Biology subjects

Kroemer, N. B.

Publications and source records attributed to Kroemer, N. B..

At least 19 recordsLinked to original sources

bioRxiv2026

Stronger brain responses to acute stress reflect greater everyday stress variability

Laboratory stress tasks are widely used to assess individual differences in acute stress reactivity, yet it remains unclear how these responses correspond to stress experienced in everyday life. Here, we combined the Montreal imaging stress task (MIST) with ecological momentary assessment (EMA) over three months to assess acute and everyday stress in 67 healthy women. Greater within-person variability in everyday stress, but not average stress levels, were associated with stronger overall stress-related brain responses (b = 0.73, p = .039), with a whole-brain association particularly evident in the bilateral caudate (rROI = .32, pcluster.FWE < .001). Greater everyday stress variability was also associated with stronger stress-related functional connectivity between the ventromedial prefrontal cortex (vmPFC) and parietal and posterior medial regions (pcluster.FWE < .001). We conclude that acute neural stress responses relate more closely to fluctuations in perceived stress than to how stressed an individual feels on average. This suggests that laboratory stress tasks capture acute stress responsivity that is distinct from average stress exposure, highlighting the importance of considering what these tasks measure when interpreting individual differences in acute stress responses.

neuroscience↗

bioRxiv2025

Non-invasive vagus nerve stimulation modulates Pavlovian bias in a state-dependent manner

The vagus nerve transmits vital signals between organ systems of the body and the brain. Despite growing interest in non-invasive transcutaneous vagus nerve stimulation (tVNS) for treatments of various disorders, it is not known whether its modulatory effects on behavior are dependent on bodily states. Here, we used a single-blind randomized crossover design with two within-participant factors, stimulation (right tVNS vs. sham) and metabolic state (water vs. caloric load), to investigate 54 healthy participants (210 sessions). To evaluate state-dependent changes in reinforcement learning, we used a valenced go/no-go task. Performance on this task can be used to estimate a Pavlovian choice bias, which captures improved performance for valence-congruent actions (e.g., go to win rewards) versus valence-incongruent actions (e.g., no-go to win rewards) and has been associated with dopaminergic neurotransmission. In line with theorized state-dependency of tVNS-induced changes, we observed that tVNS decreased Pavlovian response biases (Go x Win) after the caloric load (Stimulation x Load: p =.038). Taking into account individual changes in hunger but not satiety ratings best captured behavioral modulation, indicating that this modulatory effect could be driven by motivational effects related to metabolic interoception (sensed "need"). We conclude that right tVNS decreases Pavlovian response biases if the body is in a postprandial, but not a fasting state. Since fasting and Pavlovian biases have been previously associated with elevated dopamine neurotransmission, our results call for additional research on state-dependent motivational effects of tVNS to optimize interventions.

neuroscience↗

bioRxiv2025

Higher glucose levels buffer against everyday stress load

Adaptive stress responses are dependent on the availability of energy and the bodys effectiveness in metabolizing glucose as fuel. However, it is not well understood if glucose levels contribute to the functional regulation of daily stress in healthy individuals. Here, we used 4,307 ratings of stress during a four-week period of ecological momentary assessment (EMA) with concurrent recordings from continuous glucose monitoring (CGM) in 91 participants (47 women). In accordance with the hypothesized metabolic link, we found that higher glucose levels were associated with lower self-reported stress (b = -.038, p = .035, controlling for mood). Crucially, dynamic changes in glucose levels also precipitated subsequent increases in stress levels (0-2h before EMA: p = .013; incremental effect 10-12h before: p < .001), with lower glucose levels associated with subsequent stress increases and elevated glucose with stress relief, highlighting the potential of monitoring physiological biosensor data to improve adaptive stress regulation. We conclude that metabolic signals, such as glucose, play an important role in channeling stress responsiveness in healthy adults, pointing to a pivotal avenue for improved interventions to avoid excessive stress experiences.

