Aging and the cholinergic system on attention and timing

老年人往往患有几种认知过程的障碍，包括能力下降， 集中注意力，执行多项任务，以及短时间间隔。一些模型表明， 时间和注意力。这项研究假设注意力和时间控制涉及类似的大脑活动， 区域，特别是额叶的运动区域。此外，据预测，额叶功能障碍 运动区负责与年龄有关的注意力和时间的损伤。这种功能障碍是由于， 部分与基底核大细胞胆碱能神经元的丢失有关。拟议 研究做了以下几点：1）检查运动皮层损伤和NBM投射对运动的影响， 2）比较大鼠注意和时间估计的年龄相关变化， 人类，3）研究与年龄相关的NBM神经元损失和注意力障碍之间的关系 和时间，以及4）研究衰老和脑损伤对注意力相关神经元活动的影响， 运动皮层对大鼠和人类的拟议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听觉联系起来， 视觉线索与短和长的固定时间间隔，然后测试他们的能力，产生/估计 不同注意力需求下的时间间隔。在集中注意力的情况下，只有一个线索， 呈现给受试者。在注意力分散的情况下，两种线索都出现了，必须注意到。 为了正确的回答。集中注意力的条件作为一个基线的表现衡量。 中心的实证问题是关于衰老和病变（大鼠）如何影响不同时间的时间表现。 相对于集中注意力的条件。使用标量期望理论拟合模型 促进人类和大鼠行为数据之间的比较，并可能提供一个功能 解释衰老和病变对集中注意力和分散注意力的影响。总的来说，这项研究 这项提案将增进我们对参与注意力和时间控制的大脑系统的了解。重要的是， 新的信息将被揭示，这将阐明负责年龄相关的神经机制。 注意力和时间的障碍。这些新知识将为发展 治疗。

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 functinoal 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.