title: Error signals in the subthalamic nucleus are related to post-error slowing in patients with Parkinson's disease.
abstract: Error monitoring is essential for optimizing motor behavior. It has been linked to the medial frontal cortex, in particular to the anterior midcingulate cortex (aMCC). The aMCC subserves its performance-monitoring function in interaction with the basal ganglia (BG) circuits, as has been demonstrated in patients suffering from BG lesions or from Parkinson's disease (PD). The subthalamic nucleus (STN) has been assumed an integrative structure for emotional, cognitive and motor processing. Error-related behavioral adaptation such as post-error slowing has been linked to motor inhibition involving activation of an inhibitory network including the STN. However, direct involvement of the STN in error monitoring and post-error behavioral adjustment has not yet been demonstrated. Here, we used simultaneous scalp electroencephalogram (EEG) and local field potential (LFP) recordings from the BG in 17 patients undergoing deep brain stimulation (DBS) for PD to investigate error-related evoked activity in the human STN, its relation to post-error behavioral adjustment and the influence of dopamine during the performance of a speeded flanker task. We found an error-related positive deflection (STN-Pe) in the STN-LFP 260-450 msec after error commission. Importantly, the STN-Pe amplitude was larger in trials with post-error slowing compared to trials with post-error speeding. There was no overall effect of dopamine on error processing. Subgroup analysis revealed a higher error rate (ER) in younger patients with earlier disease onset ON medication compared to OFF medication (and vice versa in the older patient group), which was associated with modulatory effects of the early cortical error-related negativity (ERN) and late STN-Pe. The late error-related STN-Pe that is associated with post-error reaction time (RT) adjustments supports the notion that post-error slowing is implemented by motor inhibition involving the STN. Further, the modulation of behavioral performance by dopaminergic therapy depending on patients' age may suggest a dopamine overdose effect in patients with earlier onset of PD.
authors: Department of Neurology, Charité-University Medicine Berlin, Berlin, Germany.
authors: Sandy
authors: S
authors: Siegert
authors: Department of Neurology, Charité-University Medicine Berlin, Berlin, Germany.
authors: Maria
authors: M
authors: Herrojo Ruiz
authors: Department of Neurology, Charité-University Medicine Berlin, Berlin, Germany.
authors: Christof
authors: C
authors: Brücke
authors: Department of Neurology, Charité-University Medicine Berlin, Berlin, Germany.
authors: Julius
authors: J
authors: Huebl
authors: Department of Neurosurgery, Charité-University Medicine Berlin, Berlin, Germany.
authors: Gerd-Helge
authors: GH
authors: Schneider
authors: Center for Behavioral Brain Sciences, Magdeburg, Germany; Otto von Guericke University, Institute of Psychology II, Magdeburg, Germany; Radboud University Nijmegen, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, The Netherlands.
authors: Markus
authors: M
authors: Ullsperger
authors: Department of Neurology, Charité-University Medicine Berlin, Berlin, Germany; NeuroCure, Charité, Charité-University Medicine Berlin, Berlin, Germany; Berlin School of Mind and Brain, Berlin, Germany. Electronic address: andrea.kuehn@charite.de.
authors: Andrea A
authors: AA
authors: Kühn
mesh_terms: D000368:Aged; D046690:Deep Brain Stimulation; D004569:Electroencephalography; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D010300:Parkinson Disease / Q000503:physiopathology* / Q000628:therapy; D011930:Reaction Time / Q000502:physiology; D020531:Subthalamic Nucleus / Q000503:physiopathology*
keywords: Dopamine; Error processing; Error-related negativity; Post-error slowing; Subthalamic nucleus