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.

项目摘要 帕金森氏病（PD）是一种神经退行性疾病，可导致运动症状和非运动症状。 虽然尚无PD治疗，但已经开发出有效靶向的医学和外科疗法 PD的运动症状。在电动机发作之前，非运动症状更为残疾 十年来的症状在发病方面更加阴险，对临床医生的看法较低，并且较少 睡眠功能障碍通常是非运动符号中最朴实的人 - 患者及其护理人员 - PD患者普遍存在，包括睡眠破碎，失眠， 白天过度嗜睡，REM行为障碍和不安的腿综合症。选择有限 用于治疗PD中的睡眠功能障碍，而治疗的主要是使用掩盖睡眠的药物 扰动（例如镇静性催眠药），没有解决基本机制。 尽管已经关注PD运动症状，但PD的睡眠功能障碍在很大程度上是 被忽略。睡眠对体内平衡，认知和神经系统修复至关重要，睡眠失调 参与PD会对运动症状和非运动症状产生不利影响，从而导致生活质量降低， 情绪和行为障碍，发病率和死亡率增加。 PD患者证明 考虑下丘脑核（STN）深脑的明显运动波动和运动障碍。 刺激（DBS）手术。尽管STN-DBS通常用于治疗PD运动症状，但几项研究 报告说STN-DBS还通过睡眠正常化为睡眠失调提供了好处 建筑学。此外，从植入用于治疗的STN DBS电极记录的局部场电位 PD的，导致识别与与 独特的睡眠周期，可深入了解睡眠失调。在这项工作的基础上，并回应RFA-NS- 18-023，该提案将利用新颖的研究DBS电池技术（RC+S Summit系统； Medtronic）允许探索睡眠生物标志物和闭环刺激算法的原型制作， 为了检验以下假设，即STN（基底神经节内高度相互连接的节点）归属于 人类睡眠行为的调节和破坏，可以通过治疗优势进行操纵。 具体而言，在接受STN-DBS的PD患者中，我们将确定STN振荡是否与 睡眠阶段过渡，然后构建和评估感应和适应性刺激范式 持续的睡眠阶段识别，并通过自适应刺激诱导睡眠时间的增加 与恢复性睡眠有关的阶段。这项工作将导致发现当前未满足的发现 临床需求，并且与Ninds和大脑倡议的使命相关，将评估使用 PD患者对STN的适应性刺激治疗睡眠功能障碍。