Motor Map Plasticity in Constraint Therapy for Stroke

本研究将利用经颅磁刺激（TMS）和功能磁共振成像（fMRI）评估明确的物理干预（约束诱导运动疗法（CIMT））对脑卒中后皮层运动重组的影响。主要目的是1)确定TMS运动图或fMRI激活是否可预测地在CIMT后发生变化，2)评估这种变化是否与运动恢复相关，以及3)确定这种变化背后的可能机制。80名参加CIMT随机多中心试验（EXCITE）的患者将被研究，他们要么立即接受治疗，要么在一年后接受治疗。临床评估、TMS和fMRI将在随机分配到治疗组之前进行，并在完成CIMT后3天内（或随机分配到延迟治疗组的患者的等效时间）和一年后重复进行。本研究的主要焦点将是每个半球的初级运动皮质（FMC）对CIMT的反应，但我们也将定性地评估其他运动区域的激活变化。经颅磁刺激的结果测量将包括皮质地图面积和重心指数，以评估运动地图的大小和方向随时间的变化。功能性MRI结果测量将从运动任务期间PMC激活的兴趣量（VOI）分析中产生，并将与TMS测量相平行。此外，“侧性指数”将测量PMC对侧和同侧手运动的相对激活。临床结果测量将作为EXCITE试验的一部分获得，包括基于实验室的Wolf运动功能测试和对中风影响臂的实际使用的测量：运动活动日志。非参数统计分析将用于检查每组患者TMS图的变化、fMRI激活和临床结果之间的关系。与对照组相比，该研究是一个独特的机会，可以使用非侵入性方法研究接受特定治疗干预的受试者的皮质可塑性。我们期望在响应CIMT干预时确定TMS运动图和fMRI激活模式的特定变化模式。该项目将验证脑卒中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。这可能会导致基于治疗干预和恢复的生理和解剖学之间的相互作用的新的康复策略的发展。

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.