Cognitive, Pharmacological and fMRI Studies of Memory

记忆的认知、药理学和功能磁共振成像研究

• 批准号: 6540452
• 负责人: CHANTAL E. STERN
• 金额: $ 34.89万
• 依托单位: BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-04-15 至 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6540452
• 关键词: acetylcholine; association learning; behavioral /social science research tag; clinical research; functional magnetic resonance imaging; human subject; memory; neural information processing; neuropharmacology; performance; prefrontal lobe /cortex; psychopharmacology; quaternary ammonium compound; scopolamine; temporal lobe /cortex

DESCRIPTION:(from applicant's abstract) The proposed experiments will use cognitive and pharmacological manipulations coupled with functional MRI (fMRI) to test the modulatory regulation of memory formation. The experiments will test the hypothesis that acetylcholine enhances the sensory activation of cortical regions, and decreases interference from previously stored information during long term encoding and working memory. In Experiment #1, subjects will perform an encoding task using sequential lists of complex images in the fMRI scanner before and after iv injections of the centrally acting muscarinic cholinergic antagonist scopolamine, or after injections of the peripherally selective muscarinic antagonist glycopyrrolate. We predict that scopolamine, but not glycopyrrolate, will prevent an increase in fMRI activation during episodic encoding, and will be associated with a decrease in list-specific recognition. In Experiment #2, subjects will perform a delayed match to sample task in the scanner with either novel or familiar stimuli before and after scopolamine. We predict that activation of medial temporal lobe (MTL) regions will be stronger for novel stimuli relative to activation of prefrontal cortex (PFC) which will be stronger for familiar stimuli. Effects of scopolamine on task performance will be associated with changes in prefrontal cortex activation for the familiar task and changes in medial temporal activation for the novel task. In experiment #3, subjects will perform a two-back working memory task before and after infections of scopolamine. We predict that delay period activation will be stronger in PFC relative to MTL for this task, and scopolamine will decrease delay period activity and match enhancement. Experiment #4 will localize regions activated by face and house stimuli before and after encoding of paired associations. We predict that learning of associations will enhance the co-activation of these two regions, and that scopolamine will enhance this co-activation and proactive interference from associations learned before injections of scopolamine. The use of pharmacological manipulations provides an opportunity to test hypotheses by experimentally manipulating circuit level mechanisms important for cognitive tasks. This research is particularly relevant for understanding the cortical dynamics induced by cholinergic modulation, This isrelevant to the pathological states of low cholinergic innervation in Alzheimer's disease and Lewy-body dementia, and the potential therapeutic efficacy of different agents, including acetyleholinesterase inhibitors and other agents on selective processes involved in human memory.

描述：（来自申请人摘要） 拟议的实验将使用认知和药理操作 结合功能性MRI（fMRI）来测试记忆的调节 阵实验将检验乙酰胆碱增强 皮层区域的感觉激活，并减少来自 在长期编码和工作记忆中存储的信息。在 实验#1，受试者将执行编码任务，使用序列列表 在静脉注射前和注射后，fMRI扫描仪中的复杂图像 中枢作用的毒蕈碱胆碱能拮抗剂东莨菪碱，或之后 注射外周选择性毒蕈碱拮抗剂格隆溴铵。 我们预测东莨菪碱，而不是格隆溴铵，将防止增加 在fMRI激活过程中的情节编码，并将与一个 减少对特定名单的认可。在实验#2中，受试者将执行 延迟匹配到扫描仪中的样本任务， 在东莨菪碱之前和之后的刺激。我们预测， 颞叶（MTL）区域对于新刺激将更强， 激活前额叶皮层（PFC），这将是更强的熟悉 刺激。东莨菪碱对任务绩效的影响将与 熟悉任务的前额叶皮层激活的变化， 新任务的内侧颞叶激活。在实验#3中，受试者将 在感染前和感染后执行两次工作记忆任务， 东莨菪碱我们预测PFC的延迟期激活将更强 东莨菪碱可缩短延迟时间 活动和比赛增强。实验#4将定位激活的区域 在配对联想编码之前和之后，我们 预测，协会的学习将增强这些共同激活 两个地区，东莨菪碱将加强这种共同激活和积极主动 注射东莨菪碱前习得的联想的干扰。的 药理学操作的使用提供了检验假设的机会 通过实验性地操纵对认知重要的电路级机制， 任务这项研究对于理解大脑皮层 胆碱能调节引起的动力学，这与病理相关 Alzheimer病和Lewy小体的低胆碱能神经支配状态 痴呆症，以及不同药物的潜在治疗效果，包括 乙酰胆碱酯酶抑制剂和其他药物对选择性过程的影响 与人类记忆有关