Neurophysiology of Working Memory in Bipolar Disorder

描述(由申请人提供)：NIMH指导的以患者为导向的职业发展(K23)奖的申请是为了支持Caleb M.Adler博士在神经成像和双相情感障碍方面的发展专长。双相情感障碍是一种常见的精神疾病，伴随着严重的发病率和死亡率。传统上被认为是一种周期性疾病，在情感发作之间恢复到基线功能，有证据表明，双相情感障碍与特定认知领域的显著缺陷有关，特别是工作记忆。双相情感障碍患者的神经成像研究表明，与工作记忆相关的大脑区域网络相关的结构功能障碍。与这些观察结果一致的是，在整个情感光谱中，双相患者都观察到了工作记忆缺陷，这表明这些缺陷代表了双相情感障碍的“核心症状”，源于疾病的神经生理学。 该奖项支持的具体研究将包括研究与工作记忆相关的神经元活动，双相情感障碍患者和健康志愿者。候选人将使用功能磁共振成像来研究双相情感障碍患者和健康志愿者在执行一系列工作记忆任务时的激活模式，这些任务的难度随着参数的增加而增加。服药和未服药的双相情感障碍患者都将被纳入。除了增加对双相患者工作记忆缺陷背后的神经生理学的理解外，候选人还寻求提高我们对药物对激活模式的影响的理解。更好地了解这一“核心症状”可能有助于阐明双相情感障碍的潜在神经生理学基础，最终建议未来的治疗方向。作为后续方案，候选人将比较双相情感障碍患者在急性情绪状态下工作记忆诱导的激活与之前获得的心境数据。工作记忆缺陷在抑郁症和躁狂症中加剧；这些比较可能澄清双相情感障碍在急性情感发作期间的神经生理学变化。 在这个K23奖项的过程中，候选人将获得双相精神病理学、功能成像技术、认知测试和统计分析以及研究伦理方面的额外培训。应聘者将把这些技能与以前在功能成像和临床精神病学其他领域的培训和经验结合起来，以发展双相情感障碍的神经生理学研究方面的专业知识。在这个奖项结束时，候选人将很好地发挥独立调查者的作用，使用其他认知范式扩展这项工作，并进一步检查双相情感障碍中与状态相关的认知缺陷。

DESCRIPTION (provided by applicant): This NIMH Mentored Patient-Oriented Career Development (K23) Award application is to support Dr. Caleb M. Adler's developing expertise in neuroimaging and bipolar disorder. Bipolar disorder is a common psychiatric illness accompanied by severe morbidity and mortality. Traditionally viewed as a cyclic illness with a return to baseline function between affective episodes, evidence suggests that bipolar disorder is associated with significant deficits in specific cognitive domains, particularly working memory. Neuroimaging studies in bipolar patients suggest dysfunction of structures associated with the "network" of brain regions involved in working memory. Consistent with these observations, working memory deficits are observed in bipolar patients across the affective spectrum, suggesting that these deficits represent a "core symptom" of bipolar disorder, rising out of the neurophysiology of the illness. The specific research supported by this award will involve studying neuronal activity associated with working memory inpatients with bipolar disorder and healthy volunteers. The candidate will use fMRI to study patterns of activation in bipolar patients and healthy volunteers while they are performing a series of working memory tasks increasing parametrically in difficulty. Both medicated and unmedicated bipolar patients will be enrolled. In addition to increasing understanding of the neurophysiology underlying working memory deficits in bipolar patients, the candidate seeks to improve our understanding of the effects of medication on activation patterns. A better understanding of this "core symptom" may help clarify the underlying neurophysiologic substrates of bipolar disorder, ultimately suggesting future treatment directions. As a follow-up protocol, the candidate will compare working memory-induced activation in bipolar patients during acute mood states with the previously obtained euthymic data. Working memory deficits are exacerbated in depression and mania; these comparisons may clarify changes in the neurophysiology of bipolar disorder during acute affective episodes. During the course of this K23 award, the candidate will obtain additional training in bipolar psychopathology, functional imaging techniques, cognitive testing and statistical analysis, as well as research ethics. The candidate will integrate these skills with previous training and experience in other areas of functional imaging and clinical psychiatry in order to develop expertise in the investigation of the neurophysiology of bipolar disorder. At the conclusion of this award, the candidate will be well positioned to function as an independent investigator extending this work using other cognitive paradigms and to further examine state-related cognitive deficits in bipolar disorder.