LAUSR

Abstract Introduction: The objective of this work was to predict preoperatively the maximum extent to which direct stimulation therapy can propagate through an epileptic circuit for stabilizing refractory focal-onset epilepsy. A pre-surgical workflow is presented which comprises a computationally intensive process for calculating the volume of cortical activation (VOCA) surrounding cylindrical depth contacts virtually placed in white matter. The process employs an activation function (AF) derived from cable modeling of an axon. The AF was extrapolated to describe the three-dimensional activation of axon bundles facilitated by patient-specific diffusion tensor imaging (DTI). Methods: The modeling process consisted of the following steps: (1) acquisition of structural MRI and DTI; (2) computation of the electric potential using the finite element method; (3) analysis of the effect of the modeled electric field on depolarizing axon bundles using the AF; (4) predicting distant cortical activation by strategically placing the AF seeds for creating a modulated circuit tractography (MCT) map; and finally, (5) post-implant in vivo validation using Subtracted Activated SPECT (SAS). Results: The pre-implant simulation calculated non-spherical volumetric regions around the contacts representing areas of hyperpolarization and depolarization. Furthermore, the generated MCT map predicted the extent to which white matter connected epileptic sources were influenced during direct stimulation therapy. Validation of this map was demonstrated post-implantation employing RNS electrocorticography and SAS. The latter technique captured transient alterations in blood flow synched to neural metabolism potentially distant to the stimulated contacts. Conclusion: This pre-implant modeling system offers the potential for predicting optimal depth lead implant sites with a limited set of contacts for modulating the maximal extent of a refractory epileptogenic network.