Research Article| Volume 54, ISSUE 8, P818-825, October 15, 2003

Intensity-dependent regional cerebral blood flow during 1-Hz repetitive transcranial magnetic stimulation (rTMS) in healthy volunteers studied with H215O positron emission tomography: i. effects of primary motor cortex rTMS



      Repetitive transcranial magnetic stimulation (rTMS) affects the excitability of the motor cortex and is thought to influence activity in other brain areas as well. We combined the administration of varying intensities of 1-Hz rTMS of the motor cortex with simultaneous positron emission tomography (PET) to delineate local and distant effects on brain activity.


      Ten healthy subjects received 1-Hz rTMS to the optimal position over motor cortex (M1) for producing a twitch in the right hand at 80, 90, 100, 110, and 120% of the twitch threshold, while regional cerebral blood flow (rCBF) was measured using H215O and PET. Repetitive transcranial magnetic stimulation (rTMS) was delivered in 75-pulse trains at each intensity every 10 min through a figure-eight coil. The regional relationship of stimulation intensity to normalized rCBF was assessed statistically.


      Intensity-dependent rCBF increases were produced under the M1 stimulation site in ipsilateral primary auditory cortex, contralateral cerebellum, and bilateral putamen, insula, and red nucleus. Intensity-dependent reductions in rCBF occurred in contralateral frontal and parietal cortices and bilateral anterior cingulate gyrus and occipital cortex.


      This study demonstrates that 1-Hz rTMS delivered to the primary motor cortex (M1) produces intensity-dependent increases in brain activity locally and has associated effects in distant sites with known connections to M1.


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        • Bohning D.E.
        • Shastri A.
        • McConnell K.A.
        • Nahas Z.
        • Lorberbaum J.P.
        • Roberts D.R.
        • et al.
        A combined TMS/fMRI study of intensity-dependent TMS over motor cortex.
        Biol Psychiatry. 1999; 45: 385-394
        • Brodal A.
        Neurological Anatomy in Relation to Clinical Medicine. Oxford University Press, New York, Oxford1981
        • Chen R.
        • Classen J.
        • Gerloff C.
        • Celnik P.
        • Wassermann E.M.
        • Hallett M.
        • et al.
        Depression of motor cortex excitability by low frequency transcranial magnetic stimulation.
        Neurology. 1997; 48: 1398-1403
        • Colebatch J.G.
        • Deiber M.-P.
        • Passingham R.E.
        • Friston K.J.
        • Frackowiak R.S.J.
        Regional cerebral blood flow during voluntary arm and hand movement in human subjects.
        J Neurophysiol. 1991; 65: 1392-1401
        • DeGrado T.R.
        • Turkington T.G.
        • Williams J.J.
        • Stearns C.W.
        • Hoffman J.M.
        Performance characteristics of a whole-body PET scanner.
        J Nucl Med. 1994; 35: 1398-1406
        • Fox P.
        • Ingham R.
        • George M.S.
        • Mayberg H.
        • Ingham J.
        • Roby J.
        • et al.
        Imaging human intra-cerebral connectivity by PET during TMS.
        Neuroreport. 1997; 8: 2787-2791
        • Friston K.J.
        • Holmes A.P.
        • Worsley K.J.
        • Poline J.B.
        • Frith C.D.
        • Frackowiack R.S.J.
        Statistical parametric maps in functional imaging.
        Hum Brain Mapp. 1995; 2: 189-210
        • Friston K.J.
        • Worsley K.J.
        • Frackowiack R.S.J.
        • Mazziota J.C.
        • Evans A.C.
        Assessing the significance of focal activations using their spatial extent.
        Hum Brain Mapp. 1994; 1: 210-220
        • Grafton S.T.
        • Woods R.P.
        • Mazziotta J.C.
        • Phelps M.E.
        Somatotopic mapping of the primary motor cortex in humans.
        J Neurophysiol. 1991; 66: 735-743
        • Herscovitch P.
        • Markham J.
        • Raichle M.E.
        Brain blood flow measured with intravenous H2150. I. Theory and error analysis.
        J Nucl Med. 1983; 24: 782-789
        • Indovina I.
        • Sanes J.N.
        On somatotopic representation centers for finger movements in human primary motor cortex and supplementary motor area.
        Neuroimage. 2001; 13: 1027-1034
        • Ketter T.A.
        • Kimbrell T.A.
        • George M.S.
        • Willis M.W.
        • Benson B.E.
        • Danielson A.
        • et al.
        Baseline cerebral hypermetabolism associated with carbamazepine response, and hypometabolism with nimodipine response in mood disorders.
        Biol Psychiatry. 1999; 46: 1364-1374
        • Kosslyn S.M.
        • Pascual-Leone A.
        • Felician O.
        • Camposano S.
        • Keenan J.P.
        • Thompson W.L.
        • et al.
        The role of area 17 in visual imagery.
        Science. 1999; 284: 167-170
      1. Lewellen TK, Kohlmeyer SG, Miyaoka RS, Kaplan MS, Steams CW, Schubert SF (1996): Investigation of the performance of the General Electric Advance positron emission tomograph in 3D mode. IEEE Trans Nucl Sci 43:2199–2206

