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障碍的困扰，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。提出的研究假设，注意力和时间涉及类似的大脑区域，特别是额叶的运动区域。此外，我们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。这种功能障碍部分是由于大细胞基底核（NBM）胆碱能神经元的丧失。拟开展的研究包括：1)研究运动皮层损伤和NBM投射对注意和时间估计的影响；2)比较大鼠和人的年龄相关的注意和时间变化；3)研究NBM神经元的年龄相关损失与注意和时间损伤的关系；4)研究衰老和脑损伤对运动皮层中注意相关神经元活动的影响。提出的对大鼠和人类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时间和长时间的固定间隔联系起来，然后测试他们在不同的注意需求下产生/估计这个时间间隔的能力。在集中注意条件下，只向受试者提供一个线索。在注意力分散的情况下，两种提示都出现了，为了做出正确的反应，必须注意这两种提示。集中注意力的条件可以作为衡量表现的基准。核心的经验问题是，相对于集中注意力，衰老和损伤（在大鼠中）如何影响分散注意力条件下的时间表现。使用标量期望理论的模型拟合促进了人类和大鼠行为数据之间的比较，并可能提供衰老和病变对集中和分散注意力影响的功能解释。总的来说，本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，新的信息将揭示神经机制负责与年龄有关的注意力和时间障碍。这一新发现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.