Trial Parameters
Brief Summary
Veterans are at higher risk than non-Veterans of falling ill with amyotrophic lateral sclerosis (ALS). The investigators have shown that synchronized stimulation over the brain and cervical spinal cord can temporarily strengthen weakened nerve circuits between the brain and hand muscles in people with ALS. The current proposal will take the next step of individualizing this intervention, then applying it repetitively in an attempt to achieve direct clinical benefit on hand strength and function. Following an initial 2-3 month period of optimizing the intervention for each individual, the investigators will compare the effects of two-week programs of paired brain-spinal stimulation with or without hand exercises.
Eligibility Criteria
Inclusion Criteria: * Diagnosis of ALS by Gold Coast Criteria (Shefner et al. 2020) or "definite" or "probable" ALS by revised El Escorial Criteria (Brooks et al. 2000) * Incomplete weakness: Score of 1, 2, 3, or 4 (out of 5) on manual muscle testing of finger extension, finger flexion, or finger abduction in left or right hand * TSCS-evoked potential amplitude of at least 25 V in left or right abductor pollicis brevis (APB) or first dorsal interosseous (FDI) muscles with a resting motor threshold of 55 mA or lower * TMS-evoked potential amplitude of at least 25 V in left or right abductor pollicis brevis (APB) or first dorsal interosseous (FDI) muscles with a resting motor threshold of 65% MSO or lower Exclusion Criteria: * History of seizures * Ventilator dependence or patent tracheostomy site * Use of medications that significantly lower seizure threshold, such as amphetamines and dalfampridine * History of severe head trauma (evidence of brain contusion or hemorrhage or depressed s