Dimensional connectomics of anxious misery

 描述(申请人提供)：每年有超过30%(20亿)的世界人口和7500万美国成年人患有被归类为“焦虑的痛苦”的疾病。在接受治疗的患者中，大量患者仍有虚弱的症状，通常持续数年或数十年。最近，NIMH领导了定义负价系统(NVS)中跨越此类障碍的结构的努力，以推动对潜在机制的研究。这项应用将集中在潜在的大脑回路和与“损失”和“对持续威胁的反应”相关的行为，这是NVS最核心的两个维度。通过联合考虑这些大脑回路，我们可以解开这些维度，以便更具体地针对残疾症状。通过绘制个体解剖和连接模式图来定位区域的研究表明，最近在治疗效果方面取得了进展。这份申请是根据PAR-14-281提交的，由一组处于了解NVS疾病前沿的研究人员提交，将使用RDoC框架全面描述NVS谱系障碍，重点关注在整个损失谱和对持续威胁的反应中重要的大脑回路。通过在单个Prisma扫描仪上实施神经成像评估，并针对与人类连接组协议(HCP)的兼容性进行优化，通过收集人口统计数据、使用NIH工具箱和宾夕法尼亚大学计算机化神经认知电池(CNB)的神经认知数据和DNA样本，以及与NVS疾病相关的专门评估，我们将使用对人类健康具有高度重要性的病理生理学样本来扩展HCP数据库。这些目标将通过从宾夕法尼亚大学的门诊诊所招募50名对照参与者和200名有焦虑痛苦症状的参与者来实现，他们将在那里接受广泛的多模式评估，以表征这些NVS领域的横断面现象，并进行为期一年的随访以评估后续症状。拟议的项目既有目标，也有假设。主要目标是获取并公开一个庞大的数据库，其中包括焦虑痛苦患者的大脑成像和行为数据，以及用于分析大脑连接体变化的创新工具。这一目标包括仔细的质量保证和协调程序。需要检验的主要假设是，对持续威胁和丧失的反应的严重程度与结构和功能连接体中的可分离回路异常相关；此外，这些异常将预测疾病的进程。

 DESCRIPTION (provided by applicant): Every year more than 30% (2 billion) of the world's population and 75 million adult Americans suffer from disorders that have been lumped under the term "anxious misery." Among patients who receive treatment, a large number remain with debilitating symptoms, often for years or decades. Recently the NIMH has led efforts to define constructs within the Negative Valence System (NVS) that cut across such disorders in order to spur research on underlying mechanisms. This application will focus on potential brain circuitry and behaviors associated with "loss", and "responses to sustained threat," two of the most central NVS dimensions. By considering these brain circuits jointly, we can disentangle these dimensions for more specific targeting of disabling symptoms. Recent improvements in treatment efficacy have been shown in studies that target regions by mapping individual anatomy and connectivity patterns. This application, submitted in response to PAR-14-281, by a team of investigators at the forefront of understanding NVS disorders, will comprehensively characterize NVS spectrum disorders using the RDoC framework, focusing on brain circuits important in pathophysiology across the spectrum of loss and responses to sustained threat. By implementing neuroimaging assessment on a single Prisma scanner optimized for compatibility with the Human Connectome Protocol (HCP) and by collecting demographic data, neurocognitive data using the NIH Toolbox and Penn Computerized Neurocognitive Battery (CNB), and DNA samples, along with specialized assessments pertinent to NVS disorders, we will expand the HCP database with a highly significant pathophysiology sample for human health. These goals will be achieved by recruiting 50 control participants and 200 participants with anxious misery symptoms from the Outpatient Clinics of the University of Pennsylvania, where they will undergo an extensive multi-modal assessment to characterize the cross-sectional phenomenology of these NVS domains and a one-year followup to assess subsequent symptoms. The proposed project has both objectives and hypotheses. The main objective is to acquire and make public a vast database of brain imaging and behavioral data from patients with anxious misery as well as innovative new tools to analyze brain connectome changes. This objective includes careful QA and harmonization procedures. The main hypothesis to be tested is that severity of responses to sustained threat and loss correlate with dissociable circuit abnormalities in the structural and functional connectome; further, these abnormalities will predict course of illness.