neuroscience↗

bioRxiv2025

From stomach to striatum: Ghrelin infusions increase work for rewards

Preclinical evidence demonstrates that gut signals influence motivated behavior through the dopaminergic system. However, translational research in humans is scarce, and it is not known if surges of the stomach-derived hormone ghrelin acutely boost motivation via dopamine transmission. To close this gap, we investigated the effects of acyl ghrelin infusions (vs. saline) on instrumental work for rewards, brain responses, and dopamine transmission in healthy adults in a double-blind, randomized and placebo-controlled crossover study with [11C]raclopride PET-fMRI. In line with preclinical findings, ghrelin enhanced hunger sensations (p = .007), and effort for food and small rewards. Crucially, ghrelin enhanced functional connectivity between the hypothalamus and the striatum (NAcc: pSVC = .016), as well as within the striatum (NAcc<>Putamen: pSVC = .001), pointing to an enhanced coupling between homeostatic and motivational circuits. However, ghrelin did not alter dopamine binding potential (reflecting changes in endogenous tone), but boosted task-free phasic pulses of the NAcc BOLD signal (p = .020), which were negatively associated with binding potential (p = .034). During the task, ghrelin increased cue- (precentral gyrus: pFWE = .003) and effort-evoked brain responses (e.g., VTA/SN: psvc = .002) in accordance with increases in motivation. Together, these findings recapitulate preclinical work that ghrelin primarily boosts phasic dopamine release, reflecting enhanced incentive salience of food and smaller rewards. This highlights the potential of targeting gut-brain interactions to improve motivational symptoms, such as loss of appetite or anhedonia. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=131 SRC="FIGDIR/small/691596v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@4321e6org.highwire.dtl.DTLVardef@166bda5org.highwire.dtl.DTLVardef@2ca69dorg.highwire.dtl.DTLVardef@16e93a9_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2025

Metabolic state shapes cortisol reactivity to acute stress: A systematic review and meta-analysis of metabolic and hormonal modulators

Individual variability in cortisol stress responses is shaped by multiple physiological factors. Yet the interaction with metabolic and hormonal states remains poorly understood. Therefore, we conducted a systematic review and meta-analysis to examine how metabolic factors (particularly glucose) and sex hormone levels (progesterone and estradiol) influence cortisol reactivity to acute stress. We identified 21 studies (N = 1216 participants) and conducted random-effects meta-analyses for metabolic and hormonal states. Across studies, glucose administration was associated with a significant increase in cortisol responses to acute stress compared to fasting or non-glucose control conditions (d = 0.30, 95% CI = [0.05, 0.60], BF10 = 2.42, NNT = 10.63). In contrast, the effects of sex hormones on cortisol responses were smaller and more variable, with both progesterone and estradiol showing weak and inconsistent associations. Our results highlight a robust modulatory role of metabolic state, specifically glucose availability, on HPA axis reactivity, while evidence for sex hormone effects remains inconclusive. Future research should focus on better harmonization of designs concerning sex hormones and systematically examine interactions between metabolic and hormonal states to better explain sex differences in the prevalences of metabolic and stress-related disorders.

physiology↗

bioRxiv2025

Effects of non-invasive vagus nerve stimulation on pupil dilation are dependent on sensory matching

Transcutaneous auricular vagus nerve stimulation (taVNS) is a promising non-invasive method to modulate motivation, cognition, and affect. According to a recent meta-analysis, pulsed taVNS induces larger pupil dilation (vs. sham), but sensory aspects of the stimulation may contribute to these differences. Moreover, included studies were often small and stimulation was only applied to the left ear, so that questions about the robustness and generalization remain. Here, we investigated the effects of pulsed taVNS (1s, 20Hz, 400{micro}s pulse width) at the right ear on phasic pupil dilation using a randomized crossover design in 94 participants (47 women). We initially calibrated the stimulation amplitude to match the perceived sensation across conditions and tracked sensation over time. Contrary to our hypothesis, taVNS did not elicit greater pupil dilation versus sham (b = -0.42, 95% CI [-1.30; 0.46], p = .35). However, taVNS effects were larger if sham was perceived as less intense despite the initial matching (b = 3.39, 95% CI [0.62; 6.17], p = .017). Differences in intensity ratings were mainly associated with sham-induced pupil dilation (r = -.25, 95% CI [-.43; -.05], p = .013). To summarize, our results recapitulate the findings of other studies using fixed amplitudes by showing that right-sided pulsed taVNS only induced larger pupil dilation against sham if differences in sensation arose. These findings highlight the challenge of establishing a suitable sham condition since both taVNS and sham affect sensory nerves, potentially leading to confounding effects.

neuroscience↗

bioRxiv2025

Glucose levels are associated with mood, but the association is mediated by ratings of metabolic state

