Going with your gut: Ghrelin’s action on dopamine and effort 

Cartoon visualizing the interaction between the stomach/gut and the brain.

Every day, we are faced with decisions about how much effort to exert to receive different rewards. Do I walk to my favorite restaurant across town, or do I choose the fast-food option right around the corner? Our brain constantly performs such cost-benefit analyses. However, the brain is not a separate entity, and there is growing evidence for a tight coupling between the brain and signals originating from the gut. After all, not having eaten all day is likely to influence the previously outlined dining decision towards the least effortful option. 

In this project, we are investigating the role of the stomach-derived hormone ghrelin in motivation and effort via dopamine transmission in the brain. Ultimately, researching the role of gut-brain coupling in reward processing can inspire new treatment options for motivational deficits prevalent in psychiatric disorders such as depression. 

Ghrelin is the only known hormone to stimulate appetite, and peripheral ghrelin levels increase before meal intake. Therefore, it is an ideal candidate as a potential moderator of effort-based decision-making. To understand the neural mechanism of the proposed coupling, we will measure neural activity with functional magnetic resonance imaging (fMRI), and neurotransmitters such as dopamine with positron emission tomography (PET) after injections of ghrelin, or placebo. Additionally, we are running a behavioral study using a battery of reward tasks, including patients with depression, to better understand associations of ghrelin with reward deficiencies (“anhedonia”)–a core symptom of depression. 

Contact: Corinna Schulz, study coordinator; Nils B. Kroemer, PI

Impact of transcutaneous vagus nerve stimulation (tVNS) on effort-based decision-making

Cost-benefit analyses are part of our lives: Shall I make the effort of grocery shopping and preparing a fresh home-cooked meal, or just pick up the phone and order a pizza instead? In the long run, the first option might be healthier. Yet, the second option offers a tempting and instantly gratifying solution. In this project, we aim to better understand how bodily signals shape cost-benefit computations. What predisposes someone to go for fast food; what motivates a person to take the time and effort to prepare a meal and, ultimately: how can we facilitate a healthy lifestyle?

Vagus nerve stimulation (VNS) has been previously applied to improve symptoms in treatment-resistant depression. It has been repeatedly shown to alter food intake and energy metabolism. Moreover, vagal projections prominently modulate neurotransmission in the brain, for example, by altering dopamine release. Thereby, VNS can alter reward processing. However, the exact neurobiological mechanism of the antidepressive effects of VNS remains to be revealed.

Therefore, we apply non-invasive transcutaneous VNS and investigate participants’ willingness to exert effort to gain rewards. In a second step, we investigate which metabolic parameters and neural correlates are mediating tVNS effects on reward-related decisions.

Contact: Vanessa Teckentrup, study coordinator; Nils B. Kroemer, PI

Publications and preprints

Müller, F.K., Teckentrup, V., Kühnel, A., Ferstl, M., Kroemer, N.B. (2021) Acute vagus nerve stimulation does not affect liking or wanting ratings of food in healthy participants. Appetite, preprint on bioRxiv

Wolf, V., Kühnel, A., Teckentrup, V., Koenig, J., Kroemer, N.B. (2021) Does transcutaneous auricular vagus nerve stimulation affect vagally-mediated heart rate variability? A living and interactive Bayesian meta-analysis. Psychophysiology, preprint on bioRxiv

Ferstl, M., Teckentrup, V., Lin, W.M., Kräutlein, F., Kühnel, A., Klaus, J., Walter, M., Kroemer, N.B. (2021) Non-invasive vagus nerve stimulation boosts mood recovery after effort exertion. Psychol Med, preprint on bioRxiv

Neuser, M.P., Teckentrup, V., Kühnel, A., Hallschmid, M., Walter, M., Kroemer, N.B. (2020) Vagus nerve stimulation increases the drive to work for rewards. Nat Commun, 11: 3555. doi: 10.1038/s41467-020-17344-9, preprint on bioRxiv

Kühnel, A., Teckentrup, V., Neuser, M.P., Huys, Q.J.M., Burrasch, C., Walter, M., Kroemer, N.B. (2020) Stimulation of the vagus nerve reduces learning in a go/no-go reinforcement learning task. Eur Neuropsychopharmacol, 35:17-29, preprint on bioRxiv.

Teckentrup, V., Neubert, S., Santiago, J.C.P., Hallschmid, M., Walter, M., Kroemer, N.B. (2020) Non-invasive stimulation of vagal afferents reduces gastric frequency. Brain Stimul, 13:470-473. doi: 10.1016/j.brs.2019.12.018, preprint on bioRxiv

Evaluation of fMRI biomarkers

Personalized medicine promises to fundamentally improve health by tailoring treatments to individual characteristics (“biomarkers”). However, functional magnetic resonance imaging studies (fMRI) do not routinely assess the diagnostic characteristics of alleged biomarkers. Several elements contribute to the poor reliability of results such as a limited number of trials, ineffective experimental designs, and inadequate statistical models.

