Optimizing Cortical Priming

Optimizing Cortical Priming to Enhance Bimanual Arm Coordination in Individuals With Chronic Stroke

Each year over 795,000 people suffer from stroke resulting in the primary cause of adult disability. Persistent upper limb dysfunction due to stroke significantly impairs performance and results in a serious decline of quality of life. As most daily activities involve the use of both arms, restoring the coordination between upper limbs is essential for regaining functional independence. Only a few interventions have been designed for improving function of both arms, and most of these interventions have focused on movement retraining without directly facilitating the injured brain. The purpose of this study is to design and test a noninvasive brain stimulation protocol tailored to enhance the coordination between the arms in individuals with chronic stroke. The investigators propose that the dorsal premotor cortex on the noninjured side of the brain (cPMd) could serve as a potential stimulation target for enhancing arm coordination and brain function. In the first part of this study (Aim 1), the investigators will examine its effects on modulating arm movements in individuals with chronic stroke. In the second part of this study (Aim 2), the investigators will upregulate the activity of the most responsive region (cPMd or iM1) of each participant prior to arm movement training (bilateral arm training, BAT) to determine the combined effects on augmenting bilateral arm coordination and brain function in individuals with chronic stroke.

Study Overview

• Status: Completed
• Conditions: Stroke; Hemiparesis After Stroke
• Intervention / Treatment: Device: 5 Hz Repetitive transcranial magnetic stimulation (rTMS) on the contralesional dorsal premotor cortex (cPMd); Device: 5 Hz Repetitive transcranial magnetic stimulation (rTMS) on the ipsilesional primary motor cortex (iM1)

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States
      • Physical Therapy & Rehabilitation Science, University of Maryland Baltimore

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Stroke Participants:

• Age 50 years and older
• Unilateral ischemic cortical or white matter subcortical stroke
• At least 6 months post-stroke and have completed all inpatient and outpatient therapy
• Residual arm paresis as indicated by Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) scores between 25 and 65 (individuals in this range have demonstrated the ability to generate motor evoked potentials during active muscle contraction)
• Able to reach forward for at least 15 centimeters

Healthy Controls:

• Age-matched to a stroke participant within plus or minus 3 years
• Gender-matched to a stroke participant

Exclusion Criteria:

Stroke Participants and Healthy Controls:

