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      Ups and downs in catch-up saccades following single-pulse TMS-methodological considerations

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          Abstract

          Transcranial magnetic stimulation (TMS) can interfere with smooth pursuit or with saccades initiated from a fixed position toward a fixed target, but little is known about the effect of TMS on catch-up saccade made to assist smooth pursuit. Here we explored the effect of TMS on catch-up saccades by means of a situation in which the moving target was driven by an external agent, or moved by the participants’ hand, a condition known to decrease the occurrence of catch-up saccade. Two sites of stimulation were tested, the vertex and M1 hand area. Compared to conditions with no TMS, we found a consistent modulation of saccadic activity after TMS such that it decreased at 40-100ms, strongly resumed at 100-160ms, and then decreased at 200-300ms. Despite this modulatory effect, the accuracy of catch-up saccade was maintained, and the mean saccadic activity over the 0-300ms period remained unchanged. Those findings are discussed in the context of studies showing that single-pulse TMS can induce widespread effects on neural oscillations as well as perturbations in the latency of saccades during reaction time protocols. At a more general level, despite challenges and interpretational limitations making uncertain the origin of this modulatory effect, our study provides direct evidence that TMS over presumably non-oculomotor regions interferes with the initiation of catch-up saccades, and thus offers methodological considerations for future studies that wish to investigate the underlying neural circuitry of catch-up saccades using TMS.

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          Recasting the smooth pursuit eye movement system.

          Primates use a combination of smooth pursuit and saccadic eye movements to stabilize the retinal image of selected objects within the high-acuity region near the fovea. Pursuit has traditionally been viewed as a relatively automatic behavior, driven by visual motion signals and mediated by pathways that connect visual areas in the cerebral cortex to motor regions in the cerebellum. However, recent findings indicate that this view needs to be reconsidered. Rather than being controlled primarily by areas in extrastriate cortex specialized for processing visual motion, pursuit involves an extended network of cortical areas, and, of these, the pursuit-related region in the frontal eye fields appears to exert the most direct influence. The traditional pathways through the cerebellum are important, but there are also newly identified routes involving structures previously associated with the control of saccades, including the basal ganglia, the superior colliculus, and nuclei in the brain stem reticular formation. These recent findings suggest that the pursuit system has a functional architecture very similar to that of the saccadic system. This viewpoint provides a new perspective on the processing steps that occur as descending control signals interact with circuits in the brain stem and cerebellum responsible for gating and executing voluntary eye movements. Although the traditional view describes pursuit and saccades as two distinct neural systems, it may be more accurate to consider the two movements as different outcomes from a shared cascade of sensory-motor functions.
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            Synchronization of neuronal activity in the human primary motor cortex by transcranial magnetic stimulation: an EEG study.

            Using multichannel electroencephalography (EEG), we investigated temporal dynamics of the cortical response to transcranial magnetic stimulation (TMS). TMS was applied over the left primary motor cortex (M1) of healthy volunteers, intermixing single suprathreshold pulses with pairs of sub- and suprathreshold pulses and simultaneously recording EEG from 60 scalp electrodes. Averaging of EEG data time locked to the onset of TMS pulses yielded a waveform consisting of a positive peak (30 ms after the pulse P30), followed by two negative peaks [at 45 (N45) and 100 ms]. Peak-to-peak amplitude of the P30-N45 waveform was high, ranging from 12 to 70 microV; in most subjects, the N45 potential could be identified in single EEG traces. Spectral analysis revealed that single-pulse TMS induced a brief period of synchronized activity in the beta range (15-30 Hz) in the vicinity of the stimulation site; again, this oscillatory response was apparent not only in the EEG averages but also in single traces. Both the N45 and the oscillatory response were lower in amplitude in the 12-ms (but not 3-ms) paired-pulse trials, compared with the single-pulse trials. These findings are consistent with the possibility that TMS applied to M1 induces transient synchronization of spontaneous activity of cortical neurons within the 15- to 30-Hz frequency range. As such, they corroborate previous studies of cortical oscillations in the motor cortex and point to the potential of the combined TMS/EEG approach for further investigations of cortical rhythms in the human brain.
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              Frontal eye field, where art thou? Anatomy, function, and non-invasive manipulation of frontal regions involved in eye movements and associated cognitive operations

              The planning, control and execution of eye movements in 3D space relies on a distributed system of cortical and subcortical brain regions. Within this network, the Eye Fields have been described in animals as cortical regions in which electrical stimulation is able to trigger eye movements and influence their latency or accuracy. This review focuses on the Frontal Eye Field (FEF) a “hub” region located in Humans in the vicinity of the pre-central sulcus and the dorsal-most portion of the superior frontal sulcus. The straightforward localization of the FEF through electrical stimulation in animals is difficult to translate to the healthy human brain, particularly with non-invasive neuroimaging techniques. Hence, in the first part of this review, we describe attempts made to characterize the anatomical localization of this area in the human brain. The outcome of functional Magnetic Resonance Imaging (fMRI), Magneto-encephalography (MEG) and particularly, non-invasive mapping methods such a Transcranial Magnetic Stimulation (TMS) are described and the variability of FEF localization across individuals and mapping techniques are discussed. In the second part of this review, we will address the role of the FEF. We explore its involvement both in the physiology of fixation, saccade, pursuit, and vergence movements and in associated cognitive processes such as attentional orienting, visual awareness and perceptual modulation. Finally in the third part, we review recent evidence suggesting the high level of malleability and plasticity of these regions and associated networks to non-invasive stimulation. The exploratory, diagnostic, and therapeutic interest of such interventions for the modulation and improvement of perception in 3D space are discussed.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Funding acquisitionRole: InvestigationRole: MethodologyRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                11 October 2018
                2018
                : 13
                : 10
                : e0205208
                Affiliations
                [001]Aix Marseille University, CNRS, Institut de Neurosciences de la Timone UMR 7289, Marseille, France
                Universita degli Studi di Verona, ITALY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0003-4296-7300
                Article
                PONE-D-18-19448
                10.1371/journal.pone.0205208
                6181330
                30307976
                8e20ef74-4488-47b7-85ee-a43cdd725580
                © 2018 Mathew, Danion

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 June 2018
                : 20 September 2018
                Page count
                Figures: 6, Tables: 0, Pages: 14
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100010665, H2020 Marie Skłodowska-Curie Actions;
                Award ID: 642961
                This work was part of Innovative Training Network 'Perception and Action in Complex Environment' ( http://itn-pace.eu/) that has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement N° 642961. This paper reflects only the authors’ view and that the Research Executive Agency (REA) of the European Commission is not responsible for any use that may be made of the information it contains. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
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                Sensory Physiology
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                Eye Movements
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                All relevant data are available from the Figshare repository at the following DOI: 10.6084/m9.figshare.7137899.

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