fMRI Analysis of Aging and Awareness in Conditioning

衰老和调节意识的功能磁共振成像分析

• 批准号: 7169424
• 负责人: JOHN E DESMOND
• 金额: $ 31.62万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-06-15 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7169424
• 关键词: age difference; aging; association learning; awareness; behavioral /social science research tag; bioimaging /biomedical imaging; cerebellum; clinical research; conditioning; functional magnetic resonance imaging; human old age (65+); human subject; neocortex; neuroimaging; neurophysiology; neuropsychology; performance; prefrontal lobe /cortex; reflex; short term memory; temporal lobe /cortex; transcranial magnetic stimulation; young adult human (21-34)

DESCRIPTION (provided by applicant): The overall goal of this research is to elucidate, using functional magnetic resonance imaging (fMRI), how aging in humans affects neural systems critical for eyeblink conditioning, including the cerebellum and the medial temporal lobe (MTL). While the cerebellum is essential for conditioned eyeblink responses, the MTL is also necessary for a specific type of learning referred to as "trace" conditioning, in which there is a gap in time between the offset of the conditioned stimulus (CS) and the onset of the unconditioned stimulus (US). Trace conditioning is also impaired in older subjects, and in both older and younger subjects who do not acquire awareness of the stimulus contingencies during the conditioning training. Our hypothesis is that in trace conditioning differences in MTL activation, along with differences in patterns of functional connectivity among neocortical and subcortical structures, will account for differences in trace conditioning behavioral performance in both older and unaware subjects. We predict that when the gap in time is absent (i.e., "delay" conditioning), awareness will have less effect on either performance or cerebellar activations, age group differences in cerebellar activation will account for more of the age differences in conditioned eyeblink performance than will MTL activation differences, and age group differences in patterns of functional connectivity will differ from those observed in trace conditioning. We plan to first characterize age-related changes in CS and US pathways using unpaired CS and US presentations, and hypothesize that any age differences will be observed in the cerebellum for short CSs and in the MTL during the trace period. We will investigate age-related changes in brain activation during delay and trace conditioning protocols, and hypothesize differential importance of cerebellar and MTL activations, respectively, for age-related changes in performance of delay and trace conditioning. Finally, we will investigate the role of awareness in age-related changes in brain activation underlying eyeblink conditioning by (a) disrupting the acquisition of awareness and observing its effect on conditioning and brain activation and (b) measuring the concurrent development of awareness, eyeblink conditioning, and brain activation. We predict that in trace conditioning, subjects that acquire awareness will condition better and exhibit greater MTL activation than unaware subjects, age differences in conditioning and MTL activation will be reduced or eliminated after equating for awareness, age-related changes in functional connectivity will differ between delay and trace conditioning, patterns of functional connectivity will change as a function of awareness for trace conditioning, and left prefrontal cortex will be a critical node in awareness-related functional circuits. Finally, we will examine the link between age-related differences in trace conditioning and other types of age-related cognitive decline, and we will test a model of MTL/neocortical involvement in trace conditioning and awareness using transcranial magnetic stimulation.

描述（由申请人提供）：本研究的总体目标是利用功能磁共振成像（fMRI）阐明人类衰老如何影响对眨眼调节至关重要的神经系统，包括小脑和内侧颞叶（MTL）。虽然小脑对于条件性眨眼反应至关重要，但 MTL 对于称为“痕迹”条件反射的特定类型的学习也是必要的，其中条件刺激 (CS) 的偏移和开始之间存在时间间隙无条件刺激（美国）。老年受试者以及在调节训练期间没有意识到刺激意外事件的老年受试者和年轻受试者中，微量调节也会受到损害。我们的假设是，在微量调节中，MTL 激活的差异，以及新皮质和皮质下结构之间功能连接模式的差异，将解释老年和无意识受试者的微量调节行为表现的差异。我们预测，当时间间隙不存在时（即“延迟”条件反射），意识对表现或小脑激活的影响较小，小脑激活的年龄组差异将更多地解释条件性眨眼表现的年龄差异。 MTL 激活差异和功能连接模式的年龄组差异将与微量条件反射中观察到的不同。我们计划首先使用不配对的 CS 和 US 表现来描述 CS 和 US 通路中与年龄相关的变化，并假设在跟踪期间，在短 CS 的小脑和 MTL 中将观察到任何年龄差异。我们将研究延迟和微量调节方案期间大脑激活的与年龄相关的变化，并假设小脑和 MTL 激活分别对于延迟和微量调节性能的年龄相关变化的不同重要性。最后，我们将通过（a）破坏意识的获得并观察其对条件反射和大脑激活的影响，以及（b）测量意识、眨眼条件反射的同时发展，来研究意识在眨眼条件反射的大脑激活中与年龄相关的变化中的作用。调节和大脑激活。我们预测，在痕量条件反射中，获得意识的受试者比无意识的受试者条件更好，并表现出更强的 MTL 激活，在等同于意识后，条件反射和 MTL 激活的年龄差异将减少或消除，功能连接的年龄相关变化将有所不同延迟和痕迹条件作用，功能连接模式将随着痕迹条件意识的变化而变化，左前额叶皮层将成为意识相关功能回路的关键节​​点。最后，我们将研究痕迹调节的年龄相关差异与其他类型的年龄相关认知衰退之间的联系，并且我们将使用经颅磁刺激测试 MTL/新皮质参与痕迹调节和意识的模型。