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

2021 ◽  
Author(s):  
Sophie J Mueller ◽  
Vanessa Teckentrup ◽  
Ignacio Rebollo ◽  
Manfred Hallschmid ◽  
Nils B Kroemer
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Energy Homeostasis ◽  
Solitary Tract ◽  
Afferent Pathway ◽  
Preclinical Research ◽  
Novel Treatments ◽  
Induced Changes ◽  
The Brain

Maintaining energy homeostasis is vital and supported by vagal signaling between digestive organs and the brain. Previous research has established a gastric network in the brain that is phase synchronized with the rhythm of the stomach, but tools to perturb its function were lacking. Here, we investigated the effect of acute right-sided transcutaneous auricular vagus nerve stimulation (taVNS) versus sham stimulation (randomized crossover-design) on stomach-brain coupling. In line with preclinical research, taVNS increased stomach-brain coupling in the nucleus of the solitary tract (NTS) and the midbrain while boosting coupling across the brain. Crucially, in the cortex, taVNS-induced changes in coupling occurred primarily in transmodal regions and were associated with changes in hunger ratings as indicators of the subjective metabolic state. Hence, taVNS alters stomach-brain coupling via an NTS-midbrain pathway that signals gut-induced reward, potentially paving the way for novel treatments in disorders such as Parkinson's disease or depression.

Transcutaneous Vagus Nerve Stimulation Enhances Post-error Slowing

2015 ◽  
Vol 27 (11) ◽  
pp. 2126-2132 ◽  
Author(s):  
Roberta Sellaro ◽  
Jelle W. R. van Leusden ◽  
Klodiana-Daphne Tona ◽  
Bart Verkuil ◽  
Sander Nieuwenhuis ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Direct Evidence ◽  
Noradrenergic System ◽  
Group Design ◽  
Transcutaneous Vagus Nerve Stimulation ◽  
The Brain ◽  
Single Blind

People tend to slow down after they commit an error, a phenomenon known as post-error slowing (PES). It has been proposed that slowing after negative feedback or unforeseen errors is linked to the activity of the locus coeruleus–norepinephrine (LC–NE) system, but there is little direct evidence for this hypothesis. Here, we assessed the causal role of the noradrenergic system in modulating PES by applying transcutaneous vagus nerve stimulation (tVNS), a new noninvasive and safe method to stimulate the vagus nerve and to increase NE concentrations in the brain. A single-blind, sham-controlled, between-group design was used to assess the effect of tVNS in healthy young volunteers (n = 40) during two cognitive tasks designed to measure PES. Results showed increased PES during active tVNS, as compared with sham stimulation. This effect was of similar magnitude for the two tasks. These findings provide evidence for an important role of the noradrenergic system in PES.

Far field potentials from the brain stem after transcutaneous vagus nerve stimulation

2003 ◽  
Vol 110 (12) ◽  
pp. 1437-1443 ◽  
Author(s):  
A. J. Fallgatter ◽  
B. Neuhauser ◽  
M. J. Herrmann ◽  
A.-C. Ehlis ◽  
A. Wagener ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Brain Stem ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Far Field ◽  
Field Potentials ◽  
Transcutaneous Vagus Nerve Stimulation ◽  
The Brain

EEG Derived Brain Activity Reflects Treatment Response from Vagus Nerve Stimulation in Patients with Epilepsy

2017 ◽  
Vol 27 (04) ◽  
pp. 1650048 ◽  
Author(s):  
Simon Wostyn ◽  
Willeke Staljanssens ◽  
Leen De Taeye ◽  
Gregor Strobbe ◽  
Stefanie Gadeyne ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Seizure Frequency ◽  
Mechanism Of Action ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Brain Activity ◽  
P300 Amplitude ◽  
Eeg Recordings ◽  
Patients With Epilepsy ◽  
The Brain

