title: Coordinated Reset Deep Brain Stimulation of Subthalamic Nucleus Produces Long-Lasting, Dose-Dependent Motor Improvements in the 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine Non-Human Primate Model of Parkinsonism.
abstract: Novel deep brain stimulation (DBS) paradigms are being explored in an effort to further optimize therapeutic outcome for patients with Parkinson's disease (PD). One approach, termed 'Coordinated Reset' (CR) DBS, was developed to target pathological oscillatory network activity. with desynchronizing effects and associated therapeutic benefit hypothesized to endure beyond cessation of stimulus delivery.
  
  
  
  To characterize the acute and carry-over effects of low-intensity CR DBS versus traditional DBS (tDBS) in the region of the subthalamic nucleus (STN).
  
  
  
  A within-subject, block treatment design involving the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) non-human primate model of parkinsonism was used. Each treatment block consisted of five days of daily DBS delivery followed by a one week minimum post-treatment observation window. Motor behavior was quantified using a modified rating scale for both animals combined with an objective, upper-extremity reach task in one animal.
  
  
  
  Both animals demonstrated significant motor improvements during acute tDBS; however, within-session and post-treatment carry-over was limited. Acute motor improvements were also observed in response to low-intensity CR DBS; however, both within- and between-session therapeutic carry-over enhanced progressively following each daily treatment. Moreover, in contrast to tDBS, five consecutive days of CR DBS treatment yielded carry-over benefits that persisted for up to two weeks without additional intervention. Notably, the magnitude and time-course of CR DBS' effects on each animal varied with daily dose-duration, pointing to possible interaction effects involving baseline parkinsonian severity.
  
  
  
  Our results support the therapeutic promise of CR DBS for PD, including its potential to induce carryover while reducing both side effect risk and hardware power consumption.
authors.affiliation: Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Shane
authors.initials: S
authors.lastname: Nebeck
authors.affiliation: Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Abirami
authors.initials: A
authors.lastname: Muralidharan
authors.affiliation: Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Johnson
authors.affiliation: Department of Neurology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Jerrold L
authors.initials: JL
authors.lastname: Vitek
authors.affiliation: Department of Neuroscience, Cleveland Clinic Lerner College of Medicine, Cleveland, OH 44195, USA. Electronic address: bakerk6@ccf.org.
authors.forename: Kenneth B
authors.initials: KB
authors.lastname: Baker
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D046690:Deep Brain Stimulation / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D020267:MPTP Poisoning; D008253:Macaca mulatta; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000628:therapy*; D020531:Subthalamic Nucleus
keywords: Coordinated reset; Deep brain stimulation; MPTP; Neuromodulation; Rhesus macaque