Biology subjects

Kroemer, N. B.

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

27 records · Page 2Linked to original sources

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.

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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

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.

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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.

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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.

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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.

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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.

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bioRxiv2016

L-DOPA reduces model-free control of behavior by attenuating the transfer of value to action

Dopamine is a key neurotransmitter in reinforcement learning and action control. Recent findings suggest that these components are inherently entangled. Here, we tested if increases in dopamine tone by administration of L-DOPA upregulate deliberative \"model-based\" control of behavior or reflexive \"model-free\" control as predicted by dual-control reinforcement-learning models. Alternatively, L-DOPA may impair learning as suggested by \"value\" or \"thrift\" theories of dopamine. To this end, we employed a two-stage Markov decision-task to investigate the effect of L-DOPA (randomized cross-over) on behavioral control while brain activation was measured using fMRI. L-DOPA led to attenuated model-free control of behavior as indicated by the reduced impact of reward on choice and increased stochasticity of model-free choices. Correspondingly, in the brain, L-DOPA decreased the effect of reward while prediction-error signals were unaffected. Taken together, our results suggest that L-DOPA reduces model-free control of behavior by attenuating the transfer of value to action.

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