Neurophysiological characteristics of apathy in Parkinson's disease

Apathy in Parkinson’s disease (PD) is often resistant to therapy, difficult to quantify and poorly understood. It is commonly characterized by a lack of motivation and emotional blunting. Neural responses recorded using electroencephalography (EEG), such as neural oscillations and event-related potentials (ERPs), are often associated with motivated behaviour and emotion processing, but few studies have examined how these characteristics are affected in apathetic PD patients. To examine the behavioural and neural oscillatory characteristics of motivated movement in apathetic PD patients, we used an incentivized motor task, in which subjects could win money based on the amount of effort they produced on a hand grip. We demonstrated that PD patients with lower apathy scores could modulate their effort production to increasing rewards, whereas patients with more severe apathy could not. EEG results showed that apathetic PD patients exhibited a higher resting power in the alpha and theta frequency bands compared to non-apathetic PD subjects and healthy subjects. Furthermore, there was a significant correlation between absolute resting alpha power and relative alpha power during squeezing. These two factors were able to predict patient apathy scores, irrespective of age or disease severity. The same was true for absolute resting theta power and relative theta power during squeezing. To explore emotion processing in PD, we investigated ERPs from EEG recordings as subjects viewed emotionally evocative visual stimuli. We employed a data-driven approach to separate unique ERP time courses from one another called multiset canonical correlation analysis (MCCA). Results showed that the late positive potential (LPP), an ERP that responds to emotional stimuli, had a blunted amplitude in response to negative visual stimuli compared to healthy subjects. Interestingly, there was also a greater centro-parietal topographical representation of the LPP in PD subjects compared to healthy subjects, suggesting the presence of potential compensatory mechanisms for blunted neural reactivity to emotional stimuli in PD patients. This work lays the foundation for further understanding apathy and provides a quantitative test to measure apathy in people living with Parkinson’s. Medicine, Faculty ofGraduat