26 research outputs found

    Typical vagus nerve stimulation pattern (solid line), synchronized with the cardiac activity (dashed line).

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    <p>The controller can modulate the following VNS parameters: number of pulses (<i>P</i><sub>npulses</sub>), the interpulse period (<i>P</i><sub>ipp</sub>, ms), delay (<i>P</i><sub>del</sub>, ms), current amplitude (<i>P</i><sub>cur</sub>, mA), and pulse width (<i>P</i><sub>pw</sub>, ms).</p

    A novel controller based on state-transition models for closed-loop vagus nerve stimulation: Application to heart rate regulation - Fig 8

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    <p>The top panel of the figure shows the WMARR response when the P<sub>30</sub> (dotted line) and F<sub>30</sub> (solid line) controllers are used to regulate RR to 700 ms. The bottom panel shows the dynamics of the P<sub>30</sub> (dotted line) and F<sub>30</sub> (solid line) controllers.</p

    A novel controller based on state-transition models for closed-loop vagus nerve stimulation: Application to heart rate regulation

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    <div><p>Vagus nerve stimulation (VNS) is an established adjunctive therapy for pharmacologically refractory epilepsy and depression and is currently in active clinical research for other applications. In current clinical studies, VNS is delivered in an open-loop approach, where VNS parameters are defined during a manual titration phase. However, the physiological response to a given VNS configuration shows significant inter and intra-patient variability and may significantly evolve through time. VNS closed-loop approaches, allowing for the optimization of the therapy in an adaptive manner, may be necessary to improve efficacy while reducing side effects. This paper proposes a generic, closed-loop control VNS system that is able to optimize a number of VNS parameters in an adaptive fashion, in order to keep a control variable within a specified range. Although the proposed control method is completely generic, an example application using the cardiac beat to beat interval (RR) as control variable will be developed in this paper. The proposed controller is based on a state transition model (STM) that can be configured using a partially or a fully-connected architecture, different model orders and different state-transition algorithms. The controller is applied to the adaptive regulation of heart rate and evaluated on 6 sheep, for 13 different targets, using partially-connected STM with 10 states. Also, partially and fully-connected STM defined by 30 states were applied to 7 other sheep for the same 10 targets. Results illustrate the interest of the proposed fully-connected STM and the feasibility of integrating this control system into an implantable neuromodulator.</p></div

    A novel controller based on state-transition models for closed-loop vagus nerve stimulation: Application to heart rate regulation - Fig 7

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    <p>The top of the figure shows the WMARR response when P<sub>10</sub> (dotted line) and P<sub>30</sub> (solid line) controllers are used to regulate RR to 600 ms. The middle shows the dynamics of the P<sub>30</sub>. The bottom shows the dynamics of the P<sub>10</sub> controller.</p

    Performance indicators of three STM-based controllers.

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    <p>P<sub>10</sub> is a partially-connected STM-based controller of <i>N</i> = 10 states, evaluated on 6 sheep for 13 different targets. P<sub>30</sub> is a partially- connected STM-based controller of <i>N</i> = 30 states, evaluated on 7 sheep for 10 different targets. F<sub>30</sub> is a fully-connected STM-based controller of <i>N</i> = 30 states evaluated on the same 7 sheep for the same 10 targets. The three controllers were used on sheep anesthetized by etomidate. Most of the sheep used in the experimental protocol P<sub>10</sub> are different from the sheep used in the control tests of the P<sub>30</sub> and F<sub>30</sub> controllers. The sheep involved in the P<sub>30</sub> and F<sub>30</sub> protocols were the same. p-values are calculated between the three controllers. In the box plots, the dotted lines represent a Wilcoxon unpaired test and the solid line represents a Wilcoxon paired test. * denotes P < 0.05, and ** denotes P < 0.01.</p

    State-transition algorithm.

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    <p>The STA determines the optimal VNS parameters <i>S</i><sub><i>i</i></sub> minimizing the value <i>ϵ</i>, which represents the difference between the target RR and WMARR(b). Variable <i>i</i> is bounded between 0 and <i>N</i>. Parameter <i>E</i> defines the acceptable level of error on <i>ϵ</i>.</p

    Proposed closed-loop control system, based on a fully-connected state transition model (STM).

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    <p>The system consists of three components: a real-time control application, a neuromodulator prototype and a sheep used for animal experimentation. An intracardiac electrogram (EGM) is obtained via a cardiac lead implanted into the right ventricle of the sheep, analogically processed by the neuromodulator, and acquired via the analog to digital converter into the real-time control application. R-wave instants are detected and used for calculating a Weighted Moving Average of the RR intervals WMARR(b), which will be used as control variable. An error <i>ϵ</i> is obtained from the difference between the target (RR<sub>T</sub>) and WMARR(b). The STM-based controller estimates a new set of VNS parameters <i>S</i><sub><i>i</i></sub>, minimizing <i>ϵ</i>. VNS is triggered synchronously to the R-wave, with the new set of parameters <i>S</i><sub><i>i</i></sub>, to deliver VNS to the right vagus nerve of the sheep. VNS with these new parameters will modify the acquired EGM and a weighted moving average of the new RR interval is computed, closing the loop.</p

    Example output of the training phase for a particular sheep and <i>N</i> = 30.

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    <p>Top panel: ΔRR<sub>i</sub> as a function of sorted states. Bottom panel: Colormap of the normalized VNS parameters associated with each state, expressed as percentage of their corresponding range values.</p

    Diagram depicting the main signals and the VNS parameters analyzed in this paper.

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    <p>A) Representation of the left ventricular pressure signal (red), electrogram (EGM, green) and Vagus Nerve Stimulation signal (blue). B) Zoom displaying the main markers extracted from each beat: the inter-beat interval (RR interval) representing the chronotropic effect, the interval between the P-wave and the R-wave (PR inteval) used as a marker of the dromotropic effect and the maximum of the first of the <i>P</i><sub><i>lv</i></sub> signal (). C) A typical VNS burst delivered synchronously with a cardiac beat (after a given delay <i>P</i><sub>del</sub>), showing the VNS parameters studied in this paper.</p