Oscillatory Beta Activity Mediates Neuroplastic Effects of Motor Cortex Stimulation in Humans

Continuous theta burst stimulation (cTBS) is a repetitive transcranial magnetic stimulation protocol that can inhibit human motor cortex (M1) excitability and impair movement for ≤1 h. While offering valuable insights into brain function and potential therapeutic benefits, these neuroplastic effects are highly variable between individuals. The source of this variability, and the electrophysiological mechanisms underlying the inhibitory after-effects, are largely unknown. In this regard, oscillatory activity at beta frequency (15–35 Hz) is of particular interest as it is elevated in motor disorders such as Parkinson's disease and modulated during the generation of movements. Here, we used a source-level magnetoencephalography approach to investigate the hypothesis that the presence of neuroplastic effects following cTBS is associated with concurrent changes in oscillatory M1 beta activity. M1 cortices were localized with a synthetic aperture magnetometry beamforming analysis of visually cued index finger movements. Virtual electrode analysis was used to reconstruct the spontaneous and movement-related oscillatory activity in bilateral M1 cortices, before and from 10 to 45 min after cTBS. We demonstrate that 40 s of cTBS applied over left M1 reduced corticospinal excitability in the right index finger of 8/16 participants. In these responder participants only, cTBS increased the power of the spontaneous beta oscillations in stimulated M1 and delayed reaction times in the contralateral index finger. No further changes were observed in the latency or power of movement-related beta oscillations. These data provide insights into the electrophysiological mechanisms underlying cTBS-mediated impairment of motor function and demonstrate the association between spontaneous oscillatory beta activity in M1 and the inhibition of motor function.

[1]  P. Brown,et al.  Cortico-cortical coupling in Parkinson's disease and its modulation by therapy. , 2005, Brain : a journal of neurology.

[2]  Andrea A. Kühn,et al.  Pathological synchronisation in the subthalamic nucleus of patients with Parkinson's disease relates to both bradykinesia and rigidity , 2009, Experimental Neurology.

[3]  Jozsef Csicsvari,et al.  Disrupted Dopamine Transmission and the Emergence of Exaggerated Beta Oscillations in Subthalamic Nucleus and Cerebral Cortex , 2008, The Journal of Neuroscience.

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

[5]  W. Drongelen,et al.  Localization of brain electrical activity via linearly constrained minimum variance spatial filtering , 1997, IEEE Transactions on Biomedical Engineering.

[6]  P. Fitzgerald,et al.  A comprehensive review of the effects of rTMS on motor cortical excitability and inhibition , 2006, Clinical Neurophysiology.

[7]  P. Brown Abnormal oscillatory synchronisation in the motor system leads to impaired movement , 2007, Current Opinion in Neurobiology.

[8]  John C Rothwell,et al.  Cortical oscillatory activity and the induction of plasticity in the human motor cortex , 2011, The European journal of neuroscience.

[9]  Risto J. Ilmoniemi,et al.  EEG oscillations and magnetically evoked motor potentials reflect motor system excitability in overlapping neuronal populations , 2010, Clinical Neurophysiology.

[10]  M. Ridding,et al.  The application of spaced theta burst protocols induces long‐lasting neuroplastic changes in the human motor cortex , 2012, The European journal of neuroscience.

[11]  J. González,et al.  Brain-Derived Neurotrophic Factor Val66Met and Psychiatric Disorders: Meta-Analysis of Case-Control Studies Confirm Association to Substance-Related Disorders, Eating Disorders, and Schizophrenia , 2007, Biological Psychiatry.

[12]  N. Matsuki,et al.  Inhibition of GABAA Synaptic Responses by Brain-Derived Neurotrophic Factor (BDNF) in Rat Hippocampus , 1997, The Journal of Neuroscience.

[13]  Y. Z. Huang,et al.  Theta‐burst repetitive transcranial magnetic stimulation suppresses specific excitatory circuits in the human motor cortex , 2005, The Journal of physiology.

[14]  Ying-Zu Huang,et al.  Intermittent theta burst stimulation over primary motor cortex enhances movement-related beta synchronisation , 2011, Clinical Neurophysiology.

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

[16]  J. Vrba,et al.  Signal processing in magnetoencephalography. , 2001, Methods.

[17]  Mark Hallett,et al.  Modulation of motor cortex excitability by median nerve and digit stimulation , 1999, Experimental Brain Research.

[18]  J. Rothwell,et al.  The after-effect of human theta burst stimulation is NMDA receptor dependent , 2007, Clinical Neurophysiology.

[19]  Mark Hallett,et al.  Time course of corticospinal excitability in reaction time and self‐paced movements , 1998, Annals of neurology.

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

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

[22]  Giacomo Koch,et al.  A common polymorphism in the brain‐derived neurotrophic factor gene (BDNF) modulates human cortical plasticity and the response to rTMS , 2008, The Journal of physiology.

[23]  John C Rothwell,et al.  Effect of physiological activity on an NMDA-dependent form of cortical plasticity in human. , 2008, Cerebral cortex.

[24]  K. D. Singh,et al.  Co-registration of magnetoencephalography with magnetic resonance imaging using bite-bar-based fiducials and surface-matching , 2004, Clinical Neurophysiology.

