EXAMINING THE NEURAL SUBSTRATES OF DECLARATIVE MEMORY DEFICITS IN BIPOLAR DIS

这个子项目是众多研究子项目之一

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.