Toward Connectomic Deep Brain Stimulation in Obsessive Compulsive Disorder

项目总结：在强迫症中进行连接体脑深部电刺激 强迫症是全球残疾的主要原因，约有10%的患者 常规治疗难治，同时患有大量疾病负担。脑深部电刺激 (DBS)是这些患者的一种治疗选择，但尽管有些人对这种侵入性手术反应良好， 不是所有的病人都这样。其中一个原因可能是，我们将DBS概念化为调节大脑区域，而不是大脑区域。 脑网络这个项目的目标是因果联系症状的具体改善强迫症， 刺激特定的大脑网络。通过这样做，我们将能够获得特定于网络的目标 用于DBS治疗。在我们的初步研究中，我们确定了一个特定的网络目标， DBS后对全球应用的四种不同手术靶点的反应最佳。我们的研究结果 基于迄今为止研究的最大的DBS多中心OCD队列（N = 50），并已被 自发表以来，又增加了四个中心。虽然结果令人鼓舞，但在实现目标之前仍存在三个差距。 正在进行前瞻性临床试验。本R01的目的是缩小这些差距。首先，我们定义了 通过结构和功能连接的方式优化网络，但到目前为止，仍不清楚哪些是 这两种模式（或两者的组合）最适合于引导DBS。第二，在调整 网络导致组水平上的最佳响应，强迫症是一种异质性疾病，每个网络中的症状 病人是不同的。我们将确定哪些具体的症状（强迫症，强迫症，抑郁症和 焦虑）映射到网络的哪些特定组件。这将为个性化DBS和 定义针对个体患者的特定靶点。第三，虽然我们的大部分初步研究都是 基于人脑的标准连接体图谱，强迫症患者的连接体呈现出 个体差异我们将测试在以下情况下， 使用患者特异性连接体而不是标准连接体。这些目标的实现将验证和完善我们的 强迫症反应网络如果成功，这项研究将促进未来的试验直接针对我们的大脑回路， DBS治疗强迫症

PROJECT SUMMARY: Toward Connectomic Deep Brain Stimulation in Obsessive Compulsive Disorder Obsessive-Compulsive-Disorder is a leading cause of disability worldwide with about 10% of patients that are refractory to conventional treatment while suffering from substantial burden of disease. Deep Brain Stimulation (DBS) is a treatment option for these patients, but while some respond excellently to this invasive procedure, not all patients do. One reason could be that we conceptualize DBS to modulate a brain region, rather than a brain network. The goal of this project is to causally link symptom specific improvements in OCD to the stimulation of specific brain networks. By doing so, we will be able to derive symptom-specific network targets for treatment in DBS. In our preliminary research, we identified a specific network target that was associated with optimal response following DBS to four different surgical targets applied world-wide. Our findings were based on the largest multi-center OCD cohort with DBS studied to date (N = 50) and have been confirmed by four additional centers since they were published. While results are promising, three gaps remain before moving toward prospective clinical trials. The aim of this R01 will be to close these gaps. First, we have defined optimal networks by means of structural and functional connectivity but, so far, it remains unclear which of these two modalities (or a combination of both) is best suited to guide DBS. Second, while modulating the network leads to optimal response on a group level, OCD is a heterogeneous disease and symptoms in each patient are different. We will determine which specific symptoms (obsessions, compulsions, depression and anxiety) map to which specific components of the network. This will pave the way to personalize DBS and to define symptom-specific targets tailored to individual patients. Third, while most of our preliminary research is based on normative connectome atlases of the human brain, connectomes of patients with OCD present with individual differences. We will test how much additional variance in clinical outcomes can be explained when using patient-specific instead of normative connectomes. Completion of these aims will validate and refine our OCD response network. If successful, this study will facilitate future trials directly targeting our brain circuit with DBS for OCD.