Theta burst TMS increases cerebral blood flow in the primary motor cortex during motor performance as assessed by arterial spin labeling (ASL)

Theta burst stimulation (TBS) is a novel variant of repetitive transcranial magnetic stimulation (rTMS), which induces changes in neuronal excitability persisting up to 1h. When elicited in the primary motor cortex, such physiological modulations might also have an impact on motor behavior. In the present study, we applied TBS in combination with pseudo continuous arterial spin labeling (pCASL) in order to address the question of whether TBS effects are measurable by means of changes in physiological parameters such as cerebral blood flow (CBF) and if TBS-induced plasticity can modify motor behavior. Twelve right-handed healthy subjects were stimulated using an inhibitory TBS protocol at subthreshold stimulation intensity targeted over the right motor cortex. The control condition consisted of within-subject Sham treatment in a crossover design. PCASL was performed before (pre TBS/pre Sham) and immediately after treatment (post TBS/post Sham). During the pCASL runs, the subjects performed a sequential fingertapping task with the left hand at individual maximum speed. There was a significant increase of CBF in the primary motor cortex after TBS, but not after Sham. It is assumed that inhibitory TBS induced a "local virtual lesion" which leads to the mobilization of more neuronal resources. There was no TBS-specific modulation in motor behavior, which might indicate that acute changes in brain plasticity caused by TBS are immediately compensated. This compensatory reaction seems to be observable at the metabolic, but not at the behavioral level.

[1]  S. Lisanby,et al.  Applications of TMS to Therapy in Psychiatry , 2002, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[2]  Á. Pascual-Leone,et al.  Transcranial magnetic stimulation: studying the brain-behaviour relationship by induction of 'virtual lesions'. , 1999, Philosophical transactions of the Royal Society of London. Series B, Biological sciences.

[3]  Maria Stein,et al.  Structural plasticity in the language system related to increased second language proficiency , 2012, Cortex.

[4]  J. Detre,et al.  Perfusion magnetic resonance imaging with continuous arterial spin labeling: methods and clinical applications in the central nervous system. , 1999, European journal of radiology.

[5]  W. Byblow,et al.  Theta burst stimulation of human primary motor cortex degrades selective muscle activation in the ipsilateral arm. , 2010, Journal of neurophysiology.

[6]  Peter T. Fox,et al.  Imaging human intra‐cerebral connectivity by PET during TMS , 1997, Neuroreport.

[7]  M. Hallett,et al.  Complexity affects regional cerebral blood flow change during sequential finger movements , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

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

[9]  Karl J. Friston,et al.  Analysis of fMRI Time-Series Revisited , 1995, NeuroImage.

[10]  Thomas E. Nichols,et al.  Thresholding of Statistical Maps in Functional Neuroimaging Using the False Discovery Rate , 2002, NeuroImage.

[11]  Giovanni Abbruzzese,et al.  Clinical and Research Methods for Evaluating Cortical Excitability , 2002, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[12]  W. Strik,et al.  Comparison of spatial and temporal pattern for fMRI obtained with BOLD and arterial spin labeling , 2006, Journal of Neural Transmission.

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

[14]  Rolf Pohmann,et al.  Interleaved TMS/CASL: Comparison of different rTMS protocols , 2009, NeuroImage.

[15]  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.

[16]  A. Drzezga,et al.  Continuous Transcranial Magnetic Stimulation during Positron Emission Tomography: A Suitable Tool for Imaging Regional Excitability of the Human Cortex , 2001, NeuroImage.

[17]  D. Alsop,et al.  Continuous flow‐driven inversion for arterial spin labeling using pulsed radio frequency and gradient fields , 2008, Magnetic resonance in medicine.

[18]  H. Siebner,et al.  Imaging brain activation induced by long trains of repetitive transcranial magnetic stimulation , 1998, Neuroreport.

[19]  R. Ivry,et al.  Ipsilateral motor cortex activity during unimanual hand movements relates to task complexity. , 2005, Journal of neurophysiology.

[20]  M. Hallett Transcranial magnetic stimulation and the human brain , 2000, Nature.

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

[22]  Jack L. Lancaster,et al.  Force sensing system for automated assessment of motor performance during fMRI , 2010, Journal of Neuroscience Methods.

[23]  E. Wassermann Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. , 1998, Electroencephalography and clinical neurophysiology.

[24]  Joseph Classen,et al.  Cerebral Cortex doi:10.1093/cercor/bhi116 Temporary Occlusion of Associative Motor Cortical Plasticity by Prior Dynamic Motor Training , 2005 .

[25]  Alfredo Berardelli,et al.  Phasic voluntary movements reverse the aftereffects of subsequent theta-burst stimulation in humans. , 2008, Journal of neurophysiology.

[26]  A. Berardelli,et al.  Effects of 5 Hz subthreshold magnetic stimulation of primary motor cortex on fast finger movements in normal subjects , 2007, Experimental Brain Research.

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

[28]  Alfredo Berardelli,et al.  Effects of intermittent theta‐burst stimulation on practice‐related changes in fast finger movements in healthy subjects , 2008, The European journal of neuroscience.

