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It has recently been suggested that predictive processing principles may apply to interoception, defined as the processing of hormonal, autonomic, visceral, and immunological signals. In the current study, we aimed at providing empirical evidence for the role of cardiac interoceptive prediction errors signals on allostatic adjustments, using transcutaneous auricular vagus nerve stimulation (taVNS) as a tool to modulate the processing of interoceptive afferents. In a within‐subject design, participants performed a cardiac‐related interoceptive task (heartbeat counting task) under taVNS and sham stimulation, spaced 1‐week apart. We observed that taVNS, in contrast to sham stimulation, facilitated the maintenance of interoceptive accuracy levels over time (from the initial, stimulation‐free, baseline block to subsequent stimulation blocks), suggesting that vagus nerve stimulation may have helped to maintain engagement to cardiac afferent signals. During the interoceptive task, taVNS compared to sham, produced higher heart‐evoked potentials (HEP) amplitudes, a potential readout measure of cardiac‐related prediction error processing. Further analyses revealed that the positive relation between interoceptive accuracy and allostatic adjustments—as measured by heart rate variability (HRV)—was mediated by HEP amplitudes. Providing initial support for predictive processing accounts of interoception, our results suggest that the stimulation of the vagus nerve may increase the precision with which interoceptive signals are processed, favoring their influence on allostatic adjustments. We aimed at investigating the role of interoceptive prediction errors on allostatic adjustments, using transcutaneous auricular vagus nerve stimulation (taVNS) to increase precision. We found that taVNS facilitated the maintenance of interoceptive accuracy levels, increased heart‐evoked potentials amplitudes (correlates of cardiac‐related prediction error signals) and mediated their influence on allostatic adjustments (measured by heart rate variability).

Inhibiting fear-related thoughts and defensive behaviors when they are no longer appropriate to the situation is a prerequisite for flexible and adaptive responding to changing environments. Such inhibition of defensive systems is mediated by ventromedial prefrontal cortex (vmPFC), limbic basolateral amygdala (BLA), and brain stem locus-coeruleus noradrenergic system (LC-NAs). Non-invasive, transcutaneous vagus nerve stimulation (tVNS) has shown to activate this circuit. Using a multiple-day single-cue fear conditioning and extinction paradigm, we investigated long-term effects of tVNS on inhibition of low-level amygdala modulated fear potentiated startle and cognitive risk assessments. We found that administration of tVNS during extinction training facilitated inhibition of fear potentiated startle responses and cognitive risk assessments, resulting in facilitated formation, consolidation and long-term recall of extinction memory, and prevention of the return of fear. These findings might indicate new ways to increase the efficacy of exposure-based treatments of anxiety disorders.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising technique for modulating vagal afferent fibers non-invasively and has shown therapeutic potential in neurological, cognitive, and affective disorders. While previous research highlights its efficacy, the safety profile of taVNS has been less extensively examined. This study therefore aimed to systematically investigate side effects of taVNS in a large pooled dataset consisting of = 488 participants, utilizing a standardized questionnaire to assess ten reported side effects. Analyses included effects of stimulation type (interval vs. continuous), stimulation duration, stimulation intensity and participant characteristics (age and gender) as potential modulators. The findings support the safety of taVNS, with minimal and mild side effects reported across participants ( = 1.86, = 1.36). Although participants receiving sham stimulation were 32.4% less likely to report unpleasant feelings compared to participants receiving taVNS, this effect was driven primarily by low-end ratings (specifically, a rating of 1, indicating when experiencing the corresponding side effect), thus suggesting limited clinical relevance. Interval stimulation notably reduced the likelihood of some side effects, particularly for neck pain, dizziness and unpleasant feelings, suggesting potential for optimizing taVNS protocols. Stimulation intensity and duration showed few statistically significant, but clinically minimal (i.e., very small) effects. Overall, these findings demonstrate a favorable safety profile of taVNS, with mostly mild and transient effects, supporting its use as a suitable non-invasive tool in both research and clinical applications.

