Paired Stimulation Plasticity for Motor Recovery in Humans With and Without Spinal Cord Injury

• CST PAS (Other): transcranial magnetic stimulation and peripheral nerve stimulation are given at almost the same time to target brain-to-spinal cord connections
• RST PAS (Other): electrical stimulation with a loud sound and peripheral nerve stimulation are given at almost the same time to target brainstem-to-spinal cord connections
• sham PAS (Other): the setup will look and feel the same to the participant as the CST PAS or RST PAS. But one or both of the stimulations is not actually delivered, or it is delivered in a way that does not affect the participant

Primary outcomes

• Motor evokoed potential [Periprocedural]: Transcranial magnetic stimuli (TMS) will be delivered from a Magstim 200 stimulator (Magstim Company) through a double-cone coil with a monophasic current waveform. TMS will be delivered to the optimal scalp position for activation of upper or lower limb muscles. The optimal scalp position will be determined by moving the coil in small steps along the arm/leg muscle representation of the primary motor cortex to find the region where the largest MEP can be evoked with the minimum intensity in the targeted muscles. The muscles to be activated will be upper limb muscles such as deltoid, biceps, triceps, extensor carpi radialis, flexor carpi radialis and/or first dorsal interosseous; lower limb muscles such as quadriceps, hamstrings, tibialis anterior, soleus, and/or abductor hallucis muscles. Only the authorized research team will use the device and the investigator will comply with USFDA requirements for monitoring, records and reports. The research team will not market or promote the
• MVC [Periprocedural]: Individuals will perform a maximum voluntary contraction (MVC) of the targeted muscles through surface electrodes secured to the skin over the belly of each muscle (Ag-AgCl, 10 mm diameter). The signals will be amplified, filtered (20-1000 Hz), and sampled at 10 kHz for offline analysis.
• StartReact [Periprocedural]: The StartReact response will allow us make inferences about the contribution of the reticulospinal tract to spasticity. The StartReact response will be tested using a previously described paradigm in humans with and without SCI. Here, participants will be asked to observe a light-emitting diode (LED) located \~1 m in front of the participants' head. When the LED will illuminate (20 ms), individuals will be asked to perform an isometric elbow, knee and/or ankle flexion or an isometric elbow, knee and/or ankle extension as fast as possible. We will measure the visual reaction time (VRT) as the time from cue to onset of the EMG burst in the elbow muscles after the LED presentation. In some trials, the LED will be presented with either a quiet acoustic stimulus (80 dB, 500 Hz, 50 ms) or a startling acoustic stimulus (SAS, 120 dB, 500 Hz, 50 ms) delivered through a headphone. The time delay between the presentation of the quiet acoustic stimulus and the onset of the EMG response refer as th

Sex: All, ages: 19 Years to 85 Years, accepts healthy volunteers

Inclusion Criteria:

* Male and females between 19-85 years;
* Chronic SCI (≥ 1 years post-injury);
* T10 or above - American Spinal Injury Association (AIS) Grade C, or D;
* Ability to perform a small voluntary ankle dorsiflexion, knee extension, and ankle plantarflexion (as detected by presence of voluntary EMG activity in the rectus femoris, tibialis anterior, and soleus muscles) with at least one leg;
* Ability to tolerate standing position;
* Ability to initiate at least one step without the assistance of a therapist;
* If ambulatory, ability to walk at a minimum speed of 0.1 m/s on a treadmill. Inclusion criteria for controls:
* Male and females (19-85 years);
* Able to perform dorsiflexion;
* Able to walk.

Exclusion Criteria:

* Uncontrolled medical problems including pulmonary, cardiovascular, or orthopedic disease;
* Any debilitating disease before the SCI that caused exercise intolerance;
* Premorbid, ongoing major depression or psychosis, altered cognitive status;
* History of head injury or stroke;
* Pacemaker;
* Metal plate in skull;
* History of seizures;
* Receiving drugs acting primarily on the central nervous system, which lower the seizure threshold, such as antipsychotic drugs (chlorpromazine, clozapine) or tricyclic antidepressants;
* Pregnancy;
* Ongoing cord compression or a syrinx in the spinal cord or spinal cord disease, such as spinal stenosis, spina bifida or herniated cervical disk;
* implanted defibrillators or implanted neurostimulators;
* have large ischaemic scars;
* diagnosed sleep deprivation.

Exclusion criteria for controls:

\- Same as for subjects with SCI.

NIH grants: R01HD115345