        • Mima T.
        • Sadato N.
        • Yazawa S.
        • Hanakawa T.
        • Fukuyama H.
        • Yonekura Y.
        • et al.
        Brain structures related to active and passive finger movements in man.
        Brain. 1999; 122: 1989-1997
        • Paus T.
        • Jech R.
        • Thompson C.J.
        • Comeau R.
        • Peters T.
        • Evans A.C.
        Transcranial magnetic stimulation during positron emission tomography.
        J Neurosci. 1997; 17: 3178-3184
        • Paus T.
        • Jech R.
        • Thompson C.J.
        • Comeau R.
        • Peters T.
        • Evans A.C.
        Dose-dependent reduction of cerebral blood flow during rapid-rate transcranial stimulation of the human sensorimotor cortex.
        J Neurophysiol. 1998; 79: 1102-1107
        • Pridmore S.
        • Fernandes Filho J.A.
        • Nahas Z.
        • Liberatos C.
        • George M.S.
        Motor threshold in transcranial magnetic stimulation.
        J ECT. 1998; 14: 25-27
        • Raichle M.E.
        • Martin W.R.W.
        • Herscovitch P.
        • Mintun M.A.
        • Markham J.
        Brain blood flow measured with intravenous H215O. II. Implementation and validation.
        J Nucl Med. 1983; 24: 790-798
        • Rosenthal R.
        Meta-Analytic Procedures for Social Research. Sage, Newbury Park, CA1991 (revised ed)
        • Rothwell J.C.
        Control of Human Voluntary Movement. Aspen, Rockville, MD1987
        • Schmahmann J.
        • Doyon J.
        • Toga A.
        • Petrides M.
        • Evans A.L.
        MRI Atlas of the Human Cerebellum. Academic Press, San Diego2000
        • Siebner H.
        • Peller M.
        • Bartenstein P.
        • Willoch F.
        • Rossmeier C.
        • Schwaiger M.
        • et al.
        Activation of frontal premotor areas during suprathreshold transcranial magnetic stimulation of the left primary sensorimotor cortex.
        Hum Brain Mapp. 2001; 12: 157-167
        • Siebner H.R.
        • Peller M.
        • Willoch F.
        • Minoshima S.
        • Boecker H.
        • Auer C.
        • et al.
        Lasting cortical activation after repetitive TMS of the motor cortex.
        Neurology. 2000; 54: 956-963
        • Siebner H.R.
        • Takano B.
        • Peinemann A.
        • Schwaiger M.
        • Conrad B.
        • Drzezga A.
        Continuous transcranial magnetic stimulation during positron emission tomography.
        Neuroimage. 2001; 14: 883-890
        • Siebner H.R.
        • Willoch F.
        • Peller M.
        • Auer C.
        • Boecker H.
        • Conrad B.
        • et al.
        Imaging brain activation induced by long trains of repetitive transcranial magnetic stimulation.
        Neuroreport. 1998; 9: 943-948
        • Talairach J.
        • Tournoux P.
        Co-planar Stereotaxic Atlas of the Human Brain. Thieme, New York1988
        • Wassermann E.M.
        • Grafman J.
        • Berry C.
        • Hollnagel C.
        • Wild K.
        • Clark K.
        • et al.
        Use and safety of a new repetitive transcranial magnetic stimulator.
        Electroencephalogr Clin Neurophysiol. 1996; 101: 412-417
        • Wassermann E.M.
        • Wang B.
        • Zeffiro T.A.
        • Sadato N.
        • Pascual-Leone A.
        • Toro C.
        • et al.
        Locating the motor cortex on the MRI with transcranial magnetic stimulation.
        Neuroimage. 1996; 3: 1-9