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: 7250887
• 负责人: JOHN E DESMOND
• 金额: $ 29.42万
• 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/7250887
• 关键词: Accounting; Affect; Age; Age-associated memory impairment; Aging; Awareness; Behavioral; Blinking; Brain; Cerebellum; Clinical; Condition; Conditioned Stimulus; Development; Disruption; Exhibits; Functional Magnetic Resonance Imaging; Goals; Hippocampus (Brain); Human; Image Analysis; Impaired cognition; Knowledge; Learning; Left; Link; Magnetic Resonance Imaging; Measures; Medial; Memory; Modeling; Neurons; Pathway interactions; Patients; Pattern; Performance; Prefrontal Cortex; Procedures; Process; Protocols documentation; Research; Retrieval; Role; Scanning; Stimulus; Structure; System; Temporal Lobe; Testing; Time; Training; Transcranial magnetic stimulation; Work; age difference; age effect; age group; age related; animal data; classical conditioning; comparison group; conditioning; healthy volunteer; neocortical; neural circuit; neuroimaging; normal aging; relating to nervous system; response

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使用功能性磁共振成像（fMRI）阐明人类衰老如何影响对眨眼条件反射至关重要的神经系统，包括小脑和内侧颞叶（MTL）。虽然小脑是必不可少的条件眨眼反应，MTL也是必要的一种特殊类型的学习称为“痕迹”条件，其中有一个时间间隔之间的偏移条件刺激（CS）和非条件刺激（US）的开始。在老年受试者中，以及在条件反射训练期间没有获得对刺激偶然性的意识的老年受试者和年轻受试者中，痕迹条件反射也受损。我们的假设是，在跟踪条件反射MTL激活的差异，沿着与新皮层和皮层下结构之间的功能连接模式的差异，将占在老年人和无意识的主题的跟踪条件反射行为表现的差异。我们预测当时间上的差距不存在时（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比MTL激活差异更多地解释条件眨眼表现的年龄差异，功能连接模式的年龄组差异将不同于痕迹条件反射中观察到的那些。我们计划首先使用未配对的CS和US呈现来表征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。我们将研究延迟和跟踪条件反射协议期间大脑激活的年龄相关变化，并假设小脑和MTL激活的差异重要性，分别为延迟和跟踪条件反射性能的年龄相关变化。最后，我们将调查的作用，在年龄相关的变化，大脑激活的眨眼条件反射（a）中断收购的意识，并观察其对条件反射和大脑激活和（B）测量的同时发展的意识，眨眼条件反射，和大脑激活。我们预测，在痕迹条件反射中，获得意识的受试者将比无意识的受试者条件反射更好，表现出更大的MTL激活，在条件反射和MTL激活的年龄差异将在等同于意识后减少或消除，功能连接的年龄相关变化将在延迟和痕迹条件反射之间有所不同，功能连接的模式将随着痕迹条件反射的意识而改变，而左前额叶皮层将是意识相关功能回路的关键节点。最后，我们将研究与年龄相关的痕迹条件反射和其他类型的年龄相关的认知下降的差异之间的联系，我们将测试模型的MTL/新皮层参与痕迹条件反射和意识使用经颅磁刺激。