Abstract
BACKGROUND: Deep brain stimulation (DBS) of the subthalamic region is an established therapy for the treatment of Parkinson's disease (PD). Computational models of subthalamic DBS are commonly used in the clinical literature to estimate the brain connections activated by the stimulus. However, those analyses are typically performed with simplified DBS modeling methods. As subthalamic DBS research evolves, there is a need for more advanced modeling results. OBJECTIVE: The goal of this study was to create maps of DBS axonal pathway activation in the subthalamic region across a wide range of stimulation settings (i.e. polarity, pulse width, amplitude) and electrode locations. METHODS: We used an anatomically and biophysically detailed computational model of subthalamic DBS to calculate responses for 9 different axonal pathways of interest at 256 different DBS locations using ring mode, directional, and bipolar stimulation. An open access interactive software tool is provided for users to analyze the pathway activation results. RESULTS: Electrode location plays a major role in dictating the assortment of axonal pathways that are activated by subthalamic DBS. We implemented a pathway selectivity index to identify the electrode locations and stimulation parameter settings that theoretically bias activation toward the pallidothalamic, motor hyperdirect, or cerebellothalamic pathways, respectively. However, true selectivity is generally difficult to achieve because of pathway co-activation. CONCLUSION: Evolving hypotheses suggest that activation of specific pathways may be related to the control of specific PD symptoms. This study provides detailed predictions on stimulation conditions that facilitate pathway selective DBS, as well as an interactive software tool that quantifies DBS pathway activation throughout the subthalamic region.