Modulation of memory performance and brain activity by non-invasive auricular transcutaneous vagus nerve stimulation in a mouse model of intellectual disability disorder

Abstract Introduction: It has been demonstrated that acute vagus nerve stimulation (VNS) improves word recognition memory in epilepsy patients. Transcutaneous auricular vagus nerve stimulation (taVNS) has gained interest as a non-invasive alternative to improve cognition. In this prospective randomized cross-over study, we investigated the effect of both invasive VNS and taVNS on verbal memory performance in 15 drug-resistant epilepsy patients. Methods All patients conducted a word recognition memory paradigm in 3 conditions: VNS ON, VNS OFF and taVNS. For each condition, patients memorized 21 highlighted words from text paragraphs. Afterwards, the intervention was delivered for 30 s. Immediate recall and delayed recognition scores were obtained for each condition. This memory paradigm was repeated after 6 weeks of VNS therapy in 2 conditions: VNS ON and VNS OFF. Results Acute VNS and taVNS did not improve verbal memory performance. Immediate recall and delayed recognition scores were significantly improved after 6 weeks of VNS treatment irrespective of the acute intervention. Conclusion The previously described positive effects of invasive VNS on verbal memory performance could not be replicated with invasive VNS and taVNS. An improved verbal memory performance was seen after 6 weeks of VNS treatment, suggesting that longer and more repetitive stimulation of the vagal pathway is required to modulate verbal memory performance.

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Transcutaneous vagus nerve stimulation in humans induces pupil dilation and attenuates alpha oscillations

10.1101/2020.08.25.265876 ◽

2020 ◽

Author(s):

Omer Sharon ◽

Firas Fahoum ◽

Yuval Nir

Keyword(s):

Electrical Stimulation ◽

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Pupil Dilation ◽

Somatosensory Stimulation ◽

Alpha Oscillations ◽

Sham Stimulation ◽

Non Invasive ◽

Transcutaneous Vagus Nerve Stimulation

AbstractVagus nerve stimulation (VNS) is widely used to treat drug-resistant epilepsy and depression. While the precise mechanisms mediating its long-term therapeutic effects are not fully resolved, they likely involve locus coeruleus (LC) stimulation via the nucleus of the solitary tract (NTS), which receives afferent vagal inputs. In rats, VNS elevates LC firing and forebrain noradrenaline levels, whereas LC lesions suppress VNS therapeutic efficacy. Non-invasive transcutaneous VNS (tVNS) employs electrical stimulation that targets the auricular branch of the vagus nerve at the cymba conchae of the ear. However, the extent that tVNS mimics VNS remains unclear. Here, we investigated the short-term effects of tVNS in healthy human male volunteers (n=24), using high-density EEG and pupillometry during visual fixation at rest. We compared short (3.4s) trials of tVNS to sham electrical stimulation at the earlobe (far from the vagus nerve branch) to control for somatosensory stimulation. Although tVNS and sham stimulation did not differ in subjective intensity ratings, tVNS led to robust pupil dilation (peaking 4-5s after trial onset) that was significantly higher than following sham stimulation. We further quantified, using parallel factor analysis, how tVNS modulates idle occipital alpha (8-13Hz) activity identified in each participant. We found greater attenuation of alpha oscillations by tVNS than by sham stimulation. This demonstrates that tVNS reliably induces pupillary and EEG markers of arousal beyond the effects of somatosensory stimulation, thus supporting the hypothesis that tVNS elevates noradrenaline and other arousal-promoting neuromodulatory signaling, and mimics invasive VNS.Significance statementCurrent non-invasive brain stimulation techniques are mostly confined to modulating cortical activity, as is typical with transcranial magnetic or transcranial direct/alternating-current electrical stimulation. Transcutaneous vagus nerve stimulation (tVNS) has been proposed to stimulate subcortical arousal-promoting nuclei, though previous studies yielded inconsistent results. Here we show that short (3.4s) tVNS pulses in naïve healthy male volunteers induced transient pupil dilation and attenuation of occipital alpha oscillations. These markers of brain arousal are in line with the established effects of invasive VNS on locus coeruleus-noradrenaline signaling, and support the notion that tVNS mimics VNS. Therefore, tVNS can be used as a tool for studying the means by which endogenous subcortical neuromodulatory signaling affects human cognition, including perception, attention, memory, and decision-making; and also for developing novel clinical applications.

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Transcutaneous Vagus Nerve Stimulation

European Neurological Review ◽

10.17925/enr.2011.06.04.254 ◽

2011 ◽

Vol 6 (4) ◽

pp. 254 ◽

Cited By ~ 43

Author(s):

Jens Ellrich ◽

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Drug Resistant ◽

Non Invasive ◽

Transcutaneous Vagus Nerve Stimulation ◽

The Common ◽

Myelinated Fibres ◽

Drug Resistant Epilepsy ◽

Intended Use

Invasive vagus nerve stimulation (VNS) is an approved treatment for drug-resistant epilepsy. Besides its recognised clinical efficacy, there are major drawbacks, such as invasiveness and a great many side effects. Therefore there is a medical demand for transcutaneous VNS (t-VNS®), which combines selective, non-invasive access to vagus nerve afferents with a low risk profile. Both treatments excite thick myelinated fibres of vagus nerve branches that project to the nucleus of the solitary tract in the brainstem. Preclinical data emphasise the equivalent anticonvulsive effects of both methods. Based upon the common mode of action and the first clinical data, the t-VNS device received Conformité Européenne (CE) approval. Besides the approved intended use for drug-resistant epilepsy and depression, a future clinical trial will address the efficacy of t-VNS in chronic pain.

