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体在嘈杂的餐厅中有选择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，但在75岁以上的人中，近一半的人在听觉的感知和认知方面存在功能障碍，比如选择性听觉注意，即使在听力图正常的情况下也是如此。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。听觉注意的神经机制、不同脑区在注意中所起的因果作用以及衰老对注意的影响尚不清楚。在听觉系统中，刺激被假设通过两个皮层通路处理：(1)从听觉皮层到前额叶皮层（dPFC）的“背侧”通路，介导听觉的空间成分；(2)类似的“腹侧”通路，介导前额叶皮层（vPFC）邻近区域的非空间成分。这种解剖上的分离使我们得出了我们的假设，即PFC是选择性地关注不同听觉特征（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自上而下控制的有效性，从而导致与年龄相关的听觉注意缺陷。目的1测试PFC在听觉注意中的因果作用。当皮层冷却选择性地使vPFC或dPFC失活时，年轻成年动物参与空间或非空间听觉注意任务。我们假设背侧通路失活会导致空间任务的选择性行为缺陷，而腹侧通路失活会导致非空间任务的选择性行为缺陷。目的2通过比较幼年动物和老年动物皮层冷却的结果来测试衰老对听觉注意力的影响。我们假设，在老年猴子中，相对于年轻的成年猴子，定向注意力改善行为表现的能力将受到损害。其次，我们假设老年猴子的PFC活动减弱，因此，与年轻的成年猴子相比，两种途径的失活对老年猴子的表现影响较小。这些结果将为开发限制或逆转老年人注意力缺陷的补救疗法提供必要的知识基础。

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.