Linking persistent avoidance with abnormalities in the OCD neural network

抽象的。项目3(P3)的目标是描述强迫症患者的脑白质束和功能 推测的强迫症神经网络中与持续性相关的区域之间的神经异常 回避，这是强迫症的一个特征。我们最重要的中心更新假设，建立在我们现在的基础上 研究结果是，强迫症患者的持续回避是特定人群之间功能失调联系的一种表现 中枢，即整合和分发来自多个区域的信息的子区域，位于前额叶腹外侧 皮质(VLPFC)和嘴前扣带回(RACC)，以及强迫症网络中的其他区域，包括 脑岛、背侧ACC(DACC)、眶前叶皮质(OFC)和吻侧纹状体。这些功能失调的连接 导致行为灵活性受损，以应对不断变化的上下文线索，特别是在 不确定的令人厌恶的结果。在P3中，我们将招募和检查50个未用药/5-羟色胺再摄取 服用抑制剂/氯丙咪嗪药物的强迫症参与者和50名健康参与者(18-35岁；尽量减少 长期病史和药物对神经测量的影响)。我们将使用最先进的扩散成像技术 (DMRI)，使用声道成像、分割和声道成像-声道测量-检查WM束在 网络。我们将使用功能磁共振成像(FMRI)来检查活动、功能和有效 在一种新的概率接近避免任务(PAAT)期间网络区域之间的连通性(FC、EC) 我们旨在研究不确定的回报和厌恶结果对选择行为的影响，以及 评估和预测这些结果时的神经活动、FC和EC。我们将研究人际关系 强迫症患者的WM、活动度、Fc和EC异常与OCD的严重程度 与持续回避相关的症状维度，例如，伤害回避。年，性别将成为一个协变量 分析。Aim(A)1将比较连接VLPFC、rACC、Ial、dACC、 强迫症患者与健康受试者的OFC和嘴侧纹状体，使用一种新的联合应用， 分割和跟踪测量。A2将比较这些OCD网络区域内以及FC和EC内的活动 在强迫症和健康受试者的PAAT期间，确定PAAT表现和功能磁共振之间的关系 强迫症患者与健康受试者的异常。A3将检查强迫症症状维度之间的关系 与持续回避有关的事项：例如，避免伤害、污染/清洗、责任 损害/检查症状，以及：A1-2的WM和fMRI异常。P3将受益于以下方面的专业知识：NHP P1，2(A2)的神经解剖学和生理学；P1，Core B(A1)的dMRI数据分析；临床评估和 强迫症在P4、5(A3)的治疗；核心C(A2-3)神经解剖学的个体差异研究；以及 在核心D中整合所有项目的分析。在与其他项目和核心的密切合作中，P3将 第一项旨在阐明特定的WM束和功能性的强迫症网络异常的研究 与持续回避相关，为以这种行为为特征的障碍提供干预信息。

ABSTRACT. The goal of Project 3 (P3) is to characterize, in OCD, white matter (WM) bundle and functional neural abnormalities among regions in a putative OCD neural network that are associated with persistent avoidance, a characteristic feature of OCD. Our overarching Center renewal hypothesis, building on our present findings, is that persistent avoidance in OCD is a manifestation of dysfunctional connections among specific hubs, i.e., subregions that integrate and distribute information from multiple regions, in the ventrolateral prefrontal cortex (vlPFC) and rostral anterior cingulate cortex (rACC), and other regions in the OCD network, including the insula, dorsal ACC (dACC), orbitofrontal cortex (OFC) and rostral striatum. These dysfunctional connections lead to impaired behavioral flexibility in response to changing contextual cues, specifically in situations with uncertain aversive outcomes. In P3, we will recruit and examine 50 unmedicated/ serotonin reuptake inhibitor/clomipramine medicated participants with OCD, and 50 healthy participants (18-35 yrs; to minimize effects of long illness history and medication on neural measures). We will use state-of-the-art diffusion imaging (dMRI), using tractography, segmentation and tract profiling - tractometry - to examine WM bundles in the network. We will use functional Magnetic Resonance Imaging (fMRI) to examine activity, functional and effective connectivity (FC, EC) among network regions during a novel probabilistic approach avoidance task (PAAT) that we developed to examine the influence of uncertain rewarding and aversive outcomes on choice behavior, and neural activity, FC and EC during evaluation and anticipation of these outcomes. We will examine relationships among WM, activity, FC and EC abnormalities in the OCD network in OCD participants and the severity of OCD symptom dimensions associated with persistent avoidance, e.g., harm avoidance. Gender will be a covariate in analyses. Aim (A)1 will compare the microstructure of WM bundles that connect vlPFC, rACC, insula, dACC, OFC and rostral striatum in OCD vs. healthy participants, using a novel combination of tractography, segmentation and tractometry. A2 will compare activity within and FC and EC among these OCD network regions in OCD vs. healthy participants during the PAAT, to determine relationships among PAAT performance and fMRI abnormalities in OCD vs. healthy participants. A3 will examine relationships among OCD symptom dimensions that are relevant to persistent avoidance: e.g., harm avoidance, contamination/ washing, responsibility for harm/checking symptoms, and: WM and fMRI abnormalities in A1-2. P3 will benefit from expertise in: NHP neuroanatomy and physiology in P1, 2 (A2); dMRI data analysis in P1, Core B (A1); clinical assessment and treatment of OCD in P4, 5 (A3); the study of individual differences in neuroanatomy in Core C (A2-3); and integration of analyses across projects in Core D. In close collaboration with other projects and cores, P3 will be the first study to elucidate the specific WM bundle, and functional, OCD network abnormalities that are associated with persistent avoidance, to inform interventions for disorders characterized by this behavior.