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

描述（由申请人提供）：选择性听觉注意允许个人选择性地注意到一个用餐同伴的声音在一个响亮，嘈杂的餐厅或对不同的音乐家在乐队的位置。注意力障碍是人类衰老的标志之一。事实上，尽管衰老对听力的影响通常可以通过听力图的变化来表征，但75岁以上的所有人中有近一半患有听觉感知和认知组件功能障碍，例如选择性听觉注意力，即使在听力图正常的情况下。这些缺陷会导致社交孤立、抑郁和其他类型的认知功能障碍。听觉注意力的神经机制、不同脑区在注意力中的因果作用以及年龄对注意力的影响都还不清楚。在听觉系统中，刺激被假设为由两个皮层通路处理：（1）从听觉皮层到前额叶皮层（dPFC）的"背侧"通路，其介导听觉的空间分量;以及（2）类似的"腹侧"通路，其介导前额叶皮层（vPFC）的相邻区域中的听觉的非空间分量。这种解剖学上的分离使我们假设，PFC是一个主要的参与者在"自上而下"的控制，选择性地参加不同的听觉功能（空间和非空间）。此外，我们还假设自然衰老降低了这种自上而下的控制的有效性，从而导致与年龄相关的听觉注意力缺陷。目的#1测试th PFC在听觉注意中的因果作用。年轻的成年动物参与的空间或非空间听觉注意任务，而无论是vPFC或dPFC的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。目标#2通过比较年轻与老年动物的皮层冷却结果来测试衰老对听觉注意力的影响。我们假设，在老年猴子，定向注意的能力，以提高行为表现将受损相对于年轻的成年猴。其次，我们假设，PFC活动在老年猴子减少，因此，失活的任何途径将损害性能在老年猴子相对于年轻的成年猴子。这些结果将提供必要的知识基础，开发补救疗法，以限制或扭转老年人的注意力缺陷。

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.