The effect of inaccurate targeting of the left dorsolateral prefrontal cortex on TMS response

Transcranial magnetic stimulation (TMS) of the dorsolateral prefrontal cortex (DLPFC) is increasingly used as a non-invasive treatment for medication-resistant depression. However, this target site is commonly localized using an inaccurate standard procedure, which uses a fixed distance with respect to the motor cortical site for optimal stimulation of a hand muscle. Several studies have suggested this 5-cm distance is in average too short to reliably target the DLPFC, while others just found the opposite. Nevertheless, they all agree on the fact that the interindividual neuroanatomical variability cannot be neglected. We simulated the effect of this inaccurate targeting on the electromagnetic and neurophysiological response to TMS by displacing the stimulation coil to more rostral or dorsal areas with respect to the correct reference position. The induced electric field distribution in the brain and the spatio-temporal distribution of the membrane potentials along a traced nerve bundle, localized in the targeted brain region of interest, are computed. Our results show that the number of spikes initiated and propagating towards deeper limbic regions is highly variable, even for coil shifts of only 2 mm whereas the electric field changes are moderate. Moreover, they illustrate the increased (decreased) generation of spikes in case of targeting more dorsal (rostral) regions. This confirms that an accurate patient-specific determination of the stimulation target in combination with a neuronavigation system is mandatory to perform reliable TMS studies.