Bilateral Closed Loop Deep Brain Stimulation for Freezing of Gait using Neural and Kinematic Feedback

利用神经和运动学反馈进行双边闭环深部脑刺激以冻结步态

基本信息

批准号：
10670150
负责人：
Helen Bronte-Stewart
金额：
$ 120.97万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-08-01 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10670150
关键词：
Adverse effects Affect Age Algorithms Behavior Control Behavioral Bilateral Bluetooth Bradykinesia Brain Cessation of life Clinical Research Complication Data Deep Brain Stimulation Development Device or Instrument Development Devices Disease Progression Dose Emerging Technologies Environment Family Feedback Freezing Frequencies Future Gait Glues Home Home environment Impairment Implant Incidence Independent Living Industry Collaboration Injury Institution Lead Leg Lewy Body Dementia Locomotion Measurement Measures Motor Movement Disorder Society Unified Parkinson&apos s Disease Rating Scale National Institute of Neurological Disorders and Stroke Neurodegenerative Disorders Outcome Parkinson Disease Patients Periodicity Persons Pharmaceutical Preparations Policies Population Progressive Supranuclear Palsy Research Research Priority Safety Signal Transduction Societies Structure of subthalamic nucleus System Technology Testing Time Translating Tremor Walking arm bench to bedside cohort design disability effective therapy experience experimental study falls feasibility testing foot home test improved kinematics motor disorder motor symptom nervous system disorder neural neuroregulation next generation novel partial response participant safety patient safety prevent primary outcome response safety and feasibility safety testing secondary outcome sensor side effect symposium wearable sensor technology

项目摘要

Gait impairment and Freezing of gait (FOG), lead to falls, injury (even death), loss of independent living, and are common in neurodegenerative diseases such as Parkinson’s Disease (PD), affecting over 7 million people worldwide. The incidence of neurodegenerative diseases increases with age and as the population lives longer, the societal consequences of FOG, will be very significant. Gait impairment and FOG have a partial response to medication and subthalamic nucleus (STN) open loop deep brain stimulation (olDBS), which cannot adjust therapy in response to underlying brain signals or motor symptoms such as FOG. One reason is that FOG may respond to different parameters of DBS, such as lower frequency, than that needed for tremor and most patients do not tolerate 60 Hz DBS for long periods of time. Emerging technology using sensing neurostimulators and Bluetooth enabled wearable sensors has allowed research into closed loop or adaptive (a)DBS using neural or behavioral control variables. FOG is episodic and usually occurs in predictable environments, so it is well suited for ‘on demand’ aDBS. ADBS, responding to markers of gait impairment and intermittent FOG, with changes in DBS intensity or frequency, could then prevent FOG, falls and injury, while still treating other motor signs of PD. From over four years of research and regulatory experience in an academic-industry collaboration with Medtronic, we have provided design inputs for the next generation aDBS devices, and have determined that aDBS for tremor and bradykinesia is safe and tolerable in the largest freely-moving PD cohort implanted with a Medtronic investigative neurostimulation/sensing system (Activa® PC+S-Nexus D/D3/E). We have discovered neural and behavioral markers of gait impairment and FOG using synchronized neural and kinematic recordings during gait tasks that elicit FOG. Our research findings and the technological advances embedded in the Medtronic Summit® RC+S-system now enable the next step: the first clinical studies of lateralized, independent, bilateral STN aDBS control algorithms for FOG in PD, driven by subject-specific neural (Aim 1) or behavioral (Aim 2) control variables, and in response to medication (Aim 3). The project will translate stepwise in a ‘bench to bedside’ manner, testing aDBS during the stepping in place (SIP) task, where the subject is in a harness and steps in place on dual force-plates. Then aDBS will be tested during the forward walking Turning and Barrier Course, which mimics environments known to trigger FOG in the real world, and then how aDBS responds to subject-specific doses of medication, while freely moving. The outcome of these experiments will provide critical next-steps for safety and feasibility of testing aDBS for gait impairment and FOG in the subject’s home environment, and on their normal medication. Patient safety, tolerability, adverse effects, gait parameters, and the number and duration of freezing episodes (FEs), during no DBS, olDBS, aDBS and a control, intermittent (i)olDBS will provide inputs for future devices and novel algorithms applicable to NaDBS or KaDBS for gait impairment and FOG in other neurological diseases.

