fMRI Analysis of Aging and Awareness in Conditioning

描述(申请人提供)：这项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)。虽然小脑对于条件眨眼反应是必不可少的，但MTL也是一种特定类型的学习所必需的，即在条件刺激(CS)的偏移和非条件刺激(US)的开始之间存在一段时间间隔的特定类型的学习。痕迹条件反射在年长的受试者中也受到损害，在条件化训练中没有意识到刺激偶发事件的老年人和年轻受试者都是如此。我们的假设是，在痕迹条件反射中，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，将解释老年人和无意识受试者的痕迹条件反射行为表现的差异。我们预测，当没有时间间隔(即“延迟”条件反射)时，意识对表现或小脑激活的影响将较小，年龄组小脑激活的差异将比MTL激活差异解释更多的年龄差异，功能连接模式的年龄组差异将不同于在跟踪条件作用下观察到的差异。我们计划首先使用不配对的CS和US演示来表征CS和US通路中与年龄相关的变化，并假设在追踪期间，任何年龄差异都将在小脑的短CS和MTL中观察到。我们将研究延迟和痕迹条件反射过程中大脑激活的年龄相关变化，并分别假设小脑和MTL激活对延迟和痕迹条件反射表现的年龄相关变化的不同重要性。最后，我们将通过(A)干扰意识的获得并观察其对条件反射和脑激活的影响，以及(B)测量意识、眨眼条件反射和脑激活的同时发展，来探讨意识在大脑激活中与年龄相关的变化中的作用。我们预测，在痕迹条件反射中，获得意识的受试者会比无意识的受试者条件更好，表现出更大的MTL激活，将意识等同于意识后，条件作用和MTL激活的年龄差异将缩小或消除，延迟和痕迹条件作用下与年龄相关的功能连通性变化将不同，功能连通性的模式将作为意识对痕迹条件作用的函数而改变，左侧前额叶皮质将成为意识相关功能回路的关键节点。最后，我们将检验痕迹条件反射的年龄相关差异与其他类型的年龄相关认知下降之间的联系，并将使用经颅磁刺激测试MTL/新皮质参与痕迹条件反射和意识的模型。

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.