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      Mechanisms that allow cortical preparatory activity without inappropriate movement

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          Abstract

          We reveal a novel mechanism that explains how preparatory activity can evolve in motor-related cortical areas without prematurely inducing movement. The smooth eye movement region of the frontal eye fields (FEF SEM) is a critical node in the neural circuit controlling smooth pursuit eye movement. Preparatory activity evolves in the monkey FEF SEM during fixation in parallel with an objective measure of visual-motor gain. We propose that the use of FEF SEM output as a gain signal rather than a movement command allows for preparation to progress in pursuit without causing movement. We also show that preparatory modulation of firing rate in FEF SEM predicts movement, providing evidence against the ‘movement-null’ space hypothesis as an explanation of how preparatory activity can progress without movement. Finally, there is a partial reorganization of FEF SEM population activity between preparation and movement that would allow for a directionally non-specific component of preparatory visual-motor gain enhancement in pursuit.

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          Most cited references60

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          Neural population dynamics during reaching

          Most theories of motor cortex have assumed that neural activity represents movement parameters. This view derives from an analogous approach to primary visual cortex, where neural activity represents patterns of light. Yet it is unclear how well that analogy holds. Single-neuron responses in motor cortex appear strikingly complex, and there is marked disagreement regarding which movement parameters are represented. A better analogy might be with other motor systems, where a common principle is rhythmic neural activity. We found that motor cortex responses during reaching contain a brief but strong oscillatory component, something quite unexpected for a non-periodic behavior. Oscillation amplitude and phase followed naturally from the preparatory state, suggesting a mechanistic role for preparatory neural activity. These results demonstrate unexpected yet surprisingly simple structure in the population response. That underlying structure explains many of the confusing features of individual-neuron responses.
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            Cortical activity in the null space: permitting preparation without movement

            Neural circuits must perform computations and then selectively output the results to other circuits. Yet synapses do not change radically at millisecond timescales. A key question then is: how is communication between neural circuits controlled? In motor control, brain areas directly involved in driving movement are active well before movement begins. Muscle activity is some readout of neural activity, yet remains largely unchanged during preparation. Here we find that during preparation, while the monkey holds still, changes in motor cortical activity cancel out at the level of these population readouts. Motor cortex can thereby prepare the movement without prematurely causing it. Further, we found evidence that this mechanism also operates in dorsal premotor cortex (PMd), largely accounting for how preparatory activity is attenuated in primary motor cortex (M1). Selective use of “output-null” vs. “output-potent” patterns of activity may thus help control communication to the muscles and between these brain areas.
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              The origin of corticospinal projections from the premotor areas in the frontal lobe.

              We determined the origin of corticospinal neurons in the frontal lobe. These neurons were labeled by retrograde transport of tracers after injections into either the dorsolateral funiculus at the second cervical segment or the gray matter of the spinal cord throughout the cervical enlargement. Using retrograde transport of tracer from the arm area of the primary motor cortex, we defined the arm representation in each premotor area in another set of animals. We found that corticospinal projections to cervical segments of the spinal cord originate from the primary motor cortex and from the 6 premotor areas in the frontal lobe. These are the same premotor areas that project directly to the arm area of the primary motor cortex. The premotor areas are located in parts of cytoarchitectonic area 6 on the lateral surface and medial wall of the hemisphere, as well as in subfields of areas 23 and 24 in the cingulate sulcus. The total number of corticospinal neurons in the arm representations of the premotor areas equals or exceeds the total number in the arm representation of the primary motor cortex. The premotor areas collectively comprise more than 60% of the cortical area in the frontal lobe that projects to the spinal cord. Like the primary motor cortex, each of the premotor areas contains local regions that have a high density of corticospinal neurons. These observations indicate that a substantial component of the corticospinal system originates from the premotor areas in the frontal lobe. Each of the premotor areas has direct access to the spinal cord, and as a consequence, each has the potential to influence the generation and control of movement independently of the primary motor cortex. These findings raise serious questions about the utility of viewing the primary motor cortex as the "upper motoneuron" or "final common pathway" for the central control of movement.
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                Author and article information

                Contributors
                Role: Reviewing Editor
                Role: Senior Editor
                Journal
                eLife
                Elife
                eLife
                eLife
                eLife Sciences Publications, Ltd
                2050-084X
                21 February 2020
                2020
                : 9
                : e50962
                Affiliations
                [1]Department of Neurobiology, Duke University School of Medicine DurhamUnited States
                Peking University China
                University of Pennsylvania United States
                Peking University China
                UC Davis United States
                Author information
                https://orcid.org/0000-0001-5534-7552
                http://orcid.org/0000-0001-7859-4361
                Article
                50962
                10.7554/eLife.50962
                7060051
                32081130
                4b397073-a993-42f7-a3e5-92daa2deaeaf
                © 2020, Darlington and Lisberger

                This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.

                History
                : 08 August 2019
                : 20 February 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: R01-EY027373
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: F30-EY027684
                Award Recipient :
                The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
                Categories
                Research Article
                Neuroscience
                Custom metadata
                The use of preparatory activity in the smooth eye movement region of the frontal eye fields as a visual-motor gain signal allows preparation to progress without inappropriate movement.

                Life sciences
                motor preparation,pursuit eye movements,visual-motor gain,frontal eye fields,rhesus macaque

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