Adaptive Neurostimulation to Restore Sleep in Parkinson's Disease: An Investigation of STN LFP Biomarkers In Sleep Dysregulation and Repair

适应性神经刺激恢复帕金森病睡眠：睡眠失调和修复中 STN LFP 生物标志物的研究

• 批准号: 10456676
• 负责人: AVIVA ABOSCH
• 金额: $ 104.2万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10456676
• 关键词: Address; Affect; Algorithms; Attention; BRAIN initiative; Basal Ganglia; Beds; Behavior; Behavior Disorders; Biological Markers; Bradykinesia; Brain; Caregivers; Clinical; Cognition; Control Groups; Crossover Design; Deep Brain Stimulation; Development; Devices; Diagnosis; Double-Blind Method; Dyskinetic syndrome; Electrodes; Electrophysiology (science); Excessive Daytime Sleepiness; Exhibits; General Population; Home; Homeostasis; Human; Impairment; Implant; Implanted Electrodes; Investigation; Lead; Maintenance; Masks; Medical; Mission; Moods; Morbidity - disease rate; Motor; National Institute of Neurological Disorders and Stroke; Nature; Nervous system structure; Neurodegenerative Disorders; Operative Surgical Procedures; Parkinson Disease; Pathologic; Patients; Pattern; Pharmaceutical Preparations; Phase; Polysomnography; Population; Protocols documentation; Quality of life; REM Sleep Behavior Disorder; Regulation; Reporting; Restless Legs Syndrome; STN stimulation; Signal Transduction; Site; Sleep; Sleep Architecture; Sleep Disorders; Sleep Disorders Therapy; Sleep Fragmentations; Sleep Stages; Sleep disturbances; Sleeplessness; Slow-Wave Sleep; Structure; Structure of subthalamic nucleus; Symptoms; System; Technology; Testing; Therapeutic; Time; Tremor; Triad Acrylic Resin; Work; actigraphy; artificial neural network; clinical research site; effective therapy; efficacy testing; experience; experimental group; hypnotic; implantation; improved; insight; mortality; motor symptom; neural stimulation; non-motor symptom; novel; novel therapeutics; patient population; potential biomarker; prototype; repaired; response; sedative; side effect; sleep behavior; sleep quality; sleep regulation; specific biomarkers; symposium

Project Summary Parkinson’s disease (PD) is a neurodegenerative disorder that leads to both motor and non-motor symptoms. While there is as yet no cure for PD, medical and surgical therapies have been developed that effectively target the motor symptoms of PD. Non-motor symptoms are far more disabling for patients, precede the onset of motor symptoms by a decade, are more insidious in onset, have been less apparent to clinicians, and are less effectively treated. Sleep dysfunction is oftentimes the most burdensome of the non-motor symptoms—both to patients and to their caregivers—is pervasive in patients with PD, and includes sleep fragmentation, insomnia, excessive daytime sleepiness, REM behavioral disorder, and restless leg syndrome. There are limited options for treating sleep dysfunction in PD, and the mainstay of therapy is the use of agents that mask the sleep disturbance—such as the sedative-hypnotic drugs—without addressing the underlying mechanisms. Although much attention has been devoted to PD motor symptoms, sleep dysfunction in PD has largely been ignored. Sleep is vital to homeostasis, cognition, and nervous system repair, and the dysfunctional sleep accompanying PD adversely affects both motor and non-motor symptoms, resulting in diminished quality of life, impairments in mood and behavior, and increased morbidity and mortality. Patients with PD who demonstrate significant motor fluctuations and dyskinesia are considered for subthalamic nucleus (STN) deep brain stimulation (DBS) surgery. Although STN-DBS is routinely used to treat PD motor symptoms, several studies have reported that STN-DBS also provides benefit for sleep dysregulation through normalization of sleep architecture. Additionally, local field potentials recorded from STN DBS electrodes implanted for the treatment of PD, have led to the identification of unique spectral patterns in STN oscillatory activity that correlate with distinct sleep cycles, offering insight into sleep dysregulation. Building on this work, and in response to RFA-NS- 18-023, this proposal will leverage novel investigational DBS battery technology (RC+S Summit System; Medtronic) that allows the exploration of sleep biomarkers and prototyping of closed-loop stimulation algorithms, to test the hypothesis that STN—a highly interconnected node within the basal ganglia—contributes to the regulation and disruption of human sleep behavior and can be manipulated for therapeutic advantage. Specifically, in PD patients undergoing STN-DBS, we will determine whether STN oscillations correlate with sleep stage transitions, then construct and evaluate sensing and adaptive stimulation paradigms that allow ongoing sleep-stage identification, and induce through adaptive stimulation an increase in duration of sleep stages associated with restorative sleep. This work will lead to findings that address a currently unmet clinical need, and relevant to the mission of NINDS and the BRAIN Initiative, will evaluate the use of adaptive stimulation of the STN in PD patients for the treatment of sleep dysfunction.

项目概要 帕金森病 (PD) 是一种神经退行性疾病，会导致运动和非运动症状。 虽然帕金森病目前还没有治愈方法，但已经开发出有效针对帕金森病的药物和手术疗法。 PD 的运动症状在运动症状出现之前对患者来说更加严重。 症状在十年前出现，发病更加隐匿，对忠诚者来说不太明显，而且不太明显。 睡眠功能障碍往往是最严重的非运动症状——无论是对于 患者及其护理人员——在帕金森病患者中普遍存在，包括睡眠碎片化、失眠、 白天过度嗜睡、快速眼动行为障碍和不宁腿综合症的选择有限。 用于治疗帕金森病的睡眠障碍，主要治疗方法是使用掩盖睡眠的药物 干扰——例如镇静催眠药物——但没有解决潜在的机制。 虽然帕金森病的运动症状受到了很多关注，但帕金森病的睡眠功能障碍在很大程度上是由于 睡眠对于体内平衡、认知和神经系统修复以及功能失调的睡眠至关重要。 伴随的帕金森病会对运动和非运动症状产生不利影响，导致生活质量下降， 情绪和行为受损，以及帕金森病患者的发病率和死亡率增加。 显着的运动波动和运动障碍被认为是丘脑底核（STN）深部大脑 尽管 STN-DBS 常规用于治疗 PD 运动症状，但一些研究表明。 据报道，STN-DBS 还可以通过睡眠正常化来改善睡眠失调 此外，还记录了治疗时植入的 STN DBS 电极的局部场电位。 PD 的结果导致了 STN 振荡活动中独特光谱模式的识别，这些模式与 不同的睡眠周期，以这项工作为基础，并针对 RFA-NS- 提供了对睡眠失调的深入了解。 18-023，该提案将利用新颖的研究性 DBS 电池技术（RC+S Summit System； Medtronic）允许探索睡眠生物标志物和闭环刺激算法的原型设计， 检验 STN（基底神经节内高度互连的节点）有助于 人类睡眠行为的调节和破坏，并且可以被操纵以获得治疗优势。 具体来说，在接受 STN-DBS 的 PD 患者中，我们将确定 STN 振荡是否与 睡眠阶段转换，然后构建和评估感知和适应性刺激范式，以允许 持续的睡眠阶段识别，并通过适应性刺激诱导睡眠持续时间的增加 这项工作将导致解决当前未满足的问题。 临床需求，并与 NINDS 和 BRAIN Initiative 的使命相关，将评估 PD 患者 STN 的适应性刺激用于治疗睡眠功能障碍。