Research Area: Translational and Systems Neuroscience
1. Research Background:
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 and biological aging with studies on human physiology as well as related clinical diseases. Specifically, we explore how our organism constantly integrates information about the internal state with external environmental cues to adapt behavioral and autonomic responses to ensure physiological homeostasis, including adaptive homeostasis in aging. To that end, our group is especially interested in understanding how the brain senses the needs of the body – such as the need for food – and then generates specific behavioral responses that restore physiologic balance.
2. Research questions addresses by the group:
We investigate how the human brain represents, integrates and prioritizes internal and external signals to initiate adequate behavioural and physiological responses with a special focus on circuit-level models, metabolic mechanisms , aging processes, and human cognition. Our group’s main research focus concerns the physiological pathways by which internal bodily signals are communicated to the brain to interact with reward processing and motivated behaviour. In this regard, we examine the identity of neural systems in the regulation of energy balance and (patho-)physiological consequences of overeating, its related disorders, and biological aging.
3. Possible projects:
Basic needs manipulate behaviour in our everyday life without us noticing. Intuitively, when facing decisions we often metaphorically go with our gut, and the impact of bodily states such as hunger on motivation is well documented. From a neurobiological point of view, evolutionary valuable responses in the hypothalamus, such as the negative-valence signalling of melanocortin neurons, leave us with an unpleasant feeling when our body detects a homeostatic shortfall. Indeed humans seem hardwired to search for nutritive food and discern food-related cues even before we consciously notice. However, it is currently still poorly understood how these perceptual and interoceptive sensations prime our behaviour, can bias our decision making, and change in aging. New findings from murine experimental models obtained by Jens Burning’s group have recently demonstrated that sensory food perception is sufficient to induce sympathetic nerve activation through a hypothalamic circuit, suggesting a mechanism by which metabolic changes required for nutrient intake are anticipated. To examine the implication of this sympathetic priming effect on cognitive dimensions in humans and to relate these to aging processes, we here propose to initiate a study to perceptually manipulate human participants accordingly while they are engaging in an incentive motivation task. Harnessing the neurobiology of model systems to study the biological impact of sensory manipulations has recently led to uncovering links between sensory perception and mechanisms of healthy aging. To that end, this study will form a basis for future translational research in humans investigating the link between internal sensory signals to motivational drive and, finally, cognitive processes and their association to lifespan.
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.
- 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, Difeliceantonio AG, Albus K, Cremer AL, Hanssen R, Lippert RN, Cornely OA, Small DM, Brüning JC, Tittgemeyer M (2019) Food Intake Recruits Orosensory and Post-ingestive Dopaminergic Circuits to Affect Eating Desire in Humans. Cell Metabolism 29: 695-706
- Edwin Thanarajah S, Iglesias S, Kuzmanovic B, Rigoux L, Stephan KE, Brüning JC, Tittgemeyer M (2019) Modulation of midbrain neurocircuitry by intranasal insulin. NeuroImage 194: 120-127
- Edwin Thanarajah S, Tittgemeyer M (2020). Food reward and gut-brain signalling Neuroforum 26(1), 1-9.
- Edwin Thanarajah S, Hoffstall V, Rigoux L, Hanssen R, Brüning JC, Tittgemeyer M (2019). The role of insulin sensitivity and intranasally applied insulin on olfactory perception. Scientific reports 9(1), 7222.