Problems with Sustained Motor Performance in Parkinson's Disease and Effect of Neurofeedback: A Functional MRI Investigation

7.项目总结/摘要 帕金森病（PD）影响全球超过600万人。随着预期寿命的增加， 预计到2040年将翻一番。维持稳定的运动表现的能力受损是一个主要的 PD患者发病的原因。其特征在于速度的快速渐进递减， 幅度或连续任务期间的运动力（例如，行走，写作）。标准 药物和手术治疗在改善减少方面是无效的。需要新颖 靶向治疗，副作用最小，更好地控制症状。建议的指导目标 研究项目是评估功能性磁共振成像（fMRI）的影响， 神经反馈干预对帕金森病患者大脑可塑性和持续运动表现的影响功能磁共振成像- 神经反馈是一种非侵入性的干预措施，可以提高个人控制大脑的能力。 实时活动。通过练习，个人也可以学习如何自我调节与之相关的行为。 大脑的活动。这种干预已成功地用于几种神经精神疾病（例如， 焦虑，成瘾），但其在PD中使用的报道很少。使用基于fMRI的神经反馈结合 运动想象，我们将训练PD患者，以增加他们的右侧之间的功能连接强度， 前额叶皮层和背内侧额叶皮层。这些大脑区域在启动和维持自愿的 运动，并受到PD病理过程的影响。我们将研究这种训练对 静息状态下大脑网络的功能连接和运动表现。这项建议符合 NINDS的使命是寻求有关大脑和神经系统的基础知识，并利用这些知识， 减少神经系统疾病的负担。如果成功的话，这种神经反馈引导的运动 想象训练可以纳入PD的康复计划。候选人：蒂娜兹博士是一个运动 神经病学家她的职业目标是开发一个研究项目，研究运动的神经基础 疾病，特别是PD，确定新疗法的靶点，并研究大脑对 使用神经影像学进行干预。Tinaz博士寻求在先进的功能磁共振成像方法，包括额外的培训 神经反馈，行为干预开发，生物统计学，以及临床试验的设计和实施 通过教学课程和实践学习。该项目和职业发展计划将为她做好准备， 设计大规模的临床试验，以评估神经反馈干预在PD中的疗效。环境：The 研究和培训活动将在耶鲁医学院进行。磁共振研究 中心是一个国家的最先进的设施，提供基础设施和跨学科的专业知识， 神经影像学研究。Tinaz博士的导师和顾问都是功能磁共振成像和临床试验方面的专家 方法论在拟议的项目完成后，Tinaz博士将做好准备，成为一名 独立的临床医生，科学家结合她在运动障碍神经学和神经影像学的专业知识。

7. Project Summary/Abstract Parkinson’s disease (PD) affects over six million individuals globally. With increasing life expectancy, this number is estimated to double by 2040. The impaired ability to sustain a steady motor performance is a major cause of morbidity in patients with PD. This is characterized by a rapid progressive decrement in the speed, amplitude, or force of movements during continuous tasks (e.g., walking, writing). The standard pharmacological and surgical therapies are ineffective in improving the decrement. There is a need for novel targeted therapies with minimal adverse effects for better symptom control. The goal of the proposed mentored research project is to assess the effects of functional magnetic resonance imaging (fMRI)-based neurofeedback intervention on brain plasticity and sustained motor performance in patients with PD. FMRI- based neurofeedback is a noninvasive intervention that improves individuals’ abilities to control their brain activity in real-time. With practice, individuals can also learn how to self-regulate behavior that is associated with this brain activity. This intervention has been used successfully in several neuropsychiatric disorders (e.g., anxiety, addiction), but reports of its use in PD are scant. Using fMRI-based neurofeedback combined with motor imagery, we will train patients with PD to increase the functional connectivity strength between their right insula and dorsomedial frontal cortex. These brain regions are important in initiating and sustaining voluntary movement and are affected by the pathological process in PD. We will examine the effects of this training on resting-state functional connectivity of brain networks and on motor performance. This proposal is in line with the NINDS mission to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease. If successful, this neurofeedback-guided motor imagery training could be incorporated into rehabilitation programs in PD. Candidate: Dr. Tinaz is a movement disorders neurologist. Her career goal is to develop a research program to study the neural basis of movement disorders, specifically PD, identify targets for novel therapies, and investigate the brain changes in response to interventions using neuroimaging. Dr. Tinaz seeks additional training in advanced fMRI methodology including neurofeedback, behavioral intervention development, biostatistics, and in design and conduct of clinical trials via didactic courses and hands-on learning. The project and career development plan will prepare her to design large-scale clinical trials to assess the efficacy of neurofeedback intervention in PD. Environment: The research and training activities will take place at Yale School of Medicine. The Magnetic Resonance Research Center at Yale is a state-of-the-art facility providing the infrastructure and interdisciplinary expertise for neuroimaging research. Dr. Tinaz’s mentors and consultants are experts on fMRI and clinical trial methodology. Upon completion of the proposed project, Dr. Tinaz will be well poised to become an independent clinician-scientist combining her expertise in movement disorders neurology and neuroimaging.