On a related issue, some of the variation in outcome may be related to treatment factors. Quantitative models and direct in vivo measurements (Wagner et al, 2004, 2008) indicate that the electrical currents induced by TMS are predominantly confined to a brain region directly under the treatment coil. The procedure for positioning the coil over the cortical target is described in the NeuroStar TMS System User Manual (volume 2, sections 6 and 7) and involves first determining a location where stimulation leads to a contraction of the abductor policis brevis muscle (visualized with a thumb twitch on the right hand) and then positioning the coil 5.5 cm anterior to that position along the left Superior Oblique Angle line. While this target can be located with good reproducibility and was associated with therapeutic outcome in the NCT trial, it is not clear that this positions the coil over the best target within the DLPFC for all patients. Indeed, individual differences in gyral anatomy and in gross brain size both add variability to the specific neuroanatomic region being stimulated, and this may impact treatment efficiency.