[25]  V. Jousmäki,et al.  Modulation of Human Cortical Rolandic Rhythms during Natural Sensorimotor Tasks , 1997, NeuroImage.

[26]  A. Schnitzler,et al.  Motor‐cortical oscillations in early stages of Parkinson's disease , 2012, The Journal of physiology.

[27]  I. Stanford,et al.  Pharmacologically induced and stimulus evoked rhythmic neuronal oscillatory activity in the primary motor cortex in vitro , 2008, Neuroscience.

[28]  Krish D. Singh,et al.  A new approach to neuroimaging with magnetoencephalography , 2005, Human brain mapping.

[29]  A. Oliviero,et al.  Movement-related changes in synchronization in the human basal ganglia. , 2002, Brain : a journal of neurology.

[30]  J. Donoghue,et al.  Long‐term Depression of Horizontal Connections in Rat Motor Cortex , 1996, The European journal of neuroscience.

[31]  J. Rothwell,et al.  The role of interneuron networks in driving human motor cortical plasticity. , 2013, Cerebral cortex.

[32]  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 .

[33]  Daniel Zeller,et al.  Depression of human corticospinal excitability induced by magnetic theta-burst stimulation: evidence of rapid polarity-reversing metaplasticity. , 2008, Cerebral cortex.

[34]  P. Brown,et al.  Dopamine depletion increases the power and coherence of β‐oscillations in the cerebral cortex and subthalamic nucleus of the awake rat , 2005, The European journal of neuroscience.

[35]  V. Lazzaro,et al.  Physiology of repetitive transcranial magnetic stimulation of the human brain , 2010, Brain Stimulation.

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

[37]  Vincenzo Di Lazzaro,et al.  Theta Burst Stimulation in the Rehabilitation of the Upper Limb , 2012, Neurorehabilitation and neural repair.

[38]  J. Rothwell,et al.  Theta Burst Stimulation of the Human Motor Cortex , 2005, Neuron.

[39]  Klaus Funke,et al.  Theta burst and conventional low-frequency rTMS differentially affect GABAergic neurotransmission in the rat cortex , 2009, Experimental Brain Research.

[40]  K. Funke,et al.  Modulation of cortical inhibition by rTMS – findings obtained from animal models , 2011, The Journal of physiology.

[41]  Suresh D Muthukumaraswamy,et al.  Functional properties of human primary motor cortex gamma oscillations. , 2010, Journal of neurophysiology.

[42]  P. Jezzard,et al.  Neurochemical Effects of Theta Burst Stimulation as Assessed by Magnetic Resonance Spectroscopy , 2009, Journal of neurophysiology.

[43]  G. Pfurtscheller Event-related synchronization (ERS): an electrophysiological correlate of cortical areas at rest. , 1992, Electroencephalography and clinical neurophysiology.

[44]  Tipu Z. Aziz,et al.  The role of the subthalamic nucleus in response inhibition: Evidence from local field potential recordings in the human subthalamic nucleus , 2012, NeuroImage.

[45]  E. Wassermann,et al.  A safety screening questionnaire for transcranial magnetic stimulation , 2001, Clinical Neurophysiology.

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

[47]  P. Brown,et al.  New insights into the relationship between dopamine, beta oscillations and motor function , 2011, Trends in Neurosciences.

[48]  P. Manganotti,et al.  Long Lasting Modulation of Cortical Oscillations after Continuous Theta Burst Transcranial Magnetic Stimulation , 2012, PloS one.

[49]  D. Avery,et al.  EEG and the Variance of Motor Evoked Potential Amplitude , 2006, Clinical EEG and neuroscience.

[50]  Michael T. Jurkiewicz,et al.  Post-movement beta rebound is generated in motor cortex: Evidence from neuromagnetic recordings , 2006, NeuroImage.

[51]  A. Oliviero,et al.  Dopamine Dependency of Oscillations between Subthalamic Nucleus and Pallidum in Parkinson's Disease , 2001, The Journal of Neuroscience.

[52]  Daniel Zeller,et al.  Theta-burst stimulation: Remote physiological and local behavioral after-effects , 2008, NeuroImage.

[53]  G. Fink,et al.  Theta burst stimulation over the primary motor cortex does not induce cortical plasticity in Parkinson’s disease , 2010, Journal of Neurology.

[54]  J. Rothwell,et al.  Is there a future for therapeutic use of transcranial magnetic stimulation? , 2007, Nature Reviews Neuroscience.

[55]  M. Ridding,et al.  Role of the primary motor and sensory cortex in precision grasping: a transcranial magnetic stimulation study , 2008, The European journal of neuroscience.

[56]  P. Brown,et al.  Event-related beta desynchronization in human subthalamic nucleus correlates with motor performance. , 2004, Brain : a journal of neurology.

[57]  D. Wolpert,et al.  High‐frequency repetitive transcranial magnetic stimulation over the hand area of the primary motor cortex disturbs predictive grip force scaling , 2005, The European journal of neuroscience.

[58]  Klaus Funke,et al.  Theta-Burst Transcranial Magnetic Stimulation Alters Cortical Inhibition , 2011, The Journal of Neuroscience.