Importance of timing optimization for closed-loop applications of vagus nerve stimulation

Mylavarapu, Ramanamurthy; Kanumuri, Vivek V.; Vaccari, Juan Pablo de Rivero; Misra, Amrit; McMillan, David W.; Ganzer, Patrick D.

doi:10.1186/s42234-023-00110-9

Cited by 3 publications

(3 citation statements)

References 90 publications

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“…Another example of how the framework could be adapted is the inclusion of a closed-loop control mechanism (Bilgutay et al, 1968; Tosato et al, 2006; Ugalde et al, 2014; Ojeda et al, 2016; Mylavarapu et al, 2023). These studies use live monitoring of the RR interval as an input for determining the timing and/or parameters for stimulating the nerve.…”

Section: Discussionmentioning

confidence: 99%

Using neural biomarkers to personalize dosing of vagus nerve stimulation

Berthon,

Wernisch,

Stoukidi

et al. 2023

Preprint

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Background: Vagus nerve stimulation (VNS) is an established therapy for treating a variety of chronic diseases, such as epilepsy, depression, obesity, and for stroke rehabilitation. However, lack of precision and side-effects have hindered its efficacy and extension to new conditions. Objective: To achieve a better understanding of the relationship between VNS parameters and neural and physiological responses to enable the design of personalized dosing procedures to improve precision and efficacy of VNS therapies. Methods: We used biomarkers from recorded evoked neural activity and short-term physiological responses (throat muscle, cardiac and respiratory activity) to understand the response to a wide range of VNS parameters in anaesthetised pigs. Using signal processing, Gaussian processes (GP) and parametric regression models we analyse the relationship between VNS parameters and neural and physiological responses. Results: Firstly, we observe inter-subject variability for both neural and physiological responses. Secondly, we illustrate how considering multiple stimulation parameters in VNS dosing can improve the efficacy and precision of VNS therapies. Thirdly, we describe the relationship between different VNS parameters and the evoked neural activity and show how spatially selective electrodes can be used to improve fibre recruitment. Fourthly, we provide a detailed exploration of the relationship between the activations of neural fibre types and different physiological effects, and show that recordings of evoked neural activity are powerful biomarkers for predicting the short-term physiological effects of VNS. Finally, based on these results, we discuss how recordings of evoked neural activity can help design VNS dosing procedures that optimize short-term physiological effects safely and efficiently. Conclusion: Understanding of evoked neural activity during VNS provide powerful biomarkers that could improve the precision, safety and efficacy of VNS therapies.

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Section: Discussionmentioning

confidence: 99%

Using neural biomarkers to personalize dosing of vagus nerve stimulation

Berthon,

Wernisch,

Stoukidi

et al. 2023

Preprint

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show abstract

“… 2016 ; Mylavarapu et al. 2023 ). These studies use live monitoring of the RR interval as an input for determining the timing and/or parameters for stimulating the nerve.…”

Section: Discussionmentioning

confidence: 99%

Using neural biomarkers to personalize dosing of vagus nerve stimulation

Berthon,

Wernisch,

Stoukidi

et al. 2024

Bioelectron Med

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Background Vagus nerve stimulation (VNS) is an established therapy for treating a variety of chronic diseases, such as epilepsy, depression, obesity, and for stroke rehabilitation. However, lack of precision and side-effects have hindered its efficacy and extension to new conditions. Achieving a better understanding of the relationship between VNS parameters and neural and physiological responses is therefore necessary to enable the design of personalized dosing procedures and improve precision and efficacy of VNS therapies. Methods We used biomarkers from recorded evoked fiber activity and short-term physiological responses (throat muscle, cardiac and respiratory activity) to understand the response to a wide range of VNS parameters in anaesthetised pigs. Using signal processing, Gaussian processes (GP) and parametric regression models we analyse the relationship between VNS parameters and neural and physiological responses. Results Firstly, we illustrate how considering multiple stimulation parameters in VNS dosing can improve the efficacy and precision of VNS therapies. Secondly, we describe the relationship between different VNS parameters and the evoked fiber activity and show how spatially selective electrodes can be used to improve fiber recruitment. Thirdly, we provide a detailed exploration of the relationship between the activations of neural fiber types and different physiological effects. Finally, based on these results, we discuss how recordings of evoked fiber activity can help design VNS dosing procedures that optimize short-term physiological effects safely and efficiently. Conclusion Understanding of evoked fiber activity during VNS provide powerful biomarkers that could improve the precision, safety and efficacy of VNS therapies.

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“…In this system, stimulation is automatically adjusted based on the detection of specific physiological signals or biomarkers, providing a personalized and effective intervention. In therapies for stroke rehabilitation, for instance, closed-loop VNS enables precise control over when stimulation is delivered to the patient, ensuring it occurs during appropriate moments [ 7 ], maximizing functional recovery and enhancing rehabilitation efficacy [ 8 ]. Stimulation can be synchronized with specific cardiac parameters, such as heart rate or blood pressure, to aid in the treatment of cardiovascular diseases like hypertension and myocardial ischemia [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Advances in Non-Invasive Neuromodulation: Designing Closed-Loop Devices for Respiratory-Controlled Transcutaneous Vagus Nerve Stimulation

de Faria,

Lopes,

Tobaldini

et al. 2023

Healthcare

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Studies suggest non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) as a potential therapeutic option for various pathological conditions, such as epilepsy and depression. Exhalation-controlled taVNS, which synchronizes stimulation with internal body rhythms, holds promise for enhanced neuromodulation, but there is no closed-loop system in the literature capable of performing such integration in real time. In this context, the objective was to develop real-time signal processing techniques and an integrated closed-loop device with sensors to acquire physiological data. After a conditioning stage, the signal is processed and delivers synchronized electrical stimulation during the patient’s expiratory phase. Additional modules were designed for processing, software-controlled selectors, remote and autonomous operation, improved analysis, and graphical visualization. The signal processing method effectively extracted respiratory cycles and successfully attenuated signal noise. Heart rate variability was assessed in real time, using linear statistical evaluation. The prototype feedback stimulator device was physically constructed. Respiratory peak detection achieved an accuracy of 90%, and the real-time processing resulted in a small delay of up to 150 ms in the detection of the expiratory phase. Thus, preliminary results show promising accuracy, indicating the need for additional tests to optimize real-time processing and the application of the prototype in clinical studies.

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Importance of timing optimization for closed-loop applications of vagus nerve stimulation

Cited by 3 publications

References 90 publications

Using neural biomarkers to personalize dosing of vagus nerve stimulation

Using neural biomarkers to personalize dosing of vagus nerve stimulation

Using neural biomarkers to personalize dosing of vagus nerve stimulation

Advances in Non-Invasive Neuromodulation: Designing Closed-Loop Devices for Respiratory-Controlled Transcutaneous Vagus Nerve Stimulation

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