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

描述(由申请者提供)：选择性听觉注意允许个人在嘈杂的餐厅中有选择地注意到就餐同伴的声音，或者对着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岁以上的所有人中，近一半的人患有听力的感知和认知部分功能障碍，例如选择性听觉注意，即使在听力图正常的情况下也是如此。这些缺陷会导致社交孤立、抑郁和其他类型的认知功能障碍。听觉注意力背后的神经机制，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都是未知的。在听觉系统中，刺激被认为是由两条皮质通路处理的：(1)从听觉皮质到前额叶皮质(DPFC)的“背侧”通路，它调节听觉的空间成分；(2)类似的“腹侧”通路，它在前额叶皮质(VPFC)的相邻区域调节听觉的非空间成分。这种解剖学上的分离导致了我们的假设，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，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。年轻的成年动物参与空间或非空间听觉注意任务，而vPFC或DPFC被皮质降温选择性地失活。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。目的#2通过比较幼年动物和老年动物大脑皮层降温的结果，来测试衰老对听觉注意的影响。我们假设，在老年猴子中，与年轻成年猴子相比，改善行为表现的定向注意能力将受到损害。其次，我们假设老年猴子的PFC活性降低，因此，与年轻成年猴子相比，任何一条通路的失活对老年猴子表现的影响都较小。这些结果将提供必要的知识基础，以开发补救疗法来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.