Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for medically refractory Parkinson’s disease. Although DBS has recognized clinical utility, its biologic mechanisms are not fully understood, and whether dopamine release is a potential factor in those mechanisms is in dispute. We tested the hypothesis that STN DBS-evoked dopamine release depends on the precise location of the stimulation site in the STN and the site of recording in the caudate and putamen. We conducted DBS with miniature, scaled-to-animal size, multicontact electrodes and used functional magnetic resonance imaging to identify the best dopamine recording site in the brains of nonhuman primates (rhesus macaques), which are highly representative of human brain anatomy and circuitry. Real-time stimulation-evoked dopamine release was monitored using in vivo fast-scan cyclic voltammetry. This study demon-strates that STN DBS-evoked dopamine release can be reduced or increased by redirecting STN stimulation to a slightly different site.
Bibliographical noteFunding Information:
This work was supported by the National Institutes of Health (NIH; R01 NS 70872, to K.H.L.) and The Grainger Foundation. We thank Andrea McConico, Michael Marsh, Jill Anderson, Kip Ludwig, and Allan Bieber for their support and advices; Steve Goerss, Bruce Kall, and Seong Rok Han for their surgical support; Dong-Pyo Jang and Yoonbae Oh for their advice on electrochemistry; Kendall Dennis, Bruce Gustine, and their colleagues at the Mayo Clinic Division of Engineering for their support; Jodi Silvernail and the Mayo Clinic Department of Comparative Medicine for animal care; and Diane Sauter and the Mayo Clinic Center for Advanced Imaging Research at the Mayo Clinic for their support (NIH C06 RR018898).
- Deep brain stimulation
- Fast-scan cyclic voltammetry
- Functional magnetic resonance imaging
- Subthalamic nucleus