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Direct and Transcutaneous Vagus Nerve Stimulation for Treatment of Tinnitus: A Scoping Review

Frontiers in Neuroscience ◽

10.3389/fnins.2021.680590 ◽

2021 ◽

Vol 15 ◽

Author(s):

Natalia Yakunina ◽

Eui-Cheol Nam

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Neural Plasticity ◽

Vagus Nerve Stimulation ◽

Human Subjects ◽

Acoustic Stimulation ◽

Non Invasive ◽

Transcutaneous Vagus Nerve Stimulation ◽

Alternative Approach ◽

Tinnitus Treatment

Recent animal research has shown that vagus nerve stimulation (VNS) paired with sound stimuli can induce neural plasticity in the auditory cortex in a controlled manner. VNS paired with tones excluding the tinnitus frequency eliminated physiological and behavioral characteristics of tinnitus in noise-exposed rats. Several clinical trials followed and explored the effectiveness of VNS paired with sound stimuli for alleviating tinnitus in human subjects. Transcutaneous VNS (tVNS) has received increasing attention as a non-invasive alternative approach to tinnitus treatment. Several studies have also explored tVNS alone (not paired with sound stimuli) as a potential therapy for tinnitus. In this review, we discuss existing knowledge about direct and tVNS in terms of applicability, safety, and effectiveness in diminishing tinnitus symptoms in human subjects. This review includes all existing clinical and neuroimaging studies of tVNS alone or paired with acoustic stimulation in tinnitus patients and outlines the present limitations that must be overcome to maximize the potential of (t)VNS as a therapy for tinnitus.

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Transcranial Auricular Vagus Nerve Stimulation (taVNS) and Ear-EEG: Potential for Closed-Loop Portable Non-invasive Brain Stimulation

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.699473 ◽

2021 ◽

Vol 15 ◽

Author(s):

Philipp Ruhnau ◽

Tino Zaehle

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Closed Loop ◽

Brain Activity ◽

High Temporal Resolution ◽

Closed Loop System ◽

Non Invasive ◽

Current Task ◽

A Current

No matter how hard we concentrate, our attention fluctuates – a fact that greatly affects our success in completing a current task. Here, we review work from two methods that, in a closed-loop manner, have the potential to ameliorate these fluctuations. Ear-EEG can measure electric brain activity from areas in or around the ear, using small and thus portable hardware. It has been shown to capture the state of attention with high temporal resolution. Transcutaneous auricular vagus nerve stimulation (taVNS) comes with the same advantages (small and light) and critically current research suggests that it is possible to influence ongoing brain activity that has been linked to attention. Following the review of current work on ear-EEG and taVNS we suggest that a combination of the two methods in a closed-loop system could serve as a potential application to modulate attention.

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Transcutaneous vagus nerve stimulation increases locus coeruleus function and memory performance in older individuals

Alzheimer s & Dementia ◽

10.1002/alz.044766 ◽

2020 ◽

Vol 16 (S6) ◽

Author(s):

Heidi I.L. Jacobs ◽

Nikos Priovoulos ◽

Joost M Riphagen ◽

Benedikt A. Poser ◽

Vitaly Napadow ◽

...

Keyword(s):

Vagus Nerve ◽

Locus Coeruleus ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Memory Performance ◽

Older Individuals ◽

Transcutaneous Vagus Nerve Stimulation

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Effect of Transcutaneous Vagus Nerve Stimulation in Dysphagia After Lateral Medullary Infarction: A Case Report

American Journal of Speech-Language Pathology ◽

10.1044/2019_ajslp-18-0262 ◽

2019 ◽

Vol 28 (4) ◽

pp. 1381-1387

Author(s):

Ying Yuan ◽

Jie Wang ◽

Dongyu Wu ◽

Dahua Zhang ◽

Weiqun Song

Keyword(s):

Vagus Nerve ◽

Nerve Stimulation ◽

Vagus Nerve Stimulation ◽

Rating Scale ◽

Tube Feeding ◽

Nasogastric Feeding ◽

Lateral Medullary Infarction ◽

Severe Dysphagia ◽

Transcutaneous Vagus Nerve Stimulation ◽

Medullary Infarction

Purpose Severe dysphagia with weak pharyngeal peristalsis after dorsal lateral medullary infarction (LMI) requires long-term tube feeding. However, no study is currently available on therapeutic effectiveness in severe dysphagia caused by nuclear damage of vagus nerve after dorsal LMI. The purpose of the present investigation was to explore the potential of transcutaneous vagus nerve stimulation (tVNS) to improve severe dysphagia with weak pharyngeal peristalsis after dorsal LMI. Method We assessed the efficacy of 6-week tVNS in a 28-year-old woman presented with persisting severe dysphagia after dorsal LMI who had been on nasogastric feeding for 6 months. tVNS was applied for 20 min twice a day, 5 days a week, for 6 weeks. The outcome measures included saliva spitted, Swallow Function Scoring System, Functional Oral Intake Scale, Clinical Assessment of Dysphagia With Wallenberg Syndrome, Yale Pharyngeal Residue Severity Rating Scale, and upper esophagus X-ray examination. Results After tVNS, the patient was advanced to a full oral diet without head rotation or spitting. No saliva residue was found in the valleculae and pyriform sinuses. Contrast medium freely passed through the upper esophageal sphincter. Conclusion Our findings suggest that tVNS might provide a useful means for recovery of severe dysphagia with weak pharyngeal peristalsis after dorsal LMI. Supplemental Material https://doi.org/10.23641/asha.9755438

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