The mechanism of action of vagus nerve stimulation (VNS) is yet to be elucidated. To that end, the effects of VNS on the brain of epileptic patients were studied. Both when VNS was switched “On” and “Off”, the brain activity of responders (R, seizure frequency reduction of over 50%) was compared to the brain activity of nonresponders (NR, seizure frequency reduction of less than 50%). Using EEG recordings, a significant increase in P300 amplitude for R and a significant decrease in P300 amplitude for NR were found. We found biomarkers for checking the efficacy of VNS with accuracy up to 94%. The results show that P300 features recorded in nonmidline electrodes are better P300 biomarkers for VNS efficacy than P300 features recorded in midline electrodes. Using source localization and connectivity analyses, the activity of the limbic system, insula and orbitofrontal cortex was found to be dependent on VNS switched “On” versus “Off” or patient group (R versus NR). The results suggest an important role for these areas in the mechanism of action of VNS, although a larger patient study should be done to confirm the findings.

Epilepsy, Electroacupuncture and the Nucleus of the Solitary Tract

2006 ◽  
Vol 24 (4) ◽  
pp. 164-168 ◽  
Author(s):  
Yusuf Ozgur Cakmak
Keyword(s):  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagal Afferents ◽  
Auricular Acupuncture ◽  
Acupuncture Points ◽  
Solitary Tract ◽  
Laboratory Findings ◽  
Afferent Pathways ◽  
The Brain ◽  
Stimulation Of

Vagal nerve stimulation and electroacupuncture have some promise as neuroprotective therapies for patients with poorly controlled epilepsy. It has been demonstrated that stimulation of acupuncture points on the extremities results in stimulation of the vagus nerve. It is possible that the antiepileptic effects of these two applications might be targeting the same centre in the brain. The nucleus of the solitary tract, which is a primary site at which vagal afferents terminate, is also the site for afferent pathways of facial, scalp and auricular acupuncture via trigeminal, cervical spinal and glossopharyngeal nerves. Taken together with laboratory findings, the neuroprotective pathways of electroacupuncture in epileptic models may stem from the collaboration of its anti-inflammatory and neurotrophic actions through the nucleus of the solitary tract via vagus nerve stimulation.

scholarly journals Is Vagus Nerve Stimulation Brain Washing?

2019 ◽  
Author(s):  
Kevin P. Cheng ◽  
Sarah K. Brodnick ◽  
Stephan L. Blanz ◽  
Weifeng Zeng ◽  
Jack Kegel ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Intractable Epilepsy ◽  
Brain Parenchyma ◽  
Vagal Nerve ◽  
Waste Products ◽  
Adrenergic Signaling ◽  
The Brain

AbstractVagal nerve stimulation (VNS) is an FDA approved treatment method for intractable epilepsy, treatment resistant depression, cluster headaches and migraine with over 100,000 patients having received vagal nerve implants to date. Moreover, evidence in the literature has led to a growing list of possible clinical indications, with several small clinical trials applying VNS to treat conditions ranging from neurodegenerative diseases to arthritis, anxiety disorders, and obesity. Despite the growing list of therapeutic applications, the fundamental mechanisms by which VNS achieves its beneficial effects are poorly understood and an area of active research. In parallel, the glymphatic and meningeal lymphatic systems have recently been proposed and experimentally validated to explain how the brain maintains a healthy homeostasis without a traditionally defined lymphatic system. In particular, the glymphatic system relates to the interchange of cerebrospinal fluid (CSF) and interstitial fluid (ISF) whose net effect is to wash through the brain parenchyma removing metabolic waste products and misfolded proteins from the interstitium. Of note, clearance is sensitive to adrenergic signaling, and a primary driver of CSF influx into the parenchyma appears to be cerebral arterial pulsations and respiration. As VNS has well-documented effects on cardiovascular and respiratory physiology as well as brain adrenergic signaling, we hypothesized that VNS delivered at clinically derived parameters would increase CSF influx in the brain. To test this hypothesis, we injected a low molecular weight (3 kD) lysine-fixable fluorescent tracer (TxRed) into the CSF system of mice with a cervical vagus nerve cuff implant and measured the amount of CSF penetrance following VNS. We found that the clinical VNS group showed a significant increase in CSF dye penetrance as compared to the naïve control and sham groups. This study demonstrates that VNS therapeutic strategies already being applied in the clinic today may induce intended effects and/or unwanted side effects by altering CSF/ISF exchange in the brain. This may have broad ranging implications in the treatment of various CNS pathologies.One Sentence SummaryCervical vagus nerve stimulation using clinically derived parameters enhances movement of cerebrospinal fluid into the brain parenchyma presenting a previously unreported effect of vagus nerve stimulation with potential clinical utility.

