EEG and Pharmacological Exploration of Executive Dysfunctions Induced by STN-DBS in PD
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Study type: Interventional

Summary: 
      Deep brain stimulation (DBS) of the subthalamic nucleus (STN) remarkably improves motor
      functions in patients with Parkinson disease (PD). However, growing evidence suggests that
      STN-DBS also causes executive inhibitory deficits and impulsive behaviour (Jahanshahi et al
      2000; Schroeder et al 2002; Hershey et al 2004; Thobois et al 2007; Frank et al 2007;
      Ballanger et al., 2009). Despite a widespread use, the mechanisms of action of STN-DBS are
      still unclear. Two reasons might explain this. 1) From a theoretical point of view, cognitive
      models of executive control mechanisms are incomplete. 2) From a methodological point of
      view, investigating cerebral activity during STN-DBS is very limited because most techniques
      are incompatible with locally implanted electrodes.

      This project relies on a double opportunity to answer these questions offered by recent
      theoretical and methodological advances. First, investigations in healthy subjects (Jaffard
      et al 2007, 2008, Boulinguez et al 2009) revealed an essential function of inhibitory
      control, so far ignored, consisting in locking in advance movement triggering processes to
      prevent undesired automatic or anticipated responses to unattended stimuli. In other words,
      key processes of executive control may act tonically before stimulation occurs, calling brain
      imaging studies to look at proactive and not only reactive activations. Second, recent
      advances in EEG signal processing now allow suppressing from the electroencephalogram
      DBS-related artifacts (Allen et al. 2010), providing a tremendous opportunity to use a
      non-invasive technique with the high temporal resolution necessary to disentangle proactive
      from reactive brain activity. To our knowledge, up to date no study has been published using
      EEG with STN-DBS patients since Allen et al.'s paper. The first operational purpose of this
      project is to identify the anatomo-functional origin of STN-DBS-induced executive dysfunction
      using EEG recordings in classical stimulus-response tasks. Results expected from this first
      part of the project may help resolving other long-lasting issues. Indeed, reactivity as
      assessed by simple reaction time in non-implanted patients as well as impulsivity in STN-DBS
      patients are known to remain insensitive to dopaminergic medication. Since the proactive
      activity related to executive, inhibitory, control may be supported by the noradrenergic (NA)
      system, the second purpose of this project is to test the original hypothesis according to
      which NA plays a central role in both akinesia and STN-DBS side effects.
    


Intervention name(s): Clonidine (Catapressan); Placebo 90 minutes before EEG
Intervention type(s): Device; Device
Intervention description(s): Clonidine (Catapressan) : Oral administration - Single dose (150 µg) - 90 minutes before EEG; Placebo : Oral administration - Single dose (lactose) - 90 minutes before EEG
Intervention MeSH terms: Clonidine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Basic Science
Keywords: Parkinson disease; STN-DBS; Impulsivity; Akinesia; Noradrenergic; system