Determine the Effect of Targeted High-definition Transcranial Direct Current Stimulation (tDCS) on Reducing Post-stroke Upper Limb Motor Impairments

Официальное название

Determine the Effect of Targeted High-definition tDCS on Reducing Post-stroke Upper Limb Motor Impairments

Обзор

Significant motor impairments occur in 80% of individuals after moderate to severe stroke and impact the body side to the lesioned hemisphere. Typical motor impairments involve loss of dexterity with highly prevalent upper limb flexion synergy. Advances in treating flexion synergy impairments have been hampered by a lack of precision rehabilitation. Previous studies suggest and support the role of cortico-reticulospinal tract (CRST) hyperexcitability in post-stroke flexion synergy. CRST hyperexcitability is often caused by damage to the corticospinal tract (CST). We hypothesize that: 1) inhibiting the contralesional dorsal premotor cortex (cPMd) will directly reduce the CRST hyperexcitability and thus, reduce the expression of the flexion synergy; 2) facilitating the ipsilesional primary motor cortex (iM1) will improve the excitability of the damaged CST, therefore reducing the CRST hyperexcitability and the flexion synergy. we propose to use a novel targeted high-definition tDCS (THD-tDCS) to specifically modulate the targeted cortical regions for testing his hypothesis, via the following aims: Aim 1. Evaluate the effect of cathodal THD-tDCS over the cPMd on reducing the CRST hyperexcitability and the expression of flexion synergy. Aim 2. Evaluate the effect of anodal THD-tDCS over the iM1 on improving the excitability of the CST, and determine whether this, thus, also reduces the CRST hyperexcitability and the flexion synergy. Aim 3. Evaluate the confluence effect of bilateral THD-tDCS, i.e., simultaneous cathodal stimulation over the cPMd and anodal over the iM1.

Подробное описание

This sham-controlled cross-over study design will include four visits: 1) anodal stimulation targeting the ipsilesional hemisphere, 2) cathodal one at the contralesional hemisphere, 3) bilateral stimulation with anodal on the ipsilesional hemisphere and cathodal on the contralesional hemisphere and 4) a sham stimulation visit. The sequence of the stimulations will be randomized and double-blinded (assessor and participants). After each intervention, there will be at least 2 weeks wash-out period before participants receive the next intervention and assessments. Each visit will last up to 3 hours including the preparation time and breaks.

We will use neuro-navigation high-definition tDCS (NNG HD-tDCS) to target specific brain regions in a more precise way than before. A subject-specific head model will be built to evaluate the effect of lesion size and location on the electrical field of tDCS. The MR images (if available, otherwise CT images) will be used to build this subject-specific head model. The stimulation electrode montage and inter-electrode distance will be carefully examined by computer simulation to determine the optimal setup and dosage for NNG HD-tDCS.

The patient time commitment in this study is approximately 10 weeks where subjects have 4 x 1-day intervention and measurements, with 2 weeks washout the period in between.

The total number of potential enrolled subjects in this pilot study is 30.

Вмешательства

• Устройство Transcranial direct current stimulation (high- definition)
  20 minutes, 2 mA stimulation.

Первичные конечные точки

• Change in Transcranial Magnetic Stimulation-Evoke Motor-evoked Potential 1: Ispilesional stimulation in the brain and contralateral response in the muscle [Срок оценки: Baseline (initial visit), before (within 30 min range) and immediately after (within 30 min range) the intervention]
• Change in Transcranial Magnetic Stimulation-Evoke Motor-evoked Potential 2: Contralesional stimulation in the brain and ipsilateral response in the muscle [Срок оценки: Baseline (initial visit), before (within 30 minutes range) and immediately after (within 30 minutes range) the intervention]

Вторичные конечные точки (2)

• Change in a subset of Fugl-Meyer Upper Extremity assessment which is mainly related to the muscle synergies [Срок оценки: Baseline (initial visit), before (within 30 minutes range) and immediately after (within 30 minutes range) the intervention]
• Change in Fugl-Meyer Upper Extremity assessment [Срок оценки: Baseline (initial visit), before (within 30 minutes range) and immediately after (within 30 minutes range) the intervention]

Критерии участия

Критерии включения

• Paresis confined to one side, with substantial motor impairment of the paretic upper limb
• Capacity to provide informed consent

Критерии исключения

• Muscle tone abnormalities and motor or sensory impairment in the non-paretic 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 reactions to TMS and tDCS
• Pregnant

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Перекрёстный дизайн

Маскирование

Двойное слепое

Основная цель

Фундаментальное исследование

Центры проведения

США · 1 центр

• Carle Foundation Hospital — Urbana

Публикации

• Williamson JN, James SA, Mulyana B, Kim S, He D, Li S, Sidorov EV, Yang Y. Quantitative EEG Metrics for Determining HD-tDCS Induced Alteration of Brain Activity in Stroke Rehabilitation. Restor Neurol Neurosci. 2024 Nov;42(3-4):209-221. doi: 10.1177/09226028251347427. Epub 2025 Jun 16. PMID 40518976
• Yang, Y., Sidorov, E., & Dewald, J. P. (2021). Targeted tDCS reduces the expression of the upper limb flexion synergy in chronic hemiparetic stroke. Archives of Physical Medicine and Rehabilitation, 102(10), e10.
• Peng RH, He D, James SA, Williamson JN, Skadden C, Jain S, Hassaneen W, Miranpuri A, Kaur A, Sarol JN, Yang Y. Determining the effects of targeted high-definition transcranial direct current stimulation on reducing post-stroke upper limb motor impairments-a randomized cross-over study. Trials. 2024 Jan 9;25(1):34. doi: 10.1186/s13063-023-07886-w. PMID 38195605
• Williamson JN, James SA, He D, Li S, Sidorov EV, Yang Y. High-definition transcranial direct current stimulation for upper extremity rehabilitation in moderate-to-severe ischemic stroke: a pilot study. Front Hum Neurosci. 2023 Oct 12;17:1286238. doi: 10.3389/fnhum.2023.1286238. eCollection 2023. PMID 37900725

Идентификаторы

NCT: NCT05479006 · 14906

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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