scholarly journals Brain signaling dynamics after vagus nerve stimulation

2021 ◽  
Author(s):  
Vanessa Teckentrup ◽  
Marina Krylova ◽  
Hamidreza Jamalabadi ◽  
Sandra Neubert ◽  
Monja P. Neuser ◽  
...  
Keyword(s):  
Time Series ◽  
Functional Connectivity ◽  
Vagus Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Neural Circuit ◽  
Future Research ◽  
Dynamic Functional Connectivity ◽  
Wide Range ◽  
Induced Changes

The vagus nerve projects to a well-defined neural circuit via the nucleus tractus solitarii (NTS) and its stimulation elicits a wide range of metabolic, neuromodulatory, and behavioral effects. Transcutaneous vagus nerve stimulation (tVNS) has been established as a promising technique to non-invasively alter brain function. However, the precise dynamics elicited by tVNS in humans are still largely unknown. Here, we performed fMRI with concurrent right-sided tVNS (vs. sham) following a randomized cross-over design (N=40). First, to unravel the temporal profile of tVNS-induced changes in the NTS, we compared fMRI time series to canonical profiles for stimulation ON and OFF cycles. Model comparisons indicated that NTS time series were best fit by block-wise shifts in signal amplitude with stimulation ON and OFF estimates being highly correlated. Therefore, we compared stimulation (ON + OFF) versus baseline phases and found that tVNS increased fMRI BOLD activation in the NTS, but this effect was dependent on sufficient temporal signal-to-noise ratio (tSNR) in the mask. Second, to identify the spatiotemporal evolution of tVNS-induced changes in the brain, we examined lagged co-activation patterns and phase coherence. In contrast to our hypothesis, tVNS did not alter dynamic functional connectivity after correction for multiple comparisons. Third, to establish a positive control for future research, we measured changes in gastric myoelectrical frequency via an electrogastrogram. Again, in contrast to our hypothesis, tVNS induced no changes in gastric frequency. Collectively, our study provides evidence that tVNS can perturb brain signaling in the NTS, but these effects are dependent on tSNR and require precise localization. In light of an absence of acute tVNS-induced effects on dynamic functional connectivity and gastric motility, we discuss which steps are necessary to advance future research on afferent and efferent effects of tVNS.

scholarly journals Non-invasive vagus nerve stimulation normalizes food liking and improves liking ratings in depression

2021 ◽  
Author(s):  
Vincent Koepp ◽  
Johannes Klaus ◽  
Magdalena Ferstl ◽  
Franziska K Müller ◽  
Anne Kühnel ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Effective Treatment ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Food Reward ◽  
Food Cues ◽  
Subject Variables ◽  
Food Liking ◽  
Induced Changes ◽  
Healthy Participants

