Skip to main content
SpringerLink
Log in

Opposite impact on 14C-2-deoxyglucose brain metabolism following patterns of high and low frequency repetitive transcranial magnetic stimulation in the posterior parietal cortex

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

Repetitive transcranial magnetic stimulation (rTMS) appears capable of modulating human cortical excitability beyond the duration of the stimulation train. However, the basis and extent of this “off-line” modulation remains unknown. In a group of anesthetized cats, we applied patterns of real or sham focal rTMS to the visuo-parietal cortex (VP) at high (HF) or low (LF) frequency and recorded brain glucose uptake during (on-line), immediately after (off-line), or 1 h after (late) stimulation. During the on-line period LF and HF rTMS induced a significant relative reduction of 14C-2DG uptake in the stimulated VP cortex and tightly linked cortical and subcortical structures (e.g. the superficial superior colliculus, the pulvinar, and the LPl nucleus) with respect to homologue areas in the unstimulated hemisphere. During the off-line period HF rTMS induced a significant relative increase in 14C-2DG uptake in the targeted VP cortex, whereas LF rTMS generated the opposite effect, with only mild network impact. Moderate distributed effects were only recorded after LF rTMS in the posterior thalamic structures. No long lasting cortical or subcortical effects were detected during the late period. Our findings demonstrate opposite modulation of rTMS on local and distant effects along a specific network, depending on the pattern of stimulation. Such effects are demonstrated in the anesthetized animal, ruling out behavioral and non-specific reasons for the differential impact of the stimulation. The findings are consistent with previous differential electrophysiological and behavioral effects of low and high frequency rTMS patterns and provide support to uses of rTMS in neuromodulation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Amassian VE, Quirk GJ, Stewart M (1990) A comparison of corticospinal activation by magnetic coil and electrical stimulation of monkey motor cortex. Electroencephalogr Clin Neurophysiol 77:390–401

    Article  CAS  PubMed  Google Scholar 

  • Aydin-Abidin S, Moliadze V, Eysel UT, Funke K (2006) Effects of repetitive TMS on visually evoked potentials and EEG in the anesthetized cat: dependence on stimulus frequency and train duration. J Physiol 574:443–455

    Article  CAS  PubMed  Google Scholar 

  • Bestmann S, Baudewig J, Siebner HR, Rothwell JC, Frahm J (2003) Subthreshold high-frequency TMS of human primary motor cortex modulates interconnected frontal motor areas as detected by interleaved fMRI–TMS. Neuroimage 20:1685–1696

    Article  PubMed  Google Scholar 

  • Bestmann S, Baudewig J, Siebner HR, Rothwell JC, Frahm J (2004) Functional MRI of the immediate impact of transcranial magnetic stimulation on cortical and subcortical motor circuits. Eur J Neurosci 19:1950–1962

    Article  PubMed  Google Scholar 

  • Buhl EH, Singer W (1989) The callosal projection in cat visual cortex as revealed by a combination of retrograde tracing and intracellular injection. Exp Brain Res 75:470–476

    Article  CAS  PubMed  Google Scholar 

  • Castro-Alamancos MA, Donoghue JP, Connors BW (1995) Different forms of synaptic plasticity in somatosensory and motor areas of the neocortex. J Neurosci 15:5324–5333

    CAS  PubMed  Google Scholar 

  • Chen R, Classen J, Gerloff C, Celnik P, Wassermann EM, Hallett M, Cohen LG (1997) Depression of motor cortex excitability by low-frequency transcranial magnetic stimulation. Neurology 48:1398–1403

    CAS  PubMed  Google Scholar 

  • Chouinard PA, Van Der Werf YD, Leonard G, Paus T (2003) Modulating neural networks with transcranial magnetic stimulation applied over the dorsal premotor and primary motor cortices. J Neurophysiol 90:1071–1083

    Article  PubMed  Google Scholar 

  • Civardi C, Cantello R, Asselman P, Rothwell JC (2001) Transcranial magnetic stimulation can be used to test connections to primary motor areas from frontal and medial cortex in humans. Neuroimage 14:1444–1453

    Article  CAS  PubMed  Google Scholar 

  • Fox P, Ingham R, George MS, Mayberg H, Ingham J, Roby J, Martin C, Jerabek P (1997) Imaging human intra-cerebral connectivity by PET during TMS. Neuroreport 8:2787–2791

