Background: Transcranial magnetic stimulation (TMS) is used for the mapping of brain motor functions. The complexity of the brain deters determining the exact localization of the stimulation site using simplified methods (e.g., the region below the center of the TMS coil) or conventional computational approaches. Objective: This study aimed to present a high-precision localization method for a specific motor area by synthesizing computed non-uniform current distributions in the brain for multiple sessions of TMS. Methods: Peritumoral mapping by TMS was conducted on patients who had intra-axial brain neoplasms located within or close to the motor speech area. The electric field induced by TMS was computed using realistic head models constructed from magnetic resonance images of patients. A post-processing method was implemented to determine a TMS hotspot by combining the computed electric fields for the coil orientations and positions that delivered high motor-evoked potentials during peritumoral mapping. The method was compared to the stimulation site localized via intraoperative direct brain stimulation and navigated TMS. Results: Four main results were obtained: 1) the dependence of the computed hotspot area on the number of peritumoral measurements was evaluated
2) the estimated localization of the hand motor area in eight non-affected hemispheres was in good agreement with the position of a so-called “hand-knob”
3) the estimated hotspot areas were not sensitive to variations in tissue conductivity
and 4) the hand motor areas estimated by this proposal and direct electric stimulation (DES) were in good agreement in the ipsilateral hemisphere of four glioma patients. Conclusion(s): The TMS localization method was validated by well-known positions of the “hand-knob” in brains for the non-affected hemisphere, and by a hotspot localized via DES during awake craniotomy for the tumor-containing hemisphere.