Evoked midfrontal activity predicts cognitive dysfunction in Parkinson's disease

Cognitive dysfunction is a major feature of Parkinsons disease (PD), but the pathophysiology remains unknown. One potential mechanism is abnormal low-frequency cortical rhythms which engage cognitive functions and are deficient in PD. We tested the hypothesis that midfrontal delta/theta rhythms predict cognitive dysfunction in PD. We recruited 100 PD patients and 49 demographically-similar control participants who completed a series of cognitive control tasks, including the Simon, oddball, and interval timing tasks. We focused on cue-evoked delta (1-4 Hz) and theta (4-7 Hz) rhythms from a single midfrontal EEG electrode (Cz) in PD patients who were either cognitively normal, with mild-cognitive impairments (PDMCI), or had dementia (PDD). We found that PD-related cognitive dysfunction was associated with increased response latencies and decreased midfrontal delta power across all tasks. Within PD patients, the first principal component of evoked EEG features from a single electrode (Cz) strongly correlated with clinical metrics such as the Montreal Cognitive Assessment (MOCA; rho=0.36) and with NIH-toolbox Executive Function scores (rho=0.46). These data demonstrate that cue-evoked midfrontal delta/theta rhythms directly relate to cognition in PD. Our results provide insight into the nature of low-frequency frontal rhythms and suggest that PD-related cognitive dysfunction results from decreased delta/theta activity. These findings could facilitate the development of new biomarkers and targeted therapies for cognitive symptoms of PD.