Repetitive transcranial magnetic stimulation over the orbitofrontal cortex for obsessive-compulsive disorder: a double-blind, crossover study

C Nauczyciel, F Le Jeune, F Naudet, S Douabin, A Esquevin, M Vérin, T Dondaine, G Robert, D Drapier, B Millet, C Nauczyciel, F Le Jeune, F Naudet, S Douabin, A Esquevin, M Vérin, T Dondaine, G Robert, D Drapier, B Millet

Abstract

This pilot study was designed to assess the efficacy of low-frequency repetitive transcranial magnetic stimulation (rTMS) over the right orbitofrontal cortex (OFC) by means of a double-cone coil in patients suffering from obsessive-compulsive disorder. We hypothesized that low-frequency stimulation of the OFC would lead to a reduction in clinical symptoms, as measured on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A randomized, double-blind, crossover design was implemented with two 1-week treatment periods (active stimulation versus sham stimulation) separated by a 1-month washout period. Concomitantly, a subgroup of patients underwent a positron emission tomography (PET) scan after each stimulation sequence. Statistical analyses compared the Y-BOCS scores at the end of each period. At day 7, we observed a significant decrease from baseline in the Y-BOCS scores, after both active (P<0.01) and sham stimulation (P=0.02). This decrease tended to be larger after active stimulation than after sham stimulation: -6 (-29, 0) points versus -2 (-20, 4) points (P=0.07). Active versus sham PET scan contrasts showed that stimulation was related to a bilateral decrease in the metabolism of the OFC. The OFC should definitely be regarded as a key neuroanatomical target for rTMS, as it is easier to reach than either the striatum or the subthalamic nucleus, structures favored in neurosurgical approaches.

Figures

Figure 1
Figure 1
Changes in OCD severity in 19 patients during the crossover study. Data are shown at the time of inclusion in the study (month 0), after the first period of active or sham stimulation (day 7), before (month 1) and after (day 7) the second period of active or sham stimulation and at the end of the study (month 2). (a) Shows the mean (s.d.) scores on the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) for the active–sham group (lines) and sham–active group (dashed lines). (b) Shows the individual Y-BOCS scores for the active–sham and sham–active groups. The active stimulation period is shown in red and the sham stimulation period in orange. OCD, obsessive-compulsive disorder.
Figure 2
Figure 2
(a) Statistical parametric map showing decreased cerebral glucose metabolism in 10 OCD patients treated with rTMS, comparing active stimulation versus sham stimulation conditions. Areas with significant decreases (P<0.005, adjusted for multiple comparisons at cluster level) are shown on three telescoped orthogonal views. (b) Correlation between metabolic changes induced by rTMS and concomitant clinical improvement (Y-BOCS scores). Whole-brain analysis shows a significant cluster of correlation in the orbitofrontal cortex (Brodmann area 47) with the decrease in the Y-BOCS score.

