Error signals in the subthalamic nucleus are related to post-error slowing in patients with Parkinsonʹs disease

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 Parkinsonʹs 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. 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. nd 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 patientsʹ age may suggest a dopamine overdose effect in patients with earlier onset of PD.