Biology subjects

Teckentrup, V.

Publications and source records attributed to Teckentrup, V..

14 recordsLinked to original sources

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

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

Non-invasive vagus nerve stimulation boosts mood recovery after effort exertion

Mood plays an important role in our life which is illustrated by the disruptive impact of aberrant mood states in depression. Although vagus nerve stimulation (VNS) has been shown to improve symptoms of depression, the exact mechanism is still elusive, and it is an open question whether non-invasive VNS could be used to swiftly and robustly improve mood. Here, we investigated the effect of left- and right-sided transcutaneous auricular VNS (taVNS) versus a sham control condition on mood after exertion of physical and cognitive effort in 82 healthy participants (randomized cross-over design). Using linear mixed-effects and hierarchical Bayesian analyses of mood ratings, we found that 90 min of either left-sided or right-sided taVNS improved positive mood (b = 5.11, 95% credible interval, CI [1.39, 9.01], 9.6% improvement relative to the mood intercept, BF10= 7.69, pLME = .017), yet only during the post stimulation phase. Moreover, lower baseline scores of positive mood were associated with greater taVNS-induced improvements in motivation (r = -.42, 95% CI [-.58, -.21], BF10 = 249). We conclude that taVNS boosts mood after a prolonged period of effort exertion with concurrent stimulation and that acute motivational effects of taVNS are partly dependent on initial mood states. Collectively, our results show that taVNS may help quickly improve affect after a mood challenge, potentially by modulating interoceptive signals contributing to reappraisal of effortful behavior. This suggests that taVNS could be a useful add-on to current behavioral therapies.

neuroscience↗

bioRxiv2020

Can't decide how much to EAT? Effort variability for reward is associated with cognitive restraint

Food intake is inherently variable and often characterized by episodical restraint or overeating (uncontrolled eating). Such heightened variability in intake has been associated with higher variability in the brain response to food reward, but it is an open issue whether comparable associations with elevated variability in reward seeking exist. Here, we assessed whether restraint and uncontrolled eating as markers of trait-like variability in eating are associated with higher intra-individual variability in reward seeking as captured by a cost-benefit paradigm. To test this hypothesis, 81 healthy, overnight-fasting participants (MBMI= 23.0 kg/m2 {+/-} 2.95) completed an effort allocation task (EAT) twice. In the EAT, participants had to exert physical effort to earn monetary and food rewards and indicated levels of wanting through visual analog scales (VAS). As predicted, we found that greater trial-by-trial effort variability was associated with lower scores on cognitive restraint, rp(78) = -.28, p = .011 (controlled for average effort). In line with previous findings, higher wanting variability was associated with higher BMI, rp(78) = .25, p = .026 (controlled for average effort). Collectively, our results support the idea that higher variability in reward seeking is a potential risk factor for eating beyond homeostatic need. Since associations with variability measures of reward exceeded associations with average reward seeking, our findings may indicate that variability in the representation of the reward value could be a crucial aspect driving fluctuations in food intake.

neuroscience↗

bioRxiv2020

Evidence for modulation of EEG microstate sequence by vigilance level

The momentary global functional state of the brain is reflected in its electric field configuration and cluster analytical approaches have consistently shown four configurations, referred to as EEG microstate classes A to D. Changes in microstate parameters are associated with a number of neuropsychiatric disorders, task performance, and mental state establishing their relevance for cognition. However, the common practice to use eye-closed resting state data to assess the temporal dynamics of microstate parameters might induce systematic confounds related to vigilance levels. Here, we studied the dynamics of microstate parameters in two independent data sets and showed that the parameters of microstates are strongly associated with vigilance level assessed both by EEG power analysis and fMRI global signal. We found that the duration and contribution of microstate class C, as well as transition probabilities towards microstate class C were positively associated with vigilance, whereas the sign was reversed for microstate classes A and B. Furthermore, in looking for the origins of the correspondence between microstates and vigilance level, we found Granger-causal effects of vigilance levels on microstate sequence parameters. Collectively, our findings suggest that duration and occurrence of microstates have a different origin and possibly reflect different physiological processes. Finally, our findings indicate the need for taking vigilance levels into consideration in resting-sate EEG investigations.

neuroscience↗

bioRxiv2020

Localized prediction of glutamate from whole-brain functional connectivity of the pregenual anterior cingulate cortex

