Motor Map Plasticity in Constraint Therapy for Stroke

本研究将使用经颅磁刺激（TMS）和功能性磁共振成像（fMRI）评估明确的物理干预（约束诱导运动疗法（CIMT））对卒中后皮质运动重组的影响。 主要目的是：1）确定TMS运动地图或功能磁共振成像激活是否在CIMT后发生可预测的变化，2）评估这种变化是否与运动恢复相关，3）确定这种变化背后的可能机制。 将研究80例参加CIMT随机多中心试验（EXCITE）的患者，该试验立即或一年后给药。将在随机分配至治疗组之前获得临床评估、TMS和fMRI，并在完成CIMT后3天内（或对于随机分配至延迟治疗的患者，在同等时间）和1年后重复进行。 本研究的主要重点将是每个半球的初级运动皮层（FMC）对CIMT的反应变化，但我们也将定性评估其他运动区域的激活变化。 TMS的结局指标将包括皮质地图面积和重心指数，以评估运动地图随时间的大小和方向偏移变化。 功能性MRI结局指标将由运动任务期间PMC激活的感兴趣体积（VOI）分析生成，并将与TMS指标平行。 此外，“偏侧性指数”将测量手运动的对侧和同侧PMC的相对激活。 作为EXCITE试验的一部分，将获得临床结局指标，包括基于实验室的Wolf运动功能测试和卒中影响手臂的真实的生活使用指标：运动活动日志。将使用非参数统计分析来检查每组患者的TMS图变化、fMRI激活和临床结局之间的关系。 该研究是一个独特的机会，使用非侵入性方法来研究接受特定治疗干预的受试者与对照组相比的皮质可塑性。 我们希望确定特定模式的变化，TMS运动地图和功能磁共振成像激活模式的CIMT干预。 该项目将验证中风后生理皮质运动变化与运动改善密切相关并受物理干预影响的概念。 这可能会导致新的康复策略的基础上的治疗干预和恢复的生理学和解剖学之间的相互作用的发展。

This study will evaluate the effect of a well-defined physical intervention (constraint-induced movement therapy (CIMT)) on cortical motor reorganization following stroke using transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI). The primary objectives are 1) to determine whether TMS motor maps or fMRI activation predictably change following CIMT, 2) to assess whether this change correlates with motor recovery, and 3) to identify possible mechanisms underlying that change. Eighty patients participating in a randomized multicenter trial (EXCITE) of CIMT administered either immediately or one year later will be studied. Clinical assessment, TMS and fMRI will be obtained prior to randomization into the treatment arms, and repeated within three days of completing CIMT (or at the equivalent time for patients randomized to delayed treatment), and one year later. The primary focus of the study will be changes in the primary motor cortices (FMC's) of each hemisphere in response to CIMT, but we will also qualitatively evaluate activation changes in other motor regions. Outcome measures for TMS will include indices of cortical map area and center of gravity to evaluate changes in size and directional shift of motor maps over time. Functional MRI outcome measures will be generated from a volume of interest (VOI) analysis of activation in the PMC during a motor task, and will parallel TMS measures. In addition, a "laterality index" will measure the relative activation in the PMC's contralateral and ipsilateral to hand movement. Clinical outcome measures will be obtained as part of the EXCITE trial, and will include the laboratory-based Wolf Motor Function Test and a measure of real life use of the stroke-affected arm: the Motor Activity Log. Nonparametric statistical analyses will be used to examine the relationship between changes in TMS maps, fMRI activation and clinical outcome for each group of patients. The study is a unique opportunity to use non-invasive methods to study cortical plasticity in subjects receiving a specific therapy intervention, compared to a control group. We expect to identify specific patterns of change in TMS motor maps and fMRI activation patterns in response to the CIMT intervention. The project will validate the concept that physiological cortical motor changes after stroke are closely correlated with motor improvement and are influenced by a physical intervention. This could lead to the development of new rehabilitative strategies based on the interaction between therapeutic interventions and the physiology and anatomy of recovery.