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      Neural effects of transcranial magnetic stimulation at the single-cell level

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          Abstract

          Transcranial magnetic stimulation (TMS) can non-invasively modulate neural activity in humans. Despite three decades of research, the spatial extent of the cortical area activated by TMS is still controversial. Moreover, how TMS interacts with task-related activity during motor behavior is unknown. Here, we applied single-pulse TMS over macaque parietal cortex while recording single-unit activity at various distances from the center of stimulation during grasping. The spatial extent of TMS-induced activation is remarkably restricted, affecting the spiking activity of single neurons in an area of cortex measuring less than 2 mm in diameter. In task-related neurons, TMS evokes a transient excitation followed by reduced activity, paralleled by a significantly longer grasping time. Furthermore, TMS-induced activity and task-related activity do not summate in single neurons. These results furnish crucial experimental evidence for the neural effects of TMS at the single-cell level and uncover the neural underpinnings of behavioral effects of TMS.

          Abstract

          Transcranial Magnetic Stimulation (TMS) can modulate human brain activity, but the extent of the cortical area activated by TMS is unclear. Here, the authors show that TMS affects monkey single neuron activity in an area less than 2 mm diameter, while TMS-induced activity and task-related activity do not summate.

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          Breakdown of cortical effective connectivity during sleep.

          When we fall asleep, consciousness fades yet the brain remains active. Why is this so? To investigate whether changes in cortical information transmission play a role, we used transcranial magnetic stimulation together with high-density electroencephalography and asked how the activation of one cortical area (the premotor area) is transmitted to the rest of the brain. During quiet wakefulness, an initial response (approximately 15 milliseconds) at the stimulation site was followed by a sequence of waves that moved to connected cortical areas several centimeters away. During non-rapid eye movement sleep, the initial response was stronger but was rapidly extinguished and did not propagate beyond the stimulation site. Thus, the fading of consciousness during certain stages of sleep may be related to a breakdown in cortical effective connectivity.
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            Natural frequencies of human corticothalamic circuits.

            The frequency tuning of a system can be directly determined by perturbing it and by observing the rate of the ensuing oscillations, the so called natural frequency. This approach is used, for example, in physics, in geology, and also when one tunes a musical instrument. In the present study, we employ transcranial magnetic stimulation (TMS) to directly perturb a set of selected corticothalamic modules (Brodmann areas 19, 7, and 6) and high-density electroencephalogram to measure their natural frequency. TMS consistently evoked dominant alpha-band oscillations (8-12 Hz) in the occipital cortex, beta-band oscillations (13-20 Hz) in the parietal cortex, and fast beta/gamma-band oscillations (21-50 Hz) in the frontal cortex. Each cortical area tended to preserve its own natural frequency also when indirectly engaged by TMS through brain connections and when stimulated at different intensities, indicating that the observed oscillations reflect local physiological mechanisms. These findings were reproducible across individuals and represent the first direct characterization of the coarse electrophysiological properties of three associative areas of the human cerebral cortex. Most importantly, they indicate that, in healthy subjects, each corticothalamic module is normally tuned to oscillate at a characteristic rate. The natural frequency can be directly measured in virtually any area of the cerebral cortex and may represent a straightforward and flexible way to probe the state of human thalamocortical circuits at the patient's bedside.
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              Noninvasive human brain stimulation.

              Noninvasive brain stimulation with transcranial magnetic stimulation (TMS) or transcranial direct current stimulation (tDCS) is valuable in research and has potential therapeutic applications in cognitive neuroscience, neurophysiology, psychiatry, and neurology. TMS allows neurostimulation and neuromodulation, while tDCS is a purely neuromodulatory application. TMS and tDCS allow diagnostic and interventional neurophysiology applications, and focal neuropharmacology delivery. However, the physics and basic mechanisms of action remain incompletely explored. Following an overview of the history and current applications of noninvasive brain stimulation, we review stimulation device design principles, the electromagnetic and physical foundations of the techniques, and the current knowledge about the electrophysiologic basis of the effects. Finally, we discuss potential biomedical and electrical engineering developments that could lead to more effective stimulation devices, better suited for the specific applications.
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                Author and article information

                Contributors
                mela.romeropita@kuleuven.be
                marco.davare@kuleuven.be
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                14 June 2019
                14 June 2019
                2019
                : 10
                : 2642
                Affiliations
                [1 ]ISNI 0000 0001 0668 7884, GRID grid.5596.f, Laboratorium voor Neuro- en Psychofysiologie, Katholieke Universiteit Leuven, ; Leuven, Belgium
                [2 ]ISNI 0000 0001 0668 7884, GRID grid.5596.f, Onderzoeksgroep Bewegingscontrole & Neuroplasticiteit, Katholieke Universiteit Leuven, ; Leuven, Belgium
                [3 ]ISNI 0000 0001 0668 7884, GRID grid.5596.f, Leuven Brain Institute, Katholieke Universiteit Leuven, ; Leuven, Belgium
                Author information
                http://orcid.org/0000-0002-7905-1104
                Article
                10638
                10.1038/s41467-019-10638-7
                6572776
                31201331
                220a28dc-4253-470e-8733-e745f98bdc02
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 21 August 2018
                : 17 May 2019
                Funding
                Funded by: Fonds voor Wetenschappelijk Onderzoek Vlaanderen, Odysseus (G.0007.12), and Program Financing (PFV10/008)
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                transcranial magnetic stimulation,cellular neuroscience,cognitive neuroscience,neuronal physiology

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