A general principle of brain function is the ability to store information about the past to better predict and prepare for the future. Working memory and timing are two computational features that evolved to allow the brain to use recent information about the past to accomplish short-term goals. Working memory refers to the ability to transiently store information in a flexible manner, while timing refers to the ability to generate well timed motor responses, modulate attention in time, and predict when external events will occur. To date working memory and timing have primarily been treated as independent processes. Here we propose that because the brain seeks to use information about the past to predict the future, that working memory and timing are often multiplexed. Specifically, that the neural patterns of activity recorded during the delay period of many working memory tasks encodes both retrospective information about the past, as well as prospective predictions about the future. To test this hypothesis, we have developed novel variant of the delayed- nonmatch-to-sample task, in which the first cue predicts the duration of the delay, that is, how long an item must be held in working memory. This task will allow us to determine if network level population responses encode both retrospective information about the past and prospective information about delay duration. Preliminary results from a supervised recurrent neural network model predict that the temporal structure of the neural patterns of activity elicited by both cues will be different. This prediction will be tested using large scale Ca2+-imaging to characterize the spatiotemporal patterns of activity in brain areas associated with working memory and timing. Additionally, optogenetic perturbation experiments and longitudinal characterization of the emergence of neural patterns of activity will be performed. These experiments, will in turn, be used to ground computational studies aimed at understanding the neuronal and circuit level learning rules that underlie the emergence of patterns that encode working memory and time.

Public Health Relevance

Working memory and the ability to generate timed motor responses are essential for carrying out most daily tasks, and impaired in many neurological and psychiatric conditions. Yet, the brain regions, activity patterns, and learning rules that drive working memory and timing are not understood. Here we propose that the brain often multiplexes both forms of information, and we will use a novel behavioral task along with computational and experimental methods to test this hypothesis.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Special Emphasis Panel (ZRG1)
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David, Karen Kate
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University of California Los Angeles
Schools of Medicine
Los Angeles
United States
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