvements through training. The imaging data collected will also allow the investigators to investigate whether MS-related changes in brain connectivity contributes to postural response dysfunction.

The efficacy of perturbation training in people with MS (Aim 1) will be studied by measuring protective stepping performance before and after a 2-week perturbation training protocol. In addition, the investigators will gather prospective falls data through a falls calendar over the course of 8 weeks prior to and 8 weeks after the perturbation training to gain preliminary data regarding the effect of this training on falls. To determine which baseline characteristics predict "responsiveness" to training (Aims 2 and 3), the investigators will also assess baseline cognitive capacity and brain structural integrity (via diffusion tensor imaging; DTI). The investigators will determine whether these baseline participant characteristics predict which participants exhibit the most improvement through the course of training.

This project will provide insight into 1) the effectiveness of a promising fall prevention intervention, and 2) the ability to predict which patients will benefit most from the intervention. This knowledge will be an important step toward improving care of people with MS who are at risk for falls.

Inclusion Criteria:

• Neurologist diagnosed MS (for MS participants only)
• Ability to Stand for 5 minutes without aid
• Ability to comprehend English
• At risk for falls (determined via questionnaire; for MS participants only)
• EDMUS score <7 (determined by testers)

Exclusion Criteria:

• Any non-MS neurological pathology
• Orthopedic impairments affecting balance
• Previous cardiac events (stroke or heart attack)

All IPD will be collected at Arizona State University, and thus will be accessible by study-team members at this institution.

Data collected at ASU will be stored indefinitely.

Only approved study-team members at ASU will have access to IPD. These individuals will be identified and personally trained by the PI on the grant (Dr. Peterson).

57 people were originally screened and enrolled (38 MS and 19 control). Of these, 44 completed the baseline testing and are included in further analyses.

Across the training period (2 weeks)

Technical problems with neuroimaging data analyses have resulted in unreliable or uninterpretable data at this time.

Primary outcomes are objective (i.e. assessed via computer algorithms), thus reducing the need for masking.