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

This study will investigate how aging and spinal cord injury (SCI) affect the transmission and plasticity of the corticospinal and reticulospinal tracts, which are important pathways for motor control. The study includes two experiments. Experiment 1 will assess corticospinal and reticulospinal tract transmission to lower-limb muscles in older adults with and without SCI. Experiment 2 will examine how aging and spinal cord injury affect the body's ability to strengthen nerve pathways involved in movement. The investigators will compare two pathways that help control leg movement, the corticospinal and reticulospinal pathways, to determine whether aging affects these pathways differently and whether spinal cord injury has a greater effect on the corticospinal pathway.

Study Overview

• Status: Recruiting
• Conditions: Spinal Cord Injury; Healthy Control
• Intervention / Treatment: Other: CST PAS; Other: RST PAS; Other: sham PAS

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Monica Perez; Phone Number: 312-238-2886; Email: mperez04@sralab.org

Study Locations

• United States
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Shirley Ryan Abilitylab
      • Contact: Monica Perez; Phone Number: 312-238-2886; Email: mperez04@sralab.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Probability Sample

Study Population

Vulnerable populations, including children (<18 years) and pregnant women, will be excluded from this study.

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
healthy control	Other: CST PAS; transcranial magnetic stimulation and peripheral nerve stimulation are given at almost the same time to target brain-to-spinal cord connections; Other: RST PAS; transcranial magnetic stimulation and peripheral nerve stimulation are given at almost the same time to target brainstem-to-spinal cord connections; Other: sham PAS; 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
spinal cord injury	Other: CST PAS; transcranial magnetic stimulation and peripheral nerve stimulation are given at almost the same time to target brain-to-spinal cord connections; Other: RST PAS; transcranial magnetic stimulation and peripheral nerve stimulation are given at almost the same time to target brainstem-to-spinal cord connections; Other: sham PAS; 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Motor evokoed potential	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	Periprocedural
MVC	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.	Periprocedural
StartReact	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	Periprocedural

Collaborators and Investigators

• Sponsor: Shirley Ryan AbilityLab
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Study record dates

Study Major Dates

• Study Start (Actual): August 28, 2025
• Primary Completion (Estimated): September 30, 2030
• Study Completion (Estimated): September 30, 2031

Study Registration Dates

• First Submitted: September 1, 2026
• First Submitted That Met QC Criteria: September 9, 2026
• First Posted (Actual): September 10, 2026

Study Record Updates

• Last Update Posted (Actual): September 10, 2026
• Last Update Submitted That Met QC Criteria: September 9, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: aging; motor control; plasticity; motor recovery; Spinal cord injury (SCI)
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Trauma, Nervous System; Spinal Cord Diseases; Spinal Cord Injuries
• Other Study ID Numbers: STU00224061; 1R01HD115345-01A1 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No