How the brain controls voluntary movements is a central problem of cognitive neuroscience. Besides the scientific interest, understanding the neural regulation of action is necessary for diagnosing and treating disorders involving impaired control of action including psychopathologies such as schizophrenia. Neural circuits that prepare and initiate movements are being identified, but specific information is lacking about how these neural circuits mediate the decision to move. Thus, the long-term goal of this work is to understand how the brain regulates the initiation of voluntary movements. Experiments will investigate neural activity in the brain of macaque monkeys (Macaca mulatta) that are performing tasks that systematically manipulate the preparation and execution of movements. The present experiments will concentrate on movements of the eyes because so much is known about the neural basis of gaze control. Neural activity will be recorded in the frontal eye field and supplementary eye field, two cortical areas at the interface of perceptual processing and motor output, and in the thalamic nuclei innervating these areas. Neural signatures predicting movement initiation will be sought using a countermanding task which manipulates subjects' ability to inhibit a planned movement. Performance on this task is accounted for with a model of a race between a process that generates the movement and a process that inhibits the movement. The race model provides a way to estimate how long it takes to countermand a planned movement. With this information we can evaluate whether neurons, which are directly involved in producing the movement, can generate signals that could effectively prevent the movement. The hypotheses that movements are initiated when neural activity reaches either an absolute or a relative threshold will be tested. Quantitative predictions derived from data obtained in the countermanding task will be tested in an instructed delay task in which movements are delayed until presentation of an imperative trigger signal. By experimentally manipulating the statistical predictability of the time of occurrence of the trigger signal, subjects will be implicitly encouraged or discouraged to make self-generated, anticipatory movements as opposed to stimulus triggered movements. These tasks will provide a broad range of behavior with which to evaluate competing hypotheses about the neural basis of movement control. The strength of this application lies in the simultaneous assessment of behavior and of the single neurons that are involved in producing the behavior. Sophisticated, new analytical methods will be used to relate behavioral performance to underlying neural activity. Successful completion of these experiments will provide unprecedented information about the respective neural mechanisms in frontal cortex and thalamus that are responsible for controlling behavior.

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National Institute of Mental Health (NIMH)
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Cognitive Functional Neuroscience Review Committee (CFN)
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Vanderbilt University Medical Center
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Schall, Jeffrey D; Palmeri, Thomas J; Logan, Gordon D (2017) Models of inhibitory control. Philos Trans R Soc Lond B Biol Sci 372:
Godlove, David C; Schall, Jeffrey D (2016) Microsaccade production during saccade cancelation in a stop-signal task. Vision Res 118:5-16
Thakkar, Katharine N; Schall, Jeffrey D; Heckers, Stephan et al. (2015) Disrupted Saccadic Corollary Discharge in Schizophrenia. J Neurosci 35:9935-45
Ninomiya, Taihei; Dougherty, Kacie; Godlove, David C et al. (2015) Microcircuitry of agranular frontal cortex: contrasting laminar connectivity between occipital and frontal areas. J Neurophysiol 113:3242-55
Logan, Gordon D; Yamaguchi, Motonori; Schall, Jeffrey D et al. (2015) Inhibitory control in mind and brain 2.0: blocked-input models of saccadic countermanding. Psychol Rev 122:115-47
Thakkar, Katharine N; Schall, Jeffrey D; Logan, Gordon D et al. (2015) Response inhibition and response monitoring in a saccadic double-step task in schizophrenia. Brain Cogn 95:90-8
Neggers, S F W; Zandbelt, B B; Schall, M S et al. (2015) Comparative diffusion tractography of corticostriatal motor pathways reveals differences between humans and macaques. J Neurophysiol 113:2164-72
Thakkar, Katharine N; Schall, Jeffrey D; Logan, Gordon D et al. (2015) Cognitive control of gaze in bipolar disorder and schizophrenia. Psychiatry Res 225:254-62
Middlebrooks, Paul G; Schall, Jeffrey D (2014) Response inhibition during perceptual decision making in humans and macaques. Atten Percept Psychophys 76:353-66
Godlove, David C; Maier, Alexander; Woodman, Geoffrey F et al. (2014) Microcircuitry of agranular frontal cortex: testing the generality of the canonical cortical microcircuit. J Neurosci 34:5355-69

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