The neural response to transcranial magnetic stimulation of the human motor cortex. I. Intracortical and cortico-cortical contributions

We investigated the properties of the neural response to transcranial magnetic stimulation (TMS) applied over the human primary motor cortex. Consistent with our previous findings, single pulses of TMS induce a characteristic negative deflection at 45 ms (N45) and a transient oscillation in the beta frequency-range (15–30 Hz), as measured using electroencephalograpy (EEG). Here we show the relative specificity of the beta oscillation and the N45; both are stronger when elicited by stimulation applied over the primary motor cortex, as compared with stimulation over the dorsal premotor cortex. We also provide a quantitative analysis of the beta responses to single pulses of TMS and show that the responses are highly phaselocked to the TMS pulses within single subjects; this phaselocking is similar from subject to subject. A single pulse of TMS applied over the primary motor cortex thus appears to reset the ongoing oscillations of the neurons, bringing them transiently into synchrony. Finally, we examine the effect of local or distal modulation of the excitability of the primary motor cortex on the beta oscillation and the N45 in response to single-pulse TMS. We applied low-frequency subthreshold repetitive TMS either over the primary motor cortex (local modulation) or, on a separate day, over the dorsal premotor cortex (distal modulation). The modulation was evaluated with single suprathreshold test pulses of TMS applied over the primary motor cortex before and after the subthreshold low-frequency rTMS. We recorded the EEG response throughout the testing session, i.e. to both the subthreshold and the suprathreshold pulses. After repetitive TMS applied over the primary motor cortex, but not the dorsal premotor cortex, the amplitude of the N45 in response to suprathreshold pulses tended to decrease (not significant), and subsequently increased (significant); neither type of repetitive TMS affected the amplitude of the beta oscillation. We conclude that (1) the N45 depends on circuits intrinsic to the primary motor cortex; (2) the beta oscillation is specific to stimulation of the primary motor cortex, but is not affected by modulation of either cortical area and; (3) the beta oscillatory response to pulses of TMS arises from resetting of ongoing oscillations rather than their induction.

[1]  Erol Başar,et al.  EEG responses to combined somatosensory and transcranial magnetic stimulation , 2001, Clinical Neurophysiology.

[2]  Abbas F. Sadikot,et al.  The neural response to transcranial magnetic stimulation of the human motor cortex. II. Thalamocortical contributions , 2006, Experimental Brain Research.

[3]  Erol Başar,et al.  Brain oscillations : principles and approaches , 1998 .

[4]  V. Nikouline,et al.  The role of the coil click in TMS assessed with simultaneous EEG , 1999, Clinical Neurophysiology.

[5]  Giorgio Fuggetta,et al.  Modulation of cortical oscillatory activities induced by varying single-pulse transcranial magnetic stimulation intensity over the left primary motor area: A combined EEG and TMS study , 2005, NeuroImage.

[6]  Karl J. Friston,et al.  Regional cerebral blood flow during voluntary arm and hand movements in human subjects. , 1991, Journal of neurophysiology.

[7]  M. Hallett,et al.  Responses to rapid-rate transcranial magnetic stimulation of the human motor cortex. , 1994, Brain : a journal of neurology.

[8]  M. Hallett,et al.  Effects of low-frequency transcranial magnetic stimulation on motor excitability and basic motor behavior , 2000, Clinical Neurophysiology.

[9]  Antonio Oliviero,et al.  The effects of subthreshold 1 Hz repetitive TMS on cortico-cortical and interhemispheric coherence , 2002, Clinical Neurophysiology.

[10]  R. Hari Brain Function and Oscillations, Erol Basar, Springer-Verlag, Berlin, 1998. Part I: Brain Oscillations. Principles and Approaches. pp. xxxiii+363, 150 figures. Part II: Integrative Brain Function. Neurophysiology and Cognitive Processes. pp. xxxix+476, 198 figures , 2000, Biological Psychology.

[11]  Richard S. J. Frackowiak,et al.  Multiple nonprimary motor areas in the human cortex. , 1997, Journal of neurophysiology.

[12]  E. Basar Brain Function and Oscillations , 1998 .

[13]  P. Thompson,et al.  Modulation of postural wrist tremors by magnetic stimulation of the motor cortex in patients with Parkinson's disease or essential tremor and in normal subjects mimicking tremor , 1993, Annals of neurology.

[14]  J. Talairach,et al.  Co-Planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System: An Approach to Cerebral Imaging , 1988 .

[15]  H. Jasper,et al.  The ten-twenty electrode system of the International Federation. The International Federation of Clinical Neurophysiology. , 1999, Electroencephalography and clinical neurophysiology. Supplement.

[16]  G. Schlaug,et al.  Inter-subject variability of cerebral activations in acquiring a motor skill: a study with positron emission tomography , 2004, Experimental Brain Research.

[17]  H. Freund,et al.  The cerebral oscillatory network of parkinsonian resting tremor. , 2003, Brain : a journal of neurology.

[18]  J. Mazziotta,et al.  Brain Mapping: The Methods , 2002 .

[19]  H. Tsuji,et al.  Direct and indirect activation of human corticospinal neurons by transcranial magnetic and electrical stimulation , 1996, Neuroscience Letters.

[20]  T. Paus,et al.  Synchronization of neuronal activity in the human primary motor cortex by transcranial magnetic stimulation: an EEG study. , 2001, Journal of neurophysiology.

