Dimensional connectomics of anxious misery

 描述（由申请人提供）：每年超过30%（20亿）的世界人口和7500万成年美国人患有被归类为“焦虑痛苦”的疾病。“在接受治疗的患者中，大量患者仍然存在使人衰弱的症状，通常持续数年或数十年。最近，NIMH领导了在负价系统（NVS）中定义结构的努力，这些结构跨越了这些疾病，以刺激对潜在机制的研究。这个应用程序将集中在与“损失”和“对持续威胁的反应”相关的潜在大脑回路和行为上，这是NVS最核心的两个维度。通过共同考虑这些大脑回路，我们可以解开这些维度，以更具体地针对残疾症状。最近的研究表明，通过映射个体解剖结构和连接模式来靶向区域，治疗效果有所改善。本申请由一组处于了解NVS疾病前沿的研究人员提交，以响应PAR-14-281，将使用RDoC框架全面表征NVS谱系障碍，重点关注在整个损失和对持续威胁的反应谱中病理生理学重要的脑回路。通过在单个Prisma扫描仪上实施神经影像学评估（针对与人类连接组协议（HCP）的兼容性进行了优化），并通过收集人口统计学数据、使用NIH神经元和宾夕法尼亚大学计算机神经认知成套测验（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，沿着，我们将扩展HCP数据库，其中包含对人类健康具有高度重要意义的病理生理学样本。这些目标将通过招募50名对照参与者和200名来自宾夕法尼亚大学门诊部的焦虑痛苦症状参与者来实现，在那里他们将接受广泛的多模式评估，以表征这些NVS领域的横截面现象学，并进行为期一年的随访，以评估后续症状。该项目既有目标，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，以及分析大脑连接体变化的创新工具。这一目标包括认真的质量保证和协调程序。待检验的主要假设是，对持续威胁和损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病程。

 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.