    Article  CAS  PubMed  Google Scholar 

  • Galuske RA, Schmidt KE, Goebel R, Lomber SG, Payne BR (2002) The role of feedback in shaping neural representations in cat visual cortex. Proc Natl Acad Sci USA 99:17083–17088

    Article  CAS  PubMed  Google Scholar 

  • Gangitano M, Valero-Cabré A, Tormos JM, Mottaghy FM, Romero JR, Pascual-Leone A (2002) Modulation of input–output curves by low and high frequency repetitive transcranial magnetic stimulation of the motor cortex. Clin Neurophysiol 113:1249–1257

    Article  PubMed  Google Scholar 

  • Ganis G, Keenan JP, Kosslyn SM, Pascual-Leone A (2000) Transcranial magnetic stimulation of primary motor cortex affects mental rotation. Cereb Cortex 10:175–180

    Article  CAS  PubMed  Google Scholar 

  • Gerschlager W, Christensen LO, Bestmann S, Rothwell JC (2002) rTMS over the cerebellum can increase corticospinal excitability through a spinal mechanism involving activation of peripheral nerve fibres. Clin Neurophysiol 113:1435–1440

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez-Lima F (1992) Brain imaging of auditory functions in cats: studies with fluoroxyglucose autoradiography and cytochrome oxidase histochemistry. In: Gonzalez-Lima F, Finkenstaedt T, Scheich H (eds) Advances in metabolic mapping techniques for brain imaging of behavioral and learning functions. Kluwer, Dordrecht, pp 39–109

    Google Scholar 

  • Harting JK, Updyke BV, Van Lieshout DP (1992) Corticotectal projections in the cat: anterograde transport studies of twenty-five cortical areas. J Comp Neurol 324:379–414

    Article  CAS  PubMed  Google Scholar 

  • Hayashi T, Ohnishi T, Okabe S, Teramoto N, Nonaka Y, Watabe H, Imabayashi E, Ohta Y, Jino H, Ejima N, Sawada T, Iida H, Matsuda H, Ugawa Y (2004) Long-term effect of motor cortical repetitive transcranial magnetic stimulation [correction]. Ann Neurol 56:77–85

    Article  PubMed  Google Scholar 

  • Hilgetag CC, Theoret H, Pascual-Leone A (2001) Enhanced visual spatial attention ipsilateral to rTMS-induced ‘virtual lesions’ of human parietal cortex. Nat Neurosci 4:953–957

    Article  CAS  PubMed  Google Scholar 

  • Huang YZ, Edwards MJ, Rounis E, Bhatia KP, Rothwell JC (2005) Theta burst stimulation of the human motor cortex. Neuron 45:201–206

    Article  CAS  PubMed  Google Scholar 

  • Ikeda H, Wright MJ (1974) Sensitivity of neurones in visual cortex (area 17) under different levels of anaesthesia. Exp Brain Res 20:471–484

    Article  CAS  PubMed  Google Scholar 

  • Iyer MB, Schleper N, Wassermann EM (2003) Priming stimulation enhances the depressant effect of low-frequency repetitive transcranial magnetic stimulation. J Neurosci 23:10867–10872

    CAS  PubMed  Google Scholar 

  • Kanaseki T, Sprague JM (1974) Anatomical organization of pretectal nuclei and tectal laminae in the cat. J Comp Neurol 158:319–337

    Article  CAS  PubMed  Google Scholar 

  • Kennedy C, Des Rosiers MH, Jehle JW, Reivich M, Sharpe F, Sokoloff L (1975) Mapping of functional neural pathways by autoradiographic survey of local metabolic rate with (14C)deoxyglucose. Science 187:850–853

    Article  CAS  PubMed  Google Scholar 

  • Kobayashi M, Pascual-Leone A (2003) Transcranial magnetic stimulation in neurology. Lancet Neurol 2:145–156

    Article  PubMed  Google Scholar 

  • Lee L, Siebner HR, Rowe JB, Rizzo V, Rothwell JC, Frackowiak RS, Friston KJ (2003) Acute remapping within the motor system induced by low-frequency repetitive transcranial magnetic stimulation. J Neurosci 23:5308–5318

    CAS  PubMed  Google Scholar 

  • Lomber SG, Payne BR, Hilgetag CC, Rushmore J (2002) Restoration of visual orienting into a cortically blind hemifield by reversible deactivation of posterior parietal cortex or the superior colliculus. Exp Brain Res 142:463–474

