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.

深脑刺激（DBS）是一种手术干预措施，用于治疗基本运动症状 当医疗干预措施失败时，帕金森氏病（PD）。虽然DBS用于PD的运动症状 几十年来，我们关于基本行动机理的知识仍然存在差距，如果 已解决，可能会进一步增强DBS结果。在此过程中可以找到DB的一个改进点 DBS铅位置的位置。 DBS铅放置是基于射线照相的挑战，时间密集型程序 标准，然后通过确认减少运动症状并在术中评估副作用 清醒的患者。使用诱发电位（EP）作为客观，替代物可以改善DBS线索的位置 与神经活动和适当症状缓解有关的生物标志物。 EP有可能指导适当的 DBS的放置更快，准确地引导，即使在麻醉下的患者中也可能导致 在丘脑下核（STN）中。使用EPS作为生物标志物可以减少手术时间，改善 患者的结果并改善患者舒适感。该提议的目的是表征 刺激放大器，铅位置和局部和遥远EPS麻醉，以识别更可靠的 有效的铅放置方法。如果EPS与Sym Relief相关，这将特别有影响力， 消除对行为表征的需求，并加快清醒和/或入睡的DBS铅位置。 第一个目的是量化DBS放大器和位置对本地和远处EP的影响 清醒的DBS铅位置。实验将与神经外科医生和神经科医生合作进行。 局部和遥远的EPS将在DBS的DBS范围内同时记录 靶标在腹侧STN。 DBS刺激试验将包括亚治疗，治疗和超育治疗 强度。在DBS试验之前和期间，我将同时量化Bradykinesia和Tremor。接下来，我会的 一个月后在随访诊所中重复DBS试验，以确定术中EP的预测值 录制后符号处理。第二个目标将在接受的患者中重复这些步骤 入睡手术。这些研究有望定量建立DBS之间的因果关系 和EPS，以及EPS与行为之间的相关链接对于在临床环境中使用EP至关重要。 该建议最终将支持我作为双级MD/博士学位学生的培训，以准备 在长凳和床边的交叉点上是独立的身体科学家的职业。培训计划 将包括参加会议，获得进一步的临床经验以及进一步发展我的科学 推理技能。培训环境有足够的能力，可以为我做好我的未来职业做好准备 科学家。我的主要赞助商（PI）有着精神训练的悠久记录，并且是DBS领域的专家， 实验室与合作医师成功合作有很长的记录，其中一些也将 提供直接的心理支持，以帮助指导我的长期临床职业。