2023 NINDS Landis Mentoring Award

2023 年 NINDS 兰迪斯指导奖

• 批准号: 10897632
• 负责人: PHILIP Andrew STARR
• 金额: $ 15.23万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-30 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10897632
• 关键词: Acute; Adopted; Algorithms; Award; Basal Ganglia; Brain; Brain Diseases; Chronic; Clinic; Cognition; Computers; Data; Deep Brain Stimulation; Development; Devices; Dopamine; Dyskinetic syndrome; Electrodes; Electrophysiology (science); Environment; Feedback; Foundations; Frequencies; Generations; Globus Pallidus; Goals; Grant; Home; Human; Implant; Influentials; Kinetics; Knowledge; L-DOPA induced dyskinesia; Lead; Levodopa; Mental Depression; Mentors; Moods; Motor; Motor Cortex; Movement Disorders; National Institute of Neurological Disorders and Stroke; Neurosciences; Parkinson Disease; Parkinsonian Disorders; Pathway Analysis; Patients; Pattern; Pharmaceutical Preparations; Physiological; Physiology; Rest; STN stimulation; Safety; Signal Transduction; Signs and Symptoms; Site; Stream; Structure; Structure of subthalamic nucleus; Surface; Therapeutic; Therapeutic Effect; Time; Translating; Treatment Efficacy; Tremor; Walking; Work; biomarker identification; data streams; efficacy evaluation; implantable device; implantation; improved; mild cognitive impairment; neural; neural correlate; novel; preservation; profiles in patients; prototype; response; side effect; symposium; treatment response; wearable monitor; wireless

Our long-term goal is to understand the brain rhythms underlying specific signs and symptoms of movement disorders at fast time scales, determine the effects of deep brain stimulation (DBS) on these brain rhythms, and utilize this knowledge to develop closed loop or “adaptive” stimulation. DBS of the globus pallidus (GP) is increasingly performed for Parkinson's disease (PD), based on its greater safety with respect to cognition and mood compared with subthalamic nucleus (STN) DBS, but its mechanism is not well understood. Invasive field potential recordings in the basal ganglia in humans has led to the influential hypothesis that specific patterns of abnormal oscillatory synchronization underlie the motor signs of PD. Abnormal rhythms in the beta band (13-30 Hz) are thought to be “antikinetic” while higher frequency (60-90 Hz) rhythms are “prokinetic.” Other frequencies may be “tremorogenic”. Our general approach is to extend this conceptual foundation to motor cortex and utilize network analyses from simultaneous cortical and subcortical recordings. In the initial grant period 2014-18, we focused on STN and its cortical interactions. Here, we will study pallidal and pallidocortical responses to levodopa and pallidal DBS, utilizing the technical approach developed in the previous grant period: chronic multisite field potential recording from basal ganglia and cortical electrodes, utilizing a totally implantable bidirectional neural interface. We employ a newly available second generation interface, RC+S (Medtronic) which holds substantial advantages with respect to recording quality and programmability over the first generation device (PC+S). We will use this device to understand electrophysiologic effects of antiparkinsonian medications (Aim 1) and of therapeutic pallidal DBS (Aim 2) on the basal-ganglia thalamocortical circuit; and build on these results to prototype algorithms for adaptive stimulation in which brain signals are utilized to adjust stimulation parameters according to changing brain needs (Aim 3). In addition to in-clinic recordings in defined medication states (on or off), we will use home recordings, with continuous “data streaming” from the implanted device and from wearable monitors, to increase the odds of biomarker identification. The impact of these studies will be to: 1) Provide a mechanistic understanding of the effects of therapeutic pallidal DBS on the basal ganglia-thalamocortical circuit. This may translate into improved physiological criteria for electrode placement and to rational and streamlined programing strategies. 2) Create a foundation for the development of “adaptive” DBS, perhaps the first major technical advance in DBS therapy since its introduction 25 years ago. 3) Develop a novel paradigm in human neuroscience, that of chronic ambulatory brain network recording in totally naturalistic environments, providing a platform for answering fundamental questions on basal ganglia-cortical interactions. Mechanisms elucidated in this study may be applicable to other disorders of brain circuits for which DBS has shown therapeutic promise.

