Dataset Information

Digital Cardiovascular Biomarker Responses to Transcutaneous Cervical Vagus Nerve Stimulation: State-Space Modeling, Prediction, and Simulation.

ABSTRACT: BACKGROUND:Transcutaneous cervical vagus nerve stimulation (tcVNS) is a promising alternative to implantable stimulation of the vagus nerve. With demonstrated potential in myriad applications, ranging from systemic inflammation reduction to traumatic stress attenuation, closed-loop tcVNS during periods of risk could improve treatment efficacy and reduce ineffective delivery. However, achieving this requires a deeper understanding of biomarker changes over time. OBJECTIVE:The aim of the present study was to reveal the dynamics of relevant cardiovascular biomarkers, extracted from wearable sensing modalities, in response to tcVNS. METHODS:Twenty-four human subjects were recruited for a randomized double-blind clinical trial, for whom electrocardiography and photoplethysmography were used to measure heart rate and photoplethysmogram amplitude responses to tcVNS, respectively. Modeling these responses in state-space, we (1) compared the biomarkers in terms of their predictability and active vs sham differentiation, (2) studied the latency between stimulation onset and measurable effects, and (3) visualized the true and model-simulated biomarker responses to tcVNS. RESULTS:The models accurately predicted future heart rate and photoplethysmogram amplitude values with root mean square errors of approximately one-fifth the standard deviations of the data. Moreover, (1) the photoplethysmogram amplitude showed superior predictability (P=.03) and active vs sham separation compared to heart rate; (2) a consistent delay of greater than 5 seconds was found between tcVNS onset and cardiovascular effects; and (3) dynamic characteristics differentiated responses to tcVNS from the sham stimulation. CONCLUSIONS:This work furthers the state of the art by modeling pertinent biomarker responses to tcVNS. Through subsequent analysis, we discovered three key findings with implications related to (1) wearable sensing devices for bioelectronic medicine, (2) the dominant mechanism of action for tcVNS-induced effects on cardiovascular physiology, and (3) the existence of dynamic biomarker signatures that can be leveraged when titrating therapy in closed loop. TRIAL REGISTRATION:ClinicalTrials.gov NCT02992899; https://clinicaltrials.gov/ct2/show/NCT02992899. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):RR2-10.1016/j.brs.2019.08.002.

SUBMITTER: Gazi AH

PROVIDER: S-EPMC7539162 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Digital Cardiovascular Biomarker Responses to Transcutaneous Cervical Vagus Nerve Stimulation: State-Space Modeling, Prediction, and Simulation.

Gazi Asim H AH Gurel Nil Z NZ Richardson Kristine L S KLS Wittbrodt Matthew T MT Shah Amit J AJ Vaccarino Viola V Bremner J Douglas JD Inan Omer T OT

JMIR mHealth and uHealth 20200922 9

<h4>Background</h4>Transcutaneous cervical vagus nerve stimulation (tcVNS) is a promising alternative to implantable stimulation of the vagus nerve. With demonstrated potential in myriad applications, ranging from systemic inflammation reduction to traumatic stress attenuation, closed-loop tcVNS during periods of risk could improve treatment efficacy and reduce ineffective delivery. However, achieving this requires a deeper understanding of biomarker changes over time.<h4>Objective</h4>The aim o ...[more]

