Top-down brain circuits for operant bradycardia.

Heart rate (HR) can be voluntarily regulated when individuals receive real-time feedback. In a rat model of HR biofeedback, the neocortex and medial forebrain bundle were stimulated as feedback and reward, respectively. The rats reduced their HR within 30 minutes, achieving a reduction of approximately 50% after 5 days of 3-hour feedback. The reduced HR persisted for at least 10 days after training while the rats exhibited anxiolytic behavior and an elevation in blood erythrocyte count. This bradycardia was prevented by inactivating anterior cingulate cortical (ACC) neurons projecting to the ventromedial thalamic nucleus (VMT). Theta-rhythm stimulation of the ACC-to-VMT pathway replicated the bradycardia. VMT neurons projected to the dorsomedial hypothalamus (DMH) and DMH neurons projected to the nucleus ambiguus, which innervates parasympathetic neurons in the heart.