title: Influence of prefrontal target region on the efficacy of repetitive transcranial magnetic stimulation in patients with medication-resistant depression: a [(18)F]-fluorodeoxyglucose PET and MRI study.
abstract: It is currently unknown whether the antidepressant effect of repetitive transcranial magnetic stimulation (rTMS) depends on specific characteristics of the stimulated frontal area, such as metabolic changes. We investigated the effect of high-frequency rTMS, administered over the most hypometabolic prefrontal area in depressed patients in a two-site, double-blind, randomized placebo-controlled add-on study. Forty-eight patients with medication-resistant major depression underwent magnetic resonance imaging and [(18)F]-fluorodeoxyglucose positron emission tomography (PET) in order to determine a target area for rTMS. After randomization to PET-guided (n = 16), standard (n = 18), or sham rTMS (n = 14) conditions, the patients received 10 sessions of 10-Hz rTMS (1600 pulses/session) at 90% motor threshold. Change from baseline in Montgomery-Asberg Depression Rating Scale (MADRS) scores did not differ between PET-guided, standard and sham groups at 2-wk end-point. Exploratory comparison of left PET-guided (n = 9), right PET-guided, standard, and sham rTMS revealed significant effects. The highest improvement in MADRS scores was observed with left PET-guided (60 + or - 31%), significantly superior to sham (30 + or - 37%, p = 0.01) and right-guided (31 + or - 33%, p = 0.02) stimulation. Comparison between left PET-guided and standard rTMS (49 + or - 28%) was not significant (p = 0.12). Comparison between stimulation over dorsolateral prefrontal cortex (BA 9-46), stimulation of other areas, and sham rTMS was statistically significant. Stimulation over BA 9-46 region (n = 15) was superior to sham rTMS (p = 0.02). The results do not support the general hypothesis of increased antidepressant effects of high-frequency rTMS with prefrontal hypometabolism-related PET guidance. Nonetheless, whether metabolism and anatomy characteristics of left frontal area underneath the coil might account for an increase or speeding up of rTMS effects needs further investigation.
authors.affiliation: Inserm U797, CEA - INSERM U797 'Neuroimaging & Psychiatry', I2BM, IFR49. ml.paillere@cch.aphp.fr
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Paillère Martinot
authors.forename: André
authors.initials: A
authors.lastname: Galinowski
authors.forename: Damien
authors.initials: D
authors.lastname: Ringuenet
authors.forename: Thierry
authors.initials: T
authors.lastname: Gallarda
authors.forename: Jean-Pascal
authors.initials: JP
authors.lastname: Lefaucheur
authors.forename: Frank
authors.initials: F
authors.lastname: Bellivier
authors.forename: Christine
authors.initials: C
authors.lastname: Picq
authors.forename: Pascale
authors.initials: P
authors.lastname: Bruguière
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Mangin
authors.forename: Denis
authors.initials: D
authors.lastname: Rivière
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Willer
authors.forename: Bruno
authors.initials: B
authors.lastname: Falissard
authors.forename: Marion
authors.initials: M
authors.lastname: Leboyer
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Olié
authors.forename: Eric
authors.initials: E
authors.lastname: Artiges
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Martinot
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000627:therapeutic use; D001931:Brain Mapping; D003131:Combined Modality Therapy; D003865:Major Depressive Disorder / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000378:metabolism*; D004351:Drug Resistance; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism*; D007839:Functional Laterality; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000378:metabolism*; D050781:Transcranial Magnetic Stimulation / Q000379:methods* / Q000523:psychology; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D019788:Fluorodeoxyglucose F18