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

7.项目摘要/摘要 帕金森氏症(PD)在全球范围内影响着600多万人。随着预期寿命的增加，这 预计到2040年，这一数字将翻一番。维持稳定的运动性能的能力受损是一个主要的 帕金森病患者的发病原因。这以速度的快速递减为特征， 在连续任务(如行走、写作)过程中的运动幅度或力。标准 药物和手术治疗在改善这种减少方面是无效的。人们对小说的需求 有针对性的治疗，不良反应最小，以更好地控制症状。建议的被辅导者的目标 研究项目是评估基于功能磁共振成像(FMRI)的效果 神经反馈干预对帕金森病患者脑可塑性和持续性运动能力的影响。功能磁共振成像- 基于神经反馈是一种非侵入性干预，可以提高个体控制大脑的能力 实时活动。通过实践，个人还可以学习如何自我调节与之相关的行为 通过这种大脑活动。该干预已经成功地用于几种神经精神障碍(例如， 焦虑、上瘾)，但关于它在帕金森病中的应用报告很少。将基于功能磁共振成像的神经反馈与 运动表象，我们将训练帕金森病患者，以增加其右侧之间的功能连接强度 脑岛和额叶背内侧皮质。这些大脑区域在启动和维持自愿性方面很重要 并受帕金森病病理过程的影响。我们将检查这次培训的效果 静息状态下大脑网络的功能连通性和运动性能。这项建议符合 NINDS的任务是寻找关于大脑和神经系统的基础知识，并利用这些知识 减轻神经系统疾病负担的知识。如果成功，这种神经反馈引导的马达 表象训练可以纳入帕金森病患者的康复计划。候选人：蒂纳兹博士是一场运动 精神障碍神经科医生。她的职业目标是开发一个研究运动的神经基础的研究计划 障碍，特别是帕金森病，确定新疗法的靶点，并调查大脑对 使用神经成像技术进行干预。Tinaz博士寻求高级功能磁共振成像方法方面的额外培训，包括 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 通过授课课程和实践学习。项目和职业发展计划将为她做好准备 设计大规模临床试验，评估神经反馈干预对帕金森病的疗效。环境： 研究和培训活动将在耶鲁医学院进行。磁共振研究 耶鲁大学中心是一个最先进的设施，提供基础设施和跨学科的专业知识 神经影像研究。蒂纳兹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，蒂纳兹博士将成为一名 独立的临床医生-科学家，结合了她在运动障碍、神经学和神经成像方面的专业知识。

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.