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

University Of California At Davis, Davis CA

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Abstract

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.