Abstract
Patients with Parkinson’s disease (PD) can have significant cognitive dysfunction; however, the mechanisms for these cognitive symptoms are unknown. Here, we used scalp electroencephalography (EEG) to investigate the cortical basis for PD-related cognitive impairments during interval timing, which requires participants to estimate temporal intervals of several seconds. Time estimation is an ideal task demand for investigating cognition in PD because it is simple, requires medial frontal cortical areas, and recruits basic executive processes such as working memory and attention. However, interval timing has never been systematically studied in PD patients with cognitive impairments. We report three main findings. First, 71 PD patients had increased temporal variability compared to 37 demographically matched controls, and this variability correlated with cognitive dysfunction as measured by the Montreal Cognitive Assessment (MOCA). Second, PD patients had attenuated ~4 Hz EEG oscillatory activity at midfrontal electrodes in response to the interval-onset cue, which was also predictive of MOCA. Finally, trial-by-trial linear mixed-effects modeling demonstrated that cue-triggered ~4 Hz power predicted subsequent temporal estimates as a function of PD and MOCA. Our data suggest that impaired cue-evoked midfrontal ~4 Hz activity predicts increased timing variability that is indicative of cognitive dysfunction in PD. These findings link PD-related cognitive dysfunction with cortical mechanisms of cognitive control, which could advance novel biomarkers and neuromodulation for PD.
Highlights
Parkinson’s disease (PD) is a devastating neurodegenerative disease that involves motor as well as cognitive symptoms[1,2,3,4].For motor symptoms of PD, detailed neurophysiological studies led to highly targeted and effective therapies such as deep-brain stimulation (DBS)[5,6,7,8]
PD patients have impairments in interval timing[17,18] and temporal processing in general[19,20]. Since this prior work has focused on basal ganglia mechanisms in cognitively high-functioning PD patients, it remains unknown how interval timing is affected by a broader range of cognitive impairments
This study revealed that deficits in midfrontal cognitive-control processes contribute to increased variability in interval timing and to cognitive dysfunction in PD
Summary
Parkinson’s disease (PD) is a devastating neurodegenerative disease that involves motor as well as cognitive symptoms[1,2,3,4].For motor symptoms of PD, detailed neurophysiological studies led to highly targeted and effective therapies such as deep-brain stimulation (DBS)[5,6,7,8]. Cognitive deficits in PD are diverse, affecting a range of executive processes such as working memory, attention, reasoning, visuospatial dysfunction, inhibitory control, and flexibility[11,12]. One process that is ideal for studying PD-related cognitive dysfunction is interval timing, which requires participants to estimate temporal intervals of several seconds[13]. Interval timing depends on executive functions such as working memory for temporal rules and attention to the passage of time[16]. PD patients have impairments in interval timing[17,18] and temporal processing in general[19,20] Since this prior work has focused on basal ganglia mechanisms in cognitively high-functioning PD patients, it remains unknown how interval timing is affected by a broader range of cognitive impairments
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