Novelty-induced frontal-STN networks in Parkinson’s disease

Abstract

Abstract Novelty detection is a primitive subcomponent of cognitive control that is deficient in Parkinson’s disease (PD) patients with cognitive dysfunction. Here, we studied novelty-response mechanisms in PD. In participants with PD, we recorded from cortical circuits with scalp-based electroencephalography (EEG) and from subcortical circuits using intraoperative neurophysiology during surgeries for implantation of deep-brain stimulation (DBS) electrodes. We report three major results. First, novel auditory stimuli triggered midfrontal low-frequency rhythms; of these, 1-4 Hz “delta” rhythms were linked to novelty-associated slowing whereas 4-7 Hz “theta” rhythms were specifically attenuated in PD. Second, 32% of subthalamic nucleus (STN) neurons were response-modulated; nearly all (94%) of these were also modulated by novel stimuli. Third, response-modulated STN neurons were coherent with midfrontal 1-4 Hz activity. These findings link scalp-based measurements of neural activity with neuronal activity in the STN. Our results provide insight into midfrontal cognitive control mechanisms and how purported hyperdirect fronto-basal ganglia circuits evaluate new information.