Elsevier

Psychiatry Research

Volume 186, Issues 2–3, 30 April 2011, Pages 232-238
Psychiatry Research

Assessment of standard coil positioning in transcranial magnetic stimulation in depression

https://doi.org/10.1016/j.psychres.2010.06.012Get rights and content

Abstract

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.

Introduction

Transcranial magnetic stimulation (TMS) is a tool used in neurosciences 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 depressive patients (Mayberg et al., 1999, Drevets, 2000, Rogers et al., 2004) and George et al. (1996) have shown that stimulation of this target area has an antidepressant effect, this is the target we chose for our study.

The left DLPFC is localized following a “standard procedure” devised by George et al., 1995, Pascual-Leone et al., 1996. The primary motor cortex is first located by looking for the response of the controlateral abductor pollicis brevis muscle. The coil is moved 5 cm rostrally in a parasagittal plane. The stimulation point is then drawn on a cap previously placed on the patient's head, on which anatomical landmarks are drawn in order to be able to reposition it correctly for each stimulation session.

Although this method is easy to use in clinical routine, we identified three main sources of error: cap repositioning between stimulation sessions (only for groups using a cap), variability in locating the left DLPFC between the different clinicians practicing TMS (interexpert variability) and the discrepancy between the stimulation locus and the reference stimulation target recorded in the magnetic resonance imaging (MRI) coordinate system (interindividual anatomical variability). The latter is different from the operator-dependent bias and remains present even if the localization procedure is perfectly performed. Herwig et al. (2001) tested the reliability of the standard coil positioning method on 22 subjects using neuronavigation and showed that only 7 out of 22 were correctly targeted. As this is the method used to locate the left DLPFC in most previous studies, the high degree of variability in the stimulated target must surely have affected their clinical results.

The ability to stimulate the right target accurately is also a requirement in neurosurgery. Neuronavigation systems have therefore been developed for use in computer-assisted procedures and can be adapted to TMS. These systems make it possible to determine the position of the left DLPFC more accurately by finding the middle part of the middle frontal gyrus. A neuronavigation system limits localization errors, obviates the need for cap repositioning and takes account of interindividual anatomical variability. However, in order to assess the need for a neuronavigation system, we first needed to quantify the inaccuracy of the standard method arising from the three sources of error which are cap repositioning, interexpert variability in coil positioning and distance between the actual “reference” DLPFC located on the MRI and its standard determination.

Section snippets

Subjects

We recruited one healthy subject for Studies 1 (assessment of cap repositioning) and 2 (assessment of interexpert variability in coil positioning) and 10 right-handed depressed patients (4 men, 6 women) (mean age: 54 years, standard deviation: 9.77) for Study 3 (quantification of distance between actual DLPFC and its standard determination).

Patients were interviewed with the MINI (Sheehan et al., 1998) in order to diagnose current major depressive disorders and rule out other psychiatric

Study 1: Cap repositioning

The prefrontal cortex was chosen as the target, in order to reproduce the usual coil positioning situation. Standard deviations (SD) for the target along the three axes were 3.18 mm (left/right axis), 1.74 mm (head/foot axis) and 2.32 mm (anteroposterior axis) when the cap was repositioned 30 times by the same expert (Fig. 2). When the cap was repositioned by different experts, the standard deviations were 3.80 mm, 2.52 mm and 2.89 mm (20 successive cap repositioning). To analyze the variance in the

Discussion

In our study, we sought to provide a more accurate measurement of the three main sources of inaccuracy in the standard location of the DLPFC: cap repositioning, inter-expert variability in coil positioning and the intrinsic error of the standard location method.

We found that the point cloud determined after the cap had been repositioned 30 times was relatively focused and the standard deviation was lower than 5 mm. In order to avoid a bias due to a single user, different clinicians performed the

Acknowledgements

The authors would like to thank Ms. Wiles Portier for preparing the manuscript.

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