TRPMS to Improve Mobility and Depression in Multiple Sclerosis

Inclusion Criteria: In order to be eligible to participate in Arm 1 of this study, an individual must meet allof the following criteria:

1. Between ages 18 - 70
2. SDMT z-score ≥ -3.0
3. Wide Range Achievement Test-4th Edition (WRAT-4) Reading Recognition scaled score ≥ 85
4. Definite MS diagnosis as assessed by a licensed physician (all subtypes - RRMS, PPMS,SPMS)
5. Expanded Disability Status Scale (EDSS) ≤ 6.5
6. Clinically stable disease course with absence of relapse within the past 30 days
7. Able to understand the informed consent process and provide consent to participate inthe study
8. Complete the TMS screening questionnaire
9. Able to commit to study timeframe
10. Clinically significant gate deviations (T25-FW > 5.0 seconds)
11. Able to walk independently with or without assistive device (i.e. cane, crutches, orwalking frames) for medium distance
12. Able to exercise with seated elliptical machine In order to be eligible to participate in Arm 2 of this study, an individual must meet allof the following criteria:
13. Between ages 18 - 70
14. SDMT z-score ≥ -3.0
15. Wide Range Achievement Test-4th Edition (WRAT-4) Reading Recognition scaled score ≥ 85
16. Definite MS diagnosis as assessed by a licensed physician (all subtypes - RRMS, PPMS,SPMS)
17. Expanded Disability Status Scale (EDSS) ≤ 6.5
18. Clinically stable disease course with absence of relapse within the past 30 days
19. Able to understand the informed consent process and provide consent to participate inthe study
20. Complete the TMS screening questionnaire
21. Able to commit to study timeframe
22. Elevated symptoms of depression as determined by BDI of ≥ 4

Exclusion Criteria:

1. Visual, auditory or motor deficits that would influence participant safety as assessedby a licensed physician
2. History of seizure or epileptic history as assessed by licensed physician
3. Medication which significantly lower the seizure threshold as assessed by licensedphysician
4. Primary psychiatric disorder that would influence ability to participate
5. Uncontrolled headaches and migraine or recent changes in the rate or severity of headpressure, headache, or migraine in the past two weeks
6. History of stroke or head trauma (e.g., head injury, brain surgery) or medical deviceimplanted in the head (e.g. Deep Brain Stimulator) or in the neck (e.g. Vagus NerveStimulator)
7. History of uncontrolled or labile hypertension
8. Other serious uncontrolled medical condition or recent medical traumas
9. Presence of metal or electronic implants in the body contraindicated for TMS
10. Alcohol or other substance use disorder
11. Pregnant or breastfeeding
12. History of clinically significant abnormalities on electrocardiogram (EKG) (Arm 1only)
13. Presence of chronic medical illness and/or severe ataxia (Arm 1 only)
14. Functional surgery for lower limb in the past 6 months (e.g. hip or knee replacement) (Arm 1 only)
15. Lower limb Botulinum toxin injection within the past 2 months (Arm 1 only)