Several studies have proved that low-frequency transcranial magnetic stimulation (TMS) of the right dorsolateral prefrontal cortex (DLPFC) showed an antidepressant effect, although its mechanism is still not completely elucidated. The aim of the present study was to clarify the alteration in neuroanatomical function elicited by low-frequency TMS of the right DLPFC in treatment-resistant depression and to detect the difference between responders and nonresponders to TMS. Single-photon emission computed tomography with 99mTc-ethyl cysteinate dimer was performed in 14 right-handed male patients with treatment-resistant unipolar depression before and after low-frequency TMS of the right DLPFC. Five 60-second 1-Hz trains were applied and 12 treatment sessions were administered within a 3-week period (total pulses, 3,600). The Hamilton Rating Scale for Depression was administered and the regional cerebral blood flow (rCBF) was analyzed using statistical parametric mapping (SPM2). After TMS treatment in 14 patients, the score on the Hamilton Rating Scale for Depression decreased significantly, and considerable decreases in rCBF were seen in the bilateral prefrontal, orbitofrontal, anterior insula, right subgenual cingulate, and left parietal cortex, but no significant increase in rCBF occurred. Additionally, as compared with 8 nonresponders, 6 responders showed significant increases in rCBF at baseline in the left hemisphere including the prefrontal and limbic-paralimbic regions. These results suggest that the antidepressant effect of low-frequency TMS of the right DLPFC is associated with a decrease in rCBF in the limbic-paralimbic regions via the ipsilateral subgenual cingulate, and increased rCBF at baseline in the left hemisphere may be involved in the response to low-frequency TMS treatment.
© 2008 S. Karger AG, Basel
- Transcranial magnetic stimulation
- Brain imaging
- Belmaker RH, Fleischmann A: Transcranial magnetic stimulation: a potential new frontier in psychiatry. Biol Psychiatry 1995;38:419–421.
- George MS, Lisanby SH, Sackeim HA: Transcranial magnetic stimulation: applications in neuropsychiatry. Arch Gen Psychiatry 1999;56:300–311.
- Chouinard PA, Van Der Werf YD, Leonard G, Paus T: Modulating neural networks with transcranial magnetic stimulation applied over the dorsal premotor and primary motor cortices. J Neurophysiol 2003;90:1071–1083.
- Speer AM, Kimbrell TA, Wassermann EM, D Repella J, Willis MW, Herscovitch P, Post RM: Opposite effects of high and low frequency rTMS on regional brain activity in depressed patients. Biol Psychiatry 2000;48:1133–1141.
- Loo CK, Sachdev PS, Haindl W, Wen W, Mitchell PB, Croker VM, Malhi GS: High (15 Hz) and low (1 Hz) frequency transcranial magnetic stimulation have different acute effects on regional cerebral blood flow in depressed patients. Psychol Med 2003;33:997–1006.
- Baxter LR Jr, Schwartz JM, Phelps ME, Mazziotta JC, Guze BH, Selin CE, Gerner RH, Sumida RM: Reduction of prefrontal cortex glucose metabolism common to three types of depression. Arch Gen Psychiatry 1989;46:243–250.
- Biver F, Goldman S, Delvenne V, Luxen A, De Maertelaer V, Hubain P, Mendlewicz J, Lotstra F: Frontal and parietal metabolic disturbances in unipolar depression. Biol Psychiatry 1994;36:381–388.
- Bench CJ, Frackowiak RS, Dolan RJ: Changes in regional cerebral blood flow on recovery from depression. Psychol Med 1995;25:247–261.
- Kennedy SH, Evans KR, Krüger S, Mayberg HS, Meyer JH, McCann S, Arifuzzman AI, Houle S, Vaccarino FJ: Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. Am J Psychiatry 2001;158:899–905.
- Pascual-Leone A, Rubio B, Pallardó F, Catalá MD: Rapid-rate transcranial magnetic stimulation of left dorsolateral prefrontal cortex in drug-resistant depression. Lancet 1996;348:233–237.
- George MS, Nahas Z, Molloy M, Speer AM, Oliver NC, Li XB, Arana GW, Risch SC, Ballenger JC: A controlled trial of daily left prefrontal cortex TMS for treating depression. Biol Psychiatry 2000;48:962–970.
- Fitzgerald PB, Brown TL, Marston NA, Daskalakis ZJ, De Castella A, Kulkarni J: Transcranial magnetic stimulation in the treatment of depression: a double-blind, placebo-controlled trial. Arch Gen Psychiatry 2003;60:1002–1008.
- Avery DH, Holtzheimer PE 3rd, Fawaz W, Russo J, Neumaier J, Dunner DL, Haynor DR, Claypoole KH, Wajdik C, Roy-Byrne P: A controlled study of repetitive transcranial magnetic stimulation in medication-resistant major depression. Biol Psychiatry 2006;59:187–194.
- Gershon AA, Dannon PN, Grunhaus L: Transcranial magnetic stimulation in the treatment of depression. Am J Psychiatry 2003;160:835–845.
- O’reardon JP, Solvason HB, Janicak PG, Sampson S, Isenberg KE, Nahas Z, McDonald WM, Avery D, Fitzgerald PB, Loo C, Demitrack MA, George MS, Sackeim HA: Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial. Biol Psychiatry 2007;62:1208–1216.
