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Transcranial magnetic stimulation (TMS) is a noninvasive technique that can alter brain activation by inducing electrical current in neurons using dynamic magnetic fields. Because of its painless nature, clinical usage has expanded to diagnostic purposes and therapeutic treatments. However, several issues and challenges still exist for TMS. A very limited understanding of the interaction between magnetic fields, cortical structure, and consequent brain excitation is currently available. Most previously published models lack key anatomical details that are essential elements in calculating induced electric fields critical to brain activation. In this study, gross human brain and head structures were derived using multiple modality images and a finite-element model was constructed. Furthermore, microstructural detail was incorporated using neocortical columnar structures. Using this detailed model, we investigated the influence of TMS coil position, distance and orientation on induced electric fields, and neocortical activation. Several activation standards and conductivity values were tested for their impact on the distribution of neocortical activation. Optimized activation patterns agreed well with published clinical experiments, under similar coil configurations. A structurally detailed finite-element model capable of accurately predicting neocortical activation for a given coil/magnetic field profile may provide a critical resource for understanding the electrophysiological consequences of TMS and for further refinement of this important technique.