Acute Autonomic Engagement Assessed by Heart Rate Dynamics During Vagus Nerve Stimulation in Patients With Heart Failure in the ANTHEM‐HF Trial

Nearing, Bruce D.; Libbus, Imad; Amurthur, Badri; KenKnight, Bruce H.; Verrier, Richard L.

doi:10.1111/jce.13017

Cited by 32 publications

(25 citation statements)

References 28 publications

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“…After animals recovered from the vagus nerve implant surgery, proper function of the cuff electrode was validated by measuring changes in heart rate and pupil size following VNS. Both heart rate reduction (Nearing et al, 2016) and pupil dilation (Desbeaumes Jodoin et al, 2015; Bianca and Komisaruk, 2007) in response to VNS have been reported previously. We measured pupil size fluctuations over time with and without 1 sec stimulation of the vagus nerve.…”

Section: Resultssupporting

confidence: 66%

Short-term Effects of Vagus Nerve Stimulation on Learning and Evoked Activity in Auditory Cortex

Lai

David

2019

Preprint

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2Chronic vagus nerve stimulation (VNS) can facilitate learning of sensory and motor behaviors. 3 VNS is believed to trigger release of neuromodulators, including norepinephrine and acetylcholine, 4 which can mediate cortical plasticity associated with learning. Most previous work has studied 5 effects of VNS over many days, and less is known about how acute VNS influences neural coding 6 and behavior over the shorter term. To explore this question, we measured effects of VNS on 7 learning of an auditory discrimination over 1-2 days. Ferrets implanted with cuff electrodes on 8 the vagus nerve were trained by classical conditioning on a tone frequency-reward association. 9 One tone was associated with reward while another tone, was not. The frequencies and reward 10 associations of the tones were changed every two days, requiring learning of a new relationship. 11 When the tones (both rewarded and non-rewarded) were paired with VNS, rates of learning 12 increased on the first day following a change in reward association. To examine VNS effects 13 on auditory coding, we recorded single-and multi-unit neural activity in primary auditory cortex 14 (A1) of passively listening animals following brief periods of VNS (20 trials/session) paired with 15 tones. Because afferent VNS induces changes in pupil size associated with fluctuations in 16 neuromodulation, we also measured pupil during recordings. After pairing VNS with a neuron's 17 1 Jesyin Lai Short-term VNSbest-frequency (BF) tone, responses in a subpopulation of neurons were reduced. Pairing with 18 an off-BF tone or performing VNS during the inter-trial interval had no effect on responses. 19 We separated the change in A1 activity into two components, one that could be predicted by 20 fluctuations in pupil and one that persisted after VNS and was not accounted for by pupil. The 21 BF-specific reduction in neural responses remained, even after regressing out changes that 22 could be explained by pupil. In addition, the size of VNS-mediated changes in pupil predicted the 23 magnitude of persistent changes in the neural response. This interaction suggests that changes 24 in neuromodulation associated with arousal gate the long-term effects of VNS on neural activity. 25 Taken together, these results support a role for VNS in auditory learning and help establish VNS 26 as a tool to facilitate neural plasticity. 27 28

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Section: Resultssupporting

confidence: 66%

Short-term Effects of Vagus Nerve Stimulation on Learning and Evoked Activity in Auditory Cortex

Lai

David

2019

Preprint

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“…Function of the cuff electrode was validated by measuring changes in heart rate ( Nearing et al, 2016 ; see Materials and Methods) and pupil size following VNS ( Bianca and Komisaruk, 2007 ; Desbeaumes Jodoin et al, 2015 ; Fig. 2 ).…”

Section: Resultsmentioning

confidence: 99%

Short-Term Effects of Vagus Nerve Stimulation on Learning and Evoked Activity in Auditory Cortex

Lai

David

2021

eNeuro

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Chronic vagus nerve stimulation (VNS) has been shown to facilitate learning, but effects of acute VNS on neural coding and behavior remain less well understood. Ferrets implanted with cuff electrodes on the vagus nerve were trained by classical conditioning on an auditory tone frequency-reward association. One tone was associated with reward while another tone was not. Tone frequencies and reward associations were changed every 2 days, requiring learning of a new relationship. When tones were paired with VNS, animals consistently learned the new association within 2 days. When VNS occurred randomly between trials, learning within 2 days was unreliable. In passively listening animals, neural activity in primary auditory cortex and pupil size were recorded before and after acute VNS-tone pairing.After pairing with a neuron's best-frequency (BF) tone, responses by a subpopulation of neurons were reduced. VNS paired with an off-BF tone or during inter-trial intervals had no effect. The BF-specific reduction in neural responses after VNS remained, even after regressing out changes explained by pupil-indexed arousal. VNS induced brief dilation in the pupil, and the size of this change predicted the magnitude of persistent changes in the neural response. This interaction suggests that fluctuations in neuromodulation associated with arousal gate the long-term VNS effects on neural activity.

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“…The ANTHEM-HF trial used VNS in 59 heart failure patients, and found that VNS caused subtle changes in heart rate when applied on both the right and left side of the body. They concluded that the use of VNS in human subjects is a viable option for the modulation of the effects of the ANS on the heart (Nearing et al 2016). Another large-scale trial is the INOVATE-HF trial, in which 707 patients were followed over several months.…”

Section: Heart Failurementioning

confidence: 99%

Vagus Nerve Stimulation and the Cardiovascular System

Capilupi

Kerath

Becker

2019

Cold Spring Harb Perspect Med

107

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The vagus nerve plays an important role in maintaining physiological homeostasis, which includes reflex pathways that regulate cardiac function. The link between vagus nerve activity and the high-frequency component of heart rate variability (HRV) has been well established, correlating with vagal tone. Recently, vagus nerve stimulation (VNS) has been investigated as a therapeutic for a multitude of diseases, such as treatment-resistant epilepsy, rheumatoid arthritis, Crohn's disease, and asthma. Because of the vagus nerve's innervation of the heart, VNS has been identified as a potential therapy for cardiovascular disorders, such as cardiac arrest, acute myocardial infarction, and stroke. Here, we review the current state of preclinical and clinical studies, as well as the potential application of VNS in relation to the cardiovascular system.

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Acute Autonomic Engagement Assessed by Heart Rate Dynamics During Vagus Nerve Stimulation in Patients With Heart Failure in the ANTHEM‐HF Trial

Cited by 32 publications

References 28 publications

Short-term Effects of Vagus Nerve Stimulation on Learning and Evoked Activity in Auditory Cortex

Short-term Effects of Vagus Nerve Stimulation on Learning and Evoked Activity in Auditory Cortex

Short-Term Effects of Vagus Nerve Stimulation on Learning and Evoked Activity in Auditory Cortex

Vagus Nerve Stimulation and the Cardiovascular System

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