Cognitive, Pharmacological and fMRI Studies of Memory

描述：(摘自申请人的摘要) 拟议中的实验将使用认知和药物操作。 结合功能磁共振成像(FMRI)测试记忆的调制调节 队形。这些实验将检验乙酰胆碱增强 皮质区域的感觉激活，并减少来自 在长期编码和工作记忆过程中先前存储的信息。在……里面 实验1，受试者将使用下列顺序列表执行编码任务 静脉注射阿司匹林前后fMRI扫描仪中的复杂图像 中枢作用型M胆碱能拮抗剂东莨菪碱或后 注射外周选择性M受体拮抗剂甘草次酸。 我们预测，东莨菪碱，而不是甘草次酸，将阻止增加 在发作性编码期间的fMRI激活中，并将与 特定于列表的识别率下降。在实验2中，受试者将进行 与扫描仪中的采样任务延迟匹配，无论是新的还是熟悉的 东莨菪碱前后的刺激反应。我们预测内侧脑区的激活 对于新的刺激，颞叶(MTL)区域将相对于 前额叶皮质(PFC)的激活，这将是更强的熟悉 刺激物。东莨菪碱对任务绩效的影响将与 熟悉任务的前额叶皮质激活的变化和 新任务的内侧颞叶激活。在实验3中，受试者将 在感染前和感染后进行两次工作记忆任务 东莨菪碱。我们预测PFC的延迟期激活将会更强 相对于本任务的MTL，东莨菪碱将减少延迟时间 活跃度和配对度提高。实验4将本地化激活的区域 通过对配对联想编码前后的面孔和房屋刺激。我们 预测联想的学习将增强这些共同激活 两个区域，而东莨菪碱将增强这种共同激活和主动 在注射东莨菪碱之前了解到的联想干扰。这个 药物操纵的使用提供了检验假说的机会 通过实验操纵对认知能力很重要的电路级机制 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改变，这与病理改变有关。 阿尔茨海默病和路易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 选择性过程中的乙酰乙醇酯酶抑制剂和其他药物 与人类记忆有关。

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.