Impact of non-brain anatomy and coil orientation on inter- and intra-subject variability in TMS at midline

Objective: To investigate inter-subject variability with respect to cerebrospinal fluid thickness and brain-scalp distance, and to investigate intra-subject variability with different coil orientations. Methods: Simulations of the induced electric field (E-Field) using a figure-8 coil over the vertex were conducted on 50 unique head models and varying orientations on 25 models. Metrics exploring stimulation intensity, spread, and localization were used to describe inter-subject variability and effects of non-brain anatomy. Results: Both brain-scalp distance and CSF thickness were correlated with weaker stimulation intensity and greater spread. Coil rotations show that for the dorsal portion of the stimulated brain, E-Field intensities are highest when the anterior-posterior axis of the coil is perpendicular to the longitudinal fissure, but highest for the medial portion of the stimulated brain when the coil is oriented parallel to the longitudinal fissure. Conclusions: Normal anatomical variation in healthy individuals leads to significant differences in the site of TMS, the intensity, and the spread. These variables are generally neglected but could explain significant variability in basic and clinical studies. Significance: This is the first work to show how brain-scalp distance and cerebrospinal fluid thickness influence focality, and to show the disassociation between dorsal and medial TMS.