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

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.

[1]  M. Nitsche,et al.  The Importance of Timing in Segregated Theta Phase-Coupling for Cognitive Performance , 2012, Current Biology.

[2]  D. McCormick,et al.  Endogenous Electric Fields May Guide Neocortical Network Activity , 2010, Neuron.

[3]  Gregor Thut,et al.  Alpha Power Increase After Transcranial Alternating Current Stimulation at Alpha Frequency (α-tACS) Reflects Plastic Changes Rather Than Entrainment , 2015, Brain Stimulation.

[4]  B. Hille.  Ionic channels of excitable membranes , 2001 .

[5]  L. Parra,et al.  Effects of weak transcranial alternating current stimulation on brain activity—a review of known mechanisms from animal studies , 2013, Front. Hum. Neurosci..

[6]  P. Brown,et al.  Post-Movement Beta Activity in Sensorimotor Cortex Indexes Confidence in the Estimations from Internal Models , 2016, The Journal of Neuroscience.

[7]  C. Herrmann,et al.  Transcranial Alternating Current Stimulation Enhances Individual Alpha Activity in Human EEG , 2010, PloS one.

[8]  D. Feldmeyer,et al.  Cholinergic filtering in the recurrent excitatory microcircuit of cortical layer 4 , 2009, Proceedings of the National Academy of Sciences.

[9]  K. Chiappa,et al.  Variability of motor potentials evoked by transcranial magnetic stimulation. , 1993, Electroencephalography and clinical neurophysiology.

[10]  C. Marsden,et al.  Corticocortical inhibition in human motor cortex. , 1993, The Journal of physiology.

[11]  A. Antal,et al.  Transcranial alternating current stimulation (tACS) , 2013, Front. Hum. Neurosci..

[12]  B. Nolan.  Boosting slow oscillations during sleep potentiates memory , 2008 .

[13]  L. Parra,et al.  Low-Intensity Electrical Stimulation Affects Network Dynamics by Modulating Population Rate and Spike Timing , 2010, The Journal of Neuroscience.

[14]  Ulf Ziemann,et al.  The role of GABA(B) receptors in intracortical inhibition in the human motor cortex. , 2006, Experimental brain research.

[15]  Timothy P. L. Roberts,et al.  Relating MEG measured motor cortical oscillations to resting γ-Aminobutyric acid (GABA) concentration , 2011, NeuroImage.

[16]  A. Engel,et al.  Beta-band oscillations—signalling the status quo? , 2010, Current Opinion in Neurobiology.

[17]  Mikko Pohja,et al.  On the human sensorimotor-cortex beta rhythm: Sources and modeling , 2005, NeuroImage.

[18]  P. Bria,et al.  Segregating two inhibitory circuits in human motor cortex at the level of GABAA receptor subtypes: A TMS study , 2007, Clinical Neurophysiology.

[19]  Ulf Ziemann,et al.  Interference of short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF) , 2008, Clinical Neurophysiology.

[20]  Vincenzo Di Lazzaro,et al.  The contribution of transcranial magnetic stimulation in the functional evaluation of microcircuits in human motor cortex , 2013, Front. Neural Circuits.

[21]  Ernst Fernando Lopes Da Silva Niedermeyer,et al.  Electroencephalography, basic principles, clinical applications, and related fields , 1982 .

[22]  D. Schutter,et al.  Brain oscillations and frequency-dependent modulation of cortical excitability , 2011, Brain Stimulation.

[23]  J. C. Rothwell,et al.  Magnetic stimulation : motor evoked potentials , 2010 .

[24]  S. Thorpe,et al.  Spike times make sense , 2005, Trends in Neurosciences.

[25]  S. Rossi,et al.  Frequency-Dependent Tuning of the Human Motor System Induced by Transcranial Oscillatory Potentials , 2011, The Journal of Neuroscience.

[26]  Bruce R. Rosen,et al.  Parallel input makes the brain run faster , 2008, NeuroImage.

[27]  Paolo Maria Rossini,et al.  Human brain cortical correlates of short-latency afferent inhibition: a combined EEG-TMS study. , 2012, Journal of neurophysiology.

[28]  Paul L. Furlong,et al.  The Role of Gabaergic Modulation in Motor Function Related Neuronal Network Activity the Role of Gabaergic Modulation in Motor Function Related Neuronal Network Activity , 2022 .

[29]  G. Karmos,et al.  Transient cortical excitation at the onset of visual fixation. , 2008, Cerebral cortex.

[30]  C. Herrmann,et al.  Finite-Element Model Predicts Current Density Distribution for Clinical Applications of tDCS and tACS , 2012, Front. Psychiatry.

[31]  Synnöve Carlson,et al.  Electrophysiological correlates of short-latency afferent inhibition: a combined EEG and TMS study , 2009, Experimental Brain Research.

[32]  Esa Mervaala,et al.  Comparison of navigated and non-navigated transcranial magnetic stimulation for motor cortex mapping, motor threshold and motor evoked potentials , 2009, NeuroImage.

