Fundamental associative learning processes in psychosis: combined behavioural, functional neuroimaging and psychopharmacological studies. (360G-Wellcome-064351_Z_01_A)

Delusions are core symptoms of psychotic illnesses such as schizophrenia. Central to our understanding of delusions is the idea that they emerge from a background of abnormal formation of associations. Over the last decade, there has been an increasing understanding of the neuroscience of association formation. This work has emphasised prediction error signal as a drive to associative learning and a guide to allocation of attention and to selection of action. The goal of my proposed work is to test the hypothesis that delusional beliefs arise from changes in association formation as a consequence of abnormal prediction error signalling. In order to do so, I wish to combine behavioural, psychopharmacological and functional neuroimaging studies to:(i) Refine understanding of prediction error-driven associative learning processes in humans(ii) Establish the extent and nature of disruption of these processes, (both in terms of behaviour and brain response) a) in deluded individuals and b) under ketamine administration.(iii) Test directly the possibility of a link between symptoms of psychosis and disturbances in associative learning by evaluating the extent to which these behavioural and brain responses predict the existence or emergence of delusional beliefs (under ketamine and in psychosis).