Biology subjects

Kuehnel, A.

Publications and source records attributed to Kuehnel, A..

10 recordsLinked to original sources

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

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↗

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

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

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↗

bioRxiv2019

Vagus nerve stimulation increases vigor to work for rewards

Interoceptive feedback transmitted via the vagus nerve plays a vital role in motivation by tuning actions according to physiological needs. Whereas vagus nerve stimulation (VNS) reinforces actions and enhances dopamine transmission in animals, motivational effects elicited by VNS in humans are still largely elusive. Here, we applied non-invasive transcutaneous auricular VNS (taVNS) on the left or the right ear using a randomized cross-over design (vs. sham). During stimulation, 81 healthy participants had to exert effort to earn food or monetary rewards. We reasoned that taVNS enhances motivation and tested whether it does so by increasing prospective benefits (i.e., vigor) or reducing costs of action (i.e., maintenance) compared to sham stimulation. In line with preclinical studies, taVNS generally enhanced invigoration of effort (p = .004, Bayes factor, BF10 = 7.34), whereas stimulation on the left side primarily facilitated vigor for food rewards (left taVNS: Stimulation x Reward Type, p =.003, BF10 = 11.80). In contrast, taVNS did not affect effort maintenance (ps [≥] .09, BF10 < 0.52). Critically, during taVNS, vigor declined less steeply with decreases in wanting ({Delta}b = -.046, p = .031) indicating a boost in the drive to work for rewards. Collectively, our results suggest that taVNS enhances reward-seeking by boosting vigor, not effort maintenance and that the side of the stimulation affects generalization beyond food reward. We conclude that taVNS may enhance the pursuit of prospective rewards which may pave new avenues for treatment of motivational deficiencies.

neuroscience↗

bioRxiv2019

Stimulation of the vagus nerve reduces learning in a go/no-go reinforcement learning task

When facing decisions to approach rewards or to avoid punishments, we often figuratively go with our gut, and the impact of metabolic states such as hunger on motivation are well documented. However, whether and how vagal feedback signals from the gut influence instrumental actions is unknown. Here, we investigated the effect of non-invasive transcutaneous vagus nerve stimulation (tVNS) vs. sham (randomized cross-over design) on approach and avoidance behavior using an established go/no-go reinforcement learning paradigm (Guitart-Masip et al., 2012) in 39 healthy, participants after an overnight fast. First, mixed-effects logistic regression analysis of choice accuracy showed that tVNS acutely impaired decision-making, p = .045. Computational reinforcement learning models identified the cause of this as a reduction in the learning rate through tVNS ({Delta} = -0.092, pboot= .002), particularly after punishment ({Delta}Pun= -0.081, pboot= .012 vs.{Delta} Rew= -0.031, p = .22). However, tVNS had no effect on go biases, Pavlovian response biases or response time. Hence, tVNS appeared to influence learning rather than action execution. These results highlight a novel role of vagal afferent input in modulating reinforcement learning by tuning the learning rate according to homeostatic needs.

neuroscience↗