References

    1. Association Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition: DSM-IV-TR®. American Psychiatric Association: Washington, DC, USA; 2000.
    1. Aouizerate B, Guehl D, Cuny E, Rougier A, Bioulac B, Tignol J, et al. Pathophysiology of obsessive-compulsive disorder: a necessary link between phenomenology, neuropsychology, imagery and physiology. Prog Neurobiol. 2004;72:195–221.
    1. Nuttin BJ, Gabriels LA, Cosyns PR, Meyerson BA, Andreewitch S, Sunaert SG, et al. Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder Neurosurgery 2003521263–1272., discussion 1272-1264.
    1. Mallet L, Polosan M, Jaafari N, Baup N, Welter ML, Fontaine D, et al. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med. 2008;359:2121–2134.
    1. Phillips ML, Drevets WC, Rauch SL, Lane R. Neurobiology of emotion perception I: The neural basis of normal emotion perception. Biol Psychiatry. 2003;54:504–514.
    1. Evans DW, Lewis MD, Iobst E. The role of the orbitofrontal cortex in normally developing compulsive-like behaviors and obsessive-compulsive disorder. Brain Cogn. 2004;55:220–234.
    1. Modell JG, Mountz JM, Curtis GC, Greden JF. Neurophysiologic dysfunction in basal ganglia/limbic striatal and thalamocortical circuits as a pathogenetic mechanism of obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci. 1989;1:27–36.
    1. Nordahl TE, Benkelfat C, Semple WE, Gross M, King AC, Cohen RM. Cerebral glucose metabolic rates in obsessive compulsive disorder. Neuropsychopharmacology. 1989;2:23–28.
    1. Rubin RT, Villanueva-Meyer J, Ananth J, Trajmar PG, Mena I. Regional xenon 133 cerebral blood flow and cerebral technetium 99 m HMPAO uptake in unmedicated patients with obsessive-compulsive disorder and matched normal control subjects. Determination by high-resolution single-photon emission computed tomography. Arch Gen Psychiatry. 1992;49:695–702.
    1. Millet B, Dondaine T, Reymann J-M, Bourguignon A, Naudet F, Jaafari N, et al. Obsessive compulsive disorder networks: positron emission tomography and neuropsychology provide new insights. PLoS One. 2013;8:e53241.
    1. Nakao T, Nakagawa A, Yoshiura T, Nakatani E, Nabeyama M, Yoshizato C, et al. Brain activation of patients with obsessive-compulsive disorder during neuropsychological and symptom provocation tasks before and after symptom improvement: a functional magnetic resonance imaging study. Biol Psychiatry. 2005;57:901–910.
    1. Rubin RT, Ananth J, Villanueva-Meyer J, Trajmar PG, Mena I. Regional 133xenon cerebral blood flow and cerebral 99mTc-HMPAO uptake in patients with obsessive-compulsive disorder before and during treatment. Biol Psychiatry. 1995;38:429–437.
    1. Le Jeune F, Verin M, N'Diaye K, Drapier D, Leray E, Du Montcel ST, et al. Decrease of prefrontal metabolism after subthalamic stimulation in obsessive-compulsive disorder: a positron emission tomography study. Biol Psychiatry. 2010;68:1016–1022.
    1. Haynes WI, Mallet L. High-frequency stimulation of deep brain structures in obsessive-compulsive disorder: the search for a valid circuit. Eur J Neurosci. 2010;32:1118–1127.
    1. Gershon AA, Dannon PN, Grunhaus L. Transcranial magnetic stimulation in the treatment of depression. Am J Psychiatry. 2003;160:835–845.
    1. Deng ZD, Lisanby SH, Peterchev AV. Electric field depth-focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs. Brain Stimul. 2013;6:1–13.
    1. Klein E, Kreinin I, Chistyakov A, Koren D, Mecz L, Marmur S, et al. 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.
    1. Pizzagalli DA, Nitschke JB, Oakes TR, Hendrick AM, Horras KA, Larson CL, et al. Brain electrical tomography in depression: the importance of symptom severity, anxiety, and melancholic features. Biol Psychiatry. 2002;52:73–85.
    1. Alonso P, Pujol J, Cardoner N, Benlloch L, Deus J, Menchon JM, et al. Right prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a double-blind, placebo-controlled study. Am J Psychiatry. 2001;158:1143–1145.
    1. Greenberg BD, George MS, Martin JD, Benjamin J, Schlaepfer TE, Altemus M, et al. Effect of prefrontal repetitive transcranial magnetic stimulation in obsessive-compulsive disorder: a preliminary study. Am J Psychiatry. 1997;154:867–869.
    1. Prasko J, Paskova B, Zalesky R, Novak T, Kopecek M, Bares M, et al. The effect of repetitive transcranial magnetic stimulation (rTMS) on symptoms in obsessive compulsive disorder. A randomized, double blind, sham controlled study. Neuro Endocrinol Lett. 2006;27:327–332.
