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

Targeted High-definition Transcranial Direct Current Stimulation (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.

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.

This sham-controlled cross-over study design will include three visits: 1) anodal stimulation targeting ipsilesional primary motor cortex, 2) cathodal one at the contralesional premotor cortex, 3) a sham stimulation visit. The sequence of the stimulations will be randomized and double-blinded. After each intervention, there will be at least 2 weeks wash-out period before participants receive the next intervention and assessments.

Three conditions: anodal stimulation over the ipsilesional primary motor cortex cathodal one over the contralesional premotor cortex Sham

Change in a subset of Fugl-Meyer Upper Extremity assessment which is mainly related to the muscle synergies

Baseline (initial visit), before (within 30 min range) and immediately after (within 30 min range) the intervention

This is a neurophysiological measure that determines the use of ipsilesional corticospinal tract and the contralesional cortico-reticulospinal tract.

Baseline (initial visit), before (within 30 min range) and immediately after (within 30 mins range) the intervention

This is a neurophysiological measure that determines the acute effort of HD-tDCS on brain plasticity.

Baseline (initial visit), before (within 30 min range) and immediately after (within 30 mins range) the intervention

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

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.

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