Subjects with a diagnosis of schizophrenia show consistent differences from controls in neuroimaging paradigms such as resting state (rsEEG and rsfMRI), mismatch negativity (MMN) and 40 Hz auditory steady state response (ASSR). The underlying circuit changes causing these group differences are unclear, however, and it is not known whether the same abnormalities could underlie group differences in all paradigms. Nevertheless, it is widely hypothesised that schizophrenia involves a loss of synaptic gain – e.g. due to NMDA receptor dysfunction – and disrupted balance between excitatory and inhibitory transmission in cortical circuits. Here we analyse a neuroimaging dataset containing data from controls (n=107), subjects diagnosed with schizophrenia (Scz, n=108) and their first degree relatives (n=57) each undergoing rsEEG, rsfMRI, MMN and 40 Hz ASSR paradigms. We use a variety of dynamic causal modelling approaches to estimate synaptic gain and other circuit parameters in auditory and frontal areas. We find some striking commonalities across paradigms, not just in synaptic gain in the Scz group, but also in relationships with symptoms and cognitive function. The potential for development of a model-based biomarker of synaptic gain is discussed.

Rick is a Research Fellow and Consultant Psychiatrist at UCL. He is one of the leading investigators in computational psychiatry.

• Date: 05/13/20
• Time: 12:00 PM CET
• Location: Remote via Zoom
• Host: Philipp Homan