David Meder

Project title

Optimistic and pessimistic dopamine signals in the human brain: a mapping and modelling study in health and Parkinson’s Disease

What is your project about?

My project is based on a new theory about how the brain’s dopamine system works. The dopamine system allows us to generate adaptable behavior and vigorous movement. Dopamine cells release dopamine when we are positively surprised, but also when we initiate an action. The importance of dopamine is seen in Parkinson’s disease where the degeneration of dopamine cells leads to impairments in motor function and motivation. A new theory suggests that dopamine cells react differently to rewards. Some are “optimistic” (they expect high rewards and are thus rarely positively surprised), while others are “pessimistic”. It is, however, unknown, whether this is the case for the human brain. If so, this theory might explain several disease symptoms, such as apathy, anhedonia and motor impairments. I want to use MR-scans to probe the human brain for “optimistic” and “pessimistic” dopamine neurons. Additionally, I want to map the loss of dopamine neurons in Parkinson’s disease patients and investigate, whether the individual pattern of cell loss can explain some of their symptoms. These results might change our understanding of dopamine’s role in reward, motivation and movement but also why Parkinson’s patients develop their symptoms.

How did you become interested in your particular field of research?

When I started studying Psychology at the University, I had honestly no idea of where it would lead me. I did, however, quickly realize that Neuropsychology was the most fascinating topic of the curriculum. I therefore went on to do a research internship and write my thesis on how different brain areas in the rodent are involved in their ability to spatially navigate. Here I realized that neuroscience was incredibly exciting, but also that there were plenty of very fundamental questions that the field had no understanding of – and that I wanted to be part of the effort to investigate and answer some of these questions.

What are the scientific challenges and perspectives in your project?

The biggest challenge, or maybe uncertainty, about the project is whether “optimistic” and “pessimistic” dopamine cells exist in the human brain and whether they can be detected with an MR-scanner. An MR-scanner does not measure the activity of single cells, but at a resolution of hundreds of thousands neurons within one 3D-pixel (called voxel). Another challenging aspect is the investigation of Parkinson’s patients who can be very ill, especially when we test them when they have not taken their medicine. However, if I can show that there exist optimistic and pessimistic neurons in the human brain which we can measure with an MR-scanner, this would constitute a major change in the way we understand the dopaminergic system.

What is your estimate of the impact, which your project may have to society in the long term?

My project is basic research and thus to start with “only” has the intrinsic value of advancing our understanding of our brain and how it is affected by Parkinson’s disease. However, in the longer term these insights can hopefully inspire novel treatment approaches and lead to new research on other diseases that are associated with the dopamine system, such as depression and schizophrenia.

Which impact do you expect the Sapere Aude programme will have on your career as a researcher?

The Sapere Aude grant means of course that I now can gather a team of researchers to investigate these questions which I otherwise would not the time or money to pursue on my own. Moreover, the Sapere Aude grant is a major acknowledgement both for me personally, but also in terms of future grant- and job applications which will allow me to establish myself as research leader and continue working on the numerous open questions in my field. I am therefore convinced that being part of the Sapere Aude program goes much beyond the concrete sum of money that comes with it.

Background and personal life

I grew up in Hamburg, Germany and studied Psychology in Jena, a small University town in former East Germany. I finished my studies in Copenhagen in order to live with my Danish girlfriend, now wife. We still live here, now with three children aged 3, 7 and 10. After my time as a research assistant in an animal lab at Copenhagen University I got a PhD position at my current lab at Hvidovre Hospital, DRCMR. This is also where I returned to after a year as a PostDoc at Oxford University.