    1. Sachdev PS, Loo CK, Mitchell PB, McFarquhar TF, Malhi GS. Repetitive transcranial magnetic stimulation for the treatment of obsessive compulsive disorder: a double-blind controlled investigation. Psychol Med. 2007;37:1645–1649.
    1. Mantovani A, Lisanby SH, Pieraccini F, Ulivelli M, Castrogiovanni P, Rossi S. Repetitive transcranial magnetic stimulation (rTMS) in the treatment of obsessive-compulsive disorder (OCD) and Tourette's syndrome (TS) Int J Neuropsychopharmacol. 2006;9:95–100.
    1. Mantovani A, Simpson HB, Fallon BA, Rossi S, Lisanby SH. Randomized sham-controlled trial of repetitive transcranial magnetic stimulation in treatment-resistant obsessive-compulsive disorder. Int J Neuropsychopharmacol. 2010;13:217–227.
    1. Jaafari N, Rachid F, Rotge JY, Polosan M, El-Hage W, Belin D, et al. Safety and efficacy of repetitive transcranial magnetic stimulation in the treatment of obsessive-compulsive disorder: a review. World J Biol Psychiatry. 2012;13:164–177.
    1. Gomes PV, Brasil-Neto JP, Allam N. Rodrigues de Souza E. A randomized, double-blind trial of repetitive transcranial magnetic stimulation in obsessive-compulsive disorder with three-month follow-up. J Neuropsychiatry Clin Neurosci. 2012;24:437–443.
    1. Ruffini C, Locatelli M, Lucca A, Benedetti F, Insacco C, Smeraldi E. Augmentation effect of repetitive transcranial magnetic stimulation over the orbitofrontal cortex in drug-resistant obsessive-compulsive disorder patients: a controlled investigation. Prim Care Companion J Clin Psychiatry. 2009;11:226–230.
    1. Goodman WK, Price LH, Rasmussen SA, Mazure C, Delgado P, Heninger GR, et al. The Yale-Brown Obsessive Compulsive Scale. II. Validity. Arch Gen Psychiatry. 1989;46:1012–1016.
    1. Goodman WK, Price LH, Rasmussen SA, Mazure C, Fleischmann RL, Hill CL, et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use, and reliability. Arch Gen Psychiatry. 1989;46:1006–1011.
    1. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10 J Clin Psychiatry 19985922–33., quiz 34-57.
    1. Guy W.ECDEU assessment manual for psychopharmacology/William Guy. U.S. Dept. of Health, Education, and Welfare, Public Health Service, Alcohol, Drug Abuse, and Mental Health Administration, National Institute of Mental Health, Psychopharmacology Research Branch, Division of Extramural Research Programs: Rockville, MD, USA1976
    1. Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979;134:382–389.
    1. Friston K, Holmes A, Worsly K, Poline J, Frith C, Frackowiak RS. Statistical parametric maps in functional imaging: a general linear approach. Hum Brain Mapp. 1995;2:189–210.
    1. Talairach. J, Tournoux. P (eds)Co-planar Stereotaxic Atlas of the Human Brain: 3-Dimensional Proportional System – an Approach to Cerebral Imaging Thieme Medical Publishers: New York, NY, USA; 1988
    1. Eickhoff SB, Stephan KE, Mohlberg H, Grefkes C, Fink GR, Amunts K, et al. A new SPM toolbox for combining probabilistic cytoarchitectonic maps and functional imaging data. Neuroimage. 2005;25:1325–1335.
    1. Button KS, Ioannidis JP, Mokrysz C, Nosek BA, Flint J, Robinson ES, et al. Power failure: why small sample size undermines the reliability of neuroscience. Nat Rev Neurosci. 2013;14:365–376.
    1. Mansur CG, Myczkowki ML, de Barros Cabral S, Sartorelli Mdo C, Bellini BB, Dias AM, et al. Placebo effect after prefrontal magnetic stimulation in the treatment of resistant obsessive-compulsive disorder: a randomized controlled trial. Int J Neuropsychopharmacol. 2011;14:1389–1397.
    1. Menzies L, Chamberlain SR, Laird AR, Thelen SM, Sahakian BJ, Bullmore ET. Integrating evidence from neuroimaging and neuropsychological studies of obsessive-compulsive disorder: the orbitofronto-striatal model revisited. Neurosci Biobehav Rev. 2008;32:525–549.
    1. Friedlander L, Desrocher M. Neuroimaging studies of obsessive-compulsive disorder in adults and children. Clin Psychol Rev. 2006;26:32–49.
    1. Stein DJ. Neurobiology of the obsessive-compulsive spectrum disorders. Biol Psychiatry. 2000;47:296–304.
    1. Schilman EA, Klavir O, Winter C, Sohr R, Joel D. The role of the striatum in compulsive behavior in intact and orbitofrontal-cortex-lesioned rats: possible involvement of the serotonergic system. Neuropsychopharmacology. 2010;35:1026–1039.

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