Frequency specific changes in regional cerebral blood flow and motor system connectivity following rTMS to the primary motor cortex

Repetitive transcranial magnetic stimulation (rTMS) to the human primary motor cortex (M1) causes bidirectional changes in corticospinal excitability depending on the stimulation frequency used. We used functional brain imaging to compare the effects of 5 Hz and 1 Hz-rTMS on local and inter-regional connectivity within the motor system. Regional cerebral blood flow (rCBF) was measured as a marker of synaptic activity at rest and during freely selected finger movements. We hypothesized that increased cortical excitability induced by 5 Hz-rTMS over M1 has an opposite effect on the synaptic activity and the connectivity of the motor network from the decreased cortical excitability induced by 1 Hz-rTMS. rTMS at both frequencies induced similar changes in rCBF at the site of stimulation and within areas of the motor network engaged by the task. The two frequencies showed different effects on movement-related coupling between motor areas. Connectivity analyses also indicated a differential effect of 5 and 1 Hz-rTMS on motor network connectivity, suggesting a role for an inferomedial portion of left M1 and left dorsal premotor cortex in maintaining performance. These results suggest that rapid reorganization of the motor system occurs to maintain task performance during periods of altered cortical excitability. This reorganization differs according to the modulation of excitability which is a function of rTMS frequency. This study extends the work of Lee et al. (Lee, L., Siebner, H.R., Rowe, J.B., Rizzo, V. Rothwell, J.C. Frackowiak, R.S. Friston, K.J., 2003. Acute remapping within the motor system induced by low-frequency repetitive transcranial magnetic stimulation. J. Neurosci. 23, 5308-5318.) by providing evidence that the pattern of acute reorganization in the motor network following rTMS depends on the direction of conditioning.

[1]  H. Siebner,et al.  Long-lasting increase in corticospinal excitability after 1800 pulses of subthreshold 5 Hz repetitive TMS to the primary motor cortex , 2004, Clinical Neurophysiology.

[2]  Hartwig R. Siebner,et al.  Short-term modulation of regional excitability and blood flow in human motor cortex following rapid-rate transcranial magnetic stimulation , 2004, NeuroImage.

[3]  P. Mazzone,et al.  Direct demonstration of the effects of repetitive transcranial magnetic stimulation on the excitability of the human motor cortex , 2002, Experimental Brain Research.

[4]  John C Rothwell,et al.  Long lasting effects of rTMS and associated peripheral sensory input on MEPs, SEPs and transcortical reflex excitability in humans , 2002, The Journal of physiology.

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

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

[7]  Ulf Ziemann,et al.  Rapid modulation of GABA in sensorimotor cortex induced by acute deafferentation , 2002, Annals of neurology.

[8]  Alexander Münchau,et al.  Shaping the excitability of human motor cortex with premotor rTMS , 2004, The Journal of physiology.

[9]  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.

[10]  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.

[11]  Alexander Münchau,et al.  Subthreshold 5-Hz repetitive transcranial magnetic stimulation of the human primary motor cortex reduces intracortical paired-pulse inhibition , 2000, Neuroscience Letters.

[12]  M. Petrides,et al.  Cortico‐cortical connectivity of the human mid‐dorsolateral frontal cortex and its modulation by repetitive transcranial magnetic stimulation , 2001 .

[13]  M. Merzenich,et al.  Use-dependent alterations of movement representations in primary motor cortex of adult squirrel monkeys , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[14]  M. Hallett,et al.  Contribution of the ipsilateral motor cortex to recovery after chronic stroke , 2003, Annals of neurology.

[15]  S Minoshima,et al.  Lasting cortical activation after repetitive TMS of the motor cortex , 2000, Neurology.

[16]  E. M. Rouiller,et al.  Mechanisms of recovery of dexterity following unilateral lesion of the sensorimotor cortex in adult monkeys , 1999, Experimental Brain Research.

[17]  E. Ringelstein,et al.  Changing cortical excitability with low-frequency transcranial magnetic stimulation can induce sustained disruption of tactile perception , 2003, Biological Psychiatry.

[18]  J. Donoghue,et al.  Dynamic organization of primary motor cortex output to target muscles in adult rats II. Rapid reorganization following motor nerve lesions , 2004, Experimental Brain Research.

