Noninvasive extraction of microsecond‐scale dynamics from human motor cortex

State‐of‐the‐art noninvasive electromagnetic recording techniques allow observing neuronal dynamics down to the millisecond scale. Direct measurement of faster events has been limited to in vitro or invasive recordings. To overcome this limitation, we introduce a new paradigm for transcranial magnetic stimulation. We adjusted the stimulation waveform on the microsecond scale, by varying the duration between the positive and negative phase of the induced electric field, and studied corresponding changes in the elicited motor responses. The magnitude of the electric field needed for given motor‐evoked potential amplitude decreased exponentially as a function of this duration with a time constant of 17 µs. Our indirect noninvasive measurement paradigm allows studying neuronal kinetics on the microsecond scale in vivo.

[1]  Shoogo Ueno,et al.  Experimental And Modeling Studies On Properties Of Nerve Excitation Elicited By Magnetic Stimulation , 1991, Proceedings of the Annual International Conference of the IEEE Engineering in Medicine and Biology Society Volume 13: 1991.

[2]  Ljubomir Manola,et al.  Anodal vs cathodal stimulation of motor cortex: A modeling study , 2007, Clinical Neurophysiology.

[3]  M. Volgushev,et al.  Unique features of action potential initiation in cortical neurons , 2006, Nature.

[4]  B. Bean The action potential in mammalian central neurons , 2007, Nature Reviews Neuroscience.

[5]  G. Baranauskas,et al.  Sodium Currents Activate without a Hodgkin and Huxley-Type Delay in Central Mammalian Neurons , 2006, The Journal of Neuroscience.

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

[7]  Aapo Nummenmaa,et al.  Comparison of spherical and realistically shaped boundary element head models for transcranial magnetic stimulation navigation , 2013, Clinical Neurophysiology.

[8]  Seppo Kähkönen,et al.  The effect of stimulus intensity on brain responses evoked by transcranial magnetic stimulation , 2004, Human brain mapping.

[9]  B. Bromm,et al.  Numerical calculation of the response in the myelinated nerve to short symmetrical double pulses , 2004, Pflüger's Archiv für die gesamte Physiologie des Menschen und der Tiere.

[10]  G. Crevecoeur,et al.  Modeling transcranial magnetic stimulation from the induced electric fields to the membrane potentials along tractography-based white matter fiber tracts , 2016, Journal of neural engineering.

[11]  Lari M. Koponen,et al.  Experimental Characterization of the Electric Field Distribution Induced by TMS Devices , 2015, Brain Stimulation.

[12]  R Horn,et al.  Statistical properties of single sodium channels , 1984, The Journal of general physiology.

[13]  Jan Wouters,et al.  Effect of inter-phase gap on the sensitivity of cochlear implant users to electrical stimulation , 2005, Hearing Research.

[14]  S. Lisanby,et al.  Pulse width dependence of motor threshold and input–output curve characterized with controllable pulse parameter transcranial magnetic stimulation , 2013, Clinical Neurophysiology.

[15]  J. Rothwell,et al.  Effect of coil orientation on strength–duration time constant and I-wave activation with controllable pulse parameter transcranial magnetic stimulation , 2016, Clinical Neurophysiology.

[16]  W. Paulus,et al.  Half sine, monophasic and biphasic transcranial magnetic stimulation of the human motor cortex , 2006, Clinical Neurophysiology.

[17]  Alfred L George,et al.  Inherited disorders of voltage-gated sodium channels. , 2005, The Journal of clinical investigation.

[18]  E. Javel,et al.  Electrical stimulation of the auditory nerve: II. Effect of stimulus waveshape on single fibre response properties , 1999, Hearing Research.

[19]  Massimo Mantegazza,et al.  Voltage-gated sodium channels as therapeutic targets in epilepsy and other neurological disorders , 2010, The Lancet Neurology.

[20]  G. Curio,et al.  Ultra-low-noise EEG/MEG systems enable bimodal non-invasive detection of spike-like human somatosensory evoked responses at 1 kHz , 2015, Physiological measurement.

[21]  S. Ueno,et al.  The Property of Nerve Excitation Elicited by Magnetic Stimulation of Peripheral Nerve , 1993, IEEE Translation Journal on Magnetics in Japan.

[22]  Matti Stenroos,et al.  A Matlab library for solving quasi-static volume conduction problems using the boundary element method , 2007, Comput. Methods Programs Biomed..

[23]  U. Ziemann,et al.  Hysteresis effects on the input–output curve of motor evoked potentials , 2009, Clinical Neurophysiology.

[24]  Colette M. McKay,et al.  The perceptual effects of interphase gap duration in cochlear implant stimulation , 2003, Hearing Research.

[25]  C. F. Stevens,et al.  A reinterpretation of mammalian sodium channel gating based on single channel recording , 1983, Nature.

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

[27]  H. Siebner,et al.  The Role of Pulse Shape in Motor Cortex Transcranial Magnetic Stimulation Using Full-Sine Stimuli , 2014, PloS one.

[28]  A. Vincent,et al.  Autoimmune Channelopathies and Related Neurological Disorders , 2006, Neuron.

[29]  Garnham Cw,et al.  Magnetic nerve stimulation: the effect of waveform on efficiency, determination of neural membrane time constants and the measurement of stimulator output. , 1991 .

[30]  R. J. Ilmoniemi,et al.  Prefrontal transcranial magnetic stimulation produces intensity-dependent EEG responses in humans , 2005, NeuroImage.

[31]  J. Mortimer,et al.  The Effect of Stimulus Parameters on the Recruitment Characteristics of Direct Nerve Stimulation , 1983, IEEE Transactions on Biomedical Engineering.

[32]  D. Schaefer,et al.  Comparison Of Rectangular And Damped Sinusoidal dB/dt Waveforms In Magnetic Stimulation , 1997, IEEE International Magnetics Conference.

[33]  R. Salvador Numerical modelling in transcranial magnetic stimulation , 2009 .

[34]  Matti Stenroos,et al.  Coil optimisation for transcranial magnetic stimulation in realistic head geometry , 2017, Brain Stimulation.

[35]  J. Holsheimer,et al.  A model of the electrical behaviour of myelinated sensory nerve fibres based on human data , 1999, Medical & Biological Engineering & Computing.

[36]  A T Barker,et al.  Magnetic nerve stimulation: the effect of waveform on efficiency, determination of neural membrane time constants and the measurement of stimulator output. , 1991, Electroencephalography and clinical neurophysiology. Supplement.

[37]  A T Barker,et al.  Transcranial magnetic stimulation. Which part of the current waveform causes the stimulation? , 2001, Experimental brain research.

[38]  J. Reilly Peripheral nerve stimulation by induced electric currents: Exposure to time-varying magnetic fields , 1989, Medical and Biological Engineering and Computing.

[39]  D. Durand,et al.  Effects of induced electric fields on finite neuronal structures: a simulation study , 1993, IEEE Transactions on Biomedical Engineering.

[40]  P. Jonas,et al.  Functional differences in Na+ channel gating between fast‐spiking interneurones and principal neurones of rat hippocampus , 1997, The Journal of physiology.

[41]  J. Thomas Mortimer,et al.  The response of the myelinated nerve fiber to short duration biphasic stimulating currents , 2006, Annals of Biomedical Engineering.