Pilot characterization of the heartbeat evoked potential (HEP) in early-stage Parkinson disease (PD), including effects of levodopa.

Central autonomic contribution to dysautonomia in PD is incompletely understood. The HEP, an EEG-based measure of cerebral heart-to-brain signaling, represents a novel, non-invasive means of assessing central autonomic processing in PD. We predicted: 1) peripheral signs of early cardiovascular dysautonomia (reduced heart-rate variability, HRV) would be reflected by altered HEP amplitudes; 2) levodopa would ‘normalize’ HRV and HEP measures.

Seated, resting simultaneous ECG and 64-channel EEG (2.5–5min) was obtained in 10 healthy control (HC; 6 female) and 7 early-stage PD participants (4 female; Hoehn & Yahr 2; avg 3.4 years since diagnosis) without cognitive impairment or depression. PD patients were assessed both OFF and ON levodopa states. Frequency-domain HRV (low and high-frequency (LF, HF) and LF/HF ratio) was calculated using Matlab-based Fast-Fourier Transform interbeat interval modeling for spectral analysis. One-way ANOVA then tested group differences. Channel-wide HEPs were measured via averaging pre-processed and artifact-cleaned EEG data epoched around R-wave peaks. HEP amplitudes 200-400ms post R-wave were compared between groups (Control, PD-OFF, PD-ON) using channel-wide permutation testing.

Groups were similarly aged (p=0.42), and gender matched (p=1.0), without significant differences in cognition (MoCA p=0.49) or depression (Beck depression inventory p=0.09). PD-OFF and ON states had higher heart rate (p=0.042, 0.027). PD-OFF had lower LF/HF ratio compared to HC (p=0.014). PD-OFF state had significantly altered HEP amplitude compared to HC and ON-state for two left-frontocentral and right-parietal channel clusters (p<0.05).

We replicated prior findings of subtle cardiovascular dysautonomia (reduced LF/HF ratio, suggestive of impaired baroreflex function) in early OFF-state PD and found a reflection of this, centrally, in an altered HEP. Levodopa ‘normalized’ both measures. Future work will evaluate effects of autonomic maneuvers and relationships between cardiovascular dysautonomia signs/symptoms on the HEP.