Despite the widespread appreciation that the prefrontal and posterior parietal cortices (PFC/PPC) are necessary for flexible action and efficient perception, there is a fundamental gap in understanding the control mechanisms by which they accomplish these goals. This gap in knowledge is a critical problem because a host of psychiatric and neurologic disorders stem from a primary dysfunction of executive control. The long-term goal is to understand the mechanisms by which the PFC and PPC exert control over motor and sensory systems. The objective of the current proposal is to test a new model of how activity in the PFC and PPC form maps of prioritized space that tag salient and relevant locations in the visual field, which can then be used as the basis of executive control signals. The mechanisms of bias are likely to involve mechanisms used for saccade planning. The central aim of the project is to test the extent to which the patterns of neural activity in the human PFC and PPC are consistent with predictions from the priority map theory, including the functional organization of priority maps, the nature of what is prioritized, and the representation of competing priorities. The rationale for the proposed research is that a better understanding of how control is exerted will lead to a strong theoretical framework within which strategies for the understanding of mental disease will develop. The objective will be to test, refine, and possibly refute, tenets of the priority map theory which will be accomplished by pursuing three specific aims: 1) test the hypothesis that the activity in priority maps is agnostic about what led to prioritization;2) test the hypothesis that the activity in priority maps encodes the incentives associated with multiple prioritized items;and 3) test the hypothesis that the activity in priorit maps encodes the cue probabilities associated with multiple prioritized items. Strong preliminary data demonstrate the feasibility of aims in the applicant's hands. Several candidate priority maps were identified in frontoparietal cortex using novel topographical mapping approaches.
Under Aim 1, both delay period activity and multivariate patterns of brain activity in candidate priority maps were remarkably similar, if not interchangeable, across a variety of spatial cognition tasks (e.g., memory, attention, planning).
Under Aim 2, behavioral measures and spatially specific activity in frontal and parietal cortex scaled with the incentive driven priorites of locations maintained in working memory.
Under aim 3, working memory performance scaled with the likelihood that maintained locations would be later probed. The approach is innovative because it is highly programmatic;uses novel approaches to combat individual differences in the functional neuroanatomy of the PFC and PPC;sidesteps past inferential weaknesses with novel analyses;and uses powerful methods to rigorously test key hypotheses. The proposed research is significant because it is expected to test an important new model of executive control and will provide a detailed understanding of the mechanisms by which the human brain exerts control, such that models of dysfunction of these mechanisms can be targeted as causes of and potential treatments for neuropathology.

Public Health Relevance

The proposed research is relevant to public health because advancement in our understanding of the mechanisms by which the prefrontal cortex exerts executive control in the normal brain is necessary to illuminate the mechanisms that could go awry in the pathological brain. Specifically, the proposed research is relevant to NIH's mission because is expected to advance a stronger theoretical framework within which clinical researchers can develop strategies for the diagnosis and treatment of psychiatric and neurologic disorders.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Special Emphasis Panel (SPC)
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Steinmetz, Michael A
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New York University
Schools of Arts and Sciences
New York
United States
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Rahmati, Masih; Saber, Golbarg T; Curtis, Clayton E (2018) Population Dynamics of Early Visual Cortex during Working Memory. J Cogn Neurosci 30:219-233
Yoo, Aspen H; Klyszejko, Zuzanna; Curtis, Clayton E et al. (2018) Strategic allocation of working memory resource. Sci Rep 8:16162
Mackey, Wayne E; Curtis, Clayton E (2017) Distinct contributions by frontal and parietal cortices support working memory. Sci Rep 7:6188
Mackey, Wayne E; Winawer, Jonathan; Curtis, Clayton E (2017) Visual field map clusters in human frontoparietal cortex. Elife 6:
Mackey, Wayne E; Devinsky, Orrin; Doyle, Werner K et al. (2016) Human Dorsolateral Prefrontal Cortex Is Not Necessary for Spatial Working Memory. J Neurosci 36:2847-56
Mackey, Wayne E; Devinsky, Orrin; Doyle, Werner K et al. (2016) Human parietal cortex lesions impact the precision of spatial working memory. J Neurophysiol 116:1049-54
Ikkai, Akiko; Dandekar, Sangita; Curtis, Clayton E (2016) Lateralization in Alpha-Band Oscillations Predicts the Locus and Spatial Distribution of Attention. PLoS One 11:e0154796
Saber, Golbarg T; Pestilli, Franco; Curtis, Clayton E (2015) Saccade planning evokes topographically specific activity in the dorsal and ventral streams. J Neurosci 35:245-52
Markowitz, David A; Curtis, Clayton E; Pesaran, Bijan (2015) Multiple component networks support working memory in prefrontal cortex. Proc Natl Acad Sci U S A 112:11084-9
Klyszejko, Zuzanna; Rahmati, Masih; Curtis, Clayton E (2014) Attentional priority determines working memory precision. Vision Res 105:70-6

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