Flexibility, prefrontal function, and changes with normal aging

灵活性、前额叶功能以及正常衰老的变化

• 批准号: 7194728
• 负责人: GEOFFREY M SCHOENBAUM
• 金额: $ 22.35万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2012-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7194728
• 关键词: Affect; Age; Age-Years; Age-associated memory impairment; Aging; Amygdaloid structure; Area; Attention; Behavior; Behavioral; Brain; Cognitive; Cues; Dimensions; Discrimination; Elderly; Exercise; Exhibits; Human; Impaired cognition; Impairment; Individual; Learning; Lesion; Location; Medial; Mediating; Molecular; Odors; Outcome; Performance; Pliability; Prefrontal Cortex; Primates; Process; Psyche structure; Punishment; Rattus; Response to stimulus physiology; Reversal Learning; Rewards; Role; Stimulus; Structure; System; Testing; Training; abl Oncogene; age related; aged; area striata; base; behavior change; classical conditioning; cognitive function; design; experience; functional decline; improved; nerve supply; neurophysiology; normal aging; prevent; protective effect; relating to nervous system; research study; response

DESCRIPTION (provided by applicant): The experiments in this proposal are designed to investigate the basis of changes in cognitive flexibility caused by normal aging. Subsets of elderly humans and rats appear to have difficulty changing behaviors when the likely outcomes of those behaviors change. These deficits are evident in tasks that test reversal learning and set-shifting. Reversal learning and set-shifting are critically dependent on two different subdivisions of prefrontal cortex in rats and primates. These circuits are implicated in control of different forms of associative learning. Here we will test the associative basis and circuits involved in these declines in normal aging. Findings will show whether declines in these two types of cognitive flexibility occur independently in the two prefrontal systems or whether they reflect a unitary phenomenon. Associated experiments will identify regional changes in neural activity, dendritic structure, and monoaminergic innervation that correlate with performance changes to identify the location and underlying cause of miscoding associated with the inflexible behavior. Lastly we will test the hypothesis that practice on a task that emphasizes learning in one of these associative domains results in a protective effect on later performance, after aging, within the same associative domain. Improved performance may then be correlated with regional changes in neural activity, dendritic structure and innervation.

描述（申请人提供）：本提案中的实验旨在研究正常衰老引起的认知灵活性变化的基础。当老年人和老鼠的行为的可能结果发生变化时，他们似乎很难改变这些行为。这些缺陷在测试逆转学习和设定转换的任务中很明显。逆转学习和设定转换严重依赖于大鼠和灵长类动物前额皮质的两个不同细分。这些回路涉及不同形式的联想学习的控制。在这里，我们将测试正常衰老过程中这些衰退所涉及的联想基础和回路。研究结果将表明这两种认知灵活性的下降是否独立发生在两个前额叶系统中，或者是否反映了单一现象。相关实验将识别与表现变化相关的神经活动、树突结构和单胺能神经支配的区域变化，以确定与不灵活行为相关的错误编码的位置和根本原因。最后，我们将检验这样一个假设：在这些联想领域之一中进行强调学习的任务练习会对衰老后在同一联想领域内的后续表现产生保护作用。表现的提高可能与神经活动、树突结构和神经支配的区域变化相关。