Theoretical and experimental predictions of neural elements activated by deep brain stimulation

Chronic electrical stimulation of the brain, known as the deep brain stimulation (DBS), has become the preferred surgical treatment for advanced Parkinson's disease. Despite its clinical success the mechanisms of DBS are still unknown and there is limited understanding of the neural response to DBS. As a result the therapeutic neural target has not been clearly identified, which limits opportunities to improve the technology and increase treatment efficacy. We hypothesized that subthalamic (STN) projection neurons are primarily activated during clinically effective STN DBS.; Non-human primate models of DBS provide unique opportunities to study the therapeutic mechanisms of DBS in vivo. The therapeutic benefits of DBS are dependent on accurate placement of the electrode in the appropriate neuroanatomical target. Stereotactic neurosurgical navigation systems that exist for clinical applications are lacking in the area of non-human primate research. Therefore, we developed a software system (Cicerone) for stereotactic neurosurgical planning, neurophysiological data collection, and DBS visualization in primates.; Computational volume conductor models are commonly used to estimate neuronal response to electrical stimulation. To date there has been no direct validation of models aimed at investigating stimulation of subcortical structures. We have therefore measured voltages generated by DBS electrode in the thalamus of a monkey. Furthermore, we have calculated model parameters that can be used to accurately capture both spatial and temporal properties of voltage fields induced by DBS.; Utilizing the stereotactic navigation system and voltage field model we built a comprehensive computational model of STN DBS in the parkinsonian monkey. We compared our model predictions with results from experimental animals to quantify the relative activation of STN neurons and pallidothalamic (GPi) fibers during therapeutic DBS. The results indicate that activation of nearly half of the STN neurons is sufficient for the behavioral manifestation of the therapeutic effects, which confirms our hypothesis. The additional recruitment of GPi fibers of passage may also play an important role in therapeutic outcome, but large-scale activation of GPi fibers is not necessary. The position of the electrode in the STN region and the choice of active contact can strongly effect recruitment of either neural population.