Hunger is commonly linked to negative mood and mood shifts are thought to arise from sensing the bodys internal state. However, it is unclear whether circulating glucose levels affect mood subconsciously or via subjectively sensed metabolic states. Here, we continuously monitored the interstitial glucose levels of 90 healthy adults for four weeks while they completed ecological momentary assessments (EMA; M=47 runs per participant) to rate their mood and metabolic states. As expected, hungry participants reported lower mood, and metabolic state ratings were associated with glucose levels. Although glucose levels were associated with mood, the metabolic state ratings fully mediated this association. Individual differences reflecting metabolic health (i.e., BMI and insulin resistance) did not affect the interaction between glucose and metabolic state ratings on mood. Notably, individuals with higher interoceptive accuracy had fewer fluctuations in mood ratings. We conclude that hunger-related mood shifts depend on conscious sensing of the bodys internal state instead of acting subconsciously. Our study highlights the relevance of considering the self-report of bodily signals in understanding mood shifts, offering new fundamental insights into mood regulation mechanisms. Key messagesO_ST_ABSWhat is already known on this topicC_ST_ABSO_LIAlthough glucose is linked to satiety and hunger to negative mood, it is not known if this is due to the conscious perception of metabolic states. C_LI What this study addsO_LIThe longitudinal study design leveraging continuous glucose monitoring (CGM) and ecological momentary assessment (EMA) over four weeks, offers a unique perspective on glucose-mood interactions in naturalistic settings. C_LIO_LIWe found that the link between mood and glucose levels is fully mediated by consciously sensed metabolic states, clarifying the interoceptive link between glucose and mood. C_LI How this study might affect research, practice or policyO_LIMood is shaped by perceived metabolic states highlighting the relevance of metabolic health for mental health. C_LIO_LIThese insights improve our understanding of the association between metabolic and mental disorders. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/645871v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@7b1981org.highwire.dtl.DTLVardef@1c7a1f2org.highwire.dtl.DTLVardef@15944eaorg.highwire.dtl.DTLVardef@1bb802a_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2024

Does transcutaneous vagus nerve stimulation alter pupil dilation? A living Bayesian meta-analysis

Transcutaneous vagus nerve stimulation (tVNS) has emerged as a promising technique to modulate autonomic functions, and pupil dilation has been recognized as a promising biomarker for tVNS-induced monoaminergic release. Nevertheless, studies on the effectiveness of various tVNS protocols have produced heterogeneous results on pupil dilatation to date. Here, we synthesize the existing evidence and compare conventional continuous and pulsed stimulation protocols using Bayesian meta-analysis. To maintain a living version, we developed a Shiny App with the possibility to incorporate newly published studies in the future. Based on a systematic review, we included 18 studies (N = 771) applying either continuous or pulsed stimulation protocols. Across studies, we found anecdotal evidence for the alternative hypothesis that tVNS increases pupil size (g = 0.14, 95% CI = [0.001, 0.29], BF01 = 2.5). Separating studies according to continuous vs. pulsed protocols revealed that results were driven by studies using pulsed taVNS (strong evidence for the alternative hypothesis: g = 0.34, 95% CI = [0.15, 0.53], BF10 = 14.15) while continuous tVNS provided strong evidence for the null hypothesis (g = 0.01, CI = [-0.15, 0.16], BF01= 20.7). In conclusion, our meta-analysis highlights differential effects of continuous and pulsed tVNS protocols on pupil dilation. These findings underscore the relevance of tVNS protocols in optimizing its use for specific applications that may require modulation of tonic vs. phasic monoaminergic responses.

neuroscience↗

bioRxiv2023

Non-invasive vagus nerve stimulation decreases vagally mediated heart rate variability

