Aging and the cholinergic system on attention and timing

描述（由申请人提供）：老年人往往患有几种认知过程的损伤，包括注意力、执行多项任务和时间间隔短的能力下降。一些模型表明，时间和注意力之间存在密切的相互作用。这项研究假设注意力和时间控制涉及相似的大脑区域，特别是额叶的运动区域。此外，据预测，额叶运动区的功能障碍是负责与年龄相关的注意力和时间的障碍。这种功能障碍部分是由于基底核大细胞（NBM）胆碱能神经元的丢失。拟议的研究包括：1）检查运动皮层损伤和NBM向运动皮层的投射对注意力和时间估计的影响，2）比较大鼠和人类中注意力和时间的年龄相关变化，3）检查NBM神经元的年龄相关损失与注意力和时间的损伤之间的关系，（4）探讨衰老和脑损伤对运动皮层注意相关神经元活动的影响。提出的大鼠和人类的行为研究涉及类似版本的同步时间处理（STP）任务。在STP任务中，受试者学习将听觉和视觉线索与短和长的固定时间间隔相关联，然后测试他们在不同注意力需求下产生/估计该时间间隔的能力。在集中注意力的条件下，只有一个线索被呈现给受试者。在注意力分散的情况下，两种线索都存在，必须注意才能做出正确的反应。集中注意力的条件作为一个基线的表现衡量。中心的经验问题是如何老化和病变（大鼠）影响时间性能在分散注意力的条件下，相对于集中注意力的条件。模型拟合使用标量期望理论促进人类和大鼠的行为数据之间的比较，并可能提供一个功能的解释，对集中和分散注意力的老化和病变的影响。总的来说，这项提案中的研究将增强我们对参与注意力和时间的大脑系统的了解。重要的是，新的信息将被揭示，这将阐明与年龄相关的注意力和时间损伤的神经机制。这些新知识将为治疗方法的发展提供方向。

DESCRIPTION (provided by applicant): The elderly tend to be afflicted with impairments of several cognitive processes, including a decreased ability to pay attention, perform multiple tasks, and to time short intervals. Some models suggest a close interaction of timing and attention. The proposed studies hypothesize that attention and timing involve similar brain regions, in particular motor areas in the frontal lobe. In addition, it is predicted that dysfunction of the frontal motor areas is responsible for the age-related impairments in attention and timing. This dysfunction is due, in part, to the loss of cholinergic neurons of the nucleus basalis magnocellularis (NBM). The proposed studies do the following: 1) examine the effects of damage to motor cortex and NBM projections to motor cortex on attention and time estimation, 2) compare age-related changes of attention and timing in rats and humans, 3) examine the relationship between age-related loss of NBM neurons and impairments in attention and timing, and 4) investigate the effects of aging and brain damage on attention-related neuronal activity in motor cortex. The proposed behavioral studies with rats and humans involve similar versions of a simultaneous temporal processing (STP) task. In the STP task, subjects' learn to associate auditory and visual cues with short and long fixed time intervals, and are then tested on their ability to produce/estimate this time interval under different attentional demands. In a focused attention condition, only one cue is presented to subjects. In a divided attention condition, both cues are presented and must be attended to in order to respond correctly. The focused attention condition serves as a baseline measure of performance. The central empirical question concerns how aging and lesions (in rats) affect timing performance in divided attention conditions, relative to focused attention conditions. Model fits using scalar-expectance theory facilitate comparison between the human and rat behavioral data and potentially provide a functional interpretation of the effects of aging and lesions on focused and divided attention. Overall, the studies in this proposal will enhance our knowledge of the brain systems participating in attention and timing. Importantly, new information will be revealed that will elucidate the neural mechanisms responsible for age-related impairments in attention and timing. This new knowledge will provide directions for the development of treatments.