[33]  Fabrizio Vecchio,et al.  Time‐varying coupling of EEG oscillations predicts excitability fluctuations in the primary motor cortex as reflected by motor evoked potentials amplitude: An EEG‐TMS study , 2014, Human brain mapping.

[34]  P. Pasqualetti,et al.  Unilateral cortical hyperexcitability in congenital hydrocephalus: A TMS study , 2014, Neurocase.

[35]  A. Zador,et al.  Balanced inhibition underlies tuning and sharpens spike timing in auditory cortex , 2003, Nature.

[36]  M. Massimini,et al.  Natural Frequencies of Human Corticothalamic Circuits , 2009, The Journal of Neuroscience.

[37]  Sean M Montgomery,et al.  Entrainment of Neocortical Neurons and Gamma Oscillations by the Hippocampal Theta Rhythm , 2008, Neuron.

[38]  R. Hari,et al.  Human cortical oscillations: a neuromagnetic view through the skull , 1997, Trends in Neurosciences.

[39]  J. Rothwell,et al.  Corticospinal activity evoked and modulated by non‐invasive stimulation of the intact human motor cortex , 2014, The Journal of physiology.

[40]  K J Werhahn,et al.  Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans , 1999, The Journal of physiology.

[41]  A. Engel,et al.  Entrainment of Brain Oscillations by Transcranial Alternating Current Stimulation , 2014, Current Biology.

[42]  Peter Brown,et al.  Existing Motor State Is Favored at the Expense of New Movement during 13-35 Hz Oscillatory Synchrony in the Human Corticospinal System , 2005, The Journal of Neuroscience.

[43]  R. C. Oldfield.  The assessment and analysis of handedness: the Edinburgh inventory. , 1971, Neuropsychologia.

[44]  G. Barnes,et al.  Neuronal network pharmacodynamics of GABAergic modulation in the human cortex determined using pharmaco‐magnetoencephalography , 2009, Human brain mapping.

[45]  J. Rothwell,et al.  Interaction between intracortical inhibition and facilitation in human motor cortex. , 1996, The Journal of physiology.

[46]  Juliann M. Mellin,et al.  ranscranial direct current stimulation ( tDCS ) of frontal cortex ecreases performance on the WAIS-IV intelligence test , 2015 .

[47]  Robert Chen,et al.  Interactions between two different inhibitory systems in the human motor cortex , 2001, The Journal of physiology.

[48]  N. Davey,et al.  Variability in the amplitude of skeletal muscle responses to magnetic stimulation of the motor cortex in man. , 1998, Electroencephalography and clinical neurophysiology.

[49]  C T White,et al.  Perceived Number and Evoked Cortical Potentials , 1967, Science.

[50]  P. Derambure,et al.  Does post-movement beta synchronization reflect an idling motor cortex? , 2001, Neuroreport.

[51]  Emiliano Santarnecchi,et al.  State-Dependent Effects of Transcranial Oscillatory Currents on the Motor System: What You Think Matters , 2013, The Journal of Neuroscience.

[52]  Tipu Z. Aziz,et al.  Driving Oscillatory Activity in the Human Cortex Enhances Motor Performance , 2012, Current Biology.

[53]  S. Schiff,et al.  Sensitivity of Neurons to Weak Electric Fields , 2003, The Journal of Neuroscience.

[54]  P. Rossini,et al.  Magnetic stimulation: motor evoked potentials. The International Federation of Clinical Neurophysiology. , 1999, Electroencephalography and clinical neurophysiology. Supplement.

[55]  M. Scanziani,et al.  Instantaneous Modulation of Gamma Oscillation Frequency by Balancing Excitation with Inhibition , 2009, Neuron.

[56]  Timothy H. Muller,et al.  Individual differences and specificity of prefrontal gamma frequency-tACS on fluid intelligence capabilities , 2016, Cortex.

[57]  William D. Penny,et al.  Causal evidence that intrinsic beta-frequency is relevant for enhanced signal propagation in the motor system as shown through rhythmic TMS , 2016, NeuroImage.

[58]  J. Rothwell,et al.  Short latency inhibition of human hand motor cortex by somatosensory input from the hand , 2000, The Journal of physiology.

[59]  Carsten H. Wolters,et al.  Good vibrations: Oscillatory phase shapes perception , 2012, NeuroImage.

[60]  P. Derambure,et al.  Post-movement beta synchronization in subjects presenting with sensory deafferentation , 2008, Clinical Neurophysiology.

[61]  F. Wendling,et al.  From Oscillatory Transcranial Current Stimulation to Scalp EEG Changes: A Biophysical and Physiological Modeling Study , 2013, PloS one.

[62]  J. Artieda,et al.  Beta electroencephalograph changes during passive movements: sensory afferences contribute to beta event-related desynchronization in humans , 2002, Neuroscience Letters.

[63]  J. Rothwell,et al.  Noninvasive in vivo assessment of cholinergic cortical circuits in AD using transcranial magnetic stimulation , 2002, Neurology.

[64]  Vincent Walsh,et al.  Frequency-Dependent Electrical Stimulation of the Visual Cortex , 2008, Current Biology.