The vagus nerve plays a critical role in balancing the bodys physiological functions, including the cardiovascular system. Measures of heart rate (HR) and its variability (HRV) may provide non-invasive proxies of vagal activity in humans, but transcutaneous auricular vagus nerve stimulation (taVNS) has produced mixed effects so far--limited by a lack of studies stimulating the right branch. Here, we used a randomized cross-over design to study the effects of taVNS on HR and HRV. To estimate how the side of the stimulation (left vs. right ear) affects cardiovascular function, we recorded an electrocardiogram in four sessions per person (factors: Stimulation x Side). To evaluate potential interactions with physiological states, we investigated three phases per session: baseline, during stimulation (taVNS vs. sham), and after consuming a milkshake ([~]400 kcal) with concurrent stimulation. First, we found moderate evidence against an effect of taVNS on HR (BF10=0.21). Second, taVNS decreased HRV (multivariate p =.004) independent of physiological state with strong evidence for RMSSD (BF10=15.11) and HF-HRV (BF10=11.80). Third, taVNS-induced changes were comparable across sides and more strongly correlated (vs. sham), indicating similar cardiovascular effects independent of the stimulation side. We conclude that taVNS reduces HRV without altering HR, contradicting the common assumption that increased HRV indexes a heightened vagal tone. Instead, our results support a putative role of vagal afferent activation in arousal. Crucially, modulatory effects on the cardiovascular system can be safely elicited by taVNS on both sides, opening new options for treatment. Graphical AbstractCreated with BioRender.com O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/542695v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1b6a615org.highwire.dtl.DTLVardef@51bcf7org.highwire.dtl.DTLVardef@4d047forg.highwire.dtl.DTLVardef@626251_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2023

Stress-induced brain responses are associated with BMI in women

BackgroundStress is associated with elevated risk for overweight and obesity, especially in women. Since body mass index (BMI) is correlated with increased inflammation and reduced baseline cortisol, obesity may lead to altered stress responses. However, it is not well understood whether stress-induced changes in brain function scale with BMI and if peripheral inflammation contributes to this. MethodsWe investigated the subjective, autonomous, endocrine, and neural stress response in a transdiagnostic sample (N=192, 120 women, MBMI=23.7{+/-}4.0 kg/m2; N=148, 89 women, with cytokines). First, we used regression models to examine effects of BMI on stress reactivity. Second, we predicted BMI based on stress-induced changes in activation and connectivity using cross-validated elastic-nets. Third, to link stress responses with inflammation, we quantified the association of BMI-related cytokines with model predictions. ResultsBMI was associated with higher negative affect after stress and an increased response to stress in the substantia nigra and the bilateral posterior insula (pFWE<.05). Moreover, stress-induced changes in activation of the hippocampus, dACC, and posterior insula predicted BMI in women (pperm<.001), but not in men. BMI was associated with higher baseline cortisol while cytokines were not associated with predicted BMI scores. ConclusionsStress-induced changes in the hippocampus and posterior insula predicted BMI in women, indicating that acute brain responses to stress might be more strongly related to a higher BMI in women compared to men. Altered stress-induced changes were associated with baseline cortisol but independent of cytokines, suggesting that the endocrine system and not inflammation contributes to stress-related changes in BMI.

neuroscience↗

bioRxiv2022

How gut hormones shape reward: a systematic review of the role of ghrelin and GLP-1 in human fMRI

The gastrointestinal hormones ghrelin and glucagon-like peptide-1 (GLP-1) have opposite secretion patterns, as well as opposite effects on metabolism and food intake. Beyond their role in energy homeostasis, gastrointestinal hormones have also been suggested to modulate the reward system. However, the potential of ghrelin and GLP-1 to modulate reward responses in humans has not been systematically reviewed before. To evaluate the convergence of published results, we first conduct a multi-level kernel density meta-analysis of studies reporting a positive association of ghrelin (Ncomb= 353, 18 contrasts) and a negative association of GLP-1 (Ncomb = 258, 12 contrasts) and reward responses measured using task functional magnetic resonance imaging (fMRI). Second, we complement the meta-analysis using a systematic literature review, focusing on distinct reward phases and applications in clinical populations that may account for variability across studies. In line with preclinical research, we find that ghrelin increases reward responses across studies in key nodes of the motivational circuit, such as the nucleus accumbens, pallidum, putamen, substantia nigra, ventral tegmental area, and the dorsal mid insula. In contrast, for GLP-1, we did not find sufficient convergence in support of reduced reward responses. Instead, our systematic review identifies potential differences of GLP-1 on anticipatory versus consummatory reward responses. Based on a systematic synthesis of available findings, we conclude that there is considerable support for the neuromodulatory potential of gut-based circulating peptides on reward responses. To unlock their potential for clinical applications, future studies may move beyond anticipated rewards to cover other reward facets. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=109 SRC="FIGDIR/small/518539v2_ufig1.gif" ALT="Figure 1"> View larger version (46K): org.highwire.dtl.DTLVardef@19c0b00org.highwire.dtl.DTLVardef@19630e7org.highwire.dtl.DTLVardef@16498c3org.highwire.dtl.DTLVardef@169469e_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2021

