Abstract
OBJECTIVE: Parkinson disease (PD) can be difficult to diagnose and treat. Development of a biomarker for PD would reduce these challenges by providing an objective measure of disease. Emerging theories suggest PD is characterized by excessive synchronization in the beta frequency band (∼20Hz) throughout basal ganglia-thalamocortical loops. Recently we showed with invasive electrocorticography that one robust measure of this synchronization is the coupling of beta phase to broadband gamma amplitude (ie, phase-amplitude coupling [PAC]). Other recent work suggests that high-frequency activity is detectable at the scalp using electroencephalography (EEG). Motivated by these findings, we tested whether beta-gamma PAC over sensorimotor cortex, recorded noninvasively with EEG, differs between PD patients off and on medications, and healthy control subjects. METHODS: Resting EEG was compared from 15 PD patients and 16 healthy control subjects. PD patients were tested on and off medications on different days, in a counterbalanced order. For each data set we calculated PAC and compared results across groups. RESULTS: PAC was elevated in the patients off medications compared to on medications (p = 0.008) and for patients off medications compared to controls (p = 0.009). INTERPRETATION: Elevated PAC is detectable using scalp EEG in PD patients off medications compared to on medications, and compared to healthy controls. This suggests that EEG PAC may provide a noninvasive biomarker of the parkinsonian state. This biomarker could be used as a control signal for closed-loop control of deep brain stimulation devices, for adjustment of dopaminergic treatment, and also has the potential to aid in diagnosis.