Brain and Nerve Stimulation for Hand Muscles in Spinal Cord Injury and ALS

Most neurological injuries such as spinal cord injuries (SCI) and amyotrophic lateral sclerosis (ALS) spare a portion of nerve circuitry. Strengthening spared nerve circuits may be an important method to improve functional recovery. In this study, the investigators aim to use non-invasive magnetic and electrical stimulation to strengthen motor circuits between the brain and hands. Magnetic stimulation will be used over the motor cortex (scalp). Two methods of electrical stimulation will be compared: stimulation of the median nerve at the wrist; or direct stimulation of the cervical spinal cord across the skin on the back of the neck. Several different combinations of magnetic and electrical stimulation will be compared to find the conditions that best strengthen nerve circuits between the brain and hands - "Fire Together, Wire Together". PLEASE NOTE, THIS IS A PRELIMINARY STUDY. This study is testing for temporary changes in nerve transmission and hand function. THERE IS NO EXPECTATION OF LONG-TERM BENEFIT FROM THIS STUDY. If we see temporary changes in this study, then future studies would focus on how to prolong that effect.

Most neurological injuries such as spinal cord injuries (SCI) and amyotrophic lateral sclerosis (ALS) spare a portion of nerve circuitry. Strengthening spared nerve circuits represents a critical method to improve functional recovery. Different forms of magnetic and electrical stimulation have been used to activate brain, spinal cord, nerve, or muscle tissue. Although in some cases, surgically implanted electrical stimulation has delivered tremendous benefit, a non-invasive approach to nerve stimulation is preferable. In this proposed study, the investigators aim to use non-invasive magnetic and electrical stimulation to strengthen motor circuits between the brain and hands. Transcranial magnetic stimulation (TMS) will be combined with either electrical stimulation of the median nerve at the wrist; or electrical transcutaneous stimulation of the cervical spinal cord. Magnetic and electrical stimulation will be precisely timed so that the pulses arrive at the target spinal motor neurons at roughly the same time - this precise timing is responsible for the phenomenon of "spike timing-dependent plasticity". Three groups of participants will be studied: individuals with chronic incomplete cervical SCI (n=12), individuals with definite or probable ALS (n=6), and individuals without neurological injury or disease (n=12). Subjects with SCI or ALS will have one screening visit to confirm eligibility for the study. All subjects will then undergo one baseline testing session followed by 7 sessions of unpaired or paired magnetic and electrical stimulation. Functional and physiological testing will be conducted prior to each stimulation session, then at 0, 15, 30, and 90 minutes post each session. Key measures include grip strength dynamometry, timed performance on a hand dexterity test, amplitude of abductor pollicis brevis (APB) response to TMS, integrated amplitude of APB F-wave responses, and duration of the 'cortical silent period' after TMS stimulation during APB contraction. PLEASE NOTE, THIS IS A PRELIMINARY STUDY. This study is testing for temporary changes in nerve transmission and hand function. THERE IS NO EXPECTATION OF LONG-TERM BENEFIT FROM THIS STUDY. If we see temporary changes in this study, then future studies would focus on how to prolong that effect.

Spinal Cord Injuries, Amyotrophic Lateral Sclerosis, Transcranial magnetic stimulation, single pulse, non-invasive brain stimulation

All subjects undergo same full protocol, including different combinations of stimulation on different days: Transcranial Magnetic Stimulation Cervical Transcutaneous Stimulation Median Nerve Stimulation

Change in motor evoked potential (MEP) amplitude of the abductor pollicis brevis (APB) muscle response to single pulses of TMS

Vital signs are monitored throughout procedure; symptoms and degree of pain/discomfort are checked frequently.

Inclusion Criteria: Males or females age 21-65 years; No history of serious neurological injury or disease; OR Chronic (>12 months since injury) incomplete SCI between levels C2-C8 or diagnosis of definite or probable ALS; Incomplete weakness of left or right hand muscles: score of 3 or 4 (out of 5) on manual muscle testing of finger extension, finger flexion, or finger abduction; Detectable F-wave responses of the left or right abductor pollicis brevis muscle to median nerve stimulation; Detectable motor evoked potentials in left or right abductor pollicis brevis muscle to transcranial magnetic stimulation. Exclusion Criteria: Multiple spinal cord lesions; History of seizures; Ventilator dependence or patent tracheostomy site; Use of medications that significantly lower seizure threshold, such as tricyclic antidepressants, amphetamines, neuroleptics, dalfampridine, and bupropion; History of stroke, brain tumor, brain abscess, or multiple sclerosis; History of moderate to severe head trauma (loss of consciousness for greater than one hour or evidence of brain contusion or hemorrhage or depressed skull fracture on prior imaging); History of implanted brain/spine/nerve stimulators, aneurysm clips, ferromagnetic metallic implants, or cardiac pacemaker/defibrillator; Significant coronary artery or cardiac conduction disease; Recurrent history over the last 6 months of autonomic dysreflexia; History of bipolar disorder; History of suicide attempt; Active psychosis; Heavy alcohol consumption (greater than equivalent of 5 oz of liquor) within previous 48 hours; Open skin lesions over the face, neck, shoulders, or arms; Pregnancy; Unsuitable for study participation as determined by study physician.

A Limited Dataset (LDS) will be shared in electronic format pursuant to a VA-approved Data Use Agreement. Individually Identifiable Data will be shared pursuant to valid HIPAA Authorization, Informed Consent, and an appropriate written agreement limiting use of the data to the conditions as described in the authorization and consent, and a written assurance from the recipient that the information will be maintained in accordance with the security requirements of 38 CFR Part 1.466.