Emerging techniques for elucidating mechanism of action of deep brain stimulation

Abstract

Deep brain stimulation (DBS) within the basal ganglia complex is an effective neurosurgical approach for treating symptoms of Parkinson's disease (PD), Essential Tremor, Dystonia, Depression, Obssessive Compulsive Disorder, and Tourette's Syndrome, among others. Elucidating DBS mechanism has become a critical clinical and research goal in stereotactic and functional neurosurgery and in neural engineering. Along with electro-physiological and microdialysis techniques, two additional powerful technologies, notably functional Magnetic Resonance Imaging (fMRI) and in vivo neurochemical monitoring have recently been used to investigate DBS-mediated activation of basal ganglia network circuitry. For this purpose, we have previously developed WINCS (Wireless Instantaneous Neurotransmitter Concentration Sensor System), which is an MRI-compatible wireless monitoring device to obtain chemically resolved neurotransmitter measurements at implanted microsensors in a large mammalian model (pig) as well as in human patients. This device supports an array of electrochemical measurements that includes fast-scan cyclic voltammetry (FSCV) for real-time simultaneous in vivo monitoring of dopamine and adenosine release at carbon-fiber microelectrodes as well as fixed potential amperometry for monitoring of glutamate at enzyme-linked biosensors. In addition, we have utilized fMRI to investigate subthalamic nucleus (STN) DBS activation in the pig with 3Tesla MR scanner. We demonstrate the activation of specific basal ganglia circuitry during STN DBS using both fMRI and FSCV in the pig model. Our results suggest that fMRI and electrochemistry are important emerging techniques for use in elucidating mechanism of action of DBS.