Engineering Deep Brain Stimulation as a Treatment for Parkinson's Disease: from Models to Materials

This thesis analyzes deep brain stimulation (DBS) as a treatment for the motor symptoms of Parkinson's disease (PD) at multiple levels. Although this treatment is currently used on human patients, little is understood about the mechanism of action which allows patients to experience therapeutic benefits. The work here investigates efficacy of DBS in computational and experimental manners in order to enhance the understanding of the effects on neural activity and behavior. First, I examine computational models of the nuclei within the motor circuit of the brain and used these models to test novel electrical stimulation signal designs. I show that irregular spacing of stimulation pulses allows for increased variability in neuronal firing rate responses within the basal ganglia. Also, I develop a model of the stimulation-frequency-dependent nature of antidromic spiking induced in the motor cortex as a result of DBS. Second, I use the hemi-Parkinsonian rat model to demonstrate motor and cognitive behavioral effects of DBS in the globus pallidus internus (GPi). The work validates this animal model for translational research on DBS of the GPi and demonstrates results consistent with reports for DBS of the subthalamic nucleus (STN) in the same model. Additionally I study recorded neural activity in the motor cortex while stimulating the STN in order to characterize the corresponding changes in neural activity. I found that regular and irregular stimulation patterns both decrease Parkinsonian entropic noise in the output layer of the motor cortex, with irregular stimulation having the greatest benefit towards reducing this noise. Third, I consider a new material for its biocompatibility and applicability as a material for stimulating electrodes. In the rat model that I previously validated, I verify that behavioral results using a stimulating electrode made from carbon nanotube fibers (CNTf) match results from previous experiments using standard platinum iridium (PtIr) electrodes. Additionally, it is shown that CNTf electrodes produce lower inflammation, gliosis and damage to the blood brain barrier. Together, all three aspects of the work demonstrate significant contributions to the functionality and engineering of DBS as a neuromodulation therapy for PD