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An international team of scientists, including researchers at the University of Oxford's Department of Psychiatry, have built a computer ‘brain circuit’ that mirrors human decision-making processes and sheds light on how circuits might be altered in psychiatric diseases.

Laurence Hunt

The study, published in the journal eLife, identifies a potential mechanism for the impaired decision making that is commonly seen in schizophrenia, involving the reduced activity of molecules in the brain called NDMA receptors.

 

Our study sheds light on how changes in behaviour might arise as a consequence of changes occurring at the synaptic level in psychiatric disease. Linking findings between these very different scales of explanation is one of the major challenges in psychiatry; our study provides an example of how we might go about doing that using a drug manipulation that has often been used in psychiatric research over the past thirty years. - Dr Laurence Hunt, co-senior author on the study, Department of Psychiatry, University of Oxford.

 

The research team began by setting a decision-making task for two macaque monkeys and recording the pattern of their behaviours. The monkeys were presented with two series of eight bars, one on the left and one on the right of a computer screen, and they had to decide which side had the taller or shorter average height. The two monkeys made decisions based on nearly 30,000 sets of information, and the researchers studied the effect of timing and variability of the evidence on the monkeys’ choices. They found that, just like humans, the monkeys generally preferred to choose options with greater variability across the evidence.

To explore the brain processes that underlie this preference, the team built a computer-based circuit model. Two groups of excitatory nerve cells (neurons) were assigned to either the right or left option, such that high activity in one group signals a decision towards that option. These excitatory neurons are preferentially connected to their own group, and communicate with each other via synapses.

Both groups of neurons are also connected to inhibitory neurons, which counteract and balance the activity of the excitatory neurons. The circuit was then tested with the same decision tasks as the monkeys and was shown to be able to reproduce the same bias that the monkeys, and humans, used to make their decisions.

To understand how these decision processes may be impaired in neuropsychiatric diseases such as schizophrenia, the team reduced the activity of the NMDA receptors that connect the neurons in each excitatory group and each inhibitory group. They found that the decision-making performance in the model was dependent on the balance between excitation and inhibition, which in turn was influenced by the relative changes to NDMA receptors on the two groups of neurons.

 

One of the most exciting things about this project is that it was a truly international collaboration - the experiment was designed, and the data collected and analysed, here in the UK, but the computational modelling was led by a team of researchers at Yale University in the USA. It was very stimulating to be able to bring together the expertise of these different labs on such a challenging research problem. - Dr Laurence Hunt.

 

To read the full paper, A circuit mechanism for decision-making biases and NMDA receptor hypofunction.

To read the press release.

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