步态障碍和冻结步态（雾），导致跌倒，受伤（甚至死亡），失去独立生活，是在帕金森氏病（PD）等神经退行性疾病中常见，影响了700万人全世界。神经退行性疾病的事件随着年龄的增长而增加，随着人口的寿命更长，雾的社会后果将非常重要。步态障碍和雾对药物和丘脑下核（STN）开环深脑刺激（OldBS），无法调整响应潜在的脑信号或运动症状（例如雾）的治疗。一个原因是雾可能响应与震颤和大多数患者所需的DBS不同参数（例如较低的频率）长时间不要忍受60 Hz DBS。使用传感神经刺激器和启用蓝牙的可穿戴传感器已使使用神经或自适应的闭环或自适应（a）DBS进行研究行为控制变量。雾是情节性的，通常发生在可预测的环境中，因此非常适合用于“按需” ADB。 ADB，响应搅拌和间歇性雾的标记，随着变化的变化 DBS强度或频率可以防止雾，跌落和受伤，同时仍处理其他电动机迹象。从与学术行业合作的四年来研究和监管经验 Medtronic，我们为下一代ADB设备提供了设计输入，并确定在最大的自由移动的PD队列中，震颤和颤音的ADB是安全可容忍的 Medtronic研究神经刺激/传感系统（Activa®PC+S-Nexus D/D3/E）。我们发现了使用同步神经和运动学记录的搅动和雾的神经和行为标记在引起雾气的步态任务中。我们的研究发现以及嵌入的技术进步 MedtronicSummit®RC+S-System现在启用下一步：侧向，独立的临床研究由主体特异性神经（AIM 1）或行为驱动的PD中的双侧STN ADBS控制算法（AIM 2）控制变量，并响应药物治疗（AIM 3）。该项目将在“长凳上逐步翻译” 床边的方式，在踏入到位期间测试ADB（sip）任务，该主题处于安全带中，在双力平板上逐步踩踏。然后在前进的转弯和障碍期间测试ADB 当然，哪些模仿了在现实世界中触发雾的已知环境，然后ADB如何回应特定于主体的药物剂量，同时自由移动。这些实验的结果将提供关键下一步的安全性和测试ADB在受试者家中进行搅动和雾气的可行性环境及其正常药物。患者的安全性，耐受性，不良影响，收集参数和冻结剧集（FES）的数量和持续时间，在没有DBS，OldBS，ADB和控制期间，间歇性（i）OldBS将为未来的设备和适用于NADBS或KADBS的新算法提供输入其他神经疾病中的损害和雾气。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Ramp Rate Evaluation and Configuration for Safe and Tolerable Closed-Loop Deep Brain Stimulation.

DOI：
10.1109/ner49283.2021.9441336
发表时间：
2021-05
期刊：
International IEEE/EMBS Conference on Neural Engineering : [proceedings]. International IEEE EMBS Conference on Neural Engineering
影响因子：
0
作者：
Petrucci, Matthew N.;Wilkins, Kevin B.;Orthlieb, Gerrit C.;Kehnemouyi, Yasmine M.;O'Day, Johanna J.;Herron, Jeffrey A.;Bronte-Stewart, Helen M.
通讯作者：
Bronte-Stewart, Helen M.

Demonstration of Kinematic-Based Closed-loop Deep Brain Stimulation for Mitigating Freezing of Gait in People with Parkinson's Disease.

DOI：
10.1109/embc44109.2020.9176638
发表时间：
2020-07
期刊：
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
影响因子：
0
作者：
O'Day JJ;Kehnemouyi YM;Petrucci MN;Anderson RW;Herron JA;Bronte-Stewart HM
通讯作者：
Bronte-Stewart HM

A Closed-loop Deep Brain Stimulation Approach for Mitigating Burst Durations in People with Parkinson's Disease.

DOI：
10.1109/embc44109.2020.9176196
发表时间：
2020-07
期刊：
Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Annual International Conference
影响因子：
0
作者：
Petrucci MN;Anderson RW;O'Day JJ;Kehnemouyi YM;Herron JA;Bronte-Stewart HM
通讯作者：
Bronte-Stewart HM

A validated measure of rigidity in Parkinson's disease using alternating finger tapping on an engineered keyboard.

DOI：
10.1016/j.parkreldis.2020.10.047
发表时间：
2020-12
期刊：
Parkinsonism & related disorders
影响因子：
4.1
作者：
Trager MH;Wilkins KB;Koop MM;Bronte-Stewart H
通讯作者：
Bronte-Stewart H

Differential Effects of Pathological Beta Burst Dynamics Between Parkinson's Disease Phenotypes Across Different Movements.

DOI：
10.3389/fnins.2021.733203
发表时间：
2021
期刊：
Frontiers in neuroscience
影响因子：
4.3
作者：
Neuville RS;Petrucci MN;Wilkins KB;Anderson RW;Hoffman SL;Parker JE;Velisar A;Bronte-Stewart HM
通讯作者：
Bronte-Stewart HM