1,644 research outputs found
Data Driven Control of Vagus Nerve Stimulation for the Cardiovascular System: An in Silico Computational Study
Vagus nerve stimulation is an emerging therapy that seeks to offset pathological conditions by electrically stimulating the vagus nerve through cuff electrodes, where an electrical pulse is defined by several parameters such as pulse amplitude, pulse width, and pulse frequency. Currently, vagus nerve stimulation is under investigation for the treatment of heart failure, cardiac arrhythmia and hypertension. Through several clinical trials that sought to assess vagus nerve stimulation for the treatment of heart failure, stimulation parameters were determined heuristically and the results were inconclusive, which has led to the suggestion of using a closed-loop approach to optimize the stimulation parameters. A recent investigation has demonstrated highly specific control of cardiovascular physiology by selectively activating different fibers in the vagus nerve. When multiple locations and multiple stimulation parameters are considered for optimization, the design of closed-loop control becomes considerably more challenging. To address this challenge, we investigated a data-driven control scheme for both modeling and controlling the rat cardiovascular system. Using an existing in silico physiological model of a rat heart to generate synthetic input-output data, we trained a long short-term memory network (LSTM) to map the effect of stimulation on the heart rate and blood pressure. The trained LSTM was utilized in a model predictive control framework to optimize the vagus nerve stimulation parameters for set point tracking of the heart rate and the blood pressure in closed-loop simulations. Additionally, we altered the underlying in silico physiological model to consider intra-patient variability, and diseased dynamics from increased sympathetic tone in designing closed-loop VNS strategies. Throughout the different simulation scenarios, we leveraged the design of the controller to demonstrate alternative clinical objectives. Our results show that the controller can optimize stimulation parameters to achieve set-point tracking with nominal offset while remaining computationally efficient. Furthermore, we show a controller formulation that compensates for mismatch due to intra-patient variabilty, and diseased dynamics. This study demonstrates the first application and a proof-of-concept for using a purely data-driven approach for the optimization of vagus nerve stimulation parameters in closed-loop control of the cardiovascular system
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Clinically indicated electrical stimulation strategies to treat patients with medically refractory epilepsy.
Focal epilepsies represent approximately half of all diagnoses, and more than one-third of these patients are refractory to pharmacologic treatment. Although resection can result in seizure freedom, many patients do not meet surgical criteria, as seizures may be multifocal in origin or have a focus in an eloquent region of the brain. For these individuals, several U.S. Food and Drug Administration (FDA)-approved electrical stimulation paradigms serve as alternative options, including vagus nerve stimulation, responsive neurostimulation, and stimulation of the anterior nucleus of the thalamus. All of these are safe, flexible, and lead to progressive seizure control over time when used as an adjunctive therapy to antiepileptic drugs. Focal epilepsies frequently involve significant comorbidities such as cognitive decline. Similar to antiepilepsy medications and surgical resection, current stimulation targets and parameters have yet to address cognitive impairments directly, with patients reporting persistent comorbidities associated with focal epilepsy despite a significant reduction in the number of their seizures. Although low-frequency theta oscillations of the septohippocampal network are critical for modulating cellular activity and, in turn, cognitive processing, the coordination of neural excitability is also imperative for preventing seizures. In this review, we summarize current FDA-approved electrical stimulation paradigms and propose that theta oscillations of the medial septal nucleus represent a novel neuromodulation target for concurrent seizure reduction and cognitive improvement in epilepsy. Ultimately, further advancements in clinical neurostimulation strategies will allow for the efficient treatment of both seizures and comorbidities, thereby improving overall quality of life for patients with epilepsy
Vagus nerve stimulation: State of the art of stimulation and recording strategies to address autonomic function neuromodulation
International audienceObjective. Neural signals along the vagus nerve (VN) drive many somatic and autonomic functions. The clinical interest of VN stimulation (VNS) is thus potentially huge and has already been demonstrated in epilepsy. However, side effects are often elicited, in addition to the targeted neuromodulation. Approach. This review examines the state of the art of VNS applied to two emerging modulations of autonomic function: heart failure and obesity, especially morbid obesity. Main results. We report that VNS may benefit from improved stimulation delivery using very advanced technologies. However, most of the results from fundamental animal studies still need to be demonstrated in humans
