Attentional (or top-down) control enables us to focus on task goals and block out interference. Failing to properly engage these top-down mechanisms results in decreased memory performance by overloading our limited memory capacity with irrelevant information. While deficient attentional control periodically occurs in al healthy adults (e.g., distraction, mind wandering), it becomes more prevalent with age and is a prominent factor in those with psychiatric disorders, neurodegenerative disease, and brain injury. Unfortunately, it is unclear exactly how top-down control is implemented in the brain, thereby limiting therapeutic interventions. Remarkably, the brain is naturally resilient to neural decline by recruiting additional neural regions and rewiring neural networks to retain performance abilities. However, little is known about these reorganizational properties and the brain's potential to retain top-down control signals in the presence of dysfunction. The basic science goals of the proposed research project are to characterize where and when top-down signals are communicated and how they pertain to attention and memory processes. From a translational perspective, parallel goals are to assess the potential for neural compensatory mechanisms to retain performance abilities following the perturbation of brain function. To accomplish these goals, young adults will participate in two- session experiments that engage attention and memory processes. The first session will implement functional magnetic resonance imaging (fMRI) to identify putative top-down control regions within the neural networks involved in the task. The second session will utilize transcranial magnetic stimulation (TMS) to perturb neural function within the top-down control regions that were identified from the first session. Following TMS, neural data will be acquired via fMRI or electroencephalography (EEG) while participants are engaged in the same task as the first session. Temporal and spatial measures of cortical function, with an emphasis on network connectivity, will be evaluated. Comparisons between TMS, sham TMS, and TMS to areas not involved in the task will elucidate the role of these control regions from a causal perspective, help characterize the potential for neural reorganization, and offer a basis to understand the mechanistic relationship between attention and memory. In addition to advancing the limited work in this important area, we anticipate that this unique "perturb and record" methodological approach and experimental design will have a major impact on the field. This knowledge will be used to guide the targeted development of rehabilitation programs directed at the broad range of cognitive abilities and clinical populations that are susceptible to decline in attention and memory function.

Public Health Relevance

Attention and memory processes are affected by many psychiatric and neurologic disorders. With the aging of the population, this is a growing public health issue. Given the high prevalence of co-morbid deficits in attention and memory, cognitive changes in these conditions may share a common basis. The goal of this project is to understand the neural mechanisms that govern the interaction between attention and memory and characterize the effects of dysfunction in the neural networks subserving these processes. This knowledge will be used to design more effective therapeutic interventions to improve the quality of life for those afflicted with cognitive impairment from neurological and psychiatric disease.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Special Emphasis Panel (SPC)
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Rossi, Andrew
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University of California San Francisco
Schools of Medicine
San Francisco
United States
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Zanto, Theodore P; Chadick, James Z; Gazzaley, Adam (2014) Anticipatory alpha phase influences visual working memory performance. Neuroimage 85 Pt 2:794-802
Zanto, Theodore P; Pa, Judy; Gazzaley, Adam (2014) Reliability measures of functional magnetic resonance imaging in a longitudinal evaluation of mild cognitive impairment. Neuroimage 84:443-52
Zanto, Theodore P; Gazzaley, Adam (2013) Fronto-parietal network: flexible hub of cognitive control. Trends Cogn Sci 17:602-3
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