Local measures of neurotransmitters provide crucial insights into neurobiological changes underlying altered functional connectivity in psychiatric disorders. However, non-invasive neuroimaging techniques such as magnetic resonance spectroscopy (MRS) may cover anatomically and functionally distinct areas, such as p32 and p24 of the pregenual anterior cingulate cortex (pgACC). Here, we aimed to overcome this low spatial specificity of MRS by predicting local glutamate and GABA based on functional characteristics and neuroanatomy, using complementary machine learning approaches. Functional connectivity profiles of pgACC area p32 predicted pgACC glutamate better than chance (R2 = .324) and explained more variance compared to area p24 using both elastic net and partial least squares regression. In contrast, GABA could not be robustly predicted. To summarize, machine learning helps exploit the high resolution of fMRI to improve the interpretation of local neurometabolism. Our augmented multimodal imaging analysis can deliver novel insights into neurobiology by using complementary information.

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

Non-invasive stimulation of vagal afferents reduces gastric frequency

Metabolic feedback between the gut and the brain relayed via the vagus nerve contributes to energy homeostasis. We investigated in healthy adults whether non-invasive stimulation of vagal afferents impacts energy homeostasis via efferent effects on metabolism or digestion. In a randomized crossover design, we applied transcutaneous auricular vagus nerve stimulation (taVNS) while recording efferent metabolic effects using simultaneous electrogastrography (EGG) and indirect calorimetry. We found that taVNS reduced gastric myoelectric frequency (p =.008), but did not alter resting energy expenditure. We conclude that stimulating vagal afferents induces gastric slowing via vagal efferents without acutely affecting net energy expenditure at rest. Collectively, this highlights the potential of taVNS to modulate digestion by activating the dorsal vagal complex. Thus, taVNS-induced changes in gastric frequency are an important peripheral marker of brain stimulation effects.

neuroscience↗

bioRxiv2019

The anterior insula channels prefrontal expectancy signals during affective processing

Expectancy shapes our perception of impending events. Although such an interplay between cognitive and affective processes is often impaired in mental disorders, it is not well understood how top-down expectancy signals modulate future affect. We therefore track the information flow in the brain during cognitive and affective processing segregated in time using task-specific cross-correlations. Participants in two independent fMRI studies (N1 = 37 & N2 = 55) were instructed to imagine a situation with affective content as indicated by a cue, which was then followed by an emotional picture congruent with expectancy. To correct for intrinsic covariance of brain function, we calculate resting-state cross-correlations analogous to the task. First, using factorial modeling of delta cross-correlations (task-rest) of the first study, we find that the magnitude of expectancy signals in the anterior insula cortex (AIC) modulates the BOLD response to emotional pictures in the anterior cingulate and dorsomedial prefrontal cortex in opposite directions. Second, using hierarchical linear modeling of lagged connectivity, we demonstrate that expectancy signals in the AIC indeed foreshadow this opposing pattern in the prefrontal cortex. Third, we replicate the results in the second study using a higher temporal resolution, showing that our task-specific cross-correlation approach robustly uncovers the dynamics of information flow. We conclude that the AIC arbitrates the recruitment of distinct prefrontal networks during cued picture processing according to triggered expectations. Taken together, our study provides new insights into neuronal pathways channeling cognition and affect within well-defined brain networks. Better understanding of such dynamics could lead to new applications tracking aberrant information processing in mental disorders.

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↗

bioRxiv2017

Addressing the reliability fallacy: Similar group effects may arise from unreliable individual effects

To cast valid predictions of future behavior or diagnose disorders, the reliable measurement of a \"biomarker\" such as the brain activation to prospective reward is a prerequisite. Surprisingly, only a small fraction of functional magnetic resonance imaging (fMRI) studies report or cite the reliability of brain activation maps involved in group analyses. Here, using simulations and exemplary longitudinal data of 126 healthy adolescents performing an intertemporal choice task, we demonstrate that reproducing a group activation map over time is not a sufficient indication of reliable measurements at the individual level. Instead, selecting regions based on significant main effects at the group level may yield estimates that fail to reliably capture individual variance in the subjective evaluation of an offer. Collectively, our results call for more attention on the reliability of supposed biomarkers at the level of the individual. Thus, caution is warranted in employing brain activation patterns prematurely for clinical applications such as diagnosis or tailored interventions before their reliability has been conclusively established by large-scale studies. To facilitate assessing and reporting of the reliability of fMRI contrasts in future studies, we provide a toolbox that incorporates common measures of global and local reliability.

neuroscience↗