Modulation of interhemispheric interactions and arm activity after stroke

描述(由申请人提供)：本K23课程申请书由马里兰大学医学院神经学助理教授Michael A.Dimyan医学博士提交。我的长期目标是成为一名独立的临床研究员，专注于手臂运动控制的神经基础，作为开发干预措施的基础，以改善中风后的神经康复。这项K23大奖将允许我在手臂运动控制及其神经生理基础方面进行高级培训。我将接受同时进行多通道神经生理学和成像技术方面的培训。这项训练将用于研究大脑半球间抑制在整个手臂活动的时间过程中的动态调节，目的是确定干预的目标，以促进中风后手臂的康复。我将得到临床神经康复、手臂运动控制、神经生理学和多模式成像专家团队的指导，其中包括乔治·维滕伯格博士、吉尔·惠特尔博士、拉奥·古拉帕利博士和彼得·戈尔曼博士。即使经过全面康复，仍有30%的中风幸存者手臂无力。慢性偏瘫很重要，因为中风幸存者生活质量下降的50%是由于手臂无力。当前的治疗方法 偏瘫的研究是基于中风后两只手臂如何相互作用的不同模型。然而，这些模型受到对半球间竞争的不完全理解的限制。特别是，我们不知道在手臂活动期间，两个手臂之间的相互作用是如何动态调节的。我将通过1)定义单侧手臂活动时两臂之间正常的大脑间相互作用来解决这个问题，2)发现衰老和中风如何损害这些动力学，3)确定其他大脑区域如何影响两臂之间的相互作用。这将通过研究偏瘫患者和进行手臂活动的健康对照组的皮质脊髓和大脑半球间相互作用的神经生理学测量来完成。我还将使用多模式神经生理学和成像技术来检查大脑网络相互作用及其对皮质脊髓活动的影响。这项拟议的研究在概念上是创新的，它对运动过程中和中风后的大脑半球间相互作用模型进行了阐述和补充。这项研究的结果可能会对我们理解这两个手臂之间的相互作用有很大帮助。这一点很重要，因为它将使我们能够设计利用这些互动的疗法。这项提议的影响是，它将允许我们设计干预措施，在运动过程中的特定时间点检测特定的神经生理学损害，以促进中风后的康复。这项研究建议针对NIH的使命，以减轻神经疾病的负担，提高残疾人的生活质量。这项建议还解决了NIH大脑计划的目标，即开发一幅人类大脑的动态图像，描述神经电路如何在时间和空间上相互作用。

DESCRIPTION (provided by applicant): This K23 application is submitted by Michael A. Dimyan, MD, Assistant Professor of Neurology at the University Of Maryland School Of Medicine. My long-term goal is to become an independent clinical investigator focusing on the neural substrates of arm motor control as a basis for developing interventions to improve neurorehabilitation after stroke. This K23 award will allow me to pursue advanced training in arm motor control and their neurophysiological substrates. I will train in the technique of concurrent multimodal neurophysiology and imaging. This training will be applied to investigating the dynamic modulation of interhemispheric inhibition throughout the time-course of arm activity, with a goal of identifying targets for intervention to enhance arm rehabilitation after stroke. I will be mentored by a team of experts in clinical neurorehabilitation, arm motor control, neurophysiology and multi-modal imaging including Dr. George Wittenberg, Dr. Jill Whitall, Dr. Rao Gullapalli and Dr. Peter Gorman. Even after comprehensive rehabilitation, 30% of stroke survivors are left with arm weakness. Chronic hemiparesis is significant because 50% of the reduction in quality of life for stroke survivors is due to arm weakness. Current treatments of hemiparesis are based on different models of how the two arms interact after stroke. However, these models are limited by an incomplete understanding of interhemispheric competition. In particular, we do not know how interactions between the two arms are dynamically modulated during arm activity. I will pursue this problem by 1) defining normal interhemispheric interactions between the two arms during unilateral arm activity 2) discovering how aging and stroke impair those dynamics and 3) determining how other brain areas influence the interaction between the two arms. This will be done by studying neurophysiological measures of corticospinal and interhemispheric interactions in hemiparetic patients and healthy controls performing an arm activity. I will also use multimodal neurophysiological and imaging techniques to examine brain network interactions and their influence on corticospinal activity. The proposed research is innovative conceptually in its elaboration and addition to the model of interhemispheric interactions during movement and after stroke. The results of this research may significantly contribute to our understanding of the interaction between the two arms. This is important because it will allow us to design therapies that take advantage of those interactions. The impact of this proposal is that it will allow us to design interventions that taret specific neurophysiological impairments at specific time-points during movement to enhance rehabilitation after stroke. This research proposal addresses the NIH missions to reduce the burden of neurological disorders and enhance the quality of life of people with disabilities. This proposal also addresses the goals of the NIH BRAIN initiative to develop a dynamic picture of the human brain describing how neural circuits interact in time and space.