£5m programme to investigate brain networks and the workings of the mind

The studies in primates will look at how networks of millions of neurons in the brain give rise to key functions like attention, social interaction, decision-making and organisational skills – functions often impaired in mental health conditions, in dementia and normal ageing, and after head trauma or a stroke.

The five-year programme, funded by a £4.95 million Strategic Award from the Trust, will bring together a range of scientists, vets and animal technicians and involve 20 macaque monkeys. A crucial stream of the programme will involve research into animal welfare, to guide the best ways of conducting this type of research.

The research will be embedded within existing Oxford neuroscience research programmes that focus on humans, to ensure a direct link to understanding human brain processes and their impairments in disease.

Our mental processes are constructed by complex, distributed networks of neurons in the brain – allowing us to process information, focus our attention, make decisions, carry out tasks, interact with each other, and many other functions.

Brain imaging in humans has given us large-scale maps of how these networks are laid out. But these methods aren’t able to tell us how the neural networks actually work.

The new research programme will combine MRI brain imaging with fine-scale neuroscience techniques only possible in animals to probe how different parts of the brain interact with each other. Primates will be used in this research because of the focus on complex cognitive functions, which depend on brain circuits not shared with other species such as mice and rats.

The welfare stream of the research programme will involve developing better measures of the macaques’ health and wellbeing for best possible practice in animal care.

The best animal welfare doesn’t just mean using anaesthetics and painkillers for invasive procedures, or making sure techniques cause minimum discomfort. It is also about understanding what choices on housing, training and rewards are best for the health and wellbeing of the monkeys – for example, the best methods of training to reduce stress and ensure rapid learning of tasks. This requires having good physiological and behavioural measures of animal health, and long-term monitoring through the duration of a research programme.

The programme, funded through a competitive peer-reviewed grant award process, has received ethical approval and is licensed by the Home Office.

The macaques will be housed in state-of-the-art facilities in the University of Oxford’s Biomedical Sciences Building, where they can express their natural behaviours – such as living in social groups, playing, climbing and foraging for food.

MRI imaging will be used in the same way as in human studies to map networks and connections between different areas of the monkey brain. Importantly, the latest methods will also be used to record the electrical activity of neural circuits in the brain, as well as powerful new techniques for altering function in one part of a network and measuring consequences elsewhere.

Electrical activity in the brain’s circuits is recorded using implanted electrodes, similar to those used to record brain activity in some patients with epilepsy, or in deep brain stimulation in Parkinson’s disease. The type and amount of brain activity data that can be obtained with these electrodes means that very few animals are needed in these studies.

The electrodes also allow very small electrical currents to be used to stimulate brain function and see how different parts of the brain interact with each other.

Other methods the researchers will use to probe the functioning of neural circuits include optogenetics, a state-of-the-art technique that is only just beginning to be used in primates, having seen success in fruit flies and mice. Optogenetics involves introducing light-sensitive molecules into small groups of specific nerve cells and using light to cause those nerves to fire.

“We need to understand more about how our brain works, both when it is working well and when it isn’t. This is important fundamental research into the brain that will benefit humans and may lead to medical advances in the medium to long term,” says Professor John Duncan of Oxford’s Department of Experimental Psychology and lead researcher on the new Wellcome Trust Strategic Award.

Dr John Williams, Head of Clinical Activities and Neuroscience and Mental Health at the Wellcome Trust, said: “Combining current brain-imaging techniques with the detailed insight enabled by this research with macaques provides a direct bridge into understanding human cognition and our mechanisms of control, decision-making and communication. This insight will provide valuable information on how our brains function when experiencing a range of human diseases.”

The programme will create a UK centre of excellence for the study of neural networks and the training of future neuroscientists.