EMG Triggered Closed-Loop Stimulation for Spinal Cord Injury Individuals

In both animal models and humans with spinal cord injury (SCI), synaptic efficacy between
corticospinal axons and spinal motor neurons has improved temporarily after a short period of
paired stimulation between motor cortex and spinal or peripheral sites. In a demonstration of
closed-loop stimulation in SCI rats, target muscle electromyography (EMG) signals were used
to trigger spinal cord electrical stimulation while performing physical retraining. Results
showed that EMG-triggered stimulation plus physical retraining led to greater motor recovery
than non-triggered stimulation or physical training alone. However, these studies used
invasive direct spinal cord stimulation in rodent models. Whether this approach can work
non-invasively in humans remains unknown.

Twenty participants (10 able bodied and 10 SCI subjects) will be recruited. Each subject will
undergo five different 20-minute interventions. Stimulation will be delivered at the motor
cortex via transcranial magnetic stimulation (TMS), the median nerve, or both. Stimulation
will occur either while the subject is passively at rest or triggered by reaching endogenous
EMG threshold during a pinch task. Outcomes will be measured at baseline and every 20 minutes
for one hour after the intervention.

The investigators hypothesize that for at least 20 minutes after stimulation, one session of
EMG-triggered stimulation will significantly improve motor evoked potential amplitude,
increase cortical silent period duration, and decrease time required to complete a pegboard
task compared with one session of passively delivered stimulation. The investigators further
hypothesize that EMG triggered median nerve stimulation alone will provide equal or greater
benefits as EMG triggered TMS or EMG-triggered paired stimulation.

Hypothesis 1: One session of EMG-triggered stimulation will significantly improve motor
evoked potential (MEP) amplitude, increase cortical silent period duration of APB, and
decrease time required to complete a manual pegboard task compared with one session of
passively delivered stimulation or one session of voluntary contraction alone for at least 20
minutes post-stimulation.

Hypothesis 2: EMG-triggered PNS alone will result in equal or greater effects than EMG
triggered TMS or TMS+PNS paired stimulation. This would indicate that EMG triggered PNS might
be used as a potential intervention to add during physical training, a setting in which TMS
is difficult to apply.

Inclusion Criteria:

- Age between 18 and 75 years;

- Chronic (more than 12 months since injury) motor-incomplete SCI between neurological
levels C2-C8

- Score of 3 or more (out of 5) on manual muscle testing of finger extension, finger
flexion, or finger abduction in left or right hand;

- Detectable F-wave responses of the left or right abductor pollicis brevis (APB) to
median nerve stimulation;

- Detectable motor evoked potentials in left or right APB;

- Able to perform thumb-middle finger opposition pinch task with detectable APB EMG
muscle activity.

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 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);

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

- Significant coronary artery or cardiac conduction disease;

- 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);

- 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.