[29]  B R Rosen,et al.  Activation of distinct motor cortex regions during ipsilateral and contralateral finger movements. , 1999, Journal of neurophysiology.

[30]  Karl J. Friston,et al.  Acute Remapping within the Motor System Induced by Low-Frequency Repetitive Transcranial Magnetic Stimulation , 2003, The Journal of Neuroscience.

[31]  P. Bandettini,et al.  QUIPSS II with thin‐slice TI1 periodic saturation: A method for improving accuracy of quantitative perfusion imaging using pulsed arterial spin labeling , 1999, Magnetic resonance in medicine.

[32]  J. Driver,et al.  Combining TMS and fMRI: From ‘virtual lesions’ to functional-network accounts of cognition , 2009, Cortex.

[33]  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.

[34]  T. Wüstenberg,et al.  Asymmetry of cortical activation during maximum and convenient tapping speed , 2004, Neuroscience Letters.

[35]  U. Ziemann,et al.  Slowing fastest finger movements of the dominant hand with low-frequency rTMS of the hand area of the primary motor cortex , 2004, Experimental Brain Research.

[36]  Simone Rossi,et al.  TMS in cognitive plasticity and the potential for rehabilitation , 2004, Trends in Cognitive Sciences.

[37]  Joseph A Maldjian,et al.  Arterial transit time imaging with flow encoding arterial spin tagging (FEAST) , 2003, Magnetic resonance in medicine.

[38]  J. Rothwell,et al.  Theta burst stimulation induces after‐effects on contralateral primary motor cortex excitability in humans , 2008, The Journal of physiology.

[39]  Matthias Günther,et al.  Efficient visualization of vascular territories in the human brain by cycled arterial spin labeling MRI , 2006, Magnetic resonance in medicine.

[40]  M. Hallett,et al.  Involvement of the ipsilateral motor cortex in finger movements of different complexities , 1997, Annals of neurology.

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

[42]  Pascal Wurtz,et al.  One-Hertz transcranial magnetic stimulation over the frontal eye field induces lasting inhibition of saccade triggering , 2006, Neuroreport.

[43]  J. Rothwell,et al.  Transcranial magnetic stimulation in cognitive neuroscience – virtual lesion, chronometry, and functional connectivity , 2000, Current Opinion in Neurobiology.

[44]  J. Detre,et al.  A theoretical and experimental investigation of the tagging efficiency of pseudocontinuous arterial spin labeling , 2007, Magnetic resonance in medicine.

[45]  J L Lancaster,et al.  Automated Talairach Atlas labels for functional brain mapping , 2000, Human brain mapping.

[46]  Thomas Kammer,et al.  Exploring the after‐effects of theta burst magnetic stimulation on the human motor cortex: A functional imaging study , 2011, Human brain mapping.

[47]  J. Rothwell,et al.  How does transcranial magnetic stimulation modify neuronal activity in the brain? Implications for studies of cognition , 2009, Cortex.

[48]  S. Rossi,et al.  Effects of repetitive transcranial magnetic stimulation on movement-related cortical activity in humans. , 2000, Cerebral cortex.

[49]  D. Heeger,et al.  Linear Systems Analysis of Functional Magnetic Resonance Imaging in Human V1 , 1996, The Journal of Neuroscience.

[50]  Bogdan Draganski,et al.  Neuroplasticity: Changes in grey matter induced by training , 2004, Nature.

[51]  J. C. Rothwell,et al.  Exploring Theta Burst Stimulation as an intervention to improve motor recovery in chronic stroke , 2007, Clinical Neurophysiology.

[52]  Karl J. Friston,et al.  Frequency specific changes in regional cerebral blood flow and motor system connectivity following rTMS to the primary motor cortex , 2005, NeuroImage.

[53]  T. Paus,et al.  Cerebral blood-flow changes induced by paired-pulse transcranial magnetic stimulation of the primary motor cortex. , 2001, Journal of neurophysiology.

[54]  M. Ridding,et al.  Determinants of the induction of cortical plasticity by non‐invasive brain stimulation in healthy subjects , 2010, The Journal of physiology.

[55]  Thomas Dierks,et al.  Association of individual resting state EEG alpha frequency and cerebral blood flow , 2010, NeuroImage.

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

[57]  H. Sackeim,et al.  Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials , 2001, Biological Psychiatry.

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

[59]  J C Mazziotta,et al.  Automated labeling of the human brain: A preliminary report on the development and evaluation of a forward‐transform method , 1997, Human brain mapping.

[60]  Thomas Kammer,et al.  Mechanisms and Applications of Theta-burst rTMS on the Human Motor Cortex , 2009, Brain Topography.

[61]  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.

[62]  Jens Frahm,et al.  Subthreshold high-frequency TMS of human primary motor cortex modulates interconnected frontal motor areas as detected by interleaved fMRI-TMS , 2003, NeuroImage.

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

[64]  Michele Tinazzi,et al.  Modulation of ipsilateral motor cortex in man during unimanual finger movements of different complexities , 1998, Neuroscience Letters.

[65]  D Claus,et al.  [Magnetic stimulation using double coils--methodology and normal findings]. , 1991, EEG-EMG Zeitschrift fur Elektroenzephalographie, Elektromyographie und verwandte Gebiete.