Prefrontal brain regions have been proposed to modulate vagally mediated heart rate variability (HRV) through their action on subcortical structures. This study aimed at investigating the beat-to-beat influence of the brain cortex over the heart through a high temporal resolution estimation of brain-heart coupling. Electrocardiogram (ECG) and electroencephalogram (EEG) from 32 scalp positions were recorded at rest for 5鈥痬in in 38 participants. To assess beat-to-beat cortical control on vagal activity, the longest and shortest inter-beat intervals (IBIs) were identified for each participant. Then, the EEG activity was time-locked to R waves in the ECG signal and analyzed using a time-frequency approach. Logistic regression models were applied to predict the trial-by-trial occurrence of long and short IBIs from cardiac-related EEG activity. Delta power reduction over prefrontal and frontocentral areas preceding the R-wave increased the probability for a long IBI to occur, as compared to a short one. Moreover, reduced prefrontal delta power preceding the R wave was correlated to higher cardiac vagal control, as reflected by the High Frequency (HF) power of HRV calculated on the whole recording time. The present results support the hypothesis that phasic activation/deactivation of prefrontal areas modulates vagal control of heart rate at rest.