我们的长期目标是了解特定符号和符号的大脑节奏 快速时间尺度上的运动障碍，确定深脑刺激（DB）对这些大脑的影响 节奏，并利用这些知识来发展闭环或“自适应”刺激。 Globus Pallidus的DB （GP）根据帕金森氏病（PD）越来越多地根据其更大的安全性进行 与丘脑下核（STN）DBS相比，认知和情绪尚不清楚。 人类基底神经节中的侵入性野外记录导致了有影响力的假设，即 异常振荡同步的特定模式是PD的电机迹象。异常节奏 β频段（13-30 Hz）被认为是“反肯”的，而较高的频率（60-90 Hz）的节奏为 “实力。”其他频率可能是“颤抖的”。我们的一般方法是扩展这种概念 运动皮层的基础，并利用简单皮质和皮层记录的网络分析。 在2014 - 18年度最初的赠款期间，我们专注于STN及其皮质相互作用。在这里，我们将学习 使用技术方法开发的技术方法 在上一个赠款期间：基底神经节和皮质的慢性多站点潜力记录 电极，使用完全可植入的双向神经界面。我们采用新的第二 生成界面RC+S（Medtronic）在记录质量方面具有很大的优势 以及第一代设备（PC+S）上的可编程性。我们将使用此设备理解 抗帕金森药物（AIM 1）和治疗Pallidal DBS（AIM 2）的电生理作用（AIM 2） 基底 - 丘脑皮层回路；并以这些结果为基础，以适应自适应的原型算法 刺激大脑信号根据大脑的变化来调节刺激参数 需求（目标3）。除了定义的药物状态（开或关）中的临界记录外，我们还将使用家 录音，从植入设备和可穿戴器监视器到连续的“数据流”到 增加生物标记鉴定的几率。 这些研究的影响将是：1）对 基底神经节 - 丘脑皮质回路上的治疗性苍白球DB。这可能会改进 电极放置的生理标准以及理性和简化的编程策略。 2）创建 开发“自适应” DBS的基础，这也许是DBS疗法中的第一个主要技术进步 自25年前引入以来。 3）在人类神经科学中发展出一种新颖的范式 在完全自然主义的环境中，卧床性脑网络录制，为答案提供了一个平台 基础神经节相互作用的基本问题。这项研究中阐明的机制可能是 适用于DBS表现出治疗前途的其他脑回路疾病。

项目成果

Neurofeedback Control in Parkinsonian Patients Using Electrocorticography Signals Accessed Wirelessly With a Chronic, Fully Implanted Device.

• DOI: 10.1109/tnsre.2016.2597243
• 发表时间: 2017-10
• 期刊: IEEE transactions on neural systems and rehabilitation engineering : a publication of the IEEE Engineering in Medicine and Biology Society
• 作者: Khanna P;Swann NC;de Hemptinne C;Miocinovic S;Miller A;Starr PA;Carmena JM
• 通讯作者: Carmena JM

A Qualitative Analysis of Ethical Perspectives on Recruitment and Consent for Human Intracranial Electrophysiology Studies.

• DOI: 10.1080/21507740.2020.1866098
• 发表时间: 2021-01
• 期刊: AJOB neuroscience
• 作者: Mergenthaler JV;Chiong W;Dohan D;Feler J;Lechner CR;Starr PA;Arias JJ
• 通讯作者: Arias JJ

Totally Implantable Bidirectional Neural Prostheses: A Flexible Platform for Innovation in Neuromodulation.

• DOI: 10.3389/fnins.2018.00619
• 发表时间: 2018
• 期刊: Frontiers in neuroscience
• 影响因子: 4.3
• 作者: Starr PA

Adaptive Deep Brain Stimulation for sleep stage targeting in Parkinson's disease.

• DOI: 10.1016/j.brs.2023.08.006
• 发表时间: 2023-09
• 期刊: BRAIN STIMULATION
• 影响因子: 7.7
• 作者: Smyth, Clay;Anjum, Md Fahim;Ravi, Shravanan;Denison, Timothy;Starr, Philip;Little, Simon
• 通讯作者: Little, Simon

Chronic multisite brain recordings from a totally implantable bidirectional neural interface: experience in 5 patients with Parkinson's disease.

• DOI: 10.3171/2016.11.jns161162
• 发表时间: 2018-03
• 期刊: Journal of neurosurgery
• 影响因子: 4.1
• 作者: Swann NC;de Hemptinne C;Miocinovic S;Qasim S;Ostrem JL;Galifianakis NB;Luciano MS;Wang SS;Ziman N;Taylor R;Starr PA
• 通讯作者: Starr PA