Case study: Professor Matthew Rushworth

Research: Identifying the brain processes involved in making decisions and taking actions to learn what happens when they work properly and what happens when they go wrong, eg after a stroke or in psychiatric conditions.

Animals used: Rats, primates

Professor Matthew Rushworth: ‘We try and understand the basic processes in the brain that allow us to make decisions or choose a course of action according to what’s happening around us.

‘For example, just coming into work in the morning involves making many decisions based on information in the environment – looking at the traffic lights and deciding whether to stop or drive through.

‘Then there’s also a different type of decision in which there is nothing telling you what to do, and you have to weigh up the potential courses of action and make a judgement about what’s most beneficial.

‘Each decision type involves different brain structures and connections. And these processes can go wrong.

‘There are psychiatric conditions, such as schizophrenia and depression, that affect the way we read our environment and the courses of action we take as a result. In depression, you may be inclined to read the costs and benefits of a possible course of action differently. The result would be that you didn’t engage in activities that others would consider meaningful and rewarding.

‘By understanding the basic mechanisms of how decisions are made in the brain and how they work properly, it can guide our interpretation of what happens when they’re not working properly.

‘Answering these fundamental questions about brain processes is necessary in order to interpret changes in patients with brain damage. In those that have suffered stroke-induced brain damage, many find themselves unable to make movements in parts of their bodies. We want to know why that failure occurs. And why do some people fail so dramatically while others recover a great deal of movement?

‘The brain is a mosaic, with different areas doing different tasks. If a tile is lost, for example a tile that’s involved in movement, there is some degree to which other tiles can take over that role. The differences in recovery from stroke appear to arise from differences in the amount to which alternative tiles can take over from the missing tile.

‘We’re working with other groups in preclinical research to see if ways can be found to encourage those other tiles to take over lost function.

‘In the mosaic-like brain, we want to identify which areas are important for which function, the types of connections that are made, the information that’s contained in each area, and that area’s influence on other parts of the brain.

‘While part of this work involves animals, a lot of research is done with humans. We can look at how brain processes work normally by putting humans in MRI scanners and recording activity in different areas of the brain when the volunteer is making decisions.

‘We can also use a technique called transcranial magnetic stimulation (TMS) in humans to stop particular areas of the brain from working for a very short time and see what effect this has. TMS applies a pulsed magnetic field to areas on the outside of the head for a few milliseconds to interfere with the normal electrical signals in the brain.

‘Through careful and repeated measurements of the responses to the tasks we give people, we can identify the signals and brain mechanisms involved. However, it is impossible to access some brain areas – deep areas of the brain or areas where the jaw or nose would get in the way of the TMS – or it may be unsafe to disrupt brain signals for long enough to get a reading. Here it is necessary to move to animal models.

‘We have developed behavioural tests for both rats and primates to understand their decision-making processes. With rats, it’s running around mazes, while monkeys are trained to respond to images on a touch screen.

‘The monkeys are trained to touch a monitor that has been specially set up for them in return for food rewards. Motivated by the food, they can learn to touch the right of the screen when a green circle is shown and the left of the screen for a red circle, for example. If they don’t receive the food, they’ll be given food afterwards in their home cage. We don’t think that the touch-screens routines are unpleasant for the animals, and in fact they seem to like doing them.

‘After a period of months of learning the tests, we remove a limited amount of brain tissue under anaesthetic. A full course of painkillers is given under vet guidance in the same way as any human surgical procedure and the animals are up and about again within hours.

‘We don’t introduce gross damage as happens to a human who’s had a stroke. Stroke affects many areas of the brain, which makes it so catastrophic. We would rightly not be allowed to make such gross damage in an animal. We focus on one small area of the brain in a controlled way that leaves no immediately observable change in the rat or primate. Only through the sensitive behavioural tests we have set up can we see what effect this area has in decision-making brain processes.

‘The Biomedical Sciences Building has made a great difference because of the excellent conditions in which the animals are kept.

‘The animals take part in these behavioural tests for at most about an hour a day. Most of the time they are in their housing units where they live. And these got much better with the move to the Biomedical Sciences Building.

‘This might seem a minor change. Most outside concern tends to be about whether something invasive is done to the animals, but any procedure, invasive or not, is controlled very strictly. Our major worry instead is the day-to-day, round the clock welfare of the animals, which totally depends on the environment in which they live and the other animals they share it with.

‘The Biomedical Sciences Building has been better and easier for housing animals together. It has been very beneficial indeed.’