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
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.

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.