    Article  PubMed  Google Scholar 

  • Lowel S (2002) 2-deoxyglucose architecture of the cat primary visual cortex. In: Payne B, Peters A (eds) The cat primary visual cortex. Academic, San Diego, pp 167–189

  • Maeda F, Keenan JP, Tormos JM, Topka H, Pascual-Leone A (2000) Modulation of corticospinal excitability by repetitive transcranial magnetic stimulation. Clin Neurophysiol 111:800–805

    Article  CAS  PubMed  Google Scholar 

  • Moliadze V, Zhao Y, Eysel U, Funke K (2003) Effect of transcranial magnetic stimulation on single-unit activity in the cat primary visual cortex. J Physiol 553:665–679

    Article  CAS  PubMed  Google Scholar 

  • Moliadze V, Giannikopoulos D, Eysel UT, Funke K (2005) Paired-pulse transcranial magnetic stimulation protocol applied to visual cortex of anaesthetized cat: effects on visually evoked single-unit activity. J Physiol 566:955–965

    Article  CAS  PubMed  Google Scholar 

  • Mottaghy FM, Pascual-Leone A, Kemna LJ, Topper R, Herzog H, Muller-Gartner HW, Krause BJ (2003) Modulation of a brain-behavior relationship in verbal working memory by rTMS. Brain Res Cogn Brain Res 15:241–249

    Article  PubMed  Google Scholar 

  • Munchau A, Bloem BR, Irlbacher K, Trimble MR, Rothwell JC (2002) Functional connectivity of human premotor and motor cortex explored with repetitive transcranial magnetic stimulation. J Neurosci 22:554–561

    CAS  PubMed  Google Scholar 

  • Okabe S, Hanajima R, Ohnishi T, Nishikawa M, Imabayashi E, Takano H, Kawachi T, Matsuda H, Shiio Y, Iwata NK, Furubayashi T, Terao Y, Ugawa Y (2003) Functional connectivity revealed by single-photon emission computed tomography (SPECT) during repetitive transcranial magnetic stimulation (rTMS) of the motor cortex. Clin Neurophysiol 114:450–457

    Article  PubMed  Google Scholar 

  • Palmer LA, Rosenquist AC, Tusa RJ (1978) The retinotopic organization of lateral suprasylvian visual areas in the cat. J Comp Neurol 177:237–256

    Article  CAS  PubMed  Google Scholar 

  • Pascual-Leone A, Gomez-Tortosa E, Grafman J, Alway D, Nichelli P, Hallett M (1994) Induction of visual extinction by rapid-rate transcranial magnetic stimulation of parietal lobe. Neurology 44:494–498

    CAS  PubMed  Google Scholar 

  • Pascual-Leone A, Tormos JM, Keenan J, Tarazona F, Canete C, Catala MD (1998) Study and modulation of human cortical excitability with transcranial magnetic stimulation. J Clin Neurophysiol 15:333–343

    Article  CAS  PubMed  Google Scholar 

  • Pascual-Leone ADN, Wassermann EM, Rothwell J, Puri BK (2001) Handbook of transcranial magnetic stimulation. Arnold, London

    Google Scholar 

  • Paus T, Jech R, Thompson CJ, Comeau R, Peters T, Evans AC (1997) Transcranial magnetic stimulation during positron emission tomography: a new method for studying connectivity of the human cerebral cortex. J Neurosci 17:3178–3184

    CAS  PubMed  Google Scholar 

  • Paus T, Jech R, Thompson CJ, Comeau R, Peters T, Evans AC (1998) Dose-dependent reduction of cerebral blood flow during rapid-rate transcranial magnetic stimulation of the human sensorimotor cortex. J Neurophysiol 79:1102–1107

    CAS  PubMed  Google Scholar 

  • Payne BR (1994) Neuronal interactions in cat visual cortex mediated by the corpus callosum. Behav Brain Res 64:55–64

    Article  CAS  PubMed  Google Scholar 

  • Payne BR, Lomber SG (1999) A method to assess the functional impact of cerebral connections on target populations of neurons. J Neurosci Methods 86:195–208

    Article  CAS  PubMed  Google Scholar 

  • Payne BR, Lomber SG (2003) Quantitative analyses of principal and secondary compound parieto-occipital feedback pathways in cat. Exp Brain Res 152:420–433

