Vagus Nerve Stimulation Induces Widespread Cortical and Behavioral Activation

Collins, Lindsay; Boddington, Laura; McCormick, David A.

doi:10.2139/ssrn.3760656

Cited by 10 publications

(24 citation statements)

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“…Recent work demonstrated that, in addition to movement preparation and execution, M1 pyramidal neurons also report movement outcome. Neurons in superficial L2/3 of M1 represent success and failure, independent of kinematics and the food reward consumption 47 The relative selectivity of the effects of Success VNS on movement representation are somewhat in contrast to recent observations of widespread, long-lasting excitatory responses to VNS 14 . However, in the previous study, VNS elicited locomotion and whisking, both of which correlate to increased general arousal and widespread cortical activation [85][86][87] .…”

Section: Motor Cortical Neurons Are Modulated By Vns Via Cholinergic Activitymentioning

confidence: 85%

“…1b,c). First, to test if VNS drives plasticity by increasing widespread cortical excitation and general arousal during a session 14 , VNS was applied at pseudo-random intervals (Random VNS) during the 20-minute training session. Alternatively, VNS may modulate short-term attention, or influence spike timing dependent plasticity 26 .…”

Section: Vns Enhances Motor Skill Learning When Paired With Successful Task Outcomementioning

confidence: 99%

“…The variable timing of BF neuronal responses to VNS suggests the involvement of a multi-synaptic pathway, possibly through the locus coeruleus (LC), which is known to send direct projections to the BF [74][75][76] and is activated by VNS 13,77 . Additionally, VNS leads to the sequential activation of noradrenergic and cholinergic axons in cortex, with noradrenergic activity preceding cholinergic activity 14 .…”

Section: Vns-driven Motor Learning Is Mediated By Cholinergic Signalingmentioning

confidence: 99%

“…In addition to the activation of neuromodulatory nuclei, VNS has a well-documented effect of decorrelating neural activity in cortex and other brain areas [20][21][22] . Recent in vivo imaging studies have confirmed a broad, excitatory effect of VNS across multiple cortical regions 14 . Yet, the effects of VNS are specific to a paired sensory or motor stimuli, suggesting VNS may confer more specific modulation of key neural circuits.…”

Section: Introductionmentioning

confidence: 99%

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Vagus nerve stimulation accelerates motor learning through cholinergic modulation

Hickman

Bowles

Peng

et al. 2021

Preprint

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Vagus nerve stimulation (VNS) is a neuromodulation therapy for a broad and rapidly expanding set of neurologic conditions. Classically used to treat epilepsy and depression, VNS has recently received FDA approval for stroke rehabilitation and is under preclinical and clinical investigation for other neurologic indications. Despite benefits across a diverse range of neurological disorders, the mechanism through which VNS influences central nervous system circuitry is not well described, limiting therapeutic optimization. A deeper understanding of the influence of VNS on neural circuits and activity is needed to maximize the use of VNS therapy across a broad range of neurologic conditions.To investigate how VNS can influence the neurons and circuits that underlie behavior, we paired VNS with upper limb movement in mice learning a skilled motor task. We leveraged genetic tools to perform optogenetic circuit dissection, as well as longitudinal in vivo imaging of calcium activity in cortical neurons to understand the effect of VNS on neural function. We found that VNS robustly enhanced motor learning when temporally paired with successful movement outcome, while randomly applied VNS impaired learning. This suggests that temporally-precise VNS may act through augmenting outcome cues, such as reinforcement signals. Within motor cortex, VNS paired with movement outcome selectively modulates the neural population that represents outcome, but not other movement-related neurons, across both acute and behaviorally-relevant timescales. Phasic cholinergic signaling from basal forebrain is required both for VNS-driven improvements in motor learning and the effects on neural activity in M1. These results indicate that VNS enhances motor learning through precisely-timed phasic cholinergic signaling to reinforce outcome, resulting in the recruitment of specific, behaviorally-relevant cortical circuits. A deeper understanding of the mechanisms of VNS on neurons, circuits and behavior provides new opportunities to optimize VNS to treat neurologic conditions.

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Section: Motor Cortical Neurons Are Modulated By Vns Via Cholinergic Activitymentioning

confidence: 85%

Section: Vns Enhances Motor Skill Learning When Paired With Successful Task Outcomementioning

confidence: 99%

Section: Vns-driven Motor Learning Is Mediated By Cholinergic Signalingmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Vagus nerve stimulation accelerates motor learning through cholinergic modulation

Hickman

Bowles

Peng

et al. 2021

Preprint

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show abstract

“…While pupil dilation has been considered as a potential biosensor for successful VNS, particularly following findings in animal model studies [62,63], our results show no effect of taVNS on resting pupil size in humans in line with a number of other studies [27–29,64]. There are several reasons why we may have failed to detect pupil dilation changes under taVNS relative to the sham condition: (1) the transcutaneous protocol used was insufficient to stimulate the vagus nerve sufficiently, perhaps due to the stimulation parameters (pulse width, frequency and amplitude) which still need further optimization [6,65]; however our current study did find both eye-gaze and oxytocin concentration changes after the stimulation, which suggest that the taVNS parameters chosen do have functional effects; (2) the procedure used to measure pupil dilation (i.e., the way we defined baseline pupil size and selection of time points) might also have influenced the results.…”

Section: Discussionmentioning

confidence: 99%

Transcutaneous auricular vagus nerve stimulation increases eye-gaze on salient facial features and oxytocin release

Zhu

Qing

Zhang

et al. 2021

Preprint

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Background: Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique with promising therapeutic potential in the context of epilepsy, pain, and depression and which may also have beneficial effects on social cognition. However, the underlying mechanisms of taVNS are unclear and evidence regarding its role in social cognition improvement is limited. Objective: In order to investigate the impact of taVNS on social cognition we have studied its effects on gaze towards emotional faces using an eye-tracking task and also on release of the neuropeptide oxytocin which plays a key role in influencing social cognition and motivation. Methods: A total of fifty-four subjects were enrolled in a sham-controlled, participant-blind crossover experiment, consisting of two treatment sessions, separated by one week. In one session participants received 30-min taVNS (tragus), and in the other, they received 30-min sham (earlobe) stimulation with the treatment order counterbalanced across participants. Gaze duration towards the faces and facial features (eyes, nose, and mouth) were measured together with resting pupil size. Additionally, saliva samples were taken for the measurement of oxytocin concentrations by enzyme-linked immunoassay. Results: Saliva oxytocin concentrations increased significantly after taVNS compared to sham stimulation, while resting pupil size did not. In addition, taVNS increased fixation time on the nose region irrespective of face emotion, and this was positively correlated with increased saliva oxytocin concentrations. Conclusion: Our findings suggest that taVNS biases visual attention towards socially salient facial features across different emotions and this is associated with its effects on increasing endogenous oxytocin release.

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Vagus nerve stimulation increases stomach-brain coupling via a vagal afferent pathway

Müller¹,

Teckentrup²,

Rebollo³

et al. 2022

Brain Stimulation

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Vagus Nerve Stimulation Induces Widespread Cortical and Behavioral Activation

Cited by 10 publications

References 0 publications

Vagus nerve stimulation accelerates motor learning through cholinergic modulation

Vagus nerve stimulation accelerates motor learning through cholinergic modulation

Transcutaneous auricular vagus nerve stimulation increases eye-gaze on salient facial features and oxytocin release

Vagus nerve stimulation increases stomach-brain coupling via a vagal afferent pathway

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