Impaired proactive control in Parkinson's disease and right prefrontal networks: findings from cortical source analysis during subthalamic stimulation

Resumen

Background: Deep brain stimulation (DBS) of subthalamic nucleus (STN) has emerged as a safe and effective treatment for motor symptoms in Parkinson disease (PD), however the underlying cognitive effects remain unclear. Here, we investigated the underlying electrophysiological mechanisms characteristic of STN DBS over context processing and inhibition control in unmedicated PD patients. Methods: Fifteen healthy volunteers and ten PD patients treated with DBS for refractory symptoms were evaluated by the simultaneous recording of event-related brain potentials (ERPs) during a cued continuous performance test that included Go and NoGo trials. Participants were studied in the chronic postoperative period (<5 years of DBS treatment) with internalized electrodes. Patients performed the experimental session after overnight withdrawal of antiparkinson medication to evaluate the effect of STN-DBS stimulation, by contrasting STN-DBS On/Off states in a randomized order. Neural correlates by ERPs and source localization analyses underlying “Go-P3 as an electrophysiological index of proactive response inhibition were analyzed and contrasted amongst DBS states and controls. Results: Patients presented increased reaction times and committed more errors compared to the control group, particularly during Go trials (proactive impulsivity), which was increased by STN-DBS. Cluster-based permutation tests of individual Go-P3 source activity revealed that healthy controls displayed increased activation in right inferior and middle frontal gyri compared to patients during DBS Off and particularly to DBS On, whereas PD patients enhanced activations in a network that included ‘visual/posterior regions’. Conclusions: These findings show direct evidence of abnormal physiological recruitment of prefrontal and posterior brain networks in PD patients necessary for correct proactive responses, most notably during STN-DBS. This study provides updated functional evidence that supports critical dopaminergic-mediated frontal-basal ganglia network interactions in un-medicated PD patients during context monitoring necessary for achieving goals and self-control, suggesting a selective impairment of proactive control, despite clinical improvement during STN stimulation.