    PubMed  Google Scholar 

  • Payne BR, Rushmore RJ (2004) Functional circuitry underlying natural and interventional cancellation of visual neglect. Exp Brain Res 154:127–153

    Article  PubMed  Google Scholar 

  • Payne BR, Siwek DF, Lomber SG (1991) Complex transcallosal interactions in visual cortex. Vis Neurosci 6:283–289

    Article  CAS  PubMed  Google Scholar 

  • Payne BR, Lomber SG, Villa AE, Bullier J (1996) Reversible deactivation of cerebral network components. Trends Neurosci 19:535–542

    Article  CAS  PubMed  Google Scholar 

  • Payne BR, Lomber SG, Rushmore RJ, Pascual-Leone A (2003) Cancellation of visuoparietal lesion-induced spatial neglect. Exp Brain Res 150:395–398

    PubMed  Google Scholar 

  • Peinemann A, Reimer B, Loer C, Quartarone A, Munchau A, Conrad B, Siebner HR (2004) Long-lasting increase in corticospinal excitability after 1800 pulses of subthreshold 5 Hz repetitive TMS to the primary motor cortex. Clin Neurophysiol 115:1519–1526

    Article  PubMed  Google Scholar 

  • Robertson EM, Theoret H, Pascual-Leone A (2003) Studies in cognition: the problems solved and created by transcranial magnetic stimulation. J Cogn Neurosci 15:948–960

    Article  CAS  PubMed  Google Scholar 

  • Robertson EM, Tormos JM, Maeda F, Pascual-Leone A (2001) The role of the dorsolateral prefrontal cortex during sequence learning is specific for spatial information. Cereb Cortex 11:628–635

    Article  CAS  PubMed  Google Scholar 

  • Romero JR, Anschel D, Sparing R, Gangitano M, Pascual-Leone A (2002) Subthreshold low frequency repetitive transcranial magnetic stimulation selectively decreases facilitation in the motor cortex. Clin Neurophysiol 113:101–107

    Article  PubMed  Google Scholar 

  • Roth BJ, Saypol JM, Hallett M, Cohen LG (1991) A theoretical calculation of the electric field induced in the cortex during magnetic stimulation. Electroencephalogr Clin Neurophysiol 81:47–56

    Article  CAS  PubMed  Google Scholar 

  • Rounis E, Lee L, Siebner HR, Rowe JB, Friston KJ, Rothwell JC, Frackowiak RS (2005) Frequency specific changes in regional cerebral blood flow and motor system connectivity following rTMS to the primary motor cortex. Neuroimage 26:164–176

    Article  PubMed  Google Scholar 

  • Schoppmann A, Stryker MP (1981) Physiological evidence that the 2-deoxyglucose method reveals orientation columns in cat visual cortex. Nature 293:574–576

    Article  CAS  PubMed  Google Scholar 

  • Siebner HR, Rothwell J (2003) Transcranial magnetic stimulation: new insights into representational cortical plasticity. Exp Brain Res 148:1–16

    Article  PubMed  Google Scholar 

  • Siebner HR, Takano B, Peinemann A, Schwaiger M, Conrad B, Drzezga A (2001) Continuous transcranial magnetic stimulation during positron emission tomography: a suitable tool for imaging regional excitability of the human cortex. Neuroimage 14:883–890

    Article  CAS  PubMed  Google Scholar 

  • Siebner HR, Willoch F, Peller M, Auer C, Boecker H, Conrad B, Bartenstein P (1998) Imaging brain activation induced by long trains of repetitive transcranial magnetic stimulation. Neuroreport 9:943–948

    Article  CAS  PubMed  Google Scholar 

  • Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897–916

    Article  CAS  PubMed  Google Scholar 

  • Strafella AP, Paus T (2001) Cerebral blood-flow changes induced by paired-pulse transcranial magnetic stimulation of the primary motor cortex. J Neurophysiol 85:2624–2629

    CAS  PubMed  Google Scholar 

  • Takano B, Drzezga A, Peller M, Sax I, Schwaiger M, Lee L, Siebner HR (2004) Short-term modulation of regional excitability and blood flow in human motor cortex following rapid-rate transcranial magnetic stimulation. Neuroimage 23:849–859

    Article  PubMed  Google Scholar 

  • Thut G, Nietzel A, Pascual-Leone A (2005) Dorsal posterior parietal rTMS affects voluntary orienting of visuospatial attention. Cereb Cortex 15:628–638

