Selective influence of dopamine on electrocortical signatures of error monitoring: a combined EEG and immersive virtual reality study in Parkinson’s disease

Abstract

AbstractDetecting errors in one’s own and other’s actions is likely linked to the discrepancy between intended or expected and produced or observed output. To detect and process the occurrence of salient events seems associated to the release of dopamine, the balance of which is profoundly altered in Parkinson’s disease (PD). EEG studies in healthy participants indicate that the occurrence of errors in observed actions triggers a variety of electrocortical indices (like mid-frontal theta activity, error-related delta and the Error Positivity, oPe), that seem to map different aspects of error detection and performance monitoring. Whether these indices are differently modulated by dopamine in the same individual has never been investigated. To explore this issue, we recorded EEG markers of error detection by asking healthy controls (HCs) and PD patients to observe ecological reach-to-grasp a glass actions performed by a virtual arm seen in first person perspective. PD patients were tested under their dopaminergic medication (‘on-condition’), and after dopaminergic withdrawal (‘off-condition’). HCs showed a clear oPe and an increase of delta and theta power during the observation of erroneous vs. correct actions. In PD patients, oPe and delta responses were always preserved. Crucially, however, an error-related increase of theta power was found in ‘on’ but not in ‘off’ state PD patients. Thus, different EEG error signatures may index the activity of independent systems and error related theta power is selectively modulated by dopamine depletion. Our findings may pave the way to the discovery of dopamine-related biomarkers of higher-order motor cognition dysfunctions that may have crucial theoretical and clinical implications.Significance StatementDopaminergic neurons respond to salient events during performance monitoring. Yet, the impact of dopamine depletion on the human reactivity to observed errors is still unclear. We recorded EEG in patients with Parkinson’s Disease (PD) under dopaminergic treatment (‘on-condition’) and medication withdrawal (‘off-condition’) while they observed correct and erroneous goal-related actions performed by a virtual limb. Analysis of Error Positivity (oPe) and theta and delta power increase, markers of physiological error-monitoring, indicates that while the formers were intact, the latter was preserved in the ‘on’ and altered in the ‘off’ condition. Thus, different EEG markers of error monitoring likely rely on independent circuits. Moreover, mid-frontal theta activity alterations may represent a marker of dopamine-related neurophysiological impairments of higher-order cognition.