Impairments in cognitive abilities of many older adults are a well-documented phenomenon that impacts multiple domains, such as working memory, episodic memory and attention. These cognitive deficits are a cause of great distress to many older adults who feel that their ability to lead high-quality lives is negatively impacted by this decline, and it is often considered the most debilitating aspect of aging. Our objective is to utilize the tools of human neurophysiology to identify underlying alterations in fundamental neural mechanisms that lead to the wide range of age-related cognitive deficits. Functional MRI (fMRI) and electroencephalography (EEG) will be used in a series of cognitive experiments to evaluate age-related changes in top-down modulation and subserving neural networks. The fine spatial resolution of fMRI and high temporal resolution of EEG provide unique but complementary data, and by simultaneously recording activity from the entire functioning human brain they are ideally suited to study network interactions. Top-down modulation is the neural process that underlies our ability to selectively focus our cognitive resources on sensory information relevant to our goals and ignore irrelevant information, thus serving as a neural basis for selective attention and a critical foundation for successful memory storage. We recently documented an age-related deficit in top-down modulation. Specifically, healthy older adults exhibit an inability to effectively suppress neural activity associated with distracting information, and this suppression deficit correlates with impairments in working memory performance.
The specific aims of this project are to: 1) Elucidate the basis of the age-related top down suppression deficit, and 2) Explore the generalizability of age-related top-down modulation changes to different cognitive operations. The experiments proposed will inform us of the underlying neural basis of top-down modulation changes in the aging brain, assess the broader cognitive implications of this deficiency and more effectively guide the development of therapeutic interventions. Cognitive impairment that occurs with aging is a pervasive public health issue that continues to increase in magnitude as the size of the older population in our country continues to grow. The identification of underlying changes in the aging brain is necessary to establish a framework for the development of therapeutic interventions to alleviate cognitive impairments.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG030395-05
Application #
8230505
Study Section
Cognitive Neuroscience Study Section (COG)
Program Officer
Wagster, Molly V
Project Start
2008-03-15
Project End
2013-08-28
Budget Start
2012-03-01
Budget End
2013-08-28
Support Year
5
Fiscal Year
2012
Total Cost
$297,533
Indirect Cost
$102,457
Name
University of California San Francisco
Department
Neurology
Type
Schools of Medicine
DUNS #
094878337
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Chadick, James Z; Zanto, Theodore P; Gazzaley, Adam (2014) Structural and functional differences in medial prefrontal cortex underlie distractibility and suppression deficits in ageing. Nat Commun 5:4223
Mishra, Jyoti; de Villers-Sidani, Etienne; Merzenich, Michael et al. (2014) Adaptive training diminishes distractibility in aging across species. Neuron 84:1091-103
Wais, Peter E; Gazzaley, Adam (2014) External distraction impairs categorization performance in older adults. Psychol Aging 29:666-71
Zanto, Theodore P; Sekuler, Robert; Dube, Chad et al. (2013) Age-related changes in expectation-based modulation of motion detectability. PLoS One 8:e69766
Cashdollar, Nathan; Fukuda, Keisuke; Bocklage, Angelika et al. (2013) Prolonged disengagement from attentional capture in normal aging. Psychol Aging 28:77-86
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
Mishra, Jyoti; Zanto, Theodore; Nilakantan, Aneesha et al. (2013) Comparable mechanisms of working memory interference by auditory and visual motion in youth and aging. Neuropsychologia 51:1896-906
Wais, Peter E; Martin, Grant M; Gazzaley, Adam (2012) The impact of visual distraction on episodic retrieval in older adults. Brain Res 1430:78-85
Gazzaley, Adam; Nobre, Anna C (2012) Top-down modulation: bridging selective attention and working memory. Trends Cogn Sci 16:129-35
Clapp, Wesley C; Gazzaley, Adam (2012) Distinct mechanisms for the impact of distraction and interruption on working memory in aging. Neurobiol Aging 33:134-48

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