Investigating the fundamental circuit pathology in schizophrenia using computational modelling of brain imaging data – Dr Rick Adams

October 21, 2021 @ 1:00 pm – 2:00 pm
Sarah Morgan

It has long been hypothesized that there is a disruption of the normal balance between excitatory and inhibitory transmission in cortical circuits in schizophrenia. The exact nature of this disruption is unclear, however: is there insufficient excitation? Or insufficient inhibition? Or some combination of both? Furthermore, several M/EEG paradigms show well-replicated abnormalities in schizophrenia, e.g. mismatch negativity, auditory steady-state response to 40 Hz stimulation, and resting EEG spectra. Can these abnormalities all be attributed to a common excitatory or inhibitory pathology? I attempt to answer these questions using a neuroimaging dataset comprising controls (n=107), subjects diagnosed with schizophrenia (n=108) and their relatives (n=57). Each participant underwent resting EEG, mismatch negativity, auditory steady-state response at 40 Hz, and resting state fMRI, and I used dynamic causal modelling across paradigms to infer changes in synaptic gain on excitatory and inhibitory neurons in schizophrenia, and the relationship of these changes to symptoms of the disorder. I will discuss what the findings might mean for the fundamental disease process underlying schizophrenia, glutamatergic treatments, and the possibility of model-based biomarkers of synaptic gain.

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