“We aim to understand which neurons are responsible for the atypical brain network patterns observed in humans experiencing auditory hallucinations. We can investigate this using our rodent models, where we can precisely switch different types of neurons on and off to mimic these patterns and identify potential cellular targets. Additionally, we will examine critical developmental windows that may be more susceptible to early interventions. I am thrilled about this new collaborative adventure. We have a unique opportunity to integrate experimental and computational models that are vital for establishing a bridge with people with lived experience of psychosis.”
Professor Beatriz Rico, Professor of Developmental Neurobiology, King’s IoPPN
24 March 2025
Researchers receive £4.1million to research new modelling and treatment approaches for auditory hallucinations in people with psychosis
The Wellcome Trust Mental Health Award will fund testing of a computational model of the role of cortical circuits in understanding auditory hallucinations (AH).
Professor Oliver Howes and Professor Beatriz Rico from King’s IoPPN, working with Rick Adams, Professor of Computational Psychiatry at University College London (UCL), Dr Stephen Kaar, Honorary Senior Lecturer, Division of Psychology and Mental Health, University of Manchester and Consultant Psychiatrist, Greater Manchester Mental Health NHS Foundation Trust, and Emily Wheeler from MQ will lead a team including co-applicants Professor Mitul Mehta, Dr Maria Kapi, Dr Oscar Marin, Dr Kelly Dierderen, and more from King’s College London, additional researchers and lived experience experts. The research will collaborate with UK biotech company, Autifony Therapeutics to address a key gap in knowledge around the first experience of auditory hallucinations.
This £4.1 million Wellcome funded project aims to identify the mechanism underlying auditory hallucinations (AH). AH are a core symptom of psychosis, reported by approximately 70-80% of people with schizophrenia and related disorders. People with lived experience of psychosis (PWLEP) identified these as a top research priority because of their impact on daily function and the distress they cause.
“Our collaboration between King’s College London, the University of Manchester, UCL, our NHS sites and Autifony, aims to deepen understanding of the effects on brain activity of a novel potassium channel modulating compound, which targets a unique population of neurons proposed to contribute to hallucinations in psychosis. This ground breaking work hopes to offer new insights into the neurobiology of psychotic disorders.”
Dr Stephen Kaar, Honorary Senior Lecturer, Division of Psychology and Mental Health, University of Manchester and Consultant Psychiatrist, Greater Manchester Mental Health NHS Foundation Trust.
This research hypothesises that deficits in specific populations of cortical neurons cause alterations in cortical oscillatory activity to lead to AH. This will be tested using a multidisciplinary approach combining electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) in people experiencing AH, electrophysiological recordings in mouse models, and computational modelling.
“The computational modelling part of the project has two aims: first, to use models of EEG data to work out whether young people experiencing auditory hallucinations have disinhibition in the part of the brain important for speech perception, and second, to see if a brain-like neural network model that learns to perceive speech can tell us about how disinhibition in the network might actually lead to hallucinations of voices.”
Rick Adams, Professor of Computational Psychiatry, UCL.
The study will use chemogenetic mouse models to alter firing in cortical circuits in a cell-type and regionally specific manner and measure the effect on neural oscillatory activity relevant to the studies in people with lived experience of psychosis, and test effects of drugs to target oscillatory abnormalities during neurodevelopment and in a genetic model. This will determine the contribution of pyramidal, PVI and other neuronal sub-types to the loss of inhibition and other alterations seen in PWLEP and the potential for preventive interventions. These data in PWLEP and mice will be used to refine the computational model of AH, and test whether a network model can explain the lived experience of AH.
"I'm thrilled that the Wellcome Trust are supporting this project because it aims to do something we have wanted to do for years: integrating preclinical and clinical projects with computational approaches. It also brings together a fantastic team of colleagues and advisors who are also great to work with. I feel very privileged to be working with them on the project. We are focusing on understanding hallucinations. These are amongst the most terrifying symptoms and can destroy lives, as one of lived experience advisors pointed out from her experience. Current treatments don't work for many people. If we are successful, we will generate new approaches to treat them that could offer new hope to people suffering with hallucinations."
Professor Oliver Howes, Head of Department of Psychosis Studies, King’s IoPPN
The project is highly inter-disciplinary, involving researchers from lots of different backgrounds, as well as patients and carers, who will be involved as co-researchers, and experts from around the world. This study will be testing the potential for new approaches to treat auditory hallucinations.
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Professor of Molecular Psychiatry
Professor of Developmental Neurobiology
Reader in Behavioural Neuroscience and Mental Health
Director, Centre for Innovative Therapeutics
Professor of Neuroscience