Pathophysiology-based approaches to deep brain stimulation for Parkinson's disease

基于病理生理学的帕金森病脑深部刺激方法

• 批准号: 10282962
• 负责人: Jerrold L Vitek
• 金额: $ 36.76万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-17 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10282962
• 关键词: Affect; Agreement; Algorithms; Anatomy; Area; Basal Ganglia; Biological Markers; Bradykinesia; Cells; Clinical; Cognition; Cognitive; Coupling; Decision Making; Deep Brain Stimulation; Development; Devices; Disease; Electrocorticogram; Electrophysiology (science); Frequencies; Functional disorder; Future; Globus Pallidus; Goals; High Frequency Oscillation; Imaging Techniques; Individual; Lead; Levodopa; Location; Maps; Microelectrodes; Motor; Movement; Neurodegenerative Disorders; Neurons; Outcome; Parkinson Disease; Pathologic; Patients; Pattern; Performance; Phase; Phenotype; Physiological; Play; Postoperative Period; Prefrontal Cortex; Preparation; Rest; Role; STN stimulation; Sensory; Severities; Shapes; Short-Term Memory; Site; Structure of subthalamic nucleus; Therapeutic; base; cognitive function; effective therapy; high resolution imaging; improved; insight; motor disorder

ABSTRACT (Project 1) Parkinson’s disease (PD) is a progressive neurodegenerative disease affecting over 10 million people world- wide. It can be a debilitating disorder and although studied for decades the physiological changes in the basal ganglia thalamocortical (BGTC) circuit that underlie its development remain under debate. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and internal globus pallidus (GPi) has been a highly effective therapy for many patients with PD, however, the results have been highly variable and may be associated with cognitive compromise in some patients. To advance DBS therapies for PD we require a deeper understanding of the local and network-wide circuit dynamics and their relationship to motor signs and cognitive function. This understanding will provide the rationale for optimizing STN and GPi DBS, targeting specific regions within the STN and GPi, and development of patient-specific DBS based on the patients’ motor signs and cognitive profile. The goals of this study are to advance our understanding of the role of BGTC (subcortical-cortical) and cortical-cortical circuits in the development of PD, the changes that occur with DBS and L-dopa, and to use this understanding to advance current and develop new DBS approaches for its treatment. We will define the relationship between synchronized oscillations, coherence and connectivity within the broader BGTC circuit (STN, GPi, sensory, motor, premotor and dorsolateral prefrontal cortices) to the development of PD motor signs, define their role in motor performance (SA1,2), cognitive function (SA1,2,3), and corresponding changes with DBS, L-dopa and DBS+L-dopa (SA2). By defining the strength and direction of connectivity patterns at rest and during movement we will characterize the role of individual circuits within the BGTC network and define their respective roles in motor performance and cognitive function paving the way for future development of optimization algorithms for DBS that take advantage of this understanding (SA1,2,3,4). By correlating the degree of coherence between multiple single cells and local field potential (LFP) activity we will also advance our understanding of the role of spike-phase locking to the development of motor signs. Through high resolution imaging techniques and parcellation analyses we will define the optimal site for DBS within the STN and GPi (SA2,3,4) correlating motor and cognitive outcomes to biomarker activity and lead location, leading to patient- specific DBS and development of automated programming algorithms based on each patient’s phenotype and lead location. The proposed aims will be conducted using directional DBS leads, multiple independent current controlled (MICC) devices, high resolution imaging and electrophysiological recordings in PD patients with electrocorticography (ECoG) arrays undergoing microelectrode mapping (SA1,3), postoperatively in patients with ECoG arrays and externalized leads (SA2,3), and following optimization of DBS parameters (SA4).

摘要（项目1） 帕金森病 (PD) 是一种进行性神经退行性疾病，影响着全世界超过 1000 万人。 宽的。它可能是一种使人衰弱的疾病，尽管研究了几十年，但基础的生理变化 其发育背后的丘脑皮质神经节（BGTC）回路仍存在争议。脑深部刺激 丘脑底核 (STN) 和苍白球内核 (GPi) 的 DBS 治疗是一种高效的治疗方法 然而，对于许多 PD 患者来说，结果差异很大，并且可能与认知能力有关。 一些患者的妥协。为了推进 DBS 治疗 PD，我们需要更深入地了解当地的情况 和网络范围的电路动力学及其与运动信号和认知功能的关系。这 理解将为优化 STN 和 GPi DBS 提供基本原理，针对特定区域 STN 和 GPi，以及根据患者的运动体征和认知特征开发患者特异性 DBS。 这项研究的目的是加深我们对 BGTC（皮质下-皮质）和 PD 发展中的皮质-皮质回路、DBS 和左旋多巴发生的变化以及 利用这种理解来推进当前和开发新的 DBS 治疗方法。我们将 定义更广泛的 BGTC 内同步振荡、相干性和连通性之间的关系 PD 运动发育的电路（STN、GPi、感觉、运动、前运动和背外侧前额皮质） 体征，定义它们在运动表现 (SA1,2)、认知功能 (SA1,2,3) 和相应变化中的作用 含 DBS、L-多巴和 DBS+L-多巴 (SA2)。通过定义静态连接模式的强度和方向 在运动过程中，我们将描述 BGTC 网络中各个电路的作用并定义它们 在运动表现和认知功能中各自的作用为未来的发展铺平了道路 利用这种理解的 DBS 优化算法 (SA1,2,3,4)。通过关联度 多个单细胞和局部场电位（LFP）活动之间的一致性，我们还将推进我们的研究 了解尖峰锁相对运动体征发展的作用。通过高分辨率 成像技术和分区分析，我们将在 STN 和 GPi 内定义 DBS 的最佳位置 (SA2,3,4) 将运动和认知结果与生物标志物活动和引线位置相关联，导致患者- 特定的 DBS 和基于每个患者的表型和自动编程算法的开发 引导位置。所提出的目标将使用定向 DBS 引线、多个独立电流来实现 受控 (MICC) 设备、高分辨率成像和电生理记录用于 PD 患者 患者术后进行微电极测绘 (SA1,3) 的皮质电图 (ECoG) 阵列 使用 ECoG 阵列和外置导联 (SA2,3)，并优化 DBS 参数 (SA4)。