A critical step towards applying direct brain stimulation therapy in focal onset epilepsy is to effectively interface with epileptogenic neural circuits using a limited set of active contacts. This takes special relevance when interacting with networks that exhibit two or more foci. A strategy to influence the maximum extent of the epileptogenic circuit is to stimulate white matter pathways to enhance propagation to distant epileptic tissue.

A significant number of elements must be considered in the clinical response to stimulation delivered directly to neuronal populations. These variables include: stimulation parameter settings, number and interdependence of anatomical targets, electrode number, electrode location and orientation, geometry or shape of the electrode contacts, contact polarity, biophysical properties of stimulated medium, and

trajectory of axonal bundles adjacent to the stimulation site.

This document addresses the development of a computational model which takes into consideration all the mentioned variables to predict activation of distant sites via white matter pathways. A method to calculate the extracellular potential field, induced by the application of time-dependent stimulation waveforms, is discussed. Such a method considers both the anisotropic conductivity nature of neural tissue and the electrochemical phenomena of the electrode-tissue interface. The response of white matter fibers is then evaluated by solving a compartmental cable model based in the Hodgkin and Huxley membrane description.

The model was integrated into a pre-surgical workflow and was used prospectively to guide stereotactic implantation of depth leads to apply direct neurostimulation therapy in four patients with refractory focal onset epilepsy.