"Psychotic symptoms (hallucinations and delusions) have been associated with a striatal hyperdopaminergic state.Less explored, but also implicated are functional abnormalities in cognitive control, particularly in the prefrontal cortex; and a functional and structural disconnectivity between this and other areas of the brain.Such a disconnectivity would explain the lack of coherent response to conventional treatment: antipsychotic drugs do not benefit between 20 and 45 per cent of people with schizophrenia.The aim of this project is twofold: firstly, to explore the neural mechanisms underling cognitive control and the level at which cognitive control dysfunction operates in treatment refractory psychosis.The second is to test the hypothesis that cognitive dysfunction in patients who have treatment-resistant psychosis is associated with a specific neural signature – and discover whether that neural signature can be used as a biomarker of treatment resistance. Such a biomarker would help personalise treatment decisions and make treatment regimes more effective. It would also aid the development of novel treatments (other complementary work is investigating medication that enhances frontal cortical function as well as non-invasive brain stimulation techniques such as transcranial direct cortical stimulation).The project involves two linked brain imaging studies.The first will establish the indicative biomarker using both structural and functional MRI scanning and tasks to assess cognitive control at different levels of complexity.The second study will establish the validity of the biomarker by following a cohort of first episode psychosis patients for two years to discover whether their actual outcome corresponds with the outcome predicted by the neural signature shown in MRI scans."