- Keck ME, Welt T, Müller MB, Erhardt A, Ohl F, Toschi N, Holsboer F, Sillaber I: Repetitive transcranial magnetic stimulation increases the release of dopamine in the mesolimbic and mesostriatal system. Neuropharmacology 2002;43:101–109.
- Pridmore S: Rapid transcranial magnetic stimulation and normalization of the dexamethasone suppression test. Psychiatry Clin Neurosci 1999;53:33–37.
- Szuba MP, O’Reardon JP, Rai AS, Snyder-Kastenberg J, Amsterdam JD, Gettes DR, Wassermann E, Evans DL: Acute mood and thyroid stimulating hormone effects of transcranial magnetic stimulation in major depression. Biol Psychiatry 2001;50:22–27.
- Kito S, Fujita K, Koga Y: Changes in regional cerebral blood flow after repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex in treatment-resistant depression. J Neuropsychiatry Clin Neurosci 2008;20:74–80.
- Klein E, Kreinin I, Chistyakov A, Koren D, Mecz L, Marmur S, Ben-Shachar D, Feinsod M: Therapeutic efficacy of right prefrontal slow repetitive transcranial magnetic stimulation in major depression: a double-blind controlled study. Arch Gen Psychiatry 1999;56:315–320.
- Hamilton M: A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56–62.
- Thase ME, Rush AJ: When at first you don’t succeed: sequential strategies for antidepressant nonresponders. J Clin Psychiatry 1997;58(suppl 13):23–29.
- Pridmore S, Fernandes Filho JA, Nahas Z, Liberatos C, George MS: Motor threshold in transcranial magnetic stimulation: a comparison of a neurophysiological method and a visualization of movement method. J ECT 1998;14:25–27.
- Talairach J, Tournoux P: Co-Planar Stereotaxic Atlas of the Human Brain. Three-Dimensional Proportional System. New York, Thieme Medical, 1988.
- Brett M, Johnsrude IS, Owen AM: The problem of functional localization in the human brain. Nat Rev Neurosci 2002;3:243–249.
- Bench CJ, Friston KJ, Brown RG, Frackowiak RS, Dolan RJ: Regional cerebral blood flow in depression measured by positron emission tomography: the relationship with clinical dimensions. Psychol Med 1993;23:579–590.
- Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA, Silva JA, Tekell JL, Martin CC, Lancaster JL, Fox PT: Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. Am J Psychiatry 1999;156:675–682.
- Soares JC, Mann JJ: The functional neuroanatomy of mood disorder. J Psychiatr Res 1997;31:393–432.
- Goldapple K, Segal Z, Garson C, Lau M, Bieling P, Kennedy S, Mayberg H: Modulation of cortical-limbic pathways in major depression: treatment-specific effects of cognitive behavior therapy. Arch Gen Psychiatry 2004;61:34–41.
- Drevets WC, Price JL, Simpson JR Jr, Todd RD, Reich T, Vannier M, Raichle ME: Subgenual prefrontal cortex abnormalities in mood disorders. Nature 1997;386:824–827.
- Mayberg HS, Brannan SK, Tekell JL, Silva JA, Mahurin RK, McGinnis S, Jerabek PA: Regional metabolic effects of fluoxetine in major depression: serial changes and relationship to clinical response. Biol Psychiatry 2000;48:830–843.
- Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH: Deep brain stimulation for treatment-resistant depression. Neuron 2005;45:651–660.
- Stern WM, Tormos JM, Press DZ, Pearlman C, Pascual-Leone A: Antidepressant effects of high and low frequency repetitive transcranial magnetic stimulation to the dorsolateral prefrontal cortex: a double-blind, randomized, placebo-controlled trial. J Neuropsychiatry Clin Neurosci 2007;19:179–186.
- Kimbrell TA, Little JT, Dunn RT, Frye MA, Greenberg BD, Wassermann EM, Repella JD, Danielson AL, Willis MW, Benson BE, Speer AM, Osuch E, George MS, Post RM: Frequency dependence of antidepressant response to left prefrontal repetitive transcranial magnetic stimulation (rTMS) as a function of baseline cerebral glucose metabolism. Biol Psychiatry 1999;46:1603–1613.
Department of Neuropsychiatry
Kyorin University School of Medicine
6-20-2 Shinkawa, Mitaka, Tokyo 181-8611 (Japan)
Tel. +81 422 47 5511, Fax +81 422 45 4697, E-Mail email@example.com
Received: December 13, 2007
Accepted after revision: May 25, 2008
Published online: September 10, 2008
Number of Print Pages : 8
Number of Figures : 2, Number of Tables : 3, Number of References : 34
Neuropsychobiology (International Journal of Experimental and Clinical Research in Biological Psychiatry, Pharmacopsychiatry, Biological Psychology/Pharmacopsychology and Pharmacoelectroencephalography)
Vol. 58, No. 1, Year 2008 (Cover Date: October 2008)
Journal Editor: Strik W. (Bern)
ISSN: 0302–282X (Print), eISSN: 1423–0224 (Online)
For additional information: http://www.karger.com/NPS
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.