Neuromodulation of OCD Circuitry

项目摘要 本项目的总体目标是研究三种基于直接回路的顽固性强迫症干预措施，以（1） 推进我们对疾病神经回路的理解，并（2）利用这种理解， 开发个性化的治疗方法，以提高安全性和有效性。我们的首要目标是 检查MRI引导下激光热腹侧囊切开术在20例顽固性强迫症患者中的效果 使用扩散成像来识别个体中受病变影响的离皮质轴突， 治疗反应。我们还将研究病变对个体静息状态和基于任务（PAAT）的影响。 功能连接及其与治疗结果测量的关系。我们将利用新的收购 核心B和C为个人设计的分析算法，以及与项目1、3和4的交互 识别弥散扫描中的假阴性和假阳性，并比较患者的成像结果 对病变患者进行强化非手术治疗。第二个目标是进行试点 采用双盲交叉设计，在vALIC和前部植入双DBS的可行性研究 扣带束Medtronic Percept系统将允许在4名患者中刺激和记录LFP 顽固性强迫症我们将在vALIC和前扣带回中进行刺激和记录，使用植入前 扩散成像和电场建模以识别哪些神经束被激活。我们会研究 不同触点的刺激对PAAT的影响，并将其与 灵长类动物的电生理记录。利用我们的合作者开发的方法（U Goodman，Doughman），我们将确定OCD激发和治疗反应的潜在生物标志物。我们 将与项目1和项目2互动，比较人类的解剖和电生理结果， 灵长类动物以及用于成像采集和分析的核心B和C。我们的第三个目标是利用正在进行的 对24名顽固性强迫症患者进行了低强度聚焦超声研究（Doughnard，Goodman PI），并在这些患者中获得前后扩散和基于任务（PAAT）的功能成像。我们将比较 这些结果与在vALIC靶区的病变和DBS中发现的结果一致，并利用CORE B和C以及 项目1和2比较非手术OC受试者的成像结果。

PROJECT SUMMARY The overall goal of this project is to study three direct circuit based interventions for intractable OCD to (1) advance our understanding of the neurocircuitry of the disorder and to (2) leverage that understanding in order to develop individualized approaches to treatment that will improve safety and efficacy. Our first aim is to examine the effects of MRI guided laser thermal ventral capsulotomy in twenty patients with intractable OCD using diffusion imaging to identify cortifugal axons affected by the lesions in individuals that are related to treatment response. We will also study the effects of lesions on individual resting state and task based (PAAT) functional connectivity and their relationship to treatment outcome measures. We will utilize novel acquisition and analytic algorithms for individuals designed by Cores B and C as well as interact with Projects 1, 3 and 4 to identify false negatives and positives in the diffusion scans and to compare imaging results in patients undergoing intensive non-surgical treatments to those with lesions. The second aim is to conduct a pilot feasibility study, using a double blind crossover design, of a dual DBS implant in the vALIC and anterior cingulate bundle. The Medtronic Percept system will allow stimulation and recording of LFPs, in four patients with intractable OCD. We will stimulate and record in the vALIC and anterior cingulate, using pre-implant diffusion imaging and electric field modeling to identify which tracts are being activated. We will study the effects of stimulation at different contacts on the PAAT, and compare this to results obtained with electrophysiological recordings in the primate. Leveraging methodology developed by our collaborators (U Goodman, Dougherty) we will identify potential biomarkers of OCD provocation and treatment response. We will interact with Project 1 and 2 to compare anatomic and electrophysiological results across humans and primates as well as Cores B and C for imaging acquisition and analysis. Our third aim is to leverage ongoing studies of low intensity focused ultrasound in twenty-four patients with intractable OCD (Dougherty, Goodman PIs) and obtain pre post diffusion and task based (PAAT) functional imaging in those patients. We will compare these results to those found in lesions and DBS in the vALIC target and draw on CORE B and C as well as Project 1 and 2 to compare imaging results with nonsurgical OC subjects.