Aging and the cholinergic system on attention and timing

衰老和胆碱能系统对注意力和计时的影响

• 批准号: 7348107
• 负责人: Kevin C.H. Pang
• 金额: $ 21.02万
• 依托单位: VETERANS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-02-15 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7348107
• 关键词: Adult; Affect; Age; Aging; Animals; Area; Attention; Auditory; Behavioral; Brain; Brain Injuries; Brain region; Characteristics; Cholinergic Agents; Cognitive; Condition; Cues; Data; Elderly; Event; Fire - disasters; Functional disorder; Human; Ibotenic Acid; Immunoglobulin G; Immunotoxins; Impairment; Knowledge; Learning; Lesion; Measures; Modeling; Motor; Motor Cortex; Neurons; Nucleus Basalis Magnocellularis; Numbers; Pathway interactions; Pattern; Performance; Play; Population; Procedures; Process; Rattus; Relative (related person); Role; System; Testing; Time; Tracer; Visual; Work; age effect; age related; aged; aging brain; base; behavior measurement; cholinergic; cholinergic neuron; frontal lobe; immunocytochemistry; improved; neuromechanism; neuron loss; research study; theories; therapy development; time interval; young adult

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.

老年人往往会受到多种认知过程障碍的困扰，包括能力下降 集中注意力，执行多项任务，并安排较短的时间间隔。一些模型建议密切互动 的时机和注意力。拟议的研究假设注意力和时间安排涉及相似的大脑 区，特别是额叶的运动区。此外，据预测，额叶功能障碍 运动区域负责与年龄相关的注意力和时间安排障碍。这种功能障碍是由于， 部分原因是大细胞基底核（NBM）胆碱能神经元的丧失。拟议的 研究进行了以下工作：1）检查运动皮层损伤和 NBM 预测对运动的影响 皮层对注意力和时间估计的影响，2）比较大鼠和年龄相关的注意力和时间变化 人类，3) 检查与年龄相关的 NBM 神经元损失与注意力障碍之间的关系 和时间，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。拟议的大鼠和人类行为研究涉及类似的版本 同时时间处理（STP）任务。在 STP 任务中，受试者学会将听觉和 具有短和长固定时间间隔的视觉提示，然后测试它们产生/估计的能力 这个时间间隔在不同的注意力需求下。在注意力集中的情况下，只有一个提示 呈现给受试者。在注意力分散的情况下，两种提示都会出现，并且必须同时注意 以便正确响应。注意力集中状况作为绩效的基准衡量标准。 中心的实证问题涉及衰老和损伤（在大鼠中）如何影响分裂的计时表现。 注意力条件，相对于集中注意力条件。使用标量期望理论进行模型拟合 促进人类和大鼠行为数据之间的比较，并可能提供功能 解释衰老和病变对注意力集中和分散的影响。总的来说，这方面的研究 该提案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， 将揭示新信息，阐明负责与年龄相关的神经机制 注意力和时间安排受损。这些新知识将为我们的发展提供方向。 治疗。

项目成果

Dividing time: concurrent timing of auditory and visual events by young and elderly adults.

划分时间：年轻人和老年人同时进行听觉和视觉事件的时间。

• DOI: 10.1080/0361073x.2010.484744
• 发表时间: 2010
• 期刊: Experimental aging research
• 影响因子: 1.8
• 作者: McAuley,JDevin;Miller,JonathanP;Wang,Mo;Pang,KevinCH
• 通讯作者: Pang,KevinCH

Age-related disruptions of circadian rhythm and memory in the senescence-accelerated mouse (SAMP8).

衰老加速小鼠 (SAMP8) 中与年龄相关的昼夜节律和记忆中断。

• DOI: 10.1007/s11357-006-9013-9
• 发表时间: 2006
• 期刊: Age (Dordrecht, Netherlands)
• 作者: Pang,KevinCH;Miller,JonathanP;Fortress,Ashley;McAuley,JDevin
• 通讯作者: McAuley,JDevin

Circadian rhythms in SAMP8: a longitudinal study of the effects of age and experience.

SAMP8 中的昼夜节律：年龄和经验影响的纵向研究。

• DOI: 10.1016/s0197-4580(03)00029-0
• 发表时间: 2004
• 期刊: Neurobiology of aging
• 影响因子: 4.2
• 作者: Pang,KevinCH;Miller,JonathanP;McAuley,JDevin
• 通讯作者: McAuley,JDevin

Wistar-Kyoto rats as an animal model of anxiety vulnerability: support for a hypervigilance hypothesis.

• DOI: 10.1016/j.bbr.2009.05.036
• 发表时间: 2009-12-01
• 期刊: BEHAVIOURAL BRAIN RESEARCH
• 影响因子: 2.7
• 作者: McAuley, J. D.;Stewart, A. L.;Webber, E. S.;Cromwell, H. C.;Servatius, R. J.;Pang, K. C. H.
• 通讯作者: Pang, K. C. H.

Effects of the NMDA receptor antagonist MK-801 on short-interval timing in rats.

NMDA 受体拮抗剂 MK-801 对大鼠短间隔时间的影响。

• DOI: 10.1037/0735-7044.120.1.162
• 发表时间: 2006
• 期刊: Behavioral neuroscience
• 影响因子: 1.9
• 作者: Miller,JonathanP;McAuley,JDevin;Pang,KevinCH
• 通讯作者: Pang,KevinCH