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Timing control for paired plasticity
Systems, methods and devices for paired training include timing controls so that training and neural stimulation can be provided simultaneously. Paired trainings may include therapies, rehabilitation and performance enhancement training. Stimulations of nerves such as the vagus nerve that affect subcortical regions such as the nucleus basalis, locus coeruleus or amygdala induce plasticity in the brain, enhancing the effects of a variety of therapies, such as those used to treat tinnitus, stroke, traumatic brain injury and post-traumatic stress disorder.Board of Regents, University of Texas Syste
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Systems, methods and devices for treating tinnitus
Systems, methods and devices for paired training include timing controls so that training and neural stimulation can be provided simultaneously. Paired trainings may include therapies, rehabilitation and performance enhancement training. Stimulations of nerves such as the vagus nerve that affect subcortical regions such as the nucleus basalis, locus coeruleus or amygdala induce plasticity in the brain, enhancing the effects of a variety of therapies, such as those used to treat tinnitus, stroke, traumatic brain injury and post-traumatic stress disorder.Board of Regents, University of Texas Syste
Investigation of the baroreflex of the rat : steady state and dynamic features
The baroreflex is one of the most important feedback systems in the body to maintain blood pressure variation within the homeostatic range. In this dissertation, the important features of the carotid and aortic baroreflexes have been extensively investigated on ventilated, central nervous system intact, neuromuscular blocked (NMB) rats using different control system and signal processing tools. Studies have demonstrated that sinoaortic denervation (SAD) caused substantial increases in the blood pressure variability. Comparing the pre- and post-SAD blood pressure spectra, there was a significant increase of power in the very low frequency region (0.00195 -0.2 Hz), and a significant decrease of power in the low frequency region (0.2 - 0.6 Hz) after SAD. The dominant power change after SAD was in the very low frequency region of the blood pressure spectra.
The carotid and aortic baroreflexes were accessed by volumetric manipulation of the carotid sinus and electrical manipulation of the aortic depressor nerve (ADN) using step and sinusoidal stimulations. Myelinated ADN-A fibers and myelinated + unmyelinated ADN-A+C fibers were accessed separately in the experiments. Results showed that the baroreflex functions as a \u27low-pass\u27 filter, with -3dB cutoff frequency at approximately \u3c0. I Hz. The major working area of the baroreflex system is in the VLF region of the blood pressure spectra. The estimated system transportation lag was 1.07s, which would cause the baroreflex system to oscillate at frequencies around 0.4 Hz.
Analyses demonstrated that it is not likely that the baroreflex is activated only occasionally, such as in response to postural shifts, but operates continuously to bring the blood pressure into balance. It is theoretically and experimentally demonstrated that the absolute gain of the open-loop baroreflex system can be predicted by the ratio of the pre-and post- blood pressure amplitude spectra
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Methods, systems, and devices for pairing vagus nerve stimulation with motor therapy in stroke patients
A method of treating motor deficits in a stroke patient, comprising assessing a patient's motor deficits, determining therapeutic goals for the patient, based on the patient's motor deficits, selecting therapeutic tasks based on the therapeutic goals, performing each of the selected therapeutic tasks repetitively, observing the performance of the therapeutic tasks, initiating the stimulation of the vagus nerve manually at approximately a predetermined moment during the performance of the therapeutic tasks, stimulating the vagus nerve of the patient during the performance of the selected therapeutic tasks, and improving the patient's motor deficits.Board of Regents, University of Texas Syste
Acquisition of cardiac control parameters from whole vagus nerve recordings
Heart rate varies continuously depending on the amount of activity being performed or the emotional state of an individual. Both branches of the autonomic nervous system work to alter heart rate depending on the needs of the body. While healthy individuals are capable of altering their heart rate, individuals with certain types of heart disease do not have this ability. For these individuals, cardiac pacemakers are used to alter heart rate. Cardiac pacemakers use sensors to determine the pacing frequency for the heart; however, there is no current optimum sensor. In order to discover a better sensor, this study investigated the use of parasympathetic motor activity via the vagus nerve to predict heart rate.
