Modulation of interhemispheric interactions and arm activity after stroke

描述（由申请人提供）：本K23申请由Michael A.医学博士，马里兰州大学医学院神经病学助理教授。我的长期目标是成为一名独立的临床研究者，专注于手臂运动控制的神经基础，作为制定干预措施以改善中风后神经康复的基础。这个K23奖将使我能够在手臂运动控制及其神经生理学底物方面进行高级培训。我将接受多模式神经生理学和成像技术的培训。该训练将被应用于调查在手臂活动的整个时间过程中半球间抑制的动态调节，目的是确定干预目标，以提高中风后手臂康复。我将接受一个临床神经康复、手臂运动控制、神经生理学和多模态成像专家团队的指导，包括乔治·维滕贝格博士、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，30%的中风幸存者仍会出现手臂无力。慢性轻偏瘫是重要的，因为中风幸存者生活质量下降的50%是由于手臂无力。当前治疗 偏瘫的发病机制是基于中风后双臂如何相互作用的不同模型。然而，这些模型是有限的半球间的竞争的不完整的理解。特别是，我们不知道如何在手臂活动过程中动态调节双臂之间的相互作用。我将通过以下方式来研究这个问题：1）定义单侧手臂活动期间双臂之间正常的半球间相互作用; 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双臂之间的相互作用。这将通过研究进行手臂活动的轻偏瘫患者和健康对照者的皮质脊髓和半球间相互作用的神经生理学测量来完成。我也将使用多模式神经生理学和成像技术来检查大脑网络的相互作用及其对皮质脊髓活动的影响。拟议中的研究是创新的概念，在其阐述和除了运动过程中和中风后的大脑半球间的相互作用的模型。这项研究的结果可能会大大有助于我们理解两个手臂之间的相互作用。这很重要，因为它将使我们能够设计利用这些相互作用的疗法。这一建议的影响是，它将使我们能够设计干预措施，在运动过程中的特定时间点对特定的神经生理损伤进行评估，以加强中风后的康复。这项研究提案解决了美国国立卫生研究院的任务，以减轻神经系统疾病的负担，提高残疾人的生活质量。该提案还涉及NIH BRAIN计划的目标，即开发人类大脑的动态图像，描述神经回路如何在时间和空间中相互作用。

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.