Causal Role of PFC in Auditory Perception and Age-Related Plasticity

PFC 在听觉感知和年龄相关可塑性中的因果作用

• 批准号: 9050611
• 负责人: Yale E Cohen
• 金额: $ 23.76万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-15 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9050611
• 关键词: Address; Adult; Affect; Age; Age-Years; Aging; American; Animals; Area; Attention; Audiometry; Auditory; Auditory Perception; Auditory area; Auditory system; Behavior; Behavioral; Brain; Cognitive; Companions; Devices; Disease; Dorsal; Ear; Effectiveness; Elderly; Foundations; Functional disorder; Future; Health; Hearing; Hearing Aids; Human; Impaired cognition; Individual; Knowledge; Lead; Location; Mediating; Mental Depression; Monkeys; Participant; Pathway interactions; Patients; Performance; Play; Population; Prefrontal Cortex; Presbycusis; Primates; Process; Psychophysics; Qualifying; Reaction Time; Research; Restaurants; Role; Social isolation; Space Perception; Stimulus; Structure; Testing; Training; Voice; age effect; age related; aged; attentional control; auditory pathway; directed attention; disability; improved; interest; mature animal; musician; neuromechanism; neurophysiology; relating to nervous system; research study; segregation; selective attention; sound; young adult

DESCRIPTION (provided by applicant): Selective auditory attention allows individuals to selectively attend to a dining companion's voice in a loud, noisy restaurant or toward the location of different musicians in a band. Attentional dysfunction is one of the hallmarks of human aging. Indeed, whereas aging's effect on hearing can often be characterized by changes in the audiogram, nearly half of all humans over 75 years of age suffer from dysfunction in perceptual and cognitive components of audition, such as selective auditory attention, even in cases where the audiogram is normal. These deficits lead to social isolation, depression, and other types of cognitive dysfunction. The neural mechanisms underlying auditory attention, the causal role that different brain areas play in attention, and the effect that aging has on attentio are not known. In the auditory system, stimuli are hypothesized to be processed by two cortical pathways: (1) a "dorsal" pathway from the auditory cortex to the prefrontal cortex (dPFC) that mediates spatial components of audition and (2) an analogous "ventral" pathway that mediates non-spatial components of audition in adjacent regions of the prefrontal cortex (vPFC). This anatomical segregation leads us to our hypothesis that the PFC is a major participant in the "top-down" control of selectively attending to different auditory features (spatial and non-spatial. Further, we also hypothesize that natural aging reduces the effectiveness of this top-down control, giving rise to age-related auditory attention deficits. Aim #1 tests the causal role of th PFC in auditory attention. Young adult animals participate in a spatial or non-spatial auditory attention task while either the vPFC or the dPFC is selectively inactivated by cortical cooling. We hypothesize that inactivation of the dorsal pathway will cause selective behavioral deficits on the spatial task, whereas inactivation of the ventral pathway will cause selective behavioral deficits on the non-spatial task. Aim #2 tests the effect of aging on auditory attention by comparing the results of cortical cooling in young vs. aged animals. We hypothesize that, in the geriatric monkeys, the ability of directed attention to improve behavioral performance will be impaired relative to young adult monkeys. Second, we hypothesize that the PFC activity in geriatric monkeys is diminished and, as a consequence, inactivation of either pathway will impair performance less in geriatric monkeys relative to younger adult monkeys. These results will provide the foundation of knowledge necessary to develop remedial therapies to limit or reverse attention deficits in the aged.

描述（由申请人提供）：选择性的听觉关注使个人可以在大声，嘈杂的餐厅或乐队中不同音乐家的位置选择性地参加餐饮伴侣的声音。注意力障碍是人类衰老的标志之一。的确，尽管衰老对听力的影响通常可以是听力图的变化，但在75岁以上的所有人类中，几乎一半的人在试听的感知和认知成分中都患有功能障碍，例如选择性听觉注意力，即使听力图正常。这些缺陷导致社会隔离，抑郁和其他类型的认知功能障碍。尚不清楚听觉关注的神经机制，不同大脑区域在关注的因果作用以及衰老对患者的影响。在听觉系统中，假设刺激是通过两种皮质途径处理的：（1）从听觉皮层到前额叶皮层（DPFC）的“背”途径介导试听的空间成分，该途径介导了试听的空间成分，（2）介导非腹部的“腹部”途径，该途径介导了临近的邻近构造的范围。 （VPFC）。这种解剖学分离使我们提出了假设，即PFC是“自上而下”控制的主要参与者，可以选择性地参与不同的听觉功能（空间和非空间）。此外，我们还假设自然衰老会降低这种自上而下的控制能力，从而降低了年龄较大的听觉注意力，从而导致了年轻的调查。参与空间或非空间听觉注意任务，而VPFC或DPFC有选择地通过皮质冷却灭活。通过比较年轻动物的皮质冷却结果，我们的听觉关注。其次，我们假设老年猴子中的PFC活性减少了，因此，相对于年轻的成年猴子，这两种途径的灭活都会损害老年猴子的性能。这些结果将为开发补救疗法所必需的知识基础，以限制或逆转老年人的注意力缺陷。