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Repetitive negative thoughts will be investigated using a range of cutting-edge brain science techniques as part of a new study led by the University of Oxford and funded by Wellcome.

Illustration of a head with a circle inside it. Arrows on the circle indicates it goes round and round.

The £5 million project will use advanced brain stimulation as well as MRI scans, computational modelling and a pioneering approach using biofeedback from the eyes’ pupils, to better understand the mechanisms that cause repetitive negative thoughts (RNTs), also known as ‘rumination’, to start and persist.

RNTs are a risk factor for a number of mental health conditions, including anxiety and depression, but the brain systems and processes involved in causing and maintaining these thoughts are not currently well understood.

This study will be the first to employ this broad range of techniques to provide evidence of what processes in the brain cause people to develop these repetitive worrying thoughts, and to find ways to help reduce them.

The project, which starts in February and will involve 500 participants, will work closely with people with lived experience to ensure the research makes sense and takes into account their views and priorities.

Principal Investigator Michael Browning, Professor of Computational Psychiatry at the Department of Psychiatry, University of Oxford, said:

Repetitive negative thoughts can have a debilitating and detrimental effect on people’s quality of life, and are an important component of other mental health conditions, including anxiety and depression.

Despite their significance in mental ill-health, little is known about the neurocognitive mechanisms that underpin these thoughts, and there are limited treatment options available. We are aiming to improve our understanding of why they develop so we can become better at treating them.”

The teams from Oxford, Zurich and Exeter also plan to test whether the worrying thoughts can be reduced by combining brain stimulation with a simple training exercise.

Professor Jacinta O’Shea, Wellcome/Royal Society Sir Henry Dale Fellow, Professor Lilian Weber and Professor Miriam Klein-Flugge will lead the brain stimulation work which will involve both transcranial magnetic stimulation (TMS) and transcranial ultrasound stimulation (TUS). Professor O’Shea explained:

 

Non-invasive brain stimulation methods will enable us to test how different brain areas contribute to patterns of recurrent worry and rumination. Using targeted stimulation we aim to interrupt these patterns and so reduce symptoms. By pairing stimulation with cognitive training over time, we will test if this enables people to overcome worry and rumination in favour of a more adaptive thinking style that is long-lasting. 

We will use two types of non-invasive brain stimulation. TMS uses magnetic pulses while TUS uses ultrasound to transiently and reversibly change brain activity. TMS is used for surface brain regions, while TUS can reach deeper regions.”

Pupil-based biofeedback, a strand of work led and pioneered by Professor Nicole Wenderoth at ETH Zürich, involves participants learning how to control their eye pupil size which can in turn affect activity in certain parts of the brain relating to worry. The cognitive training element will be led by Professor Edward Watkins at the University of Exeter. Computational modelling will be led by Rafal Bogacz from Oxford’s Nuffield Department of Clinical Neurosciences.

The project plan was developed in partnership with the National Institute for Health and Care Research (NIHR) Oxford Health Biomedical Research Centre Depression Therapeutics Patient and Public Involvement, Engagement and Participation (PPIEP) panel.