Closed-loop rTMS-EEG During Visuomotor Integration. (SYNC)

State-dependent Entrainment of Intrinsic Brain Rhythms to Improve Interregional Functional Coupling.

This pilot study aims at establishing personalized state-based rTMS for precision neurorehabilitation, we designed a within-subject cross-over study to test closed-loop repetitive transcranial magnetic stimulation and electroencephalography (rTMS-EEG) comparing the targeting of two key nodes in the frontoparietal network during bimanual visuomotor force tracking in persons with upper extremity sensorimotor impairment affecting eye-hand control.

Study Overview

• Status: Recruiting
• Conditions: Brain Lesion (General); Visuomotor Skills
• Intervention / Treatment: Device: repetitive transcranial magnetic stimulation (rTMS)

Detailed Description

There is a need for oscillatory or repetitive neuromodulatory tools and methods that are effective in entraining intrinsic neural rhythms to improve inefficient functional coupling within neural circuits. The goal of the proposed study is to develop a closed-loop application of repetitive transcranial magnetic stimulation (rTMS) and electroencephalography (EEG) suitable for use in multidomain precision neural-circuit based rehabilitation studies that permits the time-locked application of rTMS pulses to the phase of the intrinsic neural oscillation (personalized state-based application) in a defined behavioral context (e.g., goal-directed eye-hand control).

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kirstin-Friederike Heise, PhD; Phone Number: 843-792-3435; Email: heisek@musc.edu

Study Locations

• United States
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• adult volunteers (age ≥18 years)
• right-hand dominance (defined with the Edinburg Handedness Scale)
• voluntary whole-hand grip force (Medical Research Council scale for muscle force ≥2)
• capable of repeated grasp and release with 5% of maximum voluntary contraction (standardized with an in-house computer-based assessment involving whole-hand grip force tracking upon visual cues with a digital dynamometer).

Exclusion Criteria:

• presence of any MRI risk factors (such as an electrically, magnetically, mechanically activated metal or nonmetal implant including cardiac pacemaker, intracerebral vascular clips, any other electrically sensitive support system, or claustrophobia)
• presence of any contraindications to repetitive transcranial magnetic stimulation, rTMS (e.g., history of seizures or epileptic activity, currently taking medications that lower seizure thresholds)
• any neurological or psychiatric disorders affecting cognitive function (e.g., established dementia) affecting the ability to understand the purpose of the study and give informed consent or ability to complete cognitive testing
• substance use disorder
• visual impairment that precludes completion of scanner tasks
• uncontrolled hypertension despite treatment
• intake of tricyclic anti-depressants
• musculoskeletal disorders affecting bimanual grasp- and release
• pregnancy (or suspected/possible pregnancy or plan to become pregnant in the short term). If the participant is a woman of childbearing potential, a urine pregnancy test will be performed on a standard basis.
• severe aphasia affecting particularly of receptive nature (NIH Stroke Scale, NIHSS Language subsection ≥2) affecting the ability to understand the purpose of the study and give informed consent
• pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: state-dependent repetitive transcranial magnetic stimulation (rTMS); Repetitive TMS will be applied to cortical targets based on task-based (visuomotor) brain activation.	Device: repetitive transcranial magnetic stimulation (rTMS); rTMS will be applied time-locked to the intrinsic brain rhythms to individually-defined brain regions; Other Names: non-invasive brain stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of whole hand grip force precision	Force time series will be used to extract two measures for each trial to describe distinct features of visuomotor force adjustment: 1) Root Mean Square Error (RMSE) to characterize the deviation of the actual force from the target force, i.e., over- and undershoot and 2) sample entropy (SmpEn) to quantify the randomness or uncertainty of the sampled force time series. From these measures, the trial-based relative changes in RMSE and SmpEn from baseline (before intervention) will be computed.	90 minutes
Change of functional brain connectivity.	Trial-specific phase-based connectivity will be extracted from the electroencephalography (EEG) time series and computed relative to baseline (before intervention).	90 minutes

Collaborators and Investigators

• Sponsor: Medical University of South Carolina
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Kirstin-Friederike Heise, Ph.D., Medical University of South Carolina

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2027

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: November 18, 2025
• First Posted (Actual): November 25, 2025

Study Record Updates

• Last Update Posted (Actual): November 25, 2025
• Last Update Submitted That Met QC Criteria: November 18, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: electroencephalography (EEG); transcranial magnetic stimulation (TMS); visuomotor processing; eye-hand control
• Additional Relevant MeSH Terms: Therapeutics; Magnetic Field Therapy; Transcranial Magnetic Stimulation
• Other Study ID Numbers: Pro00144782; 1P50HD118628-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We intend to comply with NIH Data Management and Sharing Policy. At this stage, the plan is to share de-identified data and supporting documentation in a manner that protects participant privacy and aligns with institutional guidelines. Specific details regarding the scope of data, timing, and access procedures will be finalized as the study progresses.
• IPD Sharing Time Frame: After primary analyses, anticipated within 12-24 months after study completion.
• IPD Sharing Access Criteria: Data will be shared through a secure repository. Requests may require a data use agreement and compliance with institutional and regulatory requirements.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

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