[65]  J. Rothwell,et al.  Direct demonstration of long latency cortico-cortical inhibition in normal subjects and in a patient with vascular parkinsonism , 2002, Clinical Neurophysiology.

[66]  B. McNaughton,et al.  Paradoxical Effects of External Modulation of Inhibitory Interneurons , 1997, The Journal of Neuroscience.

[67]  Nicholas J. Priebe,et al.  Mechanisms underlying cross-orientation suppression in cat visual cortex , 2006, Nature Neuroscience.

[68]  S. Rossi,et al.  Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research , 2009, Clinical Neurophysiology.

[69]  Ryota Kanai,et al.  Frequency Specific Modulation of Human Somatosensory Cortex , 2011, Front. Psychology.

[70]  Laura E. Matzen,et al.  Frequency-Dependent Enhancement of Fluid Intelligence Induced by Transcranial Oscillatory Potentials , 2013, Current Biology.

[71]  S. Rossi,et al.  Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee , 2015, Clinical Neurophysiology.

[72]  J. Rothwell,et al.  Muscarinic receptor blockade has differential effects on the excitability of intracortical circuits in the human motor cortex , 2000, Experimental Brain Research.

[73]  R. Malenka,et al.  Synaptic Plasticity: Multiple Forms, Functions, and Mechanisms , 2008, Neuropsychopharmacology.

[74]  Giulio Tononi,et al.  Human brain connectivity during single and paired pulse transcranial magnetic stimulation , 2011, NeuroImage.

[75]  Li I. Zhang,et al.  Broad Inhibition Sharpens Orientation Selectivity by Expanding Input Dynamic Range in Mouse Simple Cells , 2011, Neuron.

[76]  C. Gerloff,et al.  Spontaneous locally restricted EEG alpha activity determines cortical excitability in the motor cortex , 2009, Neuropsychologia.

[77]  John-Stuart Brittain,et al.  Montage Matters: The Influence of Transcranial Alternating Current Stimulation on Human Physiological Tremor , 2015, Brain Stimulation.

[78]  A. Strafella,et al.  TMS and drugs revisited 2014 , 2015, Clinical Neurophysiology.

[79]  Shozo Tobimatsu,et al.  Steady-state vibration somatosensory evoked potentials: physiological characteristics and tuning function , 1999, Clinical Neurophysiology.

[80]  J. Nielsen.  Improvement of amplitude variability of motor evoked potentials in multiple sclerosis patients and in healthy subjects. , 1996, Electroencephalography and clinical neurophysiology.

[81]  M. Tegenthoff,et al.  The glutamate antagonist Riluzole suppresses intracortical facilitation , 2005, Journal of Neural Transmission.

[82]  Simone Rossi,et al.  Optically tracked neuronavigation increases the stability of hand-held focal coil positioning: Evidence from “transcranial” magnetic stimulation-induced electrical field measurements , 2008, Brain Stimulation.

[83]  M. Hallett,et al.  Human motor evoked responses to paired transcranial magnetic stimuli. , 1992, Electroencephalography and clinical neurophysiology.

[84]  J. Ruppersberg.  Ion Channels in Excitable Membranes , 1996 .

[85]  Giacomo Koch,et al.  Ongoing cumulative effects of single TMS pulses on corticospinal excitability: An intra- and inter-block investigation , 2016, Clinical Neurophysiology.

[86]  C. Koch,et al.  Transcranial Electric Stimulation Entrains Cortical Neuronal Populations in Rats , 2010, The Journal of Neuroscience.

[87]  Perceived number and evoked cortical potentials. , 1968 .

[88]  M. Bonnard,et al.  Cortical mechanisms underlying stretch reflex adaptation to intention: A combined EEG–TMS study , 2010, NeuroImage.

[89]  Michael Okun,et al.  Instantaneous correlation of excitation and inhibition during ongoing and sensory-evoked activities , 2008, Nature Neuroscience.

[90]  Peter Brown,et al.  Boosting Cortical Activity at Beta-Band Frequencies Slows Movement in Humans , 2009, Current Biology.

[91]  L. Cohen,et al.  Transcranial direct current stimulation: State of the art 2008 , 2008, Brain Stimulation.

[92]  G. Buzsáki,et al.  Neuronal Oscillations in Cortical Networks , 2004, Science.

[93]  P. Pasqualetti,et al.  Cortical inhibition and excitation by bilateral transcranial alternating current stimulation. , 2015, Restorative neurology and neuroscience.

[94]  H. Tsuji,et al.  Intracortical facilitation and inhibition after transcranial magnetic stimulation in conscious humans. , 1997, The Journal of physiology.

[95]  David J. Nutt,et al.  The effects of elevated endogenous GABA levels on movement-related network oscillations , 2013, NeuroImage.

[96]  Lars Riecke,et al.  4-Hz Transcranial Alternating Current Stimulation Phase Modulates Hearing , 2015, Brain Stimulation.

[97]  J. Rothwell,et al.  The physiological basis of transcranial motor cortex stimulation in conscious humans , 2004, Clinical Neurophysiology.