The goal of this project is to elucidate the spatio-temporal properties of neural network components involved in top-down modulation and evaluate how these networks may change due to normal aging. Topdown modulation refers to our ability to focus attention on pertinent sensory information and ignore irrelevant stimuli thereby improving our performance on cognitive tasks such as working memory. It has seen hypothesized that the neural networks underlying top-down modulation are long-range connections between sensory and distal cortices. Moreover, the prefrontal cortex (PFC) and the visual association cortex (VAC) have been identified as components of a distributed network involved in visual working memory and have been suggested to change in functionality during normal aging. Therefore, this project will focus on the interactions within the PFC-VAC network as attentional control influences memory and evaluate what changes may occur after normal aging.
Specific Aim 1 : Characterize the spatio-temporal properties of the PFC-VAC network during a working memory task. Through the use of an fMRI guided TMS/EEG recording approach, network activity may be localized, recorded and perturbed to study the causal effects of the intrinsic connectivity and functionality. Event-related potential, spectral and bivariate analysis will help characterize the nature of the long-range reciprocal neural influences between the frontal and visual cortices. I hypothesize the PFC yields separable modulatory activity on the VAC through suppression and enhancement of neural activity.
Specific Aim 2 : Evaluate changes in the PFC-VAC network due to normal aging. The second experiment will utilize the same paradigm and address the same questions as Experiment 1;however, the subject population will consist of older (60-75 years of age) adults as opposed to the younger (18-35 years of age) population in Experiment 1. Thus, generizability of a PFC role in modulating visual working memory may be determined through the observation of age related changes. I hypothesize that older adults will display a more widely distributed processing network due to fewer suppression and more compensatory mechanisms.

Public Health Relevance

Differences in the connectivity and functionality of networks subserving top-down modulation may underlie a wide range of cognitive deficits associated with aging. The exploration of these basic neuralmechanisms is a critical step towards developing interventions that may alleviate this burden.

National Institute of Health (NIH)
National Institute on Aging (NIA)
Postdoctoral Individual National Research Service Award (F32)
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Special Emphasis Panel (ZRG1-F12A-N (20))
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Wagster, Molly V
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Padgaonkar, Namita A; Zanto, Theodore P; Bollinger, Jacob et al. (2017) Predictive cues and age-related declines in working memory performance. Neurobiol Aging 49:31-39
Zanto, Theodore P; Sekuler, Robert; Dube, Chad et al. (2013) Age-related changes in expectation-based modulation of motion detectability. PLoS One 8:e69766
Zanto, Theodore P; Chadick, James Z; Satris, Gabriela et al. (2013) Rapid functional reorganization in human cortex following neural perturbation. J Neurosci 33:16268-74
Rubens, Michael T; Zanto, Theodore P (2012) Parameterization of transcranial magnetic stimulation. J Neurophysiol 107:1257-9
Zanto, Theodore P; Pan, Peter; Liu, Helen et al. (2011) Age-related changes in orienting attention in time. J Neurosci 31:12461-70
Rubens, Michael T; Zanto, Theodore P (2011) Characterizing the involvement of rostrolateral prefrontal cortex in prospective memory. J Neurosci 31:9067-9
Zanto, Theodore P; Rubens, Michael T; Thangavel, Arul et al. (2011) Causal role of the prefrontal cortex in top-down modulation of visual processing and working memory. Nat Neurosci 14:656-61
Zanto, Theodore P; Rubens, Michael T; Bollinger, Jacob et al. (2010) Top-down modulation of visual feature processing: the role of the inferior frontal junction. Neuroimage 53:736-45