Recently, we have detailed another important, yet often neglected aspect. In most task-based analyses, we use contrasts and look at differences at a group level. However, we often do not analyze how much unique information about an individual is contained in a contrast. To provide this insight at the individual level, we look at characteristic patterns of brain activation that are elicited in response to rewards such as food pictures that uniquely identifies a person, much like a fingerprint.

To support the assessment of reliability and, ultimately, the design of reproducible fMRI studies, we developed an open-source toolbox, fmreli (read more about this here), which incorporates common measures of reliability. In the future, we will use the toolbox to identify sequences, paradigms, or mental states to optimize the reproducibility of fMRI studies based on empirical data. Our hope is that these efforts will raise awareness of reliability as a fundamentally limiting factor of design and encourage the use of more robust imaging methods.

Contact: Nils B. Kroemer, core development of fmreli (w/ Juliane Fröhner, TUD)

Publications and preprints

Kühnel, A., Czisch, M., Sämann, P., Binder, E.B., Kroemer, N.B. (2020) Threat-induced hippocampal connectivity fingerprints do not generalize to psychosocial stress. bioRxiv

Martens, L.*, Kroemer, N.B.*, Teckentrup, V., Colic, L., Palomero-Gallagher, N., Li, M., Walter, M. (2020) Localized prediction of glutamate from whole-brain functional connectivity of the pregenual anterior cingulate cortex. J Neurosci, 40:9028-9042, preprint on bioRxiv.

Fröhner, J.H., Teckentrup, V., Smolka, M.N., Kroemer, N.B. (2019) Addressing the reliability fallacy in fMRI: Similar group effects may arise from unreliable individual effects. NeuroImage, 195: 174-189. doi: 10.1016/j.neuroimage.2019.03.053; preprint on bioRxiv.

completed projects

Binge eating disorder and neural variability

Patients suffering from binge eating disorder report experiencing a loss of control regarding their eating behavior. This manifests in periods of uncontrollable consumption of an immense amount of food, so-called binges. So far, the origins of this loss of control are only insufficiently understood. A potential explanation could lie within spontaneous variations occurring in brain activity. In this study, we investigate what is driving binges, especially in binge eating disorder (BED), using extensive behavioral and brain response measurements.

Supported by the Else Kröner Fresenius Stiftung

Contact: Monja Neuser, study coordinator; Nils B. Kroemer, PI; Jennifer Svaldi, Co-PI


van den Hoek Ostende, M.M., Neuser, M.P., Teckentrup, V., Svaldi, J., Kroemer, N.B. (2021) Can’t decide how much to EAT? Variability in effort for reward is associated with cognitive control. Appetite, 159: 105067, preprint on bioRxiv.

Neuser, M.P., Kühnel, A., Svaldi, J., Kroemer, N.B. (2020) Beyond the average: The role of variable reward sensitivity in eating disorders. Physiol Behav, 223: 112971. doi: 10.1016/j.physbeh.2020.112971

The effects of mood on effort allocation during uncertainty

Supported by the Durham-Tübingen Seedcorn fund (Deutsche Forschungsgemeinschaft)

Contact: Nils B. Kroemer (PI); Ulrik Beierholm (PI)

Crowdsourcing the mosaic of the mind – Open Science Fellows Program

Even though mental disorders are one of the most pervasive problems for public health in the developed countries, our knowledge concerning these disorders is often comparable to a peek through the keyhole: Small sample sizes and sparsely validated, widely differing experimental tasks lead to results that are not replicable. Many of the reasons contributing to this lack of reproducibility could be effectively addressed by facilitating the widespread use of open and well-maintained software running on different yet commonly available platforms.

Within the Open Science Fellows Program, we will implement tasks that tap into key facets of human cognition, which have been demonstrated to be altered across disorders. To facilitate the widespread use in future research, the paradigms will be implemented using Haxe, a programming language intended for building cross-platform tools that can be directly exported to native apps for every major platform including Android and web-based HTML5. Ease of access has been a major limiting factor in collecting sufficient data required to describe individual behavior in detail. Furthermore, large-scale online testing enables dimensional approaches, which could be used to identify individuals at risk or at an early stage of the disorder in the future. To extend the functionality of the software, a web interface will be implemented which provides an easily accessible summary of the individual results of the user relative to other individuals in the database or, alternatively, a comprehensive summary for researchers, who are using the task.
All applications built including the source code and documentation on the paradigm will be made publicly available by release under an open-source license (you can find the GitHub repository here).

With this approach, we hope to help scientists in building more appropriate models of individual behavior in key dimensions of cognition. In turn, this may support healthcare professionals in identifying individuals at risk of developing a mental disorder in the future.

Contact: Vanessa Teckentrup