Dr. Marc Tittgemeyer

Research Area: Translational and systems neuroscience

Website: https://www.sf.mpg.de/forschung/tittgemeyer

1. Research Background:

Our general interest is the integration of fundamental biological research with applied research in human physiology and mechanisms of human diseases. The Translational Neurocircuitry Group complements and extends the basic research currently being pursued at the Max-Planck-Institute of Metabolism Research and CECAD on metabolic processes with studies on human physiology as well as on clinical diseases and pertaining states. Specifically, we seek to advancing our fundamental understanding of the neural circuits that support adaptive physiological and homeostatic functions, as well as complex behaviors.

2. Research questions addresses by the group:

There is a general consensus that obesity is a behavioural problem that results from a combination of a “vulnerable” brain (e.g., a predisposition to engage in impulsive food decisions) in an “unhealthy” environment (with abundant access to high-caloric food). In contemporary theories of overeating, including concepts of "food addiction”, impulsive behaviour is a key risk factor. However, obesity is a heterogeneous disorder, and only a subgroup of obese subjects may be adequately understood as suffering from impulse control problems. It is therefore crucial for pathophysiological theories of obesity as well as for diagnostic criteria of subgroups that the mechanisms causing this variability are understood. Our group has adopted both computational and physiological approaches to characterize such mechanisms. Specifically, we explore  whether individual variability in eating behaviour could arise from individual differences in neuromodulatory mechanisms. Thereby we consider genotype-specific differences in brain connectivity as well as brain morphology, humoral regulation of neurocircuitry, modulation of the dopaminergic system by nutrient signals, differential roles of nutrient rewards for motivation and impulsivity, and theoretical frameworks for framework for modelling brain-body interactions. Expanding into pathophysiology, we explore how neural circuits are perturbed by diet in humans and investigate the link between inflammation and affective disorder as well as neurodegeneration.

3. Possible projects:

Building on the achievements of our previous work, possible projects may focus on integrating the various biological factors into circuit models of interactions between homeostatic mechanisms and reward-related signals or processes underlying aging-related disease. These models will combine recent advances in generative modelling of human neuroimaging and behavioural data with genetic, metabolic, endocrine, and immunological analyses during experimental perturbations of homeostasis and reward processing.

A special emphasis may be here on the interaction between brain and periphery, the so-called gut-brain axis. The vagus nerve and spinal afferents are key communication pathways between the gut and the brain and have recently been implicated as having roles in cognition, reinforcement and affect. In teaming up with the group of Henning Fenselau, we are planning to investigate molecularly distinct phenotypes of afferent vagus and spinal nerve fibers to elucidate functional aspects of postprandial regulation of energy and glucose homeostasis. The framework will inspire and guide the development of novel interventions that can optimize glucose homeostasis in at-risk individuals in the healthy population, and can restore efficient control of energy intake in pre-clinical and clinical populations.

4. Applied Methods and model organisms:

Our research strategy requires a close interaction of theoretical and experimental work, an inter-disciplinary research environment along with an infrastructure that supports prospective validation studies in humans. To facilitate this interaction, another of our interests is to improve current techniques for probing neurocircuitry in vivo. This includes diffusion and functional MRI, positron emission tomography (PET), EEG and brain stimulation techniques, such as transcutaneous vagus nerve stimulation. Over the past years, the group has built up extensive methodological and technical expertise particularly in combining structural and functional neuroimaging approaches.

5. Desirable skills and qualifications:

A keen interest in translational neuroscience, human neurobiology and cognition. While pre-existing expertise in high-resolution in-vivo imaging methods is helpful -but not necessary, the desire to work in a multi-disciplinary research environment and to engage with statistical data analysis is requested.

6. References:

  • Difeliceantonio AG, Coppin G, Rigoux L, Edwin Thanarajah S, Dagher A, Tittgemeyer M, Small DM. Supra-Additive Effects of Combining Fat and Carbohydrate on Food Reward. Cell Metab. 2018, 28: 33–44.e3
  • Edwin Thanarajah S, Backes H, DiFeliceantonioAG, Albus K, Cremer AL, Hanssen R, LippertRL, CornelyOA, SmallDM, BrüningJC, TittgemeyerM, Food intake recruits orosensory and post-ingestive dopaminergic circuits to affect eating desire. Cell Metab, in press.
  • Kuzmanovic B, Rigoux L, Tittgemeyer M. Influence of vmPFC on dmPFC Predicts Valence-Guided Belief Formation. J Neurosci 2018, 38: 7996–8010
  • Sevgi, M, Diaconescu, AO, Tittgemeyer, M, Schilbach, L. Social bayes: Using bayesian modeling to study autistic trait-related differences in social cognition. Biol Psychiatry. 2016:80, 112-119.
  • Sevgi, M, Rigoux L, Kühn AB, Mauer J, Schilbach L, Hess ME, Gruendler TOJ, Ullsperger M, Stephan KE, Brüning JC, Tittgemeyer M. An obesity-predisposing variant of the FTO gene regulates D2R-dependent reward learning. J Neurosci. 2015,35: 12584-12592.