Anterior limbic network dysfunction in bipolar disorder

双相情感障碍的前边缘网络功能障碍

• 批准号: 7102670
• 负责人: STEPHEN M STRAKOWSKI
• 金额: $ 50.69万
• 依托单位: UNIVERSITY OF CINCINNATI
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-02 至 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7102670
• 关键词: adult human (21+); behavior test; behavioral /social science research tag; bipolar depression depressed phase; bipolar depression manic phase; brain imaging /visualization /scanning; brain mapping; clinical research; cognition disorders; functional magnetic resonance imaging; human subject; limbic system; neurophysiology; neuropsychological tests; pathologic process; patient oriented research

DESCRIPTION (provided by applicant): Bipolar disorder is a dynamic condition characterized by cycling among emotional extremes. The dynamic expression of bipolar disorder suggests that its neurophysiology involves dysfunction of brain networks that maintain emotional homeostasis, i.e. the 'anterior limbic network.' Additionally, activation of the anterior limbic network may disrupt function of attentional brain regions, leading to cognitive symptoms. Previous imaging studies in bipolar disorder reported abnormalities throughout the anterior limbic network. Moreover, in preliminary work we found that, compared with healthy subjects, euthymic bipolar patients demonstrated abnormally increased activation throughout this network during an attentional task. It may seem counter-intuitive to use attentional tasks as probes to study brain activation in bipolar disorder. However, reciprocal activation between cognitive and emotional brain networks suggests that cognitive probes may identify inappropriate emotional network activation in bipolar patients. We will use fMRI and cognitive probes to determine whether anterior limbic network dysfunction causes a loss of homeostatic control of emotional behavior, leaving bipolar patients vulnerable to mood cycling. We specifically hypothesize that anterior limbic dysfunction persists throughout the course of bipolar illness, although, as a corollary we hypothesize that during euthymia, compensatory cortical activation occurs, which is absent during mood episodes. To test these hypotheses, 144 bipolar patients will be recruited when manic and will be followed for up to one year. Brain activation will be measured with fMRI while performing cognitive tasks during mania, following recovery (i.e., during euthymia), and at the time of depressive relapse. Comparisons with healthy subjects and across mood states (within subjects) will permit tests of our major hypotheses. If these hypotheses are supported, then anterior limbic dysfunction could provide a useful endophenotype to identify individuals at risk for bipolar disorder. Clarifying the dysfunction of these brain networks may permit translation of molecular findings into understanding the clinical expression of bipolar disorder. Moreover, defining dysfunction within the anterior limbic network in bipolar disorder could provide a target for treatment development. Finally, this work will provide a neurophysiologic substrate to inform additional investigations aimed at identify mechanisms underlying anterior limbic dysfunction both in human and animal models.

描述（由申请人提供）：双相情感障碍是一种动态状况，其特征是情绪极端之间的循环。双相情感障碍的动态表达表明，其神经生理学涉及维持情绪稳态的大脑网络功能障碍，即“前边缘网络”。另外，前边缘网络的激活可能会破坏注意力大脑区域的功能，从而导致认知症状。躁郁症的先前成像研究报告了整个前边缘网络中的异常。此外，在初步工作中，我们发现，与健康受试者相比，在注意任务期间，整个网络中，整个网络的激活异常增加。使用注意任务作为研究躁郁症中的脑激活的探针似乎是违反直觉的。但是，认知和情绪大脑网络之间的相互激活表明，认知探针可能会发现双极患者的情绪网络激活不当。我们将使用功能磁共振成像和认知探针来确定前边缘网络功能障碍是否导致对情绪行为的稳态控制丧失，从而使双极患者容易受到情绪循环的影响。我们特别假设前边缘功能障碍在整个双极疾病过程中持续存在，尽管作为必然，我们假设在素质症中，会发生补偿性皮质激活，这在情绪发作过程中不存在。为了检验这些假设，躁狂时将招募144名双极患者，并最多遵循一年。脑部激活将在躁狂症期间，恢复（即在安心症期间）和抑郁复发时执行认知任务时用fMRI进行测量。与健康受试者以及跨情绪状态（在受试者内）进行比较将允许我们的主要假设进行测试。如果支持这些假设，则前边缘功能障碍可以提供有用的内表型，以识别有躁郁症风险的个体。阐明这些大脑网络的功能障碍可能允许将分子发现转化为了​​解双相情感障碍的临床表达。此外，在双相情感障碍中定义前边缘网络中的功能障碍可以为治疗发育提供目标。最后，这项工作将提供神经生理基础，以告知旨在确定人和动物模型中前边缘功能障碍的机制的其他研究。