Introduction: The vagus nerve plays a prominent role in the regulation of food reward and energy metabolism. However, previous studies using vagus nerve stimulation yielded conflicting results regarding changes in food reward in healthy participants and participants with major depressive disorder (MDD), for which vagal nerve stimulation is an effective treatment. Methods: We investigated the acute effects of right transcutaneous auricular vagus nerve stimulation (taVNS) on ratings of liking and wanting of food and non-food items in 63 participants, including 31 patients with MDD. To test for taVNS-induced changes and interactions with between-subject variables group (MDD vs. healthy controls) and questionnaire scores as well as within-subject variables, we performed linear mixed-effects analysis. In addition, we assessed whether individual taVNS-induced changes in food reward ratings were dependent on average ratings.Results: taVNS increased liking of food cues in participants with MDD (p= 0.023), but not in healthy participants (p= 0.657). Specifically, taVNS induced larger improvements in liking ratings with increasing scores of anhedonia (p= 0.029). Notably, across all participants, taVNS reduced the variance of food liking compared to sham, suggesting that taVNS normalizes extreme liking ratings towards moderate levels (p = 0.039).Discussion: Our results show that taVNS acutely ameliorates hedonic responses in MDD suggesting that it could provide an effective treatment of anhedonia. Since anhedonia is difficult to treat with conventional therapies, taVNS may provide a powerful adjuvant to rapidly improve motivational deficiencies.

scholarly journals Vagus nerve stimulation for primary headache disorders: An anatomical review to explain a clinical phenomenon

Cephalalgia ◽  
2019 ◽  
Vol 39 (9) ◽  
pp. 1180-1194 ◽  
Author(s):  
Dylan Jozef Hendrik Augustinus Henssen ◽  
Berend Derks ◽  
Mats van Doorn ◽  
Niels Verhoogt ◽  
Anne-Marie Van Cappellen van Walsum ◽  
...  
Keyword(s):  
Vagus Nerve ◽  
Trigeminal Nerve ◽  
Nerve Stimulation ◽  
Vagus Nerve Stimulation ◽  
Primary Headache ◽  
Solitary Tract ◽  
Headache Disorders ◽  
Primary Headache Disorders ◽  
Non Invasive ◽  
Stimulation Of

Background Non-invasive stimulation of the vagus nerve has been proposed as a new neuromodulation therapy to treat primary headache disorders, as the vagus nerve is hypothesized to modulate the headache pain pathways in the brain. Vagus nerve stimulation can be performed by placing an electrode on the ear to stimulate the tragus nerve, which contains about 1% of the vagus fibers. Non-invasive vagus nerve stimulation (nVNS) conventionally refers to stimulation of the cervical branch of the vagus nerve, which is made up entirely of vagal nerve fibers. While used interchangeably, most of the research to date has been performed with nVNS or an implanted vagus nerve stimulation device. However, the exact mechanism of action of nVNS remains hypothetical and no clear overview of the effectiveness of nVNS in primary headache disorders is available. Methods In the present study, the clinical trials that investigated the effectiveness, tolerability and safety of nVNS in primary headache disorders were systematically reviewed. The second part of this study reviewed the central connections of the vagus nerve. Papers on the clinical use of nVNS and the anatomical investigations were included based on predefined criteria, evaluated, and results were reported in a narrative way. Results The first part of this review shows that nVNS in primary headache disorders is moderately effective, safe and well-tolerated. Regarding the anatomical review, it was reported that fibers from the vagus nerve intertwine with fibers from the trigeminal, facial, glossopharyngeal and hypoglossal nerves, mostly in the trigeminal spinal tract. Second, the four nuclei of the vagus nerve (nuclei of the solitary tract, nucleus ambiguus, spinal nucleus of the trigeminal nerve and dorsal motor nucleus (DMX)) show extensive interconnections. Third, the efferents from the vagal nuclei that receive sensory and visceral input (i.e. nuclei of the solitary tract and spinal nucleus of the trigeminal nerve) mainly course towards the main parts of the neural pain matrix directly or indirectly via other vagal nuclei. Conclusion The moderate effectiveness of nVNS in treating primary headache disorders can possibly be linked to the connections between the trigeminal and vagal systems as described in animals.

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