Advancing patient-specific models of subthalamic deep brain stimulation

Deep brain stimulation (DBS) in the subthalamic region is an established therapy for movement disorders like Parkinson’s disease (PD). Computational models of DBS provide insight into the electric field generated by DBS and the response it has on the neural tissue in the brain.
Patient-specific models of DBS include the anatomical information of the patient to predict the effects of DBS. These models have been used to aid neurosurgeons with selecting an optimal DBS location and neurologists with the clinical programming of DBS to select therapeutic parameter settings.
The subthalamic nucleus (STN) is one of the most common surgical targets for the treatment of PD. However, there is clinical debate if optimal therapeutic effects are achieved with stimulation within, or dorsal to, the STN. As such, observations of therapeutic benefit while stimulating white matter pathways instead of the grey matter nucleus have led to the emergence of a concept known as connectomic DBS modeling, which characterizes brain network connections that are modulated by stimulation. While patient-specific DBS models have been unsuccessful in defining a singular therapeutic target for PD, the introduction of connectomic modeling has shifted hypotheses on the control of symptoms from target areas within a specific nucleus to specific axonal pathways that course in/out or around the nucleus.
This dissertation describes advances in patient-specific DBS computational modeling methodology seeking to identify a balance between biophysical realism and computational simplicity. It offers insights into DBS electric field modeling in the brain and introduces new software
tools designed for clinical research on subthalamic DBS. The influence of electrode location and stimulation parameter selection on the axonal pathways is explored, as well as how stimulation sites can theoretically be designed to target specific pathways associated with symptom reduction. The work in this dissertation demonstrates the advancements made in patient-specific models of subthalamic DBS from the biophysical concept of connectomic DBS modeling to its therapeutic application in a prospective clinical trial.