Can rTMS enhance somatosensory recovery after stroke?

 描述（由申请人提供）： 问题：中风是美国残疾的主要原因。大多数中风幸存者存在感觉缺陷。无法感受运动、触摸或疼痛会损害我们与环境互动的能力，降低生活质量。这些感觉缺陷显著损害功能活动，并减缓康复期间的恢复。目前可用的感觉康复技术只能部分恢复感觉功能。本研究的主要目的是测试一种新的方法，以改善感觉功能中风后使用非侵入性脑刺激。基本原理：感觉缺陷可以通过皮肤、肌肉和关节的外周操作使用基于感觉再教育的康复来部分恢复。感觉再教育与大脑的适应性功能和结构改变有关，称为神经可塑性。尽管重组，感觉恢复通常是缓慢和不完全的。有一种非侵入性的大脑调制方法，称为重复经颅磁刺激（rTMS），它可以潜在地驱动自适应功能和结构的大脑变化，从而导致功能的改善。虽然运动控制区域的rTMS已被证明可增强卒中后的运动康复，但缺乏支持rTMS改善感觉功能的证据。在我们的初步研究中，我们发现对侧初级感觉区（S1）的rTMS作为感觉治疗的干预是可行的和有前途的。拟议的研究将测试这种新方法。研究设计：我们将招募30名首次卒中后感觉障碍的患者 （卒中发作> 6个月前）。将有两个基线阶段，然后是三种不同的rTMS干预，目标是对侧病灶S1（促进性5Hz，抑制性1Hz和假手术），随机排序，间隔至少一周。假设1a：根据触觉辨别的测量，对侧损伤S1的易化rTMS产生比假rTMS更大的反应。假设1b对侧损伤S1的易化rTMS在改善触觉辨别方面比抑制性rTMS产生更大的反应。我们将根据2点区分（主要结局指标），通过比较对rTMS干预的反应来检验这些假设。次要结局指标将包括光栅定向测试、本体感觉、单丝辨别、振动感知和Jebsen Taylor测试。假设2：对侧S1的易化rTMS可增加双侧感觉神经元的兴奋性 网络和增强感觉运动连接。我们将通过使用正中神经刺激（主要结局指标）和短潜伏期传入抑制（次要结局指标）诱导的体感诱发电位（SSEP）来测量大脑功能变化来测试这一假设。重要性：这项研究将提供一种新的大脑刺激方法的感觉康复的信息，表征对侧病变的S1区在感觉处理中风后的功能作用，并为开发新的干预感觉康复的机会。这项研究将是确定对侧S1的rTMS刺激是否可以改善受中风影响的肢体的感觉功能的第一步。如果这一概念在这项试点研究中得到证明，那么， 该试验将为测试rTMS和外周定向治疗相结合的长期多疗程干预的有效性提供基础。

 DESCRIPTION (provided by applicant): Problem: Stroke is a leading cause of disability in the United States. Sensory deficits are present in the majority of stroke survivors. Inability to feel movement, touch or pain impairs our ability to interact with environment and diminished the quality of life. These sensory deficits significantly impair functional activity and slow down recovery during rehabilitation. Currently available sensory rehabilitation techniques can only partially restore sensory function. The main objective of this study is to test a novel approach to improve sensory function after stroke using non-invasive brain stimulation. Rationale: Sensory deficits can be partially recovered with peripheral manipulation of skin, muscles and joints using sensory re-education-based rehabilitation. Sensory re-education is associated with adaptive functional and structural alterations in the brain, called neuroplasticity. Despite reorganization, sensory recovery is usually slow and incomplete. There is a non-invasive method of brain modulation, called repetitive Transcranial Magnetic Stimulation (rTMS) that can potentially drive the adaptive functional and structural brain changes that lead to functional improvements. Although rTMS of motor control regions has been shown to enhance motor rehabilitation after stroke, evidence in support of rTMS to improve sensory function is lacking. In our preliminary studies, we discovered that rTMS of the contralesional primary sensory region (S1) is feasible and promising as an intervention for sensory treatment. The proposed study will test this novel approach. Study Design: We will enroll 30 individuals with sensory deficits after first ever stroke (stroke onset > 6 months prior). There will be two baseline sessions followed by three different rTMS interventions targeting contralesional S1 (facilitatory 5Hz, inhibitory 1 Hz and sham) randomly ordered and administered at least one week apart. Hypothesis 1a: Facilitatory rTMS of contralesional S1 produces a greater response versus sham rTMS, according to a measure of tactile discrimination. Hypothesis 1b Facilitatory rTMS of contralesional S1 produces a greater response versus inhibitory rTMS in improving tactile discrimination. We will test these hypotheses by comparing response to rTMS interventions according to 2-point discrimination (primary outcome measure). Secondary outcome measures will include grating orientation test, proprioception, monofilament discrimination, vibratory perception and Jebsen Taylor test. Hypothesis 2: Facilitatory rTMS at contralesional S1 can increase excitability of bilateral sensory networks and enhance sensory motor connectivity. We will test this hypothesis by measuring functional brain changes using somatosensory evoked potential (SSEP) induced by median nerve stimulation (primary outcome measure) and short-latency afferent inhibition (secondary outcome measure). Significance: This study will provide information about a novel brain stimulation approach for sensory rehabilitation, characterize the functional role of the contralesional S1 regions in sensory processing after stroke and open opportunities for development of new interventions for sensory rehabilitation. This study will be a first step in determining if rTMS stimulation of contralesional S1 can improve sensory function of a stroke-affected limb. If the concept is demonstrated in this pilot study, then following the lead of other investigations of this type, this pilot will provide the foundation to test the efficacy of a long-erm multi-session intervention of combined rTMS and peripherally directed therapy.