Fig. 1

Closed Loop Neuromodulation/Cardiac Devices: input a signal that modulates the output of the neuromodulation target (Dark Orange Arrows = sensing, Light Green Arrows = Stimulation). By definition, closed loop neuromodulation requires a continuous sensing modality that then continuously modifies the stimulation parameter. Autonomic Neuromodulation may include invasive electrical neural stimulation, as well as non-invasive electrical (e.g., transcutaneous vagus nerve stimulation (tcVNS)] and directed energy devices that contribute to autonomic nervous system modulation effects, (e.g., with splenic focused ultrasound stimulation (sFUS)). Current devices on the market include conventional cardiac pacemakers (Diack et al. 1979) (A), and Closed Loop Evoked Compound Action Potential (ECAP) spinal cord stimulation (SCS) marketed for pain (Caylor et al. 2019) (B). Recent advances in brain recording have resulted in development of Close Loop Deep Brain Stimulation (DBS) and Closed Loop Transcranial Magnetic Stimulation (TMS) (C). Closed Loop DBS is now FDA approved for Parkinson’s Disease (PD) and epilepsy, while other disease states are currently being studied (e.g., PTSD or Depression (Widge 2023), Pain (Shirvalkar et al. 2018), and Alzheimer's Disease (Ríos et al. 2022; Hell et al. 2019)). Future Closed Loop Autonomic Neuromodulation (D) is under development in which inflammation is sensed with Autonomic Neurography (ANG) that can then drive autonomic neuromodulation delivered or to hone in on the dosage, aimed to amplify the body’s own vagus-driven anti-inflammatory reflex, thus throttling down inflammation by regulating macrophages that circulate through the spleen