Transcranial magnetic stimulation in heterogeneous brain tissue: clinical impact on focality, reproducibility and true sham stimulation.

BACKGROUND: Transcranial magnetic stimulation (TMS) is an attractive research and possibly therapeutic tool for non-invasive central nervous system stimulation. However, relatively little is known about the direction, magnitude and distribution of induced electric field and current flows in tissue, and optimal setup characteristics as well as appropriate sham stimulation conditions remain largely undetermined, hampering reproducibility.
METHODS: We reconstruct the conductive phenomena induced by TMS by implementing digitized coil geometry and realistic stimulator parameters and solving the electromagnetic problem over an MRI-based, realistic head model of 1mm resolution. Findings are validated by recording motor evoked potentials from the right abductor pollicis brevis muscle from healthy subjects stimulated in a stereotaxic framework.
RESULTS: Several commonly used sham stimulation configurations elicit conductive patterns which achieve up to 40% of the strength of real stimulation. Also, variations in coil position of the order of a 7 degrees tilt, which are expected to occur in non-stereotaxic stimulation, can alter the stimulation intensity by up to 25%.
CONCLUSIONS: In accordance with our findings, several clinical studies observe measurable effects during sham stimulation or no significant difference between sham and real stimulation, and the sensitivity of stimulation intensity to tiny coil rotations affords a partial explanation for the poor reproducibility and partial disagreements observed across clinical TMS studies. Knowledge of coil and stimulator specifications alone is hence not sufficient to control stimulation conditions, and a stereotaxic setup coupled with individually adjusted field solvers appear essential in performing reliable TMS studies.