Aberrant effective connectivity is associated with positive symptoms in first-episode schizophrenia

Abstract

Schizophrenia is a neurodevelopmental psychiatric disorder thought to result from synaptic dysfunction that affects distributed brain connectivity, rather than any particular brain region. While symptomatology is traditionally divided into positive and negative symptoms, abnormal social cognition is now recognized a key component of schizophrenia. Nonetheless, we are still lacking a mechanistic understanding of effective brain connectivity in schizophrenia during social cognition and how it relates to clinical symptomatology. To address this question, we used fMRI and dynamic causal modelling (DCM) to test for abnormal brain connectivity in twenty-four patients with first-episode schizