Hemispheric Dominance for Ipsilesional Movement

描述(由申请人提供)： 项目摘要中风后的运动缺陷会导致长期的残疾。虽然对侧运动障碍最为明显，但肢体运动障碍也很常见，甚至在慢性中风患者中也会影响功能，尤其是依赖肢体偏瘫的患者。这笔赠款是哈兰德之前与宾夕法尼亚州立大学运动学家罗伯特·塞恩伯格建立合作关系的CSR&D拨款的延续。目前的建议旨在阐明第一笔赠款中显示的半球差异的潜在机制，这对半球特化理论和设计更具体的中风康复至关重要。之前的拨款支持了一个混合模型，该模型结合了Haaland的观点，即大脑半球对运动的专门化与开环和闭环加工的差异控制相关，以及Sainburg的假设，即两个半球在肢体动态控制(例如，关节扭矩相互作用)和稳态位置控制方面有所不同。然而，这一结论并不是基于对这两个假设的直接比较。因此，这一建议将扩展我们在三个实验中的发现，以确定：1)左右半球损伤(LHD，RHD)是否都会导致在线反应修改的缺陷，这与开环/闭环假说不一致；2)LHD和RHD后的运动错误是否会更常见，取决于在两种控制都独立操作的实验中，潜在的运动控制机制是肢体动力学规范还是稳态位置控制。3)这些大脑半球的不对称性是否与在计划过程中利用视觉和本体感觉信息的差异有关。我们还将比较有偏瘫和无偏瘫的患者，以确定这些半球差异对运动系统损害的重要性。最后，额中央和后顶叶损伤的不同影响将被评估，预测左侧额中央损伤后动态控制将比后顶损伤更严重，而稳态位置控制在右侧额中央或后顶损伤后将同样受损。60名中风后6个月的右撇子中风患者(30名右撇子中风患者，30名左撇子中风患者)将使用他们的同侧手臂进行三个运动学到达实验，60名人口统计学上匹配的右利手健康受试者使用任何一只手臂(30名右手和30名左手)进行三项运动到达实验。病变的大小和位置将使用MRIcro进行测量，这是一个将个体大脑正常化到Talairach空间的程序。将进行感兴趣区分析和基于体素的病变症状图，以确定额中央和顶后病变的作用。 公共卫生相关性： 与退伍军人病患护理任务的相关性这个项目是一个转换研究的例子，它测试了一个理论模型--动态优势假说--对于理解大脑半球运动的专门化的效用，最终目标是将这种理解转化为中风后更好的康复。大多数关于运动的神经基础的研究都集中在对侧控制上。虽然许多人已经证明了自发性运动缺陷以及这些缺陷的功能影响，但很少有人研究是否每个大脑半球都主导着肢体控制的不同方面。如果这一点在目前的赠款中得到证实，那么风湿性心脏病或LHD患者的康复策略可能会从不同的治疗策略中受益。我们从以前的CSR&D研究发现，REACH的不同方面存在半球专门化。目前的拨款将是第一个研究大脑损伤后这些大脑半球差异的机制及其大脑半球内相关性的基金。每年约有60万人罹患中风，55岁以后，发病率每十年翻一番。预计2010年55岁以上的退伍军人人数将超过1400万，其中90%以上患有某种残疾，其中许多人将患有中风。因此，中风的长期功能影响是VA系统患者护理任务中的一个重要问题。在美国，40%的中风幸存者在运动功能方面有中度功能障碍，37%的人在日常生活的基本活动方面需要帮助。最近设计用于偏瘫上肢康复的实验方案，包括减重训练、强迫诱导运动疗法、机器人辅助疗法和双边训练，已显示出实质性的前景。然而，尽管对侧手臂功能有所改善，纵向研究估计，少数偏瘫中风患者的对侧肢体功能将完全恢复。Bonifer等人。报告称，即使在进行了一项改善主动运动的强制性诱导运动疗法试验后，中度受损患者的对侧手臂仍继续用于协助双手活动，而不是作为主要控制器，即使在优势臂瘫痪的情况下也是如此。最后，一篇论文表明，慢性偏瘫中风患者使用偏瘫肢体的频率是偏瘫患者的三到六倍。因此，对于许多偏瘫患者来说，功能恢复在很大程度上依赖于患肢功能。自我缺陷的长期存在表明，这只手臂不能单独通过练习自发地提高协调性。虽然作业疗法经常采用患肢的“代偿”训练来恢复ADL的独立性，但我们现在建议，更好地了解患肢缺陷的性质可能有助于更好地适应。

DESCRIPTION (provided by applicant): Project Summary Abstract Motor deficits after stroke produce long term disability. While contralesional motor deficits are most obvious, ipsilesional deficits are common & influence functioning even in chronic stroke patients, especially hemiplegics who rely on their ipsilesional limb. This grant is a renewal of Haaland's previous CSR&D grant, which established collaboration with Robert Sainburg, a kinesiologist at Penn State. The current proposal is designed to elucidate the underlying mechanisms for the hemispheric differences demonstrated in the first grant, which is critical for theories of hemispheric specialization & for designing more specific stroke rehabilitation. The previous grant supported a hybrid model that incorporated Haaland's view that hemispheric specialization for movement was associated with differential control of open & closed loop processing and Sainburg's hypothesis that the two hemispheres differed in their control of limb dynamics (e.g., joint torque interactions) and steady state positional control. However, this conclusion was not based on a direct comparison of the two hypotheses. Therefore, this proposal will extend our previous findings in three experiments to determine: 1) Whether both left & right hemisphere damage (LHD, RHD) produce deficits in on- line response modification, which would be inconsistent with the open loop/closed loop hypothesis; 2) Whether movement errors after LHD & RHD will be more common depending on whether the underlying motor control mechanism is specification of limb dynamics or steady state positional control in an experiment where each type of control is manipulated independently. 3) Whether these hemispheric asymmetries are associated with differences in utilizing visual & proprioceptive information during planning. We will also compare patients with & without hemiparesis to determine the importance of damage to the motor system on these hemispheric differences. And, finally the differential impact of frontocentral & posterior parietal damage will be assessed with the predictions that dynamic control will be more impaired after left frontocentral than posterior parietal damage, & steady state positional control will be equally impaired after right frontocentral or posterior parietal damage. Three kinematic reaching experiments will be performed by 60 right-handed stroke patients (30 RHD, 30 LHD) who are > 6 months post stroke, using their ipsilesional arm & by 60 demographically matched, right-handed healthy control subjects using either arm (30 right & 30 left hand). Lesion size & location will be measured using MRIcro & a program to normalize individual brains to Talairach space. Region of interest analyses & voxel-based lesion symptom mapping will be done to identify the role of frontocentral & posterior parietal lesions. PUBLIC HEALTH RELEVANCE: Relevance to the VA Patient Care Mission This project is an example of translational research that tests the utility of a theoretical model, the dynamic dominance hypothesis, for understanding hemispheric specialization of movement with the eventual goal of translating that understanding into better rehabilitation after stroke. Most studies of the neural basis of movement focus upon contralateral control. While many have demonstrated ipsilesional movement deficits and the functional implications of those deficits, few have examined if each hemisphere is dominant for a different aspect of limb control. If this is confirmed in the current grant, then rehabilitation strategies for patients with RHD or LHD may benefit from different therapeutic strategies. Our findings from the previous CSR&D showed there is hemispheric specialization for different aspects of reaching. The current grant will be the first to study the mechanisms of these hemispheric differences after brain damage and their intrahemispheric correlates. About 600,000 people suffer a stroke each year, and incidence doubles for each decade of life after age 55. The number of veterans over 55 is projected to be more than 14 million in 2010 with more than 90% having some disability, many of whom will have strokes. Therefore, the long term functional impact of stroke is a significant concern for the patient care mission of the VA system. Forty percent of stroke survivors in the United States have moderate functional limitations related to motor function, and 37% require assistance with basic activities of daily living. Recent experimental protocols designed to rehabilitate the hemiparetic upper extremity including, reduced gravity training, constraint induced movement therapy, robot-assisted therapy, and bilateral training, have shown substantial promise. However, regardless of improvements in contralesional arm function, longitudinal studies have estimated that a minority of hemiplegic stroke patients will demonstrate full functional recovery in the contralesional limbs. Bonifer et al. reported that even after engaging in a constraint induced movement therapy trial that improved active movement, the contralesional arm of moderately impaired patients continued to be used to assist with bimanual activities, rather than as the lead controller, even in the case of dominant arm paresis. Finally, one paper showed that chronic hemiparetic stroke patients used the ipsilesional limb three to six times more frequently than its hemiparetic counterpart. Thus, for many hemiparetic patients, functional recovery relies heavily on ipsilesional limb function. The chronic persistence of ipsilesional deficits suggests that this arm does not spontaneously improve coordination through practice, alone. While occupational therapy has often employed "compensatory" training of the ipsilesional limb to regain independence in ADL, we now suggest that better understanding the nature of ipsilesional deficits might facilitate more adaptive.