[21]  R. Passingham,et al.  Relation between cerebral activity and force in the motor areas of the human brain. , 1995, Journal of neurophysiology.

[22]  G. Rizzolatti,et al.  Activation of precentral and mesial motor areas during the execution of elementary proximal and distal arm movements: a PET study. , 1993, Neuroreport.

[23]  H Scheich,et al.  LTD and LTP induced by transcranial magnetic stimulation in auditory cortex , 1996, Neuroreport.

[24]  R. Passingham,et al.  Self-initiated versus externally triggered movements. II. The effect of movement predictability on regional cerebral blood flow. , 2000, Brain : a journal of neurology.

[25]  Alan C. Evans,et al.  Role of the human anterior cingulate cortex in the control of oculomotor, manual, and speech responses: a positron emission tomography study. , 1993, Journal of neurophysiology.

[26]  M. Hallett,et al.  Depression of motor cortex excitability by low‐frequency transcranial magnetic stimulation , 1997, Neurology.

[27]  D. Collins,et al.  Automatic 3D Intersubject Registration of MR Volumetric Data in Standardized Talairach Space , 1994, Journal of computer assisted tomography.

[28]  Alan Cowey,et al.  Transcranial magnetic stimulation and cognitive neuroscience , 2000, Nature Reviews Neuroscience.

[29]  V. Amassian,et al.  Physiological basis of motor effects of a transient stimulus to cerebral cortex. , 1987, Neurosurgery.

[30]  Tomáš Paus,et al.  25 – Combination of Transcranial Magnetic Stimulation and Brain Mapping , 2002 .

[31]  T. Sejnowski,et al.  Dynamic Brain Sources of Visual Evoked Responses , 2002, Science.

[32]  R. Passingham,et al.  Temporary interference in human lateral premotor cortex suggests dominance for the selection of movements. A study using transcranial magnetic stimulation. , 1998, Brain : a journal of neurology.

[33]  Á. Pascual-Leone,et al.  Transcranial magnetic stimulation in neurology , 2003, The Lancet Neurology.

[34]  J. Rothwell,et al.  Are the after-effects of low-frequency rTMS on motor cortex excitability due to changes in the efficacy of cortical synapses? , 2001, Clinical Neurophysiology.

[35]  John C. Mazziotta,et al.  Within-arm somatotopy in human motor areas determined by positron emission tomography imaging of cerebral blood flow , 2004, Experimental Brain Research.

[36]  Alan C. Evans,et al.  Time-Related Changes in Neural Systems Underlying Attention and Arousal During the Performance of an Auditory Vigilance Task , 1997, Journal of Cognitive Neuroscience.

[37]  J. Rothwell,et al.  Functional Connectivity of Human Premotor and Motor Cortex Explored with Repetitive Transcranial Magnetic Stimulation , 2002, The Journal of Neuroscience.

[38]  T. Sejnowski,et al.  Simulations of cortical pyramidal neurons synchronized by inhibitory interneurons. , 1991, Journal of neurophysiology.

[39]  C. K. Yuen,et al.  Theory and Application of Digital Signal Processing , 1978, IEEE Transactions on Systems, Man, and Cybernetics.

[40]  Hongkui Jing,et al.  Observation of EEG coherence after repetitive transcranial magnetic stimulation , 2000, Clinical Neurophysiology.

[41]  Antonio Oliviero,et al.  Persistent effects of high frequency repetitive TMS on the coupling between motor areas in the human , 2003, Experimental Brain Research.

[42]  R. J. Ilmoniemi,et al.  Instrumentation for the measurement of electric brain responses to transcranial magnetic stimulation , 1999, Medical & Biological Engineering & Computing.

[43]  Philippe A. Chouinard,et al.  Modulating neural networks with transcranial magnetic stimulation applied over the dorsal premotor and primary motor cortices. , 2003, Journal of neurophysiology.

[44]  Erol Başar,et al.  Integrative brain function. Neurophysiology and cognitive processes , 1999 .

[45]  P. Ashby,et al.  Organization of Cortical Activities Related to Movement in Humans , 2000, The Journal of Neuroscience.

[46]  Á. Pascual-Leone,et al.  Interindividual variability of the modulatory effects of repetitive transcranial magnetic stimulation on cortical excitability , 2000, Experimental Brain Research.

[47]  D. Brooks,et al.  Motor sequence learning: a study with positron emission tomography , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[48]  W. Klimesch Brain Function and Oscillations, Vol. II: Integrative Brain Function. Neurophysiology and Cognitive Processes, edited by Erol Basar , 1999, Trends in Cognitive Sciences.

[49]  C. Marsden,et al.  Self-initiated versus externally triggered movements. I. An investigation using measurement of regional cerebral blood flow with PET and movement-related potentials in normal and Parkinson's disease subjects. , 1995, Brain : a journal of neurology.

[50]  Alan C. Evans,et al.  Transcranial Magnetic Stimulation during Positron Emission Tomography: A New Method for Studying Connectivity of the Human Cerebral Cortex , 1997, The Journal of Neuroscience.

[51]  Á. Pascual-Leone,et al.  Modulation of corticospinal excitability by repetitive transcranial magnetic stimulation , 2000, Clinical Neurophysiology.

[52]  J. Rothwell,et al.  Decreased corticospinal excitability after subthreshold 1 Hz rTMS over lateral premotor cortex , 2001, Neurology.