Assessment of standard coil positioning in transcranial magnetic stimulation in depression Cecilia Nauczyciel a,b,c,d, ⁎, Pierre Hellier a,b , Xavier Morandi a,b,c,e , Sophie Blestel a,b , Dominique Drapier d , Jean Christophe Ferre a,b,c,f , Christian Barillot a,b,c , Bruno Millet d a INRIA, Unit/Projet team VisAGeS, France b INSERM, U746 Visages Unit, France c CNRS, University of Rennes 1, France d Department of Psychiatry, University of Rennes 1, France e Department of Neurosurgery, University of Rennes 1, France f Department of Neuroradiology, University of Rennes 1, France abstract article info Article history: Received 6 July 2009 Received in revised form 14 June 2010 Accepted 21 June 2010 Keywords: Neuronavigation Dorsolateral prefrontal cortex Major depression Computed-assisted procedure Transcranial magnetic stimulation (TMS) is a non-invasive technique used in the treatment of major depression. Meta-analyses have shown that it is more efficient than a placebo and that its efficacy is enhanced by the optimum tuning of stimulation parameters. However, the stimulation target, the dorsolateral prefrontal cortex (DLPFC), is still located using an inaccurate method. In this study, a neuronavigation system was used to perform a comprehensive quantification of target localization errors. We identified and quantified 3 sources of error in the standard method: cap repositioning, interexpert variability in coil positioning and distance between the stimulated point and the expected target. For cap repositioning, the standard deviation was lower than 5 mm in the 3 axes. For interexpert variability in coil positioning, the spatial dispersion of the points was higher than 10 mm in 2 of the 3 axes. For interindividual anatomical variability, the distance between the actual “reference” DLPFC and its standard determination was greater than 20 mm for 54% of the subjects, while one subject out of eleven was correctly targeted which means 10 mm or less from the reference. Results showed that interindividual anatomical variability and interexpert variability were the two main sources of error using the standard method. Results demonstrate that a neuronavigation system is mandatory to conduct reproducible and reliable studies. © 2010 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Transcranial magnetic stimulation (TMS) is a tool used in neuro- sciences to investigate neuronal connections (Paus et al., 1997) and cognitive functions such as working memory by creating temporary “virtual lesions”. TMS is also used as a therapeutic tool in neurology and psychiatry. It is increasingly used for the treatment of major depression. The antidepressant properties of TMS were discovered in 1995 (George et al., 1995) and repetitive transcranial magnetic stimulation (rTMS) has been used in many studies, including randomized sham-controlled ones. These studies have demonstrated the efficacy of real rTMS compared with sham rTMS (George et al., 1997; Avery et al., 1999; Eschweiler et al., 2000; Fitzgerald et al., 2003; Avery et al., 2006). Several meta-analyses (Gershon et al., 2003; Couturier, 2005; Loo and Mitchell, 2005) have also noted a degree of efficacy, though not as great as that expected by clinicians using this tool. These disappointing results can be explained by a number of different factors: firstly, the heterogeneity of the patients; secondly, the parameters used, such as the intensity and frequency of stimulation; and thirdly, the location of the cortical area being stimulated, which is the focus of this article. In most of the published studies, the dorsolateral prefrontal cortex (DLPFC) was chosen as the stimulated target. This area is large: a broader definition defines the DLPFC as the lateral portions of Brodmann areas 9, 10, 11, 12, of areas 45, 46 and the superior part of the area 47. (Procyk and Goldman-Rakic, 2006). As others (Petrides and Pandya, 1999; Mayberg et al., 1999; Drevets, 2000; Rogers et al., 2004), we defined the DLPFC as part of the rostral frontal lobe roughly equivalent to Brodmann areas 9 and 46. The interface between these both areas roughly corresponds to the second third, i.e. middle part, of the middle frontal gyrus along an anteroposterior axis. As neuroimaging studies have revealed hypometabolism of the left prefrontal cortex in de- pressive patients (Mayberg et al., 1999; Drevets, 2000; Rogers et al., 2004) and George et al. (1996) have shown that stimulation of this Psychiatry Research 186 (2011) 232–238 ⁎ Corresponding author. Department of Psychiatry, University of Rennes 1, Guillaume Regnier Hospital, 108 avenue du Général Leclerc, 35000 Rennes, France. Tel.: + 33 299336001; fax: + 33 299333972. E-mail address: bruno.millet@univ-rennes1.fr (C. Nauczyciel). 0165-1781/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2010.06.012 Contents lists available at ScienceDirect Psychiatry Research journal homepage: www.elsevier.com/locate/psychres