Vagus nerve activity and EKG signals were recorded simultaneously; two types of recordings were taken: baseline and altered heart rate recordings achieved by performing bi-lateral carotid artery occlusion. Whole vagus nerve discharges were recorded using small silicone cuff electrodes with platinum contacts. Neural activity and EKG signals obtained from these experiments were filtered for frequency content. After filtering, the vagus motor signal was calculated by using a cross correlation technique introduced by Heetderks. The vagus motor activity was integrated between successive R waves taken from the recorded EKG and correlated with instantaneous heart rate. Consistent, high inverse correlations between integrated vagus motor activity and instantaneous heart rate were found in baseline and occlusion recordings. After obtaining consistent correlations between the integrated vagal motor activity and instantaneous heart rate, a transfer function model was developed using time series analysis methods. The transfer function model whose input was integrated vagus motor activity and whose output was heart rate was capable of predicting heart rate within a 95% confidence interval
Feasibility of pulse rate variability as feedback in closed-loop percutaneous auricular vagus nerve stimulation
Percutaneous auricular vagus nerve stimulation (pVNS) is a novel approach of treating cardiovascular and inflammatory diseases, as well as pain and neurological conditions. The treatment can be optimized by using biosignals as objective measures and feedback-control. One suitable biofeedback could be the use of pulse rate and pulse rate variability (PRV) derived from optical pulse plethysmography (PPG) instead of heart rate and heart rate variability (HRV) derived from electrocardiogram (ECG). For this purpose, a single-lead ECG on the thorax and a PPG on the earlobe were measured simultaneously on 10 healthy subjects for 420 s during three different respiratory phases. The data was analyzed and compared with scatterplots, the Pearson correlation coefficient and a Bland-Altman analysis. The outcomes show a very high correlation of heart rates from PPG and ECG (ri= 0.9663) and SDNN values (rsdnn= 0.9791). Comparison of RMSSD values showed a high positive correlation (rrmssd= 0.7963) but a mean overestimation of 10 ms in RMSSD values measured with the PPG. The results presented suggest that PRV could be and alternative biofeedback used in pVNS
Comparison of symptomatic and functional responses to vagus nerve stimulation in ANTHEM-HF, INOVATE-HF, and NECTAR-HF
AIMS: Clinical studies of vagal nerve stimulation (VNS) for heart failure with reduced ejection fraction have had mixed results to date. We sought to compare VNS delivery and associated changes in symptoms and function in autonomic regulation therapy via left or right cervical vagus nerve stimulation in patients with chronic heart failure (ANTHEM-HF), increase of vagal tone in heart failure (INOVATE-HF), and neural cardiac therapy for heart failure (NECTAR-HF) for hypothesis generation.
METHODS AND RESULTS: Descriptive statistics were used to analyse data from the public domain for differences in proportions using Pearson\u27s chi-square test, differences in mean values using Student\u27s unpaired t-test, and differences in changes of mean values using two-sample t-tests. Guideline-directed medical therapy recommendations were similar across studies. Fewer patients were in New York Heart Association 3, and baseline heart rate (HR) was higher in ANTHEM-HF. In INOVATE-HF, VNS was aimed at peripheral neural targets, using closed-loop delivery that required synchronization of VNS to R-wave sensing by an intracardiac lead. Pulse frequency was low (1-2 Hz) because of a timing schedule allowing ≤3 pulses of VNS following at most 25% of detected R waves. NECTAR-HF and ANTHEM-HF used open-loop VNS delivery (i.e. independent of any external signal) aimed at both central and peripheral targets. In NECTAR-HF, VNS delivery at 20 Hz caused off-target effects that limited VNS up-titration in a majority of patients. In ANTHEM-HF, VNS delivery at 10 Hz allowed up-titration until changes in HR dynamics were confirmed. Six months after VNS titration, significant improvements in both HR and HR variability occurred only in ANTHEM-HF. When ANTHEM-HF and NECTAR-HF were compared, greater improvements from baseline were observed in ANTHEM-HF in standard deviation in normal-to-normal R-R intervals (94 ± 26 to 111 ± 50 vs. 146 ± 48 to 130 ± 52 ms; P \u3c 0.001), left ventricular ejection fraction (32 ± 7 to 37 ± 0.4 vs. 31 ± 6 to 33 ± 6; P \u3c 0.05), and Minnesota Living with Heart Failure mean score (40 ± 14 to 21 ± 10 vs. 44 ± 22 to 36 ± 21; P \u3c 0.002). When compared with INOVATE-HF, greater improvement in 6-min walk distance was observed in ANTHEM-HF (287 ± 66 to 346 ± 78 vs. 304 ± 111 to 334 ± 111 m; P \u3c 0.04).
CONCLUSIONS: In this post-hoc analysis, differences in patient demographics were seen and may have caused the differential responses in symptoms and function observed in association with VNS. Major differences in technology platforms, neural targets, VNS delivery, and HR and HR variability responses could have also potentially played a very important role. Further study is underway in a randomized controlled trial with these considerations in mind
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