Toward Connectomic Deep Brain Stimulation in Obsessive Compulsive Disorder

项目摘要：强迫症患者的脑深部连接性刺激 强迫症是世界范围内导致残疾的主要原因，约10%的患者 对常规治疗无效，同时承受着沉重的疾病负担。脑深部刺激 (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程序反应良好， 并不是所有的病人都是这样。一个原因可能是，我们概念化DBS是为了调节大脑区域，而不是 大脑网络。这个项目的目标是将强迫症症状的具体改善与 刺激特定的大脑网络。通过这样做，我们将能够派生出特定症状的网络目标 在星展银行接受治疗。在我们的初步研究中，我们确定了一个特定的网络目标 在全球范围内，DBS对四种不同的手术靶点有最佳反应。我们的发现是 基于迄今为止研究的星展银行最大的多中心强迫症队列(N=50)，并已得到以下证实 自他们出版以来，又增加了四个中心。虽然结果令人振奋，但在此之前仍存在三个差距 正在进行预期的临床试验。这款R01的目标将是缩小这些差距。首先，我们已经定义了 通过结构和功能连接来优化网络，但到目前为止，还不清楚 这两种模式(或两者的组合)最适合指导星展银行。第二，在调制 网络导致群体层面的最佳反应，强迫症是一种异质性疾病，每种疾病都有症状 病人是不同的。我们将确定哪些特定症状(强迫症、强迫症、抑郁症和 焦虑)映射到网络的哪些特定组件。这将为星展银行的个性化和 定义针对个别患者量身定做的特定症状目标。第三，虽然我们的大部分初步研究是 基于人脑的标准连接体图谱，强迫症患者的连接体呈现 个体差异。我们将测试临床结果的额外差异在多大程度上可以解释 使用特定于患者的连接，而不是标准连接。完成这些目标将验证和完善我们的 强迫症应对网络。如果成功，这项研究将促进未来直接针对我们的大脑回路的试验 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.