    Article  PubMed  Google Scholar 

  • Tusa R, Rosenquist A, Palmer L (1981) Multiple cortical visual areas: visual field topography in the cat. In: Woolsey C (ed) Cortical sensory organization: multiple visual areas. Humana Press, Clifton, pp 1–31

  • Updyke BV (1981) Projections from visual areas of the middle suprasylvian sulcus onto the lateral posterior complex and adjacent thalamic nuclei in cat. J Comp Neurol 201:477–506

    Article  CAS  PubMed  Google Scholar 

  • Valero-Cabré A, Oliveri M, Gangitano M, Pascual-Leone A (2001) Modulation of spinal cord excitability by subthreshold repetitive transcranial magnetic stimulation of the primary motor cortex in humans. Neuroreport 12:3845–3848

    Article  PubMed  Google Scholar 

  • Valero-Cabré A, Pascual-Leone A (2005) Impact of TMS on the primary motor cortex and associated spinal systems. IEEE Eng Med Biol Mag 24:29–36

    Article  PubMed  Google Scholar 

  • Valero-Cabré A, Payne BR, Rushmore J, Lomber SG, Pascual-Leone A (2005) Impact of repetitive transcranial magnetic stimulation of the parietal cortex on metabolic brain activity: a(14) C-2DG tracing study in the cat. Exp Brain Res 163:1–12

    Article  PubMed  Google Scholar 

  • Valero-Cabré A, Rushmore RJ, Payne BR (2006) Low frequency transcranial magnetic stimulation on the posterior parietal cortex induces visuotopically specific neglect-like syndrome. Exp Brain Res 172:14–21

    Article  PubMed  Google Scholar 

  • Vanduffel W, Payne BR, Lomber SG, Orban GA (1997a) Functional impact of cerebral connections. Proc Natl Acad Sci USA 94:7617–7620

    Article  CAS  Google Scholar 

  • Vanduffel W, Vandenbussche E, Singer W, Orban GA (1995) Metabolic mapping of visual areas in the behaving cat: a [14C]2-deoxyglucose study. J Comp Neurol 354:161–180

    Article  CAS  PubMed  Google Scholar 

  • Vanduffel W, Vandenbussche E, Singer W, Orban GA (1997b) A metabolic mapping study of orientation discrimination and detection tasks in the cat. Eur J Neurosci 9:1314–1328

    Article  CAS  Google Scholar 

  • Wassermann EM, Lisanby SH (2001) Therapeutic application of repetitive transcranial magnetic stimulation: a review. Clin Neurophysiol 112:1367–1377

    Article  CAS  PubMed  Google Scholar 

  • Walsh A, Pascual-Leone A (2003) Neurochronometrics of mind: TMS in cognitive science. MIT, Cambridge

Download references

Acknowledgments

We are extremely grateful to Dr. Jarrett Rushmore for methodological assistance and fruitful discussions. Supported in part by the National Institutes of Health (NS32137, NS33975 and NS47754 to BRP/MM/AV-C). AV-C was also supported by grants from ‘La Caixa’ (Spain) and the Spanish Ministry of Education, Culture and Sports EX2002-041).

Author information

Authors and Affiliations

  1. Laboratory of Cerebral Dynamics, Plasticity and Rehabilitation, Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, 02118, USA

    Antoni Valero-Cabré & Bertram R. Payne

  2. Center for Non-invasive Brain Stimulation, Beth Israel Deaconess Medical Center and Department of Neurology, Harvard Medical School, Boston, MA, 02115, USA

    Antoni Valero-Cabré & Alvaro Pascual-Leone

  3. Department of Neurology, LPNC CNRS Unit 5105-ERT-Treat Vision, Fondation Ophtalmologique Rothschild, Paris, France

    Antoni Valero-Cabré

Authors
  1. Antoni Valero-Cabré
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bertram R. Payne
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alvaro Pascual-Leone
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Antoni Valero-Cabré.

Additional information

†Prof. Payne passed away in May 2004. This article is submitted in his memory.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Valero-Cabré, A., Payne, B.R. & Pascual-Leone, A. Opposite impact on 14C-2-deoxyglucose brain metabolism following patterns of high and low frequency repetitive transcranial magnetic stimulation in the posterior parietal cortex. Exp Brain Res 176, 603–615 (2007). https://doi.org/10.1007/s00221-006-0639-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-006-0639-8

Keywords

Search

Navigation