Given its non-invasive nature, there is increasing interest in the use of transcutaneous vagus nerve stimulation (tVNS) across basic, translational and clinical research. Contemporaneously, tVNS can be achieved by stimulating either the auricular branch or the cervical bundle of the vagus nerve, referred to as transcutaneous auricular vagus nerve stimulation(VNS) and transcutaneous cervical VNS, respectively. In order to advance the field in a systematic manner, studies using these technologies need to adequately report sufficient methodological detail to enable comparison of results between studies, replication of studies, as well as enhancing study participant safety. We systematically reviewed the existing tVNS literature to evaluate current reporting practices. Based on this review, and consensus among participating authors, we propose a set of minimal reporting items to guide future tVNS studies. The suggested items address specific technical aspects of the device and stimulation parameters. We also cover general recommendations including inclusion and exclusion criteria for participants, outcome parameters and the detailed reporting of side effects. Furthermore, we review strategies used to identify the optimal stimulation parameters for a given research setting and summarize ongoing developments in animal research with potential implications for the application of tVNS in humans. Finally, we discuss the potential of tVNS in future research as well as the associated challenges across several disciplines in research and clinical practice.

The ability to remember emotionally significant stimuli and stimulus associations is critical to survival, as it ensures that rewarding and threatening events can be recalled to guide future behavior. Consequently, events are consolidated more strongly into long-term memory as they are encoded under heightened emotional arousal. Such memory prioritization is partly driven by the release of peripheral adrenaline, which acts as a bodily signal emphasizing an event’s emotional significance and enhances plasticity in the brain. Animal research suggest that the vagus nerve translates elevated peripheral adrenaline into central noradrenergic activation of memory-relevant brain areas via its projections to the brainstem locus coeruleus–the main source of noradrenaline in the brain. The possibility of vagus nerve stimulation (VNS), both invasively (iVNS) and non-invasively (i.e., transcutaneously; tVNS), has opened up new avenues to test a potential vagal route to memory in humans whilst circumventing the necessity of actual peripheral adrenergic release. Here, we briefly review recent research applying iVNS and tVNS in a variety of animal and human emotional episodic memory and Pavlovian conditioning and extinction learning experiments, supporting a critical role of the vagus nerve in modulating emotional memories. Based on this body of evidence, we highlight clinical areas where VNS may therefore serve as an adjunct to treatments for neurocognitive, anxiety- and trauma-related disorders, that aim at improving learning and memory consolidation. In fact, a brief review of (sub-) clinical studies shows that VNS alleviates symptoms in mild cognitive impairment, Alzheimer’s disease as well as anxiety- and trauma-related disorders.

Recent research suggests that the P3b may be closely related to the activation of the locus coeruleus-norepinephrine (LC-NE) system. To further study the potential association, we applied a novel technique, the non-invasive transcutaneous vagus nerve stimulation (tVNS), which is speculated to increase noradrenaline levels. Using a within-subject cross-over design, 20 healthy participants received continuous tVNS and sham stimulation on two consecutive days (stimulation counterbalanced across participants) while performing a visual oddball task. During stimulation, oval non-targets (standard), normal-head (easy) and rotated-head (difficult) targets, as well as novel stimuli (scenes) were presented. As an indirect marker of noradrenergic activation we also collected salivary alpha-amylase (sAA) before and after stimulation. Results showed larger P3b amplitudes for target, relative to standard stimuli, irrespective of stimulation condition. Exploratory analyses, however, revealed that, in comparison to standard stimuli, easy (but not difficult) targets produced larger P3b (but not P3a) amplitudes during active tVNS, compared to sham stimulation. For sAA levels, although main analyses did not show differential effects of stimulation, direct testing revealed that tVNS (but not sham stimulation) increased sAA levels after stimulation. Additionally, larger differences between tVNS and sham stimulation in P3b magnitudes for easy targets were associated with larger increase in sAA levels after tVNS, but not after sham stimulation. Despite preliminary evidence for a modulatory influence of tVNS on the P3b, which may be partly mediated by activation of the noradrenergic system, additional research in this field is clearly warranted. Future studies need to clarify whether tVNS also facilitates other processes, such as learning and memory, and whether tVNS can be used as therapeutic tool.

