Characterizing Evoked Potentials of Deep Brain Stimulation for Parkinson's Disease

表征帕金森病深部脑刺激的诱发电位

• 批准号: 10605370
• 负责人: Jahrane Antonio Dale
• 金额: $ 5.27万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-01-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10605370
• 关键词: Acceleration; Affect; Anesthesia procedures; Behavior; Behavioral; Biological Markers; Bradykinesia; Cell Nucleus; Cessation of life; Characteristics; Clinic; Clinical; Collaborations; Complex; Deep Brain Stimulation; Disease Progression; Distant; Dorsal; Electrocorticogram; Electrodes; Environment; Equipment; Evoked Potentials; FDA approved; Feedback; Frequencies; Future; Generations; Goals; Human; Implant; Intervention; Knowledge; Lead; Link; Location; Medical; Mentors; Methods; Motor; Motor Cortex; Neurodegenerative Disorders; Neurologist; Neurology; Neurons; Neurosurgeon; Operative Surgical Procedures; Outcome; Parkinson Disease; Pathology; Patient-Focused Outcomes; Patients; Pharmaceutical Preparations; Phenotype; Physicians; Postoperative Period; Predictive Value; Preparation; Procedures; Process; Refractory; Research; Scientist; Shuffling Gaits; Stimulus; Structure of subthalamic nucleus; Surgeon; Surrogate Markers; Synapses; Techniques; Testing; Therapeutic; Time; Training; Tremor; Visit; awake; career; cohort; deep field survey; doctoral student; dopaminergic neuron; experience; experimental study; follow-up; image guided; implantation; improved; motor symptom; nervous system disorder; neural; neurosurgery; novel; posture instability; radiological imaging; reduce symptoms; response; side effect; skills; symposium; symptom treatment; symptomatic improvement

Deep brain stimulation (DBS) is a surgical intervention used to treat the cardinal motor symptoms of Parkinson’s disease (PD) when medical interventions fail. While DBS for the motor symptoms of PD has been used for decades, there are still gaps in our knowledge on the underlying mechanism of action, which, if resolved, might enhance DBS outcomes further. One point of improvement in DBS can be found in the process of DBS lead placement. DBS lead placement is a challenging, time-intensive procedure based on radiographic criteria, then refined by confirming motor symptom reduction and assessing side effects intraoperatively in awake patients. DBS lead placement may be improved using evoked potentials (EPs) as objective, surrogate biomarkers linked to neural activity and appropriate symptom relief. EPs have potential to guide appropriate placement of DBS leads more rapidly and accurately, possibly even in patients under anesthesia, particularly in subthalamic nucleus (STN) implants. The use of EPs as a biomarker may reduce surgical time, improve patient outcomes, and improve patient comfort. The goal of this proposal is to characterize the effect of stimulation amplitude, lead location, and anesthesia on local and distant EPs to identify more reliable and efficient methods of lead placement. This will be particularly impactful if EPs correlate with symptom relief, removing the need for behavioral characterization and expediting awake and/or asleep DBS lead placement. The first aim is to quantify the effect of DBS amplitude and location on local and distant EPs during awake DBS lead placement. Experiments will occur in concert with partnering neurosurgeons and neurologists. Local and distant EPs will be recorded simultaneously during DBS at the target of the dorsal STN and off- target at the ventral STN. DBS stimulation trials will include sub-therapeutic, therapeutic, and supra-therapeutic intensities. Before and during the DBS trials, I will concurrently quantify bradykinesia and tremor. Next, I will repeat DBS trials in follow-up clinic one month later to determine the predictive value of intraoperative EP recordings on post-op symptom treatment. The second aim will repeat these steps in patients undergoing asleep surgery. These studies are expected to quantitatively establish the causal relationship between DBS and EPs, and the correlative link between EPs and behavior critical for the use of EPs in the clinical setting. This proposal will ultimately support my training as a dual-degree MD/PhD student, in preparation for a career as an independent physician-scientist at the intersection of the bench and the bedside. The training plan will include attending conferences, gaining further clinical experience, and further developing my scientific reasoning skills. The training environment is well-equipped to prepare me for my future career as a physician- scientist. My primary sponsor (PI) has a long record of mentoring trainees and is an expert in the field of DBS, and the lab has a long record of successful collaboration with partnering physicians, several of which will also provide direct mentoring support, to help guide my long-term clinical career.

脑深部电刺激（DBS）是一种外科手术，用于治疗主要的运动症状， 帕金森病（PD）当医疗干预失败。虽然DBS用于PD的运动症状， 使用了几十年，我们对潜在的作用机制的认识仍然存在差距，如果 解决后，可能会进一步改善DBS结局。DBS的一个改进点可以在这个过程中找到 DBS电极导线置入的最佳时间。DBS电极导线置入是一项具有挑战性的、时间密集型手术， 标准，然后通过确认运动症状减轻和评估术中副作用来完善， 清醒的病人使用诱发电位（EP）作为客观、替代或替代电极导线， 与神经活动相关的生物标志物和适当的症状缓解。EP有潜力指导适当的 DBS电极导线的放置更快速、更准确，甚至可能在麻醉状态下的患者中， 在丘脑底核（subthalamic nucleus，简称NCN）植入物中。使用EP作为生物标志物可以减少手术时间，改善 改善患者的生活质量，提高患者的舒适度。本提案的目的是描述 刺激幅度、电极导线位置和麻醉，以确定更可靠和 有效的电极导线放置方法。如果EP与症状缓解相关，这将特别有影响力， 消除了对行为表征的需要并加速了清醒和/或睡眠DBS导线放置。 第一个目的是量化DBS幅度和位置对局部和远端EP的影响， 清醒DBS电极导线置入。实验将与神经外科医生和神经科医生合作进行。 在DBS期间，将在背侧和离侧靶点同时记录局部和远端EP。 瞄准腹侧腹部DBS刺激试验将包括亚治疗、治疗和超治疗 强度。在DBS试验之前和期间，我将同时量化运动迟缓和震颤。接下来我会 一个月后在随访诊所重复DBS试验，以确定术中EP的预测价值 术后症状治疗的记录第二个目标将在接受手术的患者中重复这些步骤。 睡眠手术这些研究有望定量确定DBS与 和EP，以及EP和临床环境中使用EP的关键行为之间的相关联系。 这个建议将最终支持我作为一个双学位的MD/博士生的培训，在准备一个 作为一个独立的医生，科学家在板凳和床边的交叉点的职业生涯。培训计划 我将参加会议，获得更多的临床经验，并进一步发展我的科学 推理能力。培训环境设备齐全，为我未来的医生职业做好准备- 科学家我的主要担保人（PI）有长期指导学员的记录，是DBS领域的专家， 该实验室与合作医生有着长期的成功合作记录，其中一些医生还将 提供直接的指导支持，帮助指导我的长期临床职业生涯。