Interactions Between Neurostimulation and Physical Exercise
Interactions Between Neurostimulation and Physical Exercise
-  People with cervical spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS)
 have reduced connections in the nerve circuits between the brain and the hands.
 Activating spared nerve circuits is one potential way to improve recovery.

 -  The investigators are testing different combinations of physical wrist and hand
 movements paired with magnetic brain stimulation and electrical spinal cord or nerve
 stimulation to see the effects on nerve transmission to hand muscles.

 -  This is a preliminary study. This study is testing for temporary changes in nerve
 transmission to hand muscles. There is no expectation of long-term benefit from this
 study. If temporary changes are seen in this study, then future studies would focus on
 how to prolong that effect.
Spinal cord injury (SCI) and amyotrophic lateral sclerosis (ALS) result in a mixture of
 destroyed, damaged, and spared neural circuits. Activating spared nerve circuits augments
 neural transmission.

 With this goal in mind, the investigators recently developed a novel method of cervical
 electrical stimulation (CES) to noninvasively activate arm and hand muscles. The
 investigators are conducting a pilot clinical study (NCT02469675) to establish CES safety in
 subjects with cervical SCI, ALS, and non-disabled volunteers. To date, 19 subjects have
 undergone >120 CES sessions without major safety or tolerability issues.

 The current study is designed to gain further mechanistic insight. In Aim 1, the
 investigators will test in more detail how CES (traveling through spinal and peripheral
 circuits) interacts with individual pulses of TMS (traveling through corticospinal circuits).
 In Aim 2, the investigators will further test CES's therapeutic potential by combining
 stimulation with simultaneous physical exercises. In Aim 3, the investigators will compare
 the acute effects on synaptic transmission of passive stimulation to stimulation triggered by
 the subject's own muscle activity.

 Please note, this is a preliminary study. This study is testing for temporary changes in
 nerve transmission to hand muscles. There is no expectation of long-term benefit from this
 study. If the investigators see temporary changes in this study, then future studies would
 focus on how to prolong that effect.
Inclusion Criteria:

 1. Age between 21 and 65 years;

 2. Chronic (more than 12 months since injury) incomplete SCI between levels C2-C8 or
 diagnosis of definite or probable ALS;

 3. Incomplete weakness of left or right hand muscles: score of 2, 3, or 4 (out of 5) on
 manual muscle testing of finger extension, finger flexion, or finger abduction;

 4. Detectable F-wave responses of the left or right abductor pollicis brevis muscle to
 median nerve stimulation.

 Exclusion Criteria:

 1. Multiple spinal cord lesions;

 2. History of seizures;

 3. Ventilator dependence or patent tracheostomy site;

 4. Use of medications that significantly lower seizure threshold, such as tricyclic
 antidepressants, amphetamines, neuroleptics, dalfampridine, and bupropion;

 5. History of stroke, brain tumor, brain abscess, or multiple sclerosis;

 6. History of moderate or 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);

 7. History of implanted brain/spine/nerve stimulators, aneurysm clips, ferromagnetic
 metallic implants, or cardiac pacemaker/defibrillator;

 8. Significant coronary artery or cardiac conduction disease;

 9. Recent history (within past 6 months) of recurrent autonomic dysreflexia, defined as a
 syndrome of sudden rise in systolic pressure greater than 20 mm Hg or diastolic
 pressure greater than 10 mm Hg, without rise in heart rate, accompanied by symptoms
 such as headache, facial flushing, sweating, nasal congestion, and blurry vision (this
 will be closely monitored during all screening and testing procedures);

 10. History of bipolar disorder;

 11. History of suicide attempt;

 12. Active psychosis;

 13. Heavy alcohol consumption (greater than equivalent of 5 oz of liquor) within previous
 48 hours;

 14. Open skin lesions over the face, neck, shoulders, or arms;

 15. Pregnancy

 16. Unsuitable for study participation as determined by study physician.