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: 6898807
• 负责人: JOHN E DESMOND
• 金额: $ 32.29万
• 依托单位: STANFORD 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 2006-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6898807
• 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）：这项研究的总体目标是使用功能性磁共振成像（fMRI）阐明人类的衰老如何影响对眉毛条件至关重要的神经系统，包括小脑和内侧颞叶（MTL）。虽然小脑对于条件的眉毛反应至关重要，但对于一种特定类型的学习，也必须使用称为“痕量”条件的特定类型的MTL，其中条件刺激（CS）的偏移与无条件刺激的偏移之间存在差距（我们）。在较老的受试者中，痕量条件也受到损害，在调节训练期间不认识刺激突发事件的年长和年轻受试者中。我们的假设是，在MTL激活的痕量调节差异中，以及新皮质和皮层结构之间功能连通性模式的差异，将解释较老和不知不觉中的痕量调理行为性能的差异。我们预测，如果没有时间的差距（即“延迟”条件），意识将对性能或小脑激活产生较小的影响，小脑激活的年龄组差异将使条件性的Eyeblink链接性能的年龄差异更大，而MTL激活差异和在功能连接中的年龄群体的差异会差异。我们计划首先使用未配对的CS和US演示来表征与年龄相关的CS和US途径变化，并假设在短CSS和痕量时期，在小脑和MTL中都会观察到任何年龄差异。我们将研究延迟和痕量调理方案期间与年龄相关的大脑激活变化，并分别假设小脑和MTL激活的差异重要性，以延迟和痕量调理的年龄相关变化。最后，我们将通过（a）破坏意识的获取并观察其对调理和大脑激活的影响，以及（b）测量认识的影响以及（b）测量意识，摩擦链接调节和大脑激活的同时发展，从而研究意识在与年龄相关的大脑激活变化中的作用。我们预测，在痕量调节中，获得意识的受试者将更好地条件和更大的MTL激活，而不是意识到的受试者，条件和MTL激活方面的年龄差异将减少或消除，在认识等于年龄相关的功能连接性变化之后，功能连接性的变化将在延迟和痕量条件下的范围preting preting awarty preting preting preting preting preting preting preting pret trange preting pret trawn of awar的范围，并且意识相关的功能电路。最后，我们将研究痕量调理与年龄相关的差异与其他类型与年龄相关的认知下降之间的联系，我们将使用经颅磁刺激测试MTL/新皮质参与模型。