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Compulsivity and inference-based predictions

Project Member(s): Bradfield, L.

Funding or Partner Organisation: National Health & Medical Research Council (NHMRC - Ideas Grants)
National Health & Medical Research Council (NHMRC - Ideas Grants)

Start year: 2024

Summary: Obsessive thoughts and compulsive behaviours are key diagnostic symptoms of obsessive-compulsive disorder (OCD) but also occur in other disorders such as frontotemporal dementia. Isolating the biological origins will advance out understanding and treatment of these disorders. While compulsive behaviours have been established in preclinical models, understanding obsessions has been more challenging. Impaired use of inferred or imagined outcomes is proposed to underlie obsessions, presenting a novel opportunity for measuring obsession-like processes in rats. Inference-based decisions have also received far less attention than decisions based on experience. In this project we will identify the neural circuit used to incorporate inferred information into predictions about future outcomes in rats. Further, we will determine is the same circuit is also required for compulsive behaviour. We will then use viral techniques to label ensembles of neurons that hold outcome information and inhibit these specific cells during inference-based decision-making and compulsive behaviour. Using this innovative approach we can manipulate the representation of outcomes, allowing us to demonstrate for the first time how this circuit is involved in inference-based decision-making and how predictions are changed when outcomes are experienced. We will also determine if the same circuits can induce and rescue compulsivity behaviour in rats. Overall, these results will establish a new model for investigating obsession-like behaviour in rats and determine if there is shared neural circuitry contributing to both obsessive and compulsive symptoms. This new knowledge will have significant ramifications for interpreting the robust changes detected in this circuitry in patient groups and for identifying the biological mechanism behind obsessive-compulsive behaviour.

FOR Codes: Expanding knowledge in psychology, Expanding knowledge in the biological sciences, Behavioural neuroscience, Cellular nervous system