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      Phase Dependency of the Human Primary Motor Cortex and Cholinergic Inhibition Cancelation During Beta tACS

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          Abstract

          The human motor cortex has a tendency to resonant activity at about 20 Hz so stimulation should more readily entrain neuronal populations at this frequency. We investigated whether and how different interneuronal circuits contribute to such resonance by using transcranial magnetic stimulation (TMS) during transcranial alternating current stimulation (tACS) at motor (20 Hz) and a nonmotor resonance frequency (7 Hz). We tested different TMS interneuronal protocols and triggered TMS pulses at different tACS phases. The effect of cholinergic short-latency afferent inhibition (SAI) was abolished by 20 Hz tACS, linking cortical beta activity to sensorimotor integration. However, this effect occurred regardless of the tACS phase. In contrast, 20 Hz tACS selectively modulated MEP size according to the phase of tACS during single pulse, GABAAergic short-interval intracortical inhibition (SICI) and glutamatergic intracortical facilitation (ICF). For SICI this phase effect was more marked during 20 Hz stimulation. Phase modulation of SICI also depended on whether or not spontaneous beta activity occurred at ~20 Hz, supporting an interaction effect between tACS and underlying circuit resonances. The present study provides in vivo evidence linking cortical beta activity to sensorimotor integration, and for beta oscillations in motor cortex being promoted by resonance in GABAAergic interneuronal circuits.

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          Synaptic plasticity: multiple forms, functions, and mechanisms.

          Experiences, whether they be learning in a classroom, a stressful event, or ingestion of a psychoactive substance, impact the brain by modifying the activity and organization of specific neural circuitry. A major mechanism by which the neural activity generated by an experience modifies brain function is via modifications of synaptic transmission; that is, synaptic plasticity. Here, we review current understanding of the mechanisms of the major forms of synaptic plasticity at excitatory synapses in the mammalian brain. We also provide examples of the possible developmental and behavioral functions of synaptic plasticity and how maladaptive synaptic plasticity may contribute to neuropsychiatric disorders.
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            Entrainment of brain oscillations by transcranial alternating current stimulation.

            Novel methods for neuronal entrainment [1-4] provide the unique opportunity to modulate perceptually relevant brain oscillations [5, 6] in a frequency-specific manner and to study their functional impact on distinct cognitive functions. Recently, evidence has emerged that tACS (transcranial alternating current stimulation) can modulate cortical oscillations [7-9]. However, the study of electrophysiological effects has been hampered so far by the absence of concurrent electroencephalogram (EEG) recordings. Here, we applied 10 Hz tACS to the parieto-occipital cortex and utilized simultaneous EEG recordings to study neuronal entrainment during stimulation. We pioneer a novel approach for simultaneous tACS-EEG recordings and successfully separate stimulation artifacts from ongoing and event-related cortical activity. Our results reveal that 10 Hz tACS increases parieto-occipital alpha activity and synchronizes cortical oscillators with similar intrinsic frequencies to the entrainment frequency. Additionally, we demonstrate that tACS modulates target detection performance in a phase-dependent fashion highlighting the causal role of alpha oscillations for visual perception. Copyright © 2014 Elsevier Ltd. All rights reserved.
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              Transcranial Alternating Current Stimulation Enhances Individual Alpha Activity in Human EEG

              Non-invasive electrical stimulation of the human cortex by means of transcranial direct current stimulation (tDCS) has been instrumental in a number of important discoveries in the field of human cortical function and has become a well-established method for evaluating brain function in healthy human participants. Recently, transcranial alternating current stimulation (tACS) has been introduced to directly modulate the ongoing rhythmic brain activity by the application of oscillatory currents on the human scalp. Until now the efficiency of tACS in modulating rhythmic brain activity has been indicated only by inference from perceptual and behavioural consequences of electrical stimulation. No direct electrophysiological evidence of tACS has been reported. We delivered tACS over the occipital cortex of 10 healthy participants to entrain the neuronal oscillatory activity in their individual alpha frequency range and compared results with those from a separate group of participants receiving sham stimulation. The tACS but not the sham stimulation elevated the endogenous alpha power in parieto-central electrodes of the electroencephalogram. Additionally, in a network of spiking neurons, we simulated how tACS can be affected even after the end of stimulation. The results show that spike-timing-dependent plasticity (STDP) selectively modulates synapses depending on the resonance frequencies of the neural circuits that they belong to. Thus, tACS influences STDP which in turn results in aftereffects upon neural activity. The present findings are the first direct electrophysiological evidence of an interaction of tACS and ongoing oscillatory activity in the human cortex. The data demonstrate the ability of tACS to specifically modulate oscillatory brain activity and show its potential both at fostering knowledge on the functional significance of brain oscillations and for therapeutic application.
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                Author and article information

                Journal
                Cereb Cortex
                Cereb. Cortex
                cercor
                cercor
                Cerebral Cortex (New York, NY)
                Oxford University Press
                1047-3211
                1460-2199
                October 2016
                19 September 2016
                19 September 2016
                : 26
                : 10
                : 3977-3990
                Affiliations
                [1 ]Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, University Campus Bio-Medico , 00128 Rome, Italy
                [2 ]Medical Research Council Brain Network Dynamics Unit, Nuffield Department of Clinical Neurosciences, University of Oxford , Oxford OX3 9DU, UK
                [3 ]Department of Clinical Neurophysiology, Kuopio University Hospital, University of Eastern Finland , Kuopio FIN-70100, Finland
                Author notes
                [†]

                Andrea Guerra and Alek Pogosyan have contributed equally to this work

                Address correspondence to Prof. Peter Brown, Medical Research Council Brain Network Dynamics Unit and Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford OX1 3TH, UK. E-mail: peter.brown@ 123456ndcn.ox.ac.uk ; Prof. Vincenzo Di Lazzaro, Unit of Neurology, Neurophysiology, Neurobiology, Department of Medicine, University Campus Bio-Medico, via Álvaro del Portillo 21, 00128 Rome, Italy. Email: v.dilazzaro@ 123456unicampus.it .
                Article
                bhw245
                10.1093/cercor/bhw245
                5028010
                27522077
                1a0d74ab-1a64-46ab-b956-b90aa4b4a1ee
                © The Author 2016. Published by Oxford University Press.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 16 July 2016
                : 14 June 2016
                : 13 July 2016
                Page count
                Pages: 14
                Categories
                Original Articles

                Neurology
                beta,phase,sai, tacs,tms
                Neurology
                beta, phase, sai, tacs, tms

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