MRC Transition Support. CDA. Jill O'Reilly.

My research is concerned with how our brains build models of the environment in which we live, and use those models to make decisions and plan behaviour.

My research group's approach to understanding the brain is to use computational modelling. We develop experimental games that simulate problems people face in the real world, such as choosing between two options that cannot be clearly seen. Then we code algorithms (implemented in computer programmes) that solve the tasks in different ways, and test which algorithm is the best fit to human behaviour. Next, we use our knowledge of brain circuits to work out how these algorithms could be computed by populations of neurons in a real brain. I measure brain activity in humans using non-invasive imaging techniques such as MRI.

Some of my models also make predictions about how different brain chemicals (neurotransmitters and neuromodulators) affect the processing of information by the brain. To test these hypotheses, I will give healthy volunteers small doses of drugs that affect neurotransmitter concentrations and observe the resulting changes in their behaviour and brain activity.

A major technical challenge for my research programme is that we cannot simply record the activity of neurons in the human brain, without opening up the skull. To test our hypotheses in non-invasive experiments, we need work out how the modelled activity of neurons will be reflected in signals we can measure using non-invasive techniques like brain scanning (functional magnetic resonance imaging or magnetoencephalography). During the last four years, we have spent most of our time on solving this problem and are now confident that we have good models. However, we have not yet been able to complete the planned drug studies, which require a lot of slow and careful work to be done safely.

I am now applying for additional funding for my research programme to help me complete the proposed research. The bulk of the funding is to retain a key staff member in my team. Some of the funding is to buy out a percentage of my time from teaching so I am able to spend more time focussing on research and supporting my team.

The research in the CDA aims to develop a computational characterization of the roles of different brain systems in the formation and tuning of predictive models of the environment, which preidcts signals measurable with human neuroimaging.

The challenges involved in the research were: [Step 1] to design suitable tasks and models for which the necessary computations could be clearly defined at an algorithmic level; [Step 2] to posit circuit-level mechanisms that could underlie the computations; [Step 3] to build physiologically specified (biophysical) models of those mechanisms; [Step 4] to conduct drug studies that are safe, ethical and sufficiently powered to test the hypotheses.

So far, we have made good progress with steps 1-3, establishing a variety of paradigms and models in which predictions at the cells-and-circuits level can really be tested in human neuroimaging, and we have found some interesting results. However, we have only recently started to attempt drug manipulations (mid-data collection for one study; two more studies planned).

Although in some respects I have made good progress (one joint first-author paper in Science and one last author paper in eLife), I do not quite have enough last-author papers to secure a major research grant to follow on from the CDA. However, a further three major last-author studies are in the data analysis/write-up stage. Once these studies are published, I would hope to be in a much better position to apply for further funding.

My lab has experienced significant disruption over the CDA period including three moves of location (two involuntary) and two periods of maternity leave (for me).

The crucial benefits of Transition Funding would be to protect 50% of my time for research (I have a permanent contract but it will involve a lot of teaching), so I can be present in the lab and focus on completing projects and writing grants, and to allow me to retain my post doc which is essential for continuity.

I have nothing specific to Transition Support to add here, except to say that the Transition Support would allow me to realise the full impact of the research by completing and publishing work in a timely manner.