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）：选择性听觉注意允许个体在喧闹、嘈杂的餐厅中选择性地注意用餐同伴的声音或乐队中不同音乐家的位置。注意力功能障碍是人类衰老的标志之一。事实上，虽然衰老对听力的影响通常可以通过听力图的变化来表征，但近一半 75 岁以上的人都患有听觉感知和认知部分的功能障碍，例如选择性听觉注意力，即使在听力图发生变化的情况下也是如此。是正常的。这些缺陷会导致社会孤立、抑郁和其他类型的认知功能障碍。听觉注意力的神经机制、不同大脑区域在注意力中所起的因果作用以及衰老对注意力的影响尚不清楚。在听觉系统中，假设刺激通过两条皮质通路进行处理：（1）从听觉皮层到前额皮质（dPFC）的“背侧”通路，介导听觉的空间成分；（2）类似的“腹侧”通路介导前额皮质 (vPFC) 邻近区域听觉非空间成分的通路。这种解剖学隔离使我们得出这样的假设：前额皮质是选择性关注不同听觉特征（空间和非空间）的“自上而下”控制的主要参与者。此外，我们还假设自然衰老会降低这种听觉特征的有效性。自上而下的控制，导致与年龄相关的听觉注意缺陷，目标#1测试了年轻成年动物参与空间或非空间听觉注意任务时PFC的因果作用。 vPFC 或 dPFC 被皮质冷却选择性失活，我们假设背侧通路的失活将导致空间任务的选择性行为缺陷，而腹侧通路的失活将导致非空间任务的选择性行为缺陷。 #2 通过比较年轻动物和老年动物的皮质冷却结果来测试衰老对听觉注意力的影响，我们假设老年猴子的定向注意力能力。相对于年轻的成年猴子，行为表现的改善会受到损害。其次，我们假设老年猴的 PFC 活性减弱，因此，与年轻的成年猴相比，任一途径的失活对老年猴的表现影响较小。这些结果将为开发限制或扭转老年人注意力缺陷的治疗方法提供必要的知识基础。