Individually targeted neuromodulation for contamination-based OCD

项目总结/摘要 强迫症（OCD）的症状似乎与皮质纹状体功能障碍有关， 丘脑-皮层回路然而，强迫症患者的强迫观念和强迫行为差异很大， 其他特定的大脑网络可能伴随着这一核心缺陷。识别这些网络可以 导致个体化治疗，改善目前的"一刀切"的方法。因素分析表明， 在强迫症中发现了不同的症状维度，但这些维度特有的神经系统仍然存在 不清楚使用新的个体水平方法进行静息态功能连接磁共振 通过功能磁共振成像（fcMRI），我们发现右额内侧回（R MFG）和 腹侧注意力网络（VAN）内的大脑区域-对重新定位注意力至关重要的区域， 相关外部刺激-特别预测污染/清洗（CONTAM）症状的严重程度， 治疗后这种超连接的减弱与CONTAM的改善相关 症状基于这些发现，我们假设，通过经颅途径降低R MFG-VAN连接， 磁刺激（TMS）将使个体的注意力重新定向正常化，并减少CONTAM症状 患有污染性强迫症因此，与R61/R33机制一致，我们提出了两阶段 研究R MFG靶向TMS作为污染型强迫症的潜在干预措施的计划。在 R61阶段，我们将通过以下方式确定降低R MFG-VAN连接性的最佳TMS范例： 向患有以下疾病的个体施用连续和间歇的θ爆发刺激（cTBS，iTBS） 基于污染的强迫症使用一种新的个人水平的方法，以最强烈地针对R MFG区域 基于每个参与者的治疗前连接数据与VAN相关。如果成功，我们将继续 在R33阶段，我们将使用R61阶段确定的TMS方法来测试 减少R MFG-VAN连接，减少注意力重定向过程中的VAN激活，并减少 在更大样本的患有CONTAM的强迫症个体中的CONTAM症状。该项目将产生几个主要的 预付款。首先，它将证明R MFG-VAN超连通性和CONTAM之间的因果关系 症状其次，它将证实R MFG-VAN超连接是一个可行的治疗目标， 污染为基础的强迫症，并证明，减少R MFG-VAN连接导致归一化 注意力重新定向和减少CONTAM症状。第三，它将为R MFG提供初步证据- 有针对性的经颅磁刺激治疗污染型强迫症总的来说，这项工作将是第一次 确定了OCD神经调节的特定维度皮质靶点，从而在以下方面取得了重大进展： 精准医学，并强调这一创新研究计划的未来应用 以确定其他强迫症症状维度的神经调节靶点。

PROJECT SUMMARY/ABSTRACT The symptoms of obsessive-compulsive disorder (OCD) appear linked to dysfunction in a cortico-striato- thalamo-cortical circuit. However, obsessions and compulsions vary widely among OCD patients, suggesting that other symptom-specific brain networks may accompany this core defect. Identifying such networks could lead to individualized treatments, improving upon current “one size fits all” approaches. Factor analyses have found distinct symptom dimensions in OCD, but the neural systems specific to these dimensions remain unclear. Using a novel individual-level approach to resting-state functional connectivity magnetic resonance imaging (fcMRI), we have shown that increased connectivity between right medial frontal gyrus (R MFG) and brain regions within the ventral attention network (VAN) – regions critical to reorienting attention in response to relevant external stimuli – specifically predicted the severity of contamination/washing (CONTAM) symptoms, and attenuation of this hyperconnectivity following treatment was associated with improvement in CONTAM symptoms. Based on these findings, we hypothesize that decreasing R MFG-VAN connectivity via transcanial magnetic stimulation (TMS) will normalize attentional reorienting and reduce CONTAM symptoms in individuals with contamination-based OCD. Therefore, consistent with the R61/R33 mechanism, we propose a two-phase program to investigate R MFG-targeted TMS as a potential intervention for contamination-based OCD. In the R61 phase, we will determine the optimal TMS paradigm to decrease R MFG-VAN connectivity by administering both continuous and intermittent theta burst stimulation (cTBS, iTBS) to individuals with contamination-based OCD using a novel individual-level approach to target the area of R MFG most strongly correlated with VAN based on each participant's pre-treatment connectivity data. If successful, we will proceed to the R33 phase in which we will use the TMS approach identified in the R61 phase to test the links between reduced R MFG-VAN connectivity, decreased VAN activation during attentional reorienting, and reduced CONTAM symptoms in a larger sample of OCD individuals with CONTAM. This project will yield several major advances. First, it will demonstrate a causal link between R MFG-VAN hyperconnectivity and CONTAM symptoms. Second, it will confirm that R MFG-VAN hyperconnectivity is a viable treatment target for contamination-based OCD, and demonstrate that decreasing R MFG-VAN connectivity leads to normalized attentional reorienting and reduced CONTAM symptoms. Third, it will provide initial evidence for R MFG- targeted TMS as a treatment for contamination-based OCD. Collectively, this work will be the first of its kind to identify a dimension-specific cortical target for neuromodulation in OCD, thus making a major advance toward precision medicine for this disorder, and highlighting the future application of this innovative research program to identify neuromodulatory targets for additional OCD symptom dimensions.