PMID: 32960179

Similar Datasets

Project description:ObjectivesTranscutaneous auricular vagus nerve stimulation (taVNS) modulates brain activity and heart function. The induced parasympathetic predominance leads to an increase of heart rate variability (HRV). Knowledge on the corresponding cortical activation pattern is, however, scarce. We hypothesized taVNS-induced HRV increases to be related to modulation of cortical activity that regulates the autonomic outflow to the heart.Materials and methodsIn thirteen healthy subjects, we simultaneously recorded 64-channel electroencephalography and electrocardiography during taVNS. Two taVNS stimulation targets were investigated, i.e., the cymba conchae and inner tragus, and compared to active control stimulation in the anatomical vicinity, i.e., at the crus helicis and outer tragus. We used intermitted stimulation bursts of 25 Hz applied at a periodicity of 1 Hz. HRV was estimated with different time-domain methodologies: standard deviation of RR (SDNN), the root mean squares of successive differences (RMSSD), the percentage of RR-intervals with at least 50 ms deviation from the preceding RR-interval (pNN50), and the difference of consecutive RR intervals weighted by their mean (rrHRV).ResultsThe stimulation-induced HRV increases corresponded to frequency-specific oscillatory modulation of different cortical areas. All stimulation targets induced power modulations that were proportional to the HRV elevation. The most prominent changes that corresponded to HRV increases across all parameters and stimulation locations were frontal elevations in the theta-band. In the delta-band, there were frontal increases (RMSSD, pNN50, rrHRV, SDNN) and decreases (SDNN) across stimulation sites. In higher frequencies, there was a more divers activity pattern: Outer tragus/crus helicis stimulation increased oscillatory activity with the most prominent changes for the SDNN in frontal (alpha-band, beta-band) and fronto-parietal (gamma-band) areas. During inner tragus/cymba conchae stimulation the predominant pattern was a distributed power decrease, particularly in the fronto-parietal gamma-band.ConclusionNeuro-cardiac interactions can be modulated by electrical stimulation at different auricular locations. Increased HRV during stimulation is correlated with frequency-specific increases and decreases of oscillatory activity in different brain areas. When applying specific HRV measures, cortical patterns related to parasympathetic (RMSSD, pNN50, rrHRV) and sympathetic (SDNN) modulation can be identified. Thus, cortical oscillations may be used to define stimulation locations and parameters for research and therapeutic purposes.

Project description:BackgroundTranscutaneous auricular Vagus Nerve Stimulation (taVNS) applies low-intensity electrical current to the ear with the intention of activating the auricular branch of the Vagus nerve. The sensitivity and selectivity of stimulation applied to the ear depends on current flow pattern produced by a given electrode montage (size and placement).ObjectiveWe compare different electrodes designs for taVNS considering both the predicted peak electric fields (sensitivity) and their spatial distribution (selectivity).MethodsBased on optimized high-resolution (0.47 mm) T1 and T2 weighted MRI, we developed an anatomical model of the left ear and the surrounding head tissues including brain, CSF/meninges, skull, muscle, blood vessels, fat, cartilage, and skin. The ear was further segmented into 6 regions of interest (ROI) based on various nerve densities: cavum concha, cymba concha, crus of helix, tragus, antitragus, and earlobe. A range of taVNS electrode montages were reproduced spanning varied electrodes sizes and placements over the tragus, cymba concha, earlobe, cavum concha, and crus of helix. Electric field across the ear (from superficial skin to cartilage) for each montage at 1 mA or 2 mA taVNS, assuming an activation threshold of 6.15 V/m, 12.3 V/m or 24.6 V/m was predicted using a Finite element method (FEM). Finally, considering every ROI, we calculated the sensitivity and selectivity of each montage.ResultsCurrent flow patterns through the ear were highly specific to the electrode montage. Electric field was maximal at the ear regions directly under the electrodes, and for a given total current, increases with decreasing electrode size. Depending on the applied current and nerves threshold, activation may also occur in the regions between multiple anterior surface electrodes. Each considered montage was selective for one or two regions of interest. For example, electrodes across the tragus restricted significant electric field to the tragus. Stimulation across the earlobe restricted significant electric field to the earlobe and the antitragus. Because of this relative selectivity, use of control ear montages in experimental studies, support testing of targeting. Relative targeting was robust across assumptions of activation threshold and tissue properties.DiscussionComputational models provide additional insight on how details in electrode shape and placement impact sensitivity (how much current is needed) and selectivity (spatial distribution), thereby supporting analysis of existing approaches and optimization of new devices. Our result suggest taVNS current patterns and relative target are robust across individuals, though (variance in) axon morphology was not represented.

Dataset Information

Digital Cardiovascular Biomarker Responses to Transcutaneous Cervical Vagus Nerve Stimulation: State-Space Modeling, Prediction, and Simulation.

Publications

Digital Cardiovascular Biomarker Responses to Transcutaneous Cervical Vagus Nerve Stimulation: State-Space Modeling, Prediction, and Simulation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets