fMRI of Frontal and Limbic Regions in Bipolar Patients

描述（由申请人提供）：几项研究结果表明，前额叶皮层的完整性对于理解双相情感障碍的病理生理学可能特别重要。具体而言，额叶系统已被证明在信息的同化和整合以及计划，抑制和启动情绪和行为反应的能力中发挥着重要作用。应用功能磁共振成像（fMRI）和扩散张量成像（DTI）的协议提供了一个重要的方法来测量功能和结构的变化与额叶功能障碍。鉴于迄今为止的研究主要集中在脑容量或功能的测量，以表征双相情感障碍患者的大脑变化，我们现在提出的评估皮质激活的认知和情感的挑战范例，除了评估的白色物质的微观结构作为一种手段，测量网络的变化。双相情感障碍患者的解剖学研究报告了前额叶和边缘系统区域的改变，而功能性神经影像学研究表明这些皮质区域内和之间的神经回路的异常反应。 在初步的BOLD功能磁共振成像研究中，我们发现，双相情感障碍患者与正常对照组相比，在完成面部情感任务时，前额叶皮层和杏仁核的激活发生了变化，在完成Stroop测试的干扰子测试时，前额叶皮层的激活也发生了变化。这些研究结果补充了以前的报告，在双相情感障碍患者的认知缺陷的测试是敏感的额叶功能，并表明，该地区可能发挥了至关重要的作用，在双相情感障碍的病理生理。拟议的研究建立在现有的情感障碍的神经生物学模型，并通过应用fMRI和DTI技术来评估40例首次发作的双相情感障碍患者，40例健康对照组和24例慢性双相情感障碍患者，同时进行认知和情感挑战措施，扩展了我们的初步研究结果。首次发作患者将以纵向方式进行评价，在基线（初治）和研究入组后12个月完成所有研究指标。结构方程模型将用于测量双相情感障碍患者的边缘系统电路功能障碍模型。DTI的测量将与路径系数相关，以试图澄清研究组之间的连接变化。该项目产生的数据将为双相情感障碍的功能连接提供新的见解，并可能导致改善干预和治疗。

DESCRIPTION (provided by applicant): Several fines of investigation suggest that the integrity of the prefrontal cortex may be particularly salient for understanding the pathophysiology of bipolar affective disorder. Specifically, the frontal system has been shown to play a major role in the assimilation and integration of information and in the ability to plan, inhibit, and initiate emotional and behavioral responses. The application of a combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) protocol provides an important approach for measuring functional and structural changes associated with frontal dysfunction. Whereas investigations to date have focused on measures of brain volume or function to characterize brain changes in bipolar patients, we now propose the assessment of cortical activation in response to cognitive and emotional challenge paradigms in addition to assessments of white matter microstructure as a means of measuring network changes. Anatomic studies of patients with bipolar disorder have reported alterations of prefrontal and limbic regions, while functional neuroimaging studies indicate anomalous response of neural circuits both within and between these cortical regions. In preliminary BOLD fMRI studies, we found that bipolar patients as compared with normal control subjects produced altered activation of the prefrontal cortex and amygdala during the completion of a facial affect task and altered prefrontal activation during the completion of the interference subtest of the Stroop test. These findings complement previous reports of cognitive deficits in bipolar patients on tests that are sensitive to frontal functions and suggest that this region may play a crucial role in the pathophysiology of bipolar disorder. The proposed research builds on existing neurobiologic models of affective disorders and extends our preliminary findings by applying fMRI and DTI techniques to the evaluation of 40 first episode bipolar patients, 40 healthy control subjects, and 24 chronic bipolar patients while performing cognitive and affective challenge measures. First episode patients will be evaluated in a longitudinal fashion, completing all study measures at baseline (treatment-naive) and 12 months following study enrollment. Structural equation modeling will be used to measure a model of limbic circuitry dysfunction in patients with bipolar disorder. Measures of DTI will be correlated with path coefficients in an attempt to clarify changes in connectivity between study groups. Data generated from this project will provide new insights into the functional connectivity underlying bipolar disorder and may lead to improved intervention and treatment.