EXAMINING THE NEURAL SUBSTRATES OF DECLARATIVE MEMORY DEFICITS IN BIPOLAR DIS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。越来越多的证据表明，双相情感障碍（BPD）患者患有陈述性记忆障碍，无论他们在评估时的临床状态如何。此外，陈述性记忆障碍也出现在BPD患者未受影响的一级亲属中，这表明记忆力差可能与该疾病的遗传介导方面有关。研究BPD患者的陈述性记忆或长期记忆可能为BPD的病理生理学提供重要线索，从而可能导致更有效的治疗方法。在此，我们建议使用功能性MRI检查20名心境性BPD患者和20名匹配的健康对照者的陈述性记忆缺陷的神经心理学相关性。我们的目标是分离BPD中记忆损伤的前额叶和内侧颞叶部分，并对比陈述性记忆任务与更典型的执行任务相关的激活模式。具体来说，我们的目标是：目的1：应用面孔-名字配对联想任务，旨在唤起双相情感障碍患者和匹配的比较受试者的内侧颞叶脑区域的活动。AIM 2：在AIM 1招募的同一组受试者中，通过我们实验室开发的执行/工作记忆任务，引发DLPFC活动。先前我们已经表明，延迟反应任务的执行涉及到一个大脑区域网络，包括背外侧和内侧前额叶，前扣带和后部分。我们假设BPD患者在配对联想任务中会表现出(1)内侧颞叶激活减少，(2)前额叶活动正常或接近正常，但在执行任务中会表现出(3)DLPFC活动减少。这种结果模式表明PBD中两个部分不同的神经系统，一个是额叶，另一个是颞叶。目前，人们对双相情感障碍的功能神经心理学影响知之甚少，这里收集的数据将是开发双相情感障碍认知神经科学模型的重要的第一步。我们期望使用这些数据来支持NIH的一项应用，该应用旨在描述双相情感障碍中发现的神经心理学和功能性神经影像学损伤。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. There is growing evidence that patients with bipolar disorder (BPD) suffer from declarative memory impairments, regardless of their clinical state at the time of assessment. Furthermore, declarative memory impairments have been shown in unaffected 1st degree relatives of BPD patients, suggesting that poor memory may be associated with a genetically mediated aspect of the disorder. Studying declarative or longer-term memory in BPD patients may provide important clues about the pathophysiology of BPD, which may in turn lead to more effective treatments of the illness. Here, we propose to examine the neuropsychological correlates of declarative memory deficits in 20 euthymic BPD patients and 20 matched healthy comparison subjects using functional MRI. Our goal is to dissociate prefrontal and medial temporal components of the memory impairment found in BPD and contrast activation patterns from a declarative memory task with those associated with a more typical executive task. Specifically, we aim to: AIM 1: Apply a face-name paired associate task designed to evoke activity from medial temporal brain regions to patients with bipolar disorder and matched comparison subjects. AIM 2: Elicit DLPFC activity in the same group of subjects recruited for AIM 1 with an executive/working memory task developed in our laboratory. Previously we have shown that performance of this delayed response task involves a network of brain regions including dorsolateral and medial prefrontal, anterior cingulate and posterior partial. We hypothesize that BPD patients will show (1) reduced medial temporal activation and (2) normal or near normal prefrontal activity during the paired associate task, but will show (3) reduced DLPFC activity during the executive task. This pattern of results would suggest disruption of two partially distinct neural systems in PBD, one frontal, the other temporal. Currently, little is know about the functional neuropsychological effects of bipolar disorder and data collected here will be an important first step in developing cognitive neuroscience models of bipolar disorder. We anticipate using these data to support an application to NIH designed to characterize the neuropsychological and functional neuroimaging impairments found in bipolar affective disorder.