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; 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） 帕金森氏病（PD）是一种进行性神经退行性疾病，影响了超过1000万人的世界 - 宽的。它可能是一种使人衰弱的疾病，尽管研究了数十年，但基本的生理变化 其发展的基础的神经节丘脑皮层（BGTC）仍在争论中。深脑刺激 （DB）的（DBS）的丘脑核（STN）和Globus pallidus（GPI）已成为一种高效的治疗 但是，对于许多PD患者，结果变化很大，可能与认知有关 在某些患者中妥协。为了推进PD的DBS疗法，我们需要更深入地了解本地 以及网络范围的电路动力学及其与电机标志和认知功能的关系。这 理解将提供优化STN和GPI DB的理由，以针对特定区域 STN和GPI，以及基于患者的运动体征和认知能力的患者特异性DBS的开发。 这项研究的目标是促进我们对BGTC（皮层皮层）和 PD发育，DB和L-DOPA发生的变化以及对 利用这种理解来促进当前的治疗方法，并开发新的DBS方法。我们将 定义较宽的BGTC内同步振荡，连贯性和连通性之间的关系 电路（STN，GPI，感觉，电机，运动前和背前额叶皮层），以开发PD电机 符号，定义其在运动性能（SA1,2），认知功能（SA1,2,3）和相应更改中的作用 使用DBS，L-DOPA和DBS+L-DOPA（SA2）。通过定义静止的连通性模式的强度和方向 在移动期间，我们将表征单个电路在BGTC网络中的作用并定义其 在运动性能和认知功能中的各自角色为未来发展铺平了道路 利用这种理解的DB的优化算法（SA1,2,3,4）。通过关联度 多个单细胞和局部场电位（LFP）活性之间的相干性，我们还将推进我们的 理解尖峰相锁定在运动符号发展中的作用。通过高分辨率 成像技术和分析分析我们将定义STN和GPI中DBS的最佳位点 （SA2,3,4）将运动和认知结果与生物标志物活性和铅位置相关联，导致患者 - 根据每个患者的表型和 线索位置。提出的目标将使用定向DBS引线，多个独立电流进行 PD患者的受控（MICC）设备，高分辨率成像和电生理记录 经过微电极图（SA1,3）的电皮质学（ECOG）阵列，术后患者 具有ECOG数组和外部铅（SA2,3），并在优化DBS参数（SA4）之后。