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

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 Parkinsons disease or depression. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=160 SRC="FIGDIR/small/463517v1_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@39c673org.highwire.dtl.DTLVardef@113b785org.highwire.dtl.DTLVardef@175af94org.highwire.dtl.DTLVardef@15a2fbc_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LITranscutaneous vagus nerve stimulation (taVNS) can emulate interoceptive signals C_LIO_LItaVNS boosts stomach-brain coupling in the brainstem, midbrain, and transmodal cortex C_LIO_LItaVNS-induced changes in stomach-brain coupling mirror subjective hunger ratings C_LI

neuroscience↗

bioRxiv2021

Spatio-temporal dynamics of stress-induced network reconfigurations reflect negative affectivity

BackgroundChronic stress is an important risk factor in the etiology of mood and anxiety disorders, but exact pathomechanisms remain to be understood. Mapping individual differences of acute stress-induced neurophysiological changes, especially on the level of neural activation and functional connectivity (FC), could provide important insights in how variation in the individual stress response is linked to disease risk. MethodsUsing an established psycho-social stress task flanked by two resting-state scans, we measured subjective, physiological, and brain responses to acute stress and recovery in 217 unmedicated participants with and without mood and anxiety disorders. To estimate block-wise changes in stress-induced brain activation and FC, we used hierarchical mixed-effects models based on denoised timeseries within a predefined stress network. We predicted inter- and intra-individual differences in stress phases (anticipation vs. acute stress vs. recovery) and transdiagnostic dimensions of stress reactivity using elastic net and support vector machines. ResultsWe identified four subnetworks showing distinct changes in FC over time. Subnetwork trajectories predicted the stress phase (accuracy: 71%, pperm<.001) and increases in pulse rate (R2=.10, pperm<.001). Critically, individual spatio-temporal trajectories of changes across networks also predicted negative affectivity ({Delta}R2=.08, pperm=.009), but not the presence or absence of a mood and anxiety disorder. ConclusionsSpatio-temporal dynamics of brain network reconfiguration induced by stress reflect individual differences in the psychopathology dimension negative affectivity. These results support the idea that vulnerability for mood and anxiety disorders can be conceptualized best at the level of network dynamics, which may pave the way for improved prediction of individual risk.

neuroscience↗

bioRxiv2021

Brain signaling dynamics after vagus nerve stimulation

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.

neuroscience↗

bioRxiv2021

Influenca: a gamified assessment of value-based decision-making for longitudinal studies

Reinforcement learning is a core facet of motivation and alterations have been associated with various mental disorders. To build better models of individual learning, repeated measurement of value-based decision-making is crucial. However, the focus on lab-based assessment of reward learning has limited the number of measurements and the test-retest reliability of many decision-related parameters is therefore unknown. Here, we developed an open-source cross-platform application Influenca that provides a novel reward learning task complemented by ecological momentary assessment (EMA) for repeated assessment over weeks. In this task, players have to identify the most effective medication by selecting the best option after integrating offered points with changing probabilities (according to random Gaussian walks). Participants can complete up to 31 levels with 150 trials each. To encourage replay on their preferred device, in-game screens provide feedback on the progress. Using an initial validation sample of 127 players (2904 runs), we found that reinforcement learning parameters such as the learning rate and reward sensitivity show low to medium intra-class correlations (ICC: 0.22-0.52), indicating substantial within- and between-subject variance. Notably, state items showed comparable ICCs as reinforcement learning parameters. To conclude, our innovative and openly customizable app framework provides a gamified task that optimizes repeated assessments of reward learning to better quantify intra- and inter-individual differences in value-based decision-making over time.

neuroscience↗

bioRxiv2021

Acute vagus nerve stimulation does not affect liking or wanting ratings of food in healthy participants

