Targeted High-definition Transcranial Direct Current Stimulation (HD-tDCS) for Reducing Post-stroke Movement Impairments

Targeted HD-tDCS for Reducing Post-stroke Movement Impairments

Stroke is the leading cause of serious, long-term disability. The emergence of abnormal muscle synergies following a stroke presents a major limitation to the recovery of independent function. Despite the development of many interventions for movement recovery post-stroke, rehabilitation treatments are minimally effective to the muscle synergy impairment. Previous studies have found that muscle synergy impairment is associated with the damage to the corticospinal tract and the maladaptive recruitment of the contralesional cortico-reticulospinal tract. The investigators hypothesize that facilitating the damaged cortico-spinal tract (via primary motor cortex) and/or inhibiting the contralesional cortico-reticulospinal tract (via dorsal premotor cortex) will reduce muscle synergy impairment. In this pilot project, the investigators propose to run a proof-of-concept pilot trial to evaluate the effect of the targeted high-definition transcranial direct current stimulation (HD-tDCS) on mitigating muscle synergy impairment.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Device: Transcranial direct current stimulation (high-definition)

Detailed Description

This randomized, double-blinded, sham-controlled cross-over study will include three stimulation conditions: 1) anodal stimulation over the ipsilesional primary motor cortex, 2) cathodal one over the contralesional premotor cortex, 3) sham stimulation in chronic hemiparetic stroke patients.

Stroke participants (> 3 months after stroke) with moderate to severe motor impairments (Fugl-Meyer Motor Assessment - Upper Extremity score between 10-40, in absence of clinically defined sensory deficits) and an ischemic unilateral subcortical lesion will receive each type of stimulation for 20 minutes.

Their brain activity and behavior data will be collected for the outcome measures.

The patient time commitment in this study is approximately 7 weeks where subjects have 3 x 1-day intervention and measurements, with 2 weeks washout period in between.

The total number of potential enrolled subjects in this pilot study is 12.

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

Contacts and Locations

Study Locations

• United States
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104-5036
      • University of Oklahoma Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Ischemic unilateral stroke lesion (confirmed by the most recent clinical or radiological reports) at least 3 months prior to participation in this project.
• Paresis confined to one side, with moderate to severe motor impairment of the upper limb (Fugl-Meyer upper extremity scores of 10-40)
• Capacity to provide informed consent

Exclusion Criteria:

• Muscle tone abnormalities and motor or sensory impairment in the unimpaired limb
• Severe wasting or contracture or significant sensory deficits in the paretic upper limb
• Severe cognitive or affective dysfunction that prevents normal communication and understanding of consent or instruction
• Severe concurrent medical problems (e.g. cardiorespiratory impairment)
• Using a pacemaker
• Metal implants in the head
• Known adverse reaction to TMS and tDCS
• Pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sham, Anodal, Cathodal; Treatment order 1: Sham, Anodal, Cathodal	Device: Transcranial direct current stimulation (high-definition); Three conditions (2 mA, 20 mins): anodal stimulation over the ipsilesional primary motor cortex; cathodal one over the contralesional premotor cortex; Sham
Experimental: Anodal, Cathodal, Sham; Treatment order 2: Anodal, Cathodal, Sham	Device: Transcranial direct current stimulation (high-definition); Three conditions (2 mA, 20 mins): anodal stimulation over the ipsilesional primary motor cortex; cathodal one over the contralesional premotor cortex; Sham
Experimental: Cathodal, Sham, Anodal; Treatment order 3: Cathodal, Sham, Anodal	Device: Transcranial direct current stimulation (high-definition); Three conditions (2 mA, 20 mins): anodal stimulation over the ipsilesional primary motor cortex; cathodal one over the contralesional premotor cortex; Sham
Experimental: Sham, Cathodal, Anodal; Treatment order 4: Sham, Cathodal, Anodal	Device: Transcranial direct current stimulation (high-definition); Three conditions (2 mA, 20 mins): anodal stimulation over the ipsilesional primary motor cortex; cathodal one over the contralesional premotor cortex; Sham
Experimental: Cathodal, Anodal, Sham; Treatment order 5: Cathodal, Anodal, Sham	Device: Transcranial direct current stimulation (high-definition); Three conditions (2 mA, 20 mins): anodal stimulation over the ipsilesional primary motor cortex; cathodal one over the contralesional premotor cortex; Sham
Experimental: Anodal, Sham, Cathodal; Treatment order 6: Anodal, Sham, Cathodal	Device: Transcranial direct current stimulation (high-definition); Three conditions (2 mA, 20 mins): anodal stimulation over the ipsilesional primary motor cortex; cathodal one over the contralesional premotor cortex; Sham