Procrastination is a self-regulatory problem of voluntarily and destructively delaying intended and necessary or personally important tasks. Previous studies showed that procrastination is associated with executive dysfunctions that seem to be particularly strong in punishing contexts. In the present event-related potential (ERP) study a monetary version of the parametric Go/No-Go task was performed by high and low academic procrastinators to verify the influence of motivational context (reward vs. punishment expectation) and task difficulty (easy vs. hard) on procrastination-related executive dysfunctions. The results revealed increased post-error slowing along with reduced P300 and error-related negativity (ERN) amplitudes in high (vs. low) procrastination participants—effects that indicate impaired attention and error-related processing in this group. This pattern of results did not differ as a function of task difficulty and motivation condition. However, when the task got more difficult executive attention deficits became even more apparent at the behavioral level in high procrastinators, as indexed by increased reaction time variability. The findings substantiate prior preliminary evidence that procrastinators show difficulties in certain aspects of executive functioning (in attention and error processing) during execution of task-relevant behavior, which may be more apparent in highly demanding situations.

The Covid-19 pandemic imposed new constraints on empirical research and forced researchers to transfer from traditional laboratory research to the online environment. This study tested the validity of a web-based episodic memory paradigm by comparing participants’ memory performance for trustworthy and untrustworthy facial stimuli in a supervised laboratory setting and an unsupervised web setting. Consistent with previous results, we observed enhanced episodic memory for untrustworthy compared to trustworthy faces. Most importantly, this memory bias was comparable in the online and the laboratory experiment, suggesting that web-based procedures are a promising tool for memory research.

IntroductionResearch in people with relapsing remitting multiple sclerosis (PwRRMS) is increasingly focusing on non-motor symptoms like cognitive impairment, fatigue and depression. Due to the high negative impact on quality of life and high socioeconomic costs based on these symptoms, more specific research to improve non-motor symptoms is needed. Transcutaneous auricular vagus nerve stimulation (taVNS) has been found to be a cognitive enhancer in preclinical research and was successfully used for the treatment of psychiatric and neurological disorders to combat dysfunctional cognitive and affective processes. However, the capacity of taVNS to improve cognitive and other non-motor symptoms in PwRRMS has not been tested yet. The aim of this study is to evaluate the therapeutic potential of taVNS on cognitive processing speed. Based on ample evidence demonstrating that taVNS promotes adaptive cognitive and affective processes, we hypothesised that taVNS would alleviate cognitive processing speed in PwRRMS.Methods and analysisThis study protocol describes the prospective, single-centre, SHAM-controlled, single-blinded trial with a planned sample size of 60 participants (30 PwRRMS, with a diagnosis of multiple sclerosis according to McDonald criteria and 30 healthy controls; age: 18–50 years). The Symbol Digit Modalities Test (SDMT) will be used to determine cognitive processing speed, Beck Depression Inventory-II to determine depression and Fatigue Scale for Motor and Cognitive Functions to determine fatigue. The severity of multiple sclerosis will be assessed using the Expanded Disability Status Scale. After baseline assessment, a taVNS protocol (duration: 30 min, tolerance threshold, pulse width: 250 μs, stimulation frequency: 25 Hz, 30 s on/30 s off) will be applied, followed by post-intervention assessment.Ethics and disseminationThe study was reviewed and approved by the local ethics committee of the University Medical Centre Greifswald (study reference number: BB137/24). Clinical trial registration: www.drks.de, number: DRKS00034912. Study results will be disseminated through academic conferences as well as peer-reviewed publications.Trial registration numberDRKS00034912.

Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) has attracted increasing interest as a neurostimulation tool with potential applications in modulating cognitive processes such as attention and memory, possibly through the modulation of the locus–coeruleus noradrenaline system. Studies examining the P300 brain-related component as a correlate of noradrenergic activity, however, have yielded inconsistent findings, possibly due to differences in stimulation parameters, thus necessitating further investigation. In this event-related potential study involving 61 participants, therefore, we examined how changes in taVNS parameters, specifically stimulation type (interval vs. continuous stimulation) and duration, influence P300 amplitudes during a visual novelty oddball task. Although no effects of stimulation were found over the whole cluster and time window of the P300, cluster-based permutation tests revealed a distinct impact of taVNS on the P300 response for a small electrode cluster, characterized by larger amplitudes observed for easy targets (i.e., stimuli that are easily discernible from standards) following taVNS compared to sham stimulation. Notably, our findings suggested that the type of stimulation significantly modulated taVNS effects on the P300, with continuous stimulation showing larger P300 differences (taVNS vs. sham) for hard targets and standards compared to interval stimulation. We observed no interaction effects of stimulation duration on the target-related P300. While our findings align with previous research, further investigation is warranted to fully elucidate the influence of taVNS on the P300 component and its potential utility as a reliable marker for neuromodulation in this field.