• A non-stroke neuromuscular disorder restricting exercise
• Stroke involving the brainstem or cerebellum
• Any medical conditions that could limit physical activity levels required for testing and training, such as acute cardiac or pulmonary/respiratory conditions, or uncontrolled hypertension (blood pressure greater than 180/100 mmHg)
• Significant orthopedic or chronic pain conditions limiting upper extremity movements
• Any medications that may adversely impact upper extremity control
• Metallic implant in the head or chest, implanted pumps/stimulators/shunts, or cardiac pacemaker
• A history of seizures
• Use of any neuropsychoactive medication
• History of fainting spells of undetermined etiology
• Pregnancy
• Any other concomitant neurological condition affecting sensorimotor systems, such as brain tumor, substance abuse, or dementia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5 Hz Repetitive Transcranial Magnetic Stimulation (rTMS) over Contralesional Dorsal Premotor Cortex; Participants received high-frequency (5 Hz) repetitive Transcranial Magnetic Stimulation (rTMS) delivered over the contralesional dorsal premotor cortex (cPMd) using a figure-of-eight magnetic coil. In Aim 1, participants received a single session of 5 Hz cPMd rTMS only. In Aim 2, participants who were responsive to cPMd stimulation received 5 Hz cPMd rTMS immediately prior to bilateral arm training (BAT) for 3 sessions.	Device: 5 Hz Repetitive transcranial magnetic stimulation (rTMS) on the contralesional dorsal premotor cortex (cPMd); Participant received 5 Hz repetitive transcranial magnetic stimulation (rTMS) on the contralesional dorsal premotor cortex (cPMd) only (Aim 1) and 5 Hz repetitive transcranial magnetic stimulation (rTMS) on the contralesional dorsal premotor cortex (cPMd) combined with 3 essions of bilateral arm training (Aim 2)
Experimental: 5 Hz Repetitive Transcranial Magnetic Stimulation (rTMS) over Ipsilesional Primary Motor Cortex; Participants received high-frequency (5 Hz) repetitive Transcranial Magnetic Stimulation (rTMS) delivered over the ipsilesional primary motor cortex (iM1) using a figure-of-eight magnetic coil. In Aim 1, participants received a single session of iM1 rTMS only. In Aim 2, participants who were responsive to iM1 stimulation received iM1 rTMS immediately prior to bilateral arm training (BAT) for 3 sessions.	Device: 5 Hz Repetitive transcranial magnetic stimulation (rTMS) on the ipsilesional primary motor cortex (iM1); Participant received 5 Hz rTMS on the ipsilesional primary motor cortex (iM1) only (Aim 1) and 5 Hz rTMS on the ipsilesional primary motor cortex (iM1) combined with 3 essions of bilateral arm training (Aim 2)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cortical Excitability Assessed by Transcranial Magnetic Stimulation (TMS)-Induced Motor Evoked Potential (MEP) Amplitude	Cortical excitability was quantified using single-pulse Transcranial Magnetic Stimulation (TMS) over the targeted motor cortex. Peak-to-peak amplitude of Motor Evoked Potentials (MEPs) recorded from the target upper limb muscle via surface electromyography (EMG) was measured in microvolts to evaluate stimulation- and training-induced neuroplastic changes.	Aim 1: Day 1 (Baseline and within 30 minutes post-stimulation); Aim 2: Day 1 (Baseline) and Day 3 (within 30 minutes after completing 3 sessions of bilateral arm training)
Interlimb Coordination Assessed by Surface Electromyography (EMG) -Interlimb Muscle Coherence	Interlimb coordination was quantified by measuring interlimb muscle coherence (intermuscular coherence) between homologous upper limb muscles via surface electromyography (EMG) during bilateral arm movements. Coherence was calculated in the frequency domain, where higher values indicated greater synchronous neural drive and coordination between the two upper limbs.	Day 1: Baseline and within 30 minutes post-stimulation (Aim 1)
Arm Reaching Kinematics (Speed, Acceleration, Interlimb Coordination, and Trajectory Smoothness) Assessed by the 3D Kinesiological Instrument for Normal and Altered Reaching Movement (KINARM)	Upper limb kinematic performance during arm reaching tasks was assessed using the 3D Kinesiological Instrument (KINARM). Specific kinematic parameters analyzed included: (1) movement speed, (2) movement acceleration, (3) interlimb coordination, and (4) arm trajectory smoothness.	Day 1 (Baseline) and Day 3 (within 60 minutes after completing 3 sessions of bilateral arm training) (Aim 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intracortical Inhibition Assessed by Paired-Pulse Transcranial Magnetic Stimulation (TMS)- Short-Interval Intracortical Inhibition (SICI)	Intracortical inhibition was quantified using paired-pulse Transcranial Magnetic Stimulation (TMS) over the motor cortex, recorded via surface electromyography (EMG) from the target upper limb muscle. A subthreshold conditioning stimulus followed by a suprathreshold test stimulus was applied. Intracortical inhibition was expressed as the ratio or percentage of the conditioned Motor Evoked Potential (MEP) amplitude relative to the unconditioned test MEP amplitude (% of test MEP), where lower percentages indicated greater intracortical inhibition.	Aim 1: Day 1 (Baseline and within 30 minutes post-stimulation); Aim 2: Day 1 (Baseline) and Day 3 (within 30 minutes after completing 3 sessions of bilateral arm training)
Interhemispheric Inhibition Assessed by Transcranial Magnetic Stimulation (TMS) Ipsilateral Silent Period (iSP)	Interhemispheric inhibition was quantified by the Ipsilateral Silent Period (iSP), elicited by delivering single-pulse Transcranial Magnetic Stimulation (TMS) to the motor cortex ipsilateral to the target upper limb during voluntary isometric muscle contraction. The iSP was recorded via surface electromyography (EMG) and quantified by duration in milliseconds (ms) and normalized area of EMG suppression (%).	Aim 1: Day 1 (Baseline and within 30 minutes post-stimulation); Aim 2: Day 1 (Baseline) and Day 3 (within 30 minutes after completing 3 sessions of bilateral arm training)
Upper Extremity Motor Function Assessed by the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE)	The Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) is a performance-based impairment index used to assess upper limb motor recovery in individuals with post-stroke hemiparesis. The upper extremity motor domain consists of 33 items assessing movement, coordination, and reflex action of the shoulder, elbow, forearm, wrist, and hand. Each item is scored on a 3-point ordinal scale (0 = cannot perform, 1 = performs partially, 2 = performs fully), yielding a total motor score ranging from 0 to 66, where higher scores indicate better upper extremity motor function (less motor impairment).	Aim 1: Day 1 (Baseline); Aim 2: Day 1 (Baseline) and Day 3 (within 60 minutes after completing 3 sessions of bilateral arm training)

Collaborators and Investigators

• Sponsor: Wan-Wen Liao
• Collaborators: University of Maryland, Baltimore

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2016
• Primary Completion (Actual): May 1, 2018
• Study Completion (Actual): May 1, 2018

Study Registration Dates

• First Submitted: February 4, 2026
• First Submitted That Met QC Criteria: October 2, 2026
• First Posted (Actual): October 6, 2026

Study Record Updates

• Last Update Posted (Actual): October 6, 2026
• Last Update Submitted That Met QC Criteria: October 2, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; Therapeutics; Magnetic Field Therapy; Transcranial Magnetic Stimulation
• Other Study ID Numbers: HP00068268

Plan for Individual participant data (IPD)

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

IPD Plan Description

To protect the privacy of stroke participants and adhere to the Institutional Review Board (IRB) guidelines, individual participant data (IPD) will not be made publicly available. The raw neurophysiological data and clinical assessments are reserved for the research team to complete the primary and secondary analyses specified in the study protocol. However, de-identified aggregate results and study documents will be shared through peer-reviewed publications. Some participant data were shared on one of our publications (https://doi.org/10.1016/j.clinph.2019.04.711)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No