The vagus nerve plays a vital role in the regulation of food intake and vagal afferent signals may help regulate food cue reactivity by providing negative homeostatic feedback. Despite strong evidence from preclinical studies on vagal afferent "satiety" signals in guiding food intake, evidence from human studies is largely inconclusive to date. Here, we investigated the acute effects of left or right transcutaneous auricular vagus nerve stimulation (taVNS) on subjective ratings of wanting and liking of various food and non-food items in 82 healthy participants (46 women, MBMI = 23.1 kg/m2). In contrast to previous reports in patients with depression, we found moderate to anecdotal evidence supporting the absence of taVNS-induced changes in food ratings. To test whether the absence of taVNS effects on food ratings is due to heterogeneity in the sample, we conducted post hoc subgroup analyses by splitting the data according to stimulation side and sex (between-subject factors) as well as caloric density, perceived healthiness, and flavor (sweet vs. savory) of the food (within-subject factors). This multiverse analysis largely supported the absence of taVNS-induced changes since the strongest subgroup effects provided only anecdotal evidence in favor of taVNS-induced changes. We conclude that acute taVNS only has a marginal effect on subjective ratings of food, suggesting that it is an unlikely mechanism for the reported long-term effects of VNS on body weight. In light of an absence of acute taVNS effects on food craving, our results call for future research on the correspondence between acute and chronic effects of vagal afferent stimulation.

neuroscience↗

bioRxiv2021

Does non-invasive vagus nerve stimulation affect heart rate variability? A living and interactive Bayesian meta-analysis

Non-invasive brain stimulation techniques, such as transcutaneous auricular vagus nerve stimulation (taVNS), have considerable potential for clinical use. Beneficial effects of taVNS have been demonstrated on symptoms in patients with mental or neurological disorders as well as transdiagnostic dimensions, including mood and motivation. However, since taVNS research is still an emerging field, the underlying neurophysiological processes are not yet fully understood, and the replicability of findings on biomarkers of taVNS effects has been questioned. Here, we perform a living Bayesian random effects meta-analysis to synthesize the current evidence concerning the effects of taVNS on heart rate variability (HRV), a candidate biomarker that has, so far, received most attention in the field. To keep the synthesis of evidence transparent and up to date as new studies are being published, we developed a Shiny web app that regularly incorporates new results and enables users to modify study selection criteria to evaluate the robustness of the inference across potential confounds. Our analysis focuses on 17 single-blind studies comparing taVNS versus sham in healthy participants. These newly synthesized results provide strong evidence for the null hypothesis (g = 0.011, CIshortest = [-0.103, 0.125], BF01 = 25.587), indicating that acute taVNS does not alter HRV compared to sham. To conclude, based on a synthesis of the available evidence to date, there is no support for the hypothesis that HRV is a robust biomarker for acute taVNS. By increasing transparency and timeliness, we believe that the concept of living meta-analyses can lead to transformational benefits in emerging fields such as non-invasive brain stimulation.

physiology↗

bioRxiv2020

Threat-induced hippocampal connectivity fingerprints do not generalize to psychosocial stress

Stress is an everyday experience and maladaptive responses play a crucial role in the etiology of affective disorders. Despite its ubiquity, the neural underpinnings of subjective stress experiences have not yet been elucidated, particularly at an individual level. In an important advance, Goldfarb et al.1 showed recently that subjective stress and arousal levels in response to threatening stimuli were successfully predicted based on changes in hippocampal connectivity during the task using a machine learning approach. Crucially, stress responses were predicted by interpretable hippocampal connectivity networks, shedding new light on the role of the hippocampus in regulating stress reactivity2. However, the authors induced stress by displaying aversive pictures, while stress research often relies on the extensively validated Trier social stress task (TSST)3. The TSST incorporates crucial factors such as unpredictability of success and the social-evaluative threat of the stressor thereby eliciting cortisol responses more robustly compared to threatening images4. Towards generalization, cross validation within a sample as conducted by Goldfarb et al.1 or independent replications are important steps, but the generalizability to different stressors allows to draw broader conclusions about the potential use of hippocampal connectivity to predict subjective stress5. Arguably, translating these findings to clinical applications would require a broad generalization of the results or the prediction algorithm to psychosocial stress. Here, we assessed the predictive performance of Goldfarb et als1 algorithm for subjective stress in an independent sample using an MR adaption of the TSST6,7. In line with Goldfarb et al.1, we observed robust stress-induced changes in hippocampal connectivity. However, the spatial correlation of the changes in connectivity was low indicating little convergence across alleged stress paradigms. Critically, stress-induced changes of hippocampal connectivity were not robustly predictive of subjective stress across a multiverse of analyses based on connectivity changes. Collectively, this indicates that the generalizability of the reported stress connectivity fingerprint to other stressors is limited at best, suggesting that specific tasks might require tailored algorithms to robustly predict stress above chance levels.

neuroscience↗