[19]  J. Donoghue,et al.  Long-term potentiation and long-term depression of horizontal connections in rat motor cortex. , 1996, Acta neurobiologiae experimentalis.

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

[21]  KM Jacobs,et al.  Reshaping the cortical motor map by unmasking latent intracortical connections , 1991, Science.

[22]  Richard S. J. Frackowiak,et al.  Patients with focal arm dystonia have increased sensitivity to slow-frequency repetitive TMS of the dorsal premotor cortex. , 2003, Brain : a journal of neurology.

[23]  K. Zilles,et al.  Structural divisions and functional fields in the human cerebral cortex 1 Published on the World Wide Web on 20 February 1998. 1 , 1998, Brain Research Reviews.

[24]  J. Rothwell,et al.  Transcranial magnetic stimulation: new insights into representational cortical plasticity , 2002, Experimental Brain Research.

[25]  R. Nudo,et al.  Reorganization of movement representations in primary motor cortex following focal ischemic infarcts in adult squirrel monkeys. , 1996, Journal of neurophysiology.

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

[27]  Á. Pascual-Leone,et al.  Study and modulation of human cortical excitability with transcranial magnetic stimulation. , 1998, Journal of clinical neurophysiology : official publication of the American Electroencephalographic Society.

[28]  D. Buonomano,et al.  Cortical plasticity: from synapses to maps. , 1998, Annual review of neuroscience.

[29]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[30]  L. Cohen,et al.  Reorganization of the human ipsilesional premotor cortex after stroke. , 2004, Brain : a journal of neurology.

[31]  Karl J. Friston,et al.  Spatial registration and normalization of images , 1995 .

[32]  J C Rothwell,et al.  Short-lasting impairment of tactile perception by 0.9Hz-rTMS of the sensorimotor cortex , 2003, Neurology.

[33]  K. Zilles,et al.  Neural activity in human primary motor cortex areas 4a and 4p is modulated differentially by attention to action. , 2002, Journal of neurophysiology.

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

[35]  E. H. Simpson.  Measurement of Diversity , 1949, Nature.

[36]  R. Nudo.  Recovery after damage to motor cortical areas , 1999, Current Opinion in Neurobiology.

[37]  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.

[38]  R. Nudo,et al.  Cortical plasticity after stroke: implications for rehabilitation. , 1999, Revue neurologique.

[39]  R Turner,et al.  Optimisation of the 3D MDEFT sequence for anatomical brain imaging: technical implications at 1.5 and 3 T , 2004, NeuroImage.

[40]  J. Rothwell,et al.  Facilitation of muscle evoked responses after repetitive cortical stimulation in man , 1998, Experimental Brain Research.

[41]  Á. Pascual-Leone,et al.  Modulation of input–output curves by low and high frequency repetitive transcranial magnetic stimulation of the motor cortex , 2002, Clinical Neurophysiology.

[42]  D. M. Feeney,et al.  Noradrenergic modulation of hemiplegia: facilitation and maintenance of recovery. , 2004, Restorative neurology and neuroscience.

[43]  Karl J. Friston,et al.  Functional reorganization of the brain in recovery from striatocapsular infarction in man , 1992, Annals of neurology.

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

[45]  Karl J. Friston,et al.  Psychophysiological and Modulatory Interactions in Neuroimaging , 1997, NeuroImage.

[46]  Robert Chen,et al.  Interactions between inhibitory and excitatory circuits in the human motor cortex , 2003, Experimental Brain Research.

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

[48]  H. Freund,et al.  Role of the premotor cortex in recovery from middle cerebral artery infarction. , 1998, Archives of neurology.

[49]  R. Nudo,et al.  Role of adaptive plasticity in recovery of function after damage to motor cortex , 2001, Muscle & nerve.

[50]  Alvaro Pascual-Leone,et al.  Handbook of transcranial magnetic stimulation , 2002 .

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

[52]  Patrick Ragert,et al.  Sustained increase of somatosensory cortex excitability by 5 Hz repetitive transcranial magnetic stimulation studied by paired median nerve stimulation in humans , 2004, Neuroscience Letters.

[53]  S. Barbay,et al.  Reorganization of remote cortical regions after ischemic brain injury: a potential substrate for stroke recovery. , 2003, Journal of neurophysiology.