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fugl-Meyer Upper Extremity Assessment Part A	The Fugl-Meyer Upper Extremity (FM-UE) subset is a component of the Fugl-Meyer Assessment (FM) assessing motor impairment in individuals with stroke or other arm impairments. The (FM-UE) subset focuses on evaluating motor impairment and recovery using movements assessing strength, coordination, sensation, and range of motion of the upper extremity. Each item in the FM-UE subset is scored on a scale from 0-2. These are added together, with higher scores indicating better motor function. The FM-UE subset has 33 items for a maximum possible (highest functioning) score of 66.	The FM-UE assessment is completed before and immediately after (within 30 min range) the intervention. The mean difference is then calculated (Post-Pre intenvention) and recorded for each treatment group (anodal, cathodal, and sham). .

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Onset Latency of Transcranial Magnetic Stimulation (TMS)-Evoke Motor-evoked Potentials (MEP)	This is a neurophysiological measure that determines the use of ipsilesional corticospinal tract. The paired-pulse TMS was applied at the respective hotspot for the elbow flexor muscle at the paretic arm over the ipsilesional primary motor cortex. The center of the coil was positioned tangentially to the skull. The patient was considered MEP+ if MEPs of any amplitude are observed at a consistent latency on at least 5 out 10 trials. After determining the status of MEP, at least eight more pulses were applied. We calculated average latency across all positive trials to determine the latency of MEP.	The latency of TMS-evoke MEP assessment is completed before and immediately after (within 30 min range) the intervention. The mean difference is then calculated (Post-Pre intevention) and recorded for each treatment group (anodal, cathodal, and sham).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Brain Symmetry Index	This is a neurophysiological measure used to quantify the symmetry or asymmetry between the left and right hemispheres of the brain. It was calculated using EEG data from a 3-minute resting state EEG recording. The scale of the index is from -1 to 1, where zero is considered perfect symmetry between hemispheres and values close to -1 and 1 indicate asymmetry.	The BSI assessment is completed before and immediately after (within 30 min range) the intervention. The mean difference is then calculated (Post-Pre intevention) and recorded for each treatment group (anodal, cathodal, and sham).

Collaborators and Investigators

• Sponsor: University of Oklahoma
• Collaborators: Oklahoma Shared Clinical and Translational Resources

Publications and helpful links

General Publications

• Williamson J, James SA, Apple B, Sharps J, Sidorov E.V., Yang Y, (2022), High Definition Transcranial Direct Current Stimulation for Improving Upper Extremity Motor Function post Stroke. June 8-10, the 3rd International Workshop on Non-Invasive Brain Stimulation (NIBS) 2022.
• Lepak L.V., Cheema C.F, James S.A., Yang Y (2023), Computer-Guided Non-Invasive High-Definition Transcranial Direct Current Brain Stimulation as a Targeted Intervention after a Stroke, American Physical Therapy Association (APTA) Combined Sections Meeting (CSM), San Diego, CA, Feb 23-25, 2023

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2022
• Primary Completion (Actual): May 12, 2023
• Study Completion (Actual): May 12, 2023

Study Registration Dates

• First Submitted: November 9, 2021
• First Submitted That Met QC Criteria: December 13, 2021
• First Posted (Actual): January 3, 2022

Study Record Updates

• Last Update Posted (Actual): July 29, 2024
• Last Update Submitted That Met QC Criteria: February 12, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: Stroke; HD-tDCS; upper limb impairment
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: 14011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We are committed to enhancing the value of research and furthering the advancement of public knowledge. We recognize that the public dissemination of our scientific results can facilitate the creation of collaborative efforts with domestic and international collaborators. Furthermore, we recognize that the proposed project may result in novel ideas for new methods, technologies, and data that could benefit the entire research community. Therefore, final research data will be shared openly and timely in accordance with the most recent NIH guidelines (http://grants.nih.gov/grants/policy/data_sharing/) while being mindful that the confidentiality and privacy of participants in research must be protected at all times.

Drug and device information, study documents

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