title: Dopamine Release in the Nonhuman Primate Caudate and Putamen Depends upon Site of Stimulation in the Subthalamic Nucleus.
abstract: 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 demonstrates that STN DBS-evoked dopamine release can be reduced or increased by redirecting STN stimulation to a slightly different site.
  
  
  
  Electrical stimulation of deep structures of the brain, or deep brain stimulation (DBS), is used to modulate pathological brain activity. However, technological limitations and incomplete understanding of the therapeutic mechanisms of DBS prevent personalization of this therapy and may contribute to less-than-optimal outcomes. We have demonstrated that DBS coincides with changes in dopamine neurotransmitter release in the basal ganglia. Here we mapped relationships between DBS and changes in neurochemical activity. Importantly, this study shows that DBS-evoked dopamine release can be reduced or increased by refocusing the DBS on a slightly different stimulation site.
authors.affiliation: Department of Neurologic Surgery, Department of Physiology and Biomedical Engineering, Department of Radiology, and.
authors.forename: Hoon-Ki
authors.initials: HK
authors.lastname: Min
authors.affiliation: Department of Neurologic Surgery.
authors.forename: Erika K
authors.initials: EK
authors.lastname: Ross
authors.affiliation: Department of Neurologic Surgery.
authors.forename: Hang Joon
authors.initials: HJ
authors.lastname: Jo
authors.affiliation: Department of Neurologic Surgery.
authors.forename: Shinho
authors.identifier: 0000-0002-3886-3106
authors.initials: S
authors.lastname: Cho
authors.affiliation: Department of Neurologic Surgery.
authors.forename: Megan L
authors.initials: ML
authors.lastname: Settell
authors.affiliation: Department of Neurologic Surgery, Department of Neurosurgery, Dongguk University Gyeongju Hospital, Gyeongbuk 780-350, Korea.
authors.forename: Ju Ho
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: Department of Neurologic Surgery.
authors.forename: Penelope S
authors.initials: PS
authors.lastname: Duffy
authors.affiliation: Department of Neurologic Surgery, Department of Physiology and Biomedical Engineering.
authors.forename: Su-Youne
authors.initials: SY
authors.lastname: Chang
authors.affiliation: Department of Neurologic Surgery, Division of Engineering, Mayo Clinic, Rochester, Minnesota 55905, and.
authors.forename: Kevin E
authors.initials: KE
authors.lastname: Bennet
authors.affiliation: Department of Neurologic Surgery.
authors.forename: Charles D
authors.identifier: 0000-0001-5155-1505
authors.initials: CD
authors.lastname: Blaha
authors.affiliation: Department of Neurologic Surgery, Department of Physiology and Biomedical Engineering, lee.kendall@mayo.edu.
authors.forename: Kendall H
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000818:Animals; D001931:Brain Mapping; D002421:Caudate Nucleus / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D021621:Imaging, Three-Dimensional; D008253:Macaca mulatta; D008279:Magnetic Resonance Imaging; D008297:Male; D009434:Neural Pathways / Q000502:physiology; D011699:Putamen / Q000378:metabolism*; D020531:Subthalamic Nucleus / Q000000981:diagnostic imaging / Q000502:physiology*
chemical_list: D004298:Dopamine
keywords: caudate; deep brain stimulation; dopamine; fast-scan cyclic voltammetry; functional magnetic resonance imaging; subthalamic nucleus