title: Interaction of noradrenergic pharmacological manipulation and subthalamic stimulation on movement initiation control in Parkinson's disease.
abstract: BACKGROUND
  Slowness in movement initiation (akinesia) is a cardinal feature of Parkinson's disease (PD), which is still poorly understood. Notably, akinesia is restored by subthalamic nucleus deep brain stimulation (STN-DBS) but not fully reversed by current dopaminergic treatments. It was recently suggested that this disorder is of executive nature (related to inhibitory control of response) and of non-dopaminergic origin (possibly noradrenergic).
  
  
  OBJECTIVE
  To test the double hypothesis that: 1) the ability to control movement initiation is modified by noradrenergic neurotransmission modulation, and 2) this effect is mediated by the regulation of STN activity.
  
  
  METHODS
  Sixteen STN-DBS PD patients were enrolled in a placebo-controlled study investigating the effects of noradrenergic attenuation by clonidine (∝2-adrenergic receptor agonist). Movement initiation latency was assessed by means of a cue-target reaction time task. Patients, who remained on their chronic dopaminergic medication, were tested on four sessions: two with placebo (ON- or OFF-DBS), and two with a 150 μg oral dose of clonidine (ON- or OFF-DBS).
  
  
  RESULTS
  In the OFF stimulation condition, patients were locked into a mode of control maintaining inappropriate response inhibition. This dysfunctional executive setting was overcome by STN-DBS. Clonidine, however, was found to impair specifically the ability to release inhibitory control in the ON-DBS state.
  
  
  CONCLUSIONS
  Overall our results suggest an important implication of the noradrenergic system in the pathophysiology of akinesia in PD. Reducing the noradrenergic "tonus" may even block the positive action of STN-DBS on akinesia, suggesting, at least by part, a noradrenergic-dependent STN-DBS efficiency.
authors.affiliation: Université de Lyon, F-69622, Lyon, France; Université Lyon 1, Villeurbanne, France; CNRS, UMR5229, Centre de Neuroscience Cognitive, Bron, France.
authors.forename: Marion
authors.initials: M
authors.lastname: Albares
authors.affiliation: Université de Lyon, F-69622, Lyon, France; Université Lyon 1, Villeurbanne, France; CNRS, UMR5229, Centre de Neuroscience Cognitive, Bron, France; Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Thobois
authors.affiliation: Université de Lyon, F-69622, Lyon, France; Université Lyon 1, Villeurbanne, France; CNRS, UMR5229, Centre de Neuroscience Cognitive, Bron, France; Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Favre
authors.affiliation: Université de Lyon, F-69622, Lyon, France; Université Lyon 1, Villeurbanne, France; CNRS, UMR5229, Centre de Neuroscience Cognitive, Bron, France; Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Broussolle
authors.affiliation: Hôpital Neurologique Pierre Wertheimer, Hospices Civils de Lyon, France.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Polo
authors.affiliation: Laboratoire de Neurosciences Cognitives, ENS/INSERM-U960, Paris, France; Innovation Thérapeutique Fonctionnelle, Service de Neurochirurgie, CHU Henri Mondor, Creteil, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Domenech
authors.affiliation: Université de Lyon, F-69622, Lyon, France; Université Lyon 1, Villeurbanne, France; CNRS, UMR5229, Centre de Neuroscience Cognitive, Bron, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Boulinguez
authors.affiliation: Université de Lyon, F-69622, Lyon, France; Université Lyon 1, Villeurbanne, France; CNRS, UMR5229, Centre de Neuroscience Cognitive, Bron, France. Electronic address: benedicte.ballanger@isc.cnrs.fr.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Ballanger
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000627:therapeutic use; D000368:Aged; D003000:Clonidine / Q000627:therapeutic use*; D003131:Combined Modality Therapy / Q000379:methods; D046690:Deep Brain Stimulation; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009068:Movement / Q000187:drug effects* / Q000502:physiology*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000503:physiopathology / Q000628:therapy*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects; D020531:Subthalamic Nucleus / Q000502:physiology*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D003000:Clonidine
keywords: Akinesia; Executive control; Noradrenaline; Reaction time; STN-DBS