Session Information
Date: Tuesday, June 21, 2016
Session Title: Parkinson's disease: Pathophysiology
Session Time: 12:30pm-2:00pm
Location: Exhibit Hall located in Hall B, Level 2
Objective: Assessing the role of the noradrenergic system underlying the effect of subthalamic nucleus stimulation (STN-DBS) on akinesia.
Background: Slowness in movement initiation, associated with akinesia, is a cardinal symptom of Parkinson’s disease. It has recently been revisited as a possible executive rather than a purely motor dysfunction (Favre et al., 2013). Patients would be locked into an inappropriate mode of proactive inhibitory control of movement initiation. Standard dopamine based medication does not fully alleviate this disorder, only STN-DBS would be efficient to release inhibition, at the expense of increased impulsivity. Recently, the effect of STN-DBS on movement initiation latency was found to be modulated by the noradrenergic (NA) system (Albares et al., 2015). But direct evidence of NA-dependent STN-DBS-induced brain activity changes is still missing.
Methods: Eighteen PD patients under STN-DBS were enrolled in a placebo-controlled study and tested in a reaction time task investigating movement initiation latency. This pharmacological protocol crossed NA manipulation (by means of Clonidine, an α-2A adrenergic agonist or Placebo) and STN-DBS manipulation (ON or OFF). EEG recordings were conducted using advanced methods for filtering out stimulation artifacts and unmixing/localizing neural sources.
Results: Under placebo, STN-DBS improved movement initiation latency (ON vs. OFF DBS). This behavioural effect was associated with a reduction of proactive tonic alpha power (a marker of neural inhibition) within the SMA. Under Clonidine, the positive effect of STN-DBS vanished. This behavioural effect was associated with an increase in tonic alpha power within the SMA.
Conclusions: These results support the hypothesis according to which clonidine counteracts the positive effect of STN-DBS that consists in restoring control of proactive inhibition over movement initiation. The opposite patterns of DBS-induced changes in alpha power observed under Clonidine and Placebo in the SMA strongly suggest that the inhibitory control of movement initiation is dysfunctional in the pathological state, restored under STN-DBS, and back to dysfunctional under combined STN-DBS/Clonidine. These results provide the first direct neural-based evidence in humans of NA-dependent STN-DBS-efficiency.
To cite this abstract in AMA style:
C. Spay, M. Albares, S. Thobois, E. Broussolle, P. Boulinguez, B. Ballanger. The effect of STN-DBS on movement initiation control is modulated by the noradrenergic system: Evidence of an interaction from a combined pharmacological/DBS/EEG study [abstract]. Mov Disord. 2016; 31 (suppl 2). https://www.mdsabstracts.org/abstract/the-effect-of-stn-dbs-on-movement-initiation-control-is-modulated-by-the-noradrenergic-system-evidence-of-an-interaction-from-a-combined-pharmacologicaldbseeg-study/. Accessed May 11, 2025.« Back to 2016 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/the-effect-of-stn-dbs-on-movement-initiation-control-is-modulated-by-the-noradrenergic-system-evidence-of-an-interaction-from-a-combined-pharmacologicaldbseeg-study/