Uncertainty quantification in transcranial magnetic stimulation via high-dimensional model representation.

A computational framework for uncertainty quantification in transcranial magnetic stimulation (TMS) is presented. The framework leverages high-dimensional model representations (HDMRs), which approximate observables (i.e., quantities of interest such as electric (E) fields induced inside targeted cortical regions) via series of iteratively constructed component functions involving only the most significant random variables (i.e., parameters that characterize the uncertainty in a TMS setup such as the position and orientation of TMS coils, as well as the size, shape, and conductivity of the head tissue). The component functions of HDMR expansions are approximated via a multielement probabilistic collocation (ME-PC) method. While approximating each component function, a quasi-static finite-difference simulator is used to compute observables at integration/collocation points dictated by the ME-PC method. The proposed framework requires far fewer simulations than traditional Monte Carlo methods for providing highly accurate statistical information (e.g., the mean and standard deviation) about the observables. The efficiency and accuracy of the proposed framework are demonstrated via its application to the statistical characterization of E-fields generated by TMS inside cortical regions of an MRI-derived realistic head model. Numerical results show that while uncertainties in tissue conductivities have negligible effects on TMS operation, variations in coil position/orientation and brain size significantly affect the induced E-fields. Our numerical results have several implications for the use of TMS during depression therapy: 1) uncertainty in the coil position and orientation may reduce the response rates of patients; 2) practitioners should favor targets on the crest of a gyrus to obtain maximal stimulation; and 3) an increasing scalp-to-cortex distance reduces the magnitude of E-fields on the surface and inside the cortex.