Real-time closed-loop brainstem stimulation modality for enhancing temporal blood pressure reduction

Traditional pharmacological interventions are well tolerated in the management of elevated blood pressure (BP) for individuals with resistant hypertension. Although neuromodulation has been investigated as an alternative solution, its open-loop (OL) modality cannot follow the patient's physiological state. In fact, neuromodulation for controlling highly fluctuating BP necessitates a closed-loop (CL) stimulation modality based on biomarkers to monitor the patient's continuously varying physiological state. By leveraging its intuitive linkage with BP responses in ongoing efforts aimed at developing a CL system to enhance temporal BP reduction effect, this study proposes a CL neuromodulation modality that controls nucleus tractus solitarius (NTS) activity to effectively reduce BP, thus reflecting continuously varying physiological states. While performing neurostimulation targeting the NTS in the rat model, the arterial BP response and neural activity of the NTS were simultaneously measured. To evaluate the temporal BP response effect of CL neurostimulation, OL (constant parameter; 20 Hz, 200 μA) and CL (Initial parameter; 11 Hz, 112 μA) stimulation protocols were performed with stimulation 180 s and rest 600 s, respectively, and examined NTS activity and BP response to the protocols. In-vivo experiments for OL versus CL protocol for direct NTS stimulation in rats demonstrated an enhancement in temporal BP reduction via the CL modulation of NTS activity. This study proposes a CL stimulation modality that enhances the effectiveness of BP control using a feedback control algorithm based on neural signals, thereby suggesting a new approach to antihypertensive neuromodulation. •Real-time closed-loop brainstem modulation using NTS activity feedback enhances BP reduction.•BP response and NTS activity were analyzed with open-loop and closed-loop protocols.•Closed-loop protocol temporally enhanced stimulus-driven BP reduction compared to open-loop protocol.•Regulation of NTS activity increased temporal BP reduction.