Aging and the cholinergic system on attention and timing

描述(由申请人提供)：老年人往往受到几种认知过程的损害，包括注意力、执行多项任务的能力降低，以及时间间隔短。一些模型表明，时间和注意力之间存在密切的相互作用。拟议中的研究假设注意力和计时涉及相似的大脑区域，特别是额叶的运动区。此外，据预测，额叶运动区的功能障碍是与年龄相关的注意力和时间障碍的原因。这种功能障碍的部分原因是基底大细胞核(NBM)胆碱能神经元的丢失。这些研究包括以下几个方面：1)研究运动皮质损伤和运动皮质NBM投射对注意力和时间估计的影响；2)比较大鼠和人类注意和时序与年龄相关的变化；3)研究与年龄相关的NBM神经元丢失与注意力和时序损伤的关系；4)研究衰老和脑损伤对运动皮质中注意相关神经元活动的影响。拟议的以大鼠和人类为对象的行为研究涉及类似版本的同时时间处理(STP)任务。在STP任务中，被试学习将听觉和视觉线索与短的和长的固定时间间隔联系起来，然后在不同的注意要求下测试他们产生/估计这个时间间隔的能力。在集中注意的情况下，只有一条线索呈现给受试者。在注意力分散的情况下，两个线索都会出现，必须注意才能做出正确的反应。注意力集中状况可作为绩效的基准衡量标准。中心的经验性问题涉及年龄和损伤(在大鼠中)如何影响分散注意条件下的计时表现，相对于集中注意条件。使用标量预期理论的模型拟合有助于比较人类和大鼠的行为数据，并潜在地提供了对衰老和损伤对集中注意力和分散注意力的影响的功能解释。总体而言，这项提案中的研究将增强我们对参与注意力和计时的大脑系统的了解。重要的是，新的信息将被揭示，这些信息将阐明与年龄相关的注意力和时间障碍的神经机制。这一新知识将为治疗的发展提供方向。

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.