Comparison of "standard" and "navigated" procedures of TMS coil positioning over motor, premotor and prefrontal targets in patients with chronic pain and depression.

Since about 15 years, transcranial magnetic stimulation (TMS) is used as a technique to investigate the function of specific cortical regions. Single pulse TMS studies have targeted the dorsolateral premotor cortex (dlPMC) to characterize premotor-motor interactions in movement disorders. Repetitive TMS (rTMS) trials have targeted the dorsolateral prefrontal cortex (dlPFC) to treat depression. In almost all previous studies, these targets have been defined according to a "standard" scalp distance to the site of stimulation evoking motor responses of maximal amplitude in the contralateral hand ("hand motor hotspot" corresponding to the primary motor cortex, M1). The "standard" procedure of coil positioning locates the dlPMC and dlPFC as 2-3 and 5cm, respectively, anterior to the "hand motor hotspot". The aim of our study was to compare the locations of M1, dlPMC and dlPFC targets provided by the "standard" procedure of coil positioning and those provided by using a neuronavigation system integrating individual brain magnetic resonance imaging (MRI). Twenty-two patients were enrolled, all being treated for depressive symptoms in the context of chronic pain syndrome. The centers of the dlPMC and dlPFC regions were accurately targeted by the "standard" procedure in 14 and eight patients (64 and 36% of the series), respectively. In the other patients, the "standard" procedure located the dlPMC target on the M1/dlPMC border and the dlPFC target on the dlPMC/dlPFC border. On average, the MRI-guided location of M1, dlPMC, and dlPFC was, respectively, 6.1mm posterior, 31.7mm anterior and 69.0mm anterior to the "hand motor hotspot". The "standard" procedure failed to accurately locate the dlPMC and dlPFC targets by about 1 and 2cm, respectively. A statistical analysis of the MRI coordinates (x, y, z) of the targets revealed that the M1 target was more posterior, the dlPMC target more superficial and the dlPFC target more anterior, lateral, and deeper, using neuronavigation compared to the "standard" procedure. This study confirms that the "standard" procedure of coil positioning is not accurate to target a desired cortical region. Target location can be improved by the use of a navigation system taking individual brain anatomy into account. The present results incline to be cautious on the pathophysiological interpretations of previous results reported in TMS studies based on "standard" targeting, e.g. regarding premotor-motor interactions. Similarly, the inaccuracy of the "standard" procedure of coil positioning could partly explain the between-study variability of the therapeutic effects produced by rTMS in patients with depression. Our results strongly support a more anterior and lateral placement of the TMS coil for dlPFC stimulation in the treatment of depression.