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Neural coupled oscillators are a useful building block in numerous models and applications. They were analyzed extensively in theoretical studies and more recently in biologically realistic simulations of spiking neural networks. The advent of mixed-signal analog/digital neuromorphic electronic circuits provides new means for implementing neural coupled oscillators on compact, low-power, spiking neural network hardware platforms. However, their implementation on this noisy, low-precision and inhomogeneous computing substrate raises new challenges with regards to stability and controllability. In this work, we present a robust, spiking neural network model of neural coupled oscillators and validate it with an implementation on a mixed-signal neuromorphic processor. We demonstrate its robustness showing how to reliably control and modulate the oscillator's frequency and phase shift, despite the variability of the silicon synapse and neuron properties. We show how this ultra-low power neural processing system can be used to build an adaptive cardiac pacemaker modulating the heart rate with respect to the respiration phases and compare it with surface ECG and respiratory signal recordings from dogs at rest. The implementation of our model in neuromorphic electronic hardware shows its robustness on a highly variable substrate and extends the toolbox for applications requiring rhythmic outputs such as pacemakers. [ABSTRACT FROM AUTHOR]

Key points: Respiratory sinus arrhythmia is physiological pacing of the heart that disappears in cardiovascular disease and is associated with poor cardiac prognosis.In heart failure, cardiac pacing has little, if any, variation in rate at rest.We proposed that reinstatement of respiratory sinus arrhythmia would improve cardiac function in rats with heart failure.Heart failure rats were paced daily for 2 weeks with either respiratory sinus arrhythmia or paced monotonically at a matched heart rate; cardiac function was measured using non‐invasive echocardiography.Cardiac output and stroke volume were increased in rats paced with respiratory sinus arrhythmia compared to monotonic pacing, via improvement in systolic function that persisted beyond the pacing treatment period.We propose that respiratory sinus arrhythmia pacing reverse‐remodels the heart in heart failure and is worth considering as a new form of cardiac pacemaking. Natural pacing of the heart results in heart rate variability, an indicator of good health and cardiac function. A contributor to heart rate variability is respiratory sinus arrhythmia or RSA – an intrinsic respiratory modulated pacing of heart rate. The loss of RSA is associated with poor cardiac prognosis and sudden cardiac death. We tested if reinstatement of respiratory‐modulated heart rate (RMH) would improve cardiac performance in heart failure. Heart failure was induced in Wistar rats by ligation of the left anterior descending coronary artery. Rats were unpaced, monotonically paced and RMH paced; the latter had the same average heart rate as the monotonically paced animals. Cardiac function was assessed non‐invasively using echocardiography before and after 2 weeks of daily pacing at a time when pacing was turned off. RMH increased cardiac output by 20 ± 8% compared to monotonic pacing (−3 ± 5%; P < 0.05). This improvement in cardiac output was associated with an increase in stroke volume compared to monotonic pacing (P = 0.03) and improvement in circumferential strain (P = 0.02). Improvements in ejection fraction (P = 0.08) and surrogate measures of left ventricle compliance did not reach significance. Increases in contractility (P < 0.05) and coronary blood flow (P < 0.05) were seen in vitro during variable pacing to mimic RMH. Thus, in rats with left ventricular dysfunction, chronic RMH pacing improved cardiac function through improvements in systolic function. As these improvements were made with pacing switched off, we propose the novel idea that RMH pacing causes reverse‐remodelling. Key points: Respiratory sinus arrhythmia is physiological pacing of the heart that disappears in cardiovascular disease and is associated with poor cardiac prognosis.In heart failure, cardiac pacing has little, if any, variation in rate at rest.We proposed that reinstatement of respiratory sinus arrhythmia would improve cardiac function in rats with heart failure.Heart failure rats were paced daily for 2 weeks with either respiratory sinus arrhythmia or paced monotonically at a matched heart rate; cardiac function was measured using non‐invasive echocardiography.Cardiac output and stroke volume were increased in rats paced with respiratory sinus arrhythmia compared to monotonic pacing, via improvement in systolic function that persisted beyond the pacing treatment period.We propose that respiratory sinus arrhythmia pacing reverse‐remodels the heart in heart failure and is worth considering as a new form of cardiac pacemaking. [ABSTRACT FROM AUTHOR]

In an emerging bioelectronics era, there is a clinical need for physiological devices incorporating biofeedback that permits natural and demand-dependent control in real time. Here, we describe a novel device termed a central pattern generator (CPG) that uses cutting edge analog circuitry producing temporally controlled, electrical stimulus outputs based on the real time integration of physiological feedback. Motivated by the fact that respiratory sinus arrhythmia (RSA), which is the cyclical changes in heart rate every breath, is an essential component of heart rate variability (HRV) (an indicator of cardiac health), we have explored the versatility and efficiency of the CPG for producing respiratory modulation of heart rate in anesthetized, spontaneously breathing rats. Diaphragmatic electromyographic activity was used as the input to the device and its output connected to either the right cervical vagus nerve or the right atrium for pacing heart rate. We found that the CPG could induce respiratory related heart rate modulation that closely mimicked RSA. Whether connected to the vagus nerve or right atrium, the versatility of the device was demonstrated by permitting: (i) heart rate modulation in any phase of the respiratory cycle, (ii) control of the magnitude of heart rate modulation, and (iii) instant adaptation to changes in respiratory frequency. Vagal nerve pacing was only possible following transection of the nerve limiting its effective use chronically. Pacing via the right atrium permitted better flexibility and control of heart rate above its intrinsic level. This investigation now lays the foundation for future studies using this biofeedback technology permitting closer analysis of both the function and dysfunction of RSA. [ABSTRACT FROM AUTHOR]

Abstract: We report on the modulation of respiratory sinus arrhythmia in rats with central pattern generator (CPG) hardware made of silicon neurons. The neurons are made to compete through mutually inhibitory synapses to provide timed electrical oscillations that stimulate the peripheral end of vagus nerve at specific points of the respiratory cycle: the inspiratory phase (φ1), the early expiratory phase (φ2) and the late expiratory phase (φ3). In this way the CPG hardware mimics the neuron populations in the brainstem which through connections with cardiac vagal motoneurones control respiratory sinus arrhythmia (RSA). Here, we time the output of the CPG hardware from the phrenic nerve activity recorded from rats while monitoring heart rate changes evoked by vagal nerve stimulation (derived from ECG) controlled by the CPG. This neuroelectric stimulation has the effect of reducing the heart rate and increasing the arterial pressure. The artificially induced RSA strongly depends on the timing of pulses within the breathing cycle. It is strongest when the vagus nerve is stimulated during the inspiratory phase (φ1) or the early expiratory phase (φ2) in which case the heart rate slows by 50% of the normal rate. Heart rate modulation is less when the same exact stimulus is applied during the late expiratory phase (φ3). These trials show that neurostimulation by CPG hardware can augment respiratory sinus arrhythmia. The CPG hardware technology opens a new line of therapeutic possibilities for prosthetic devices that restore RSA in patients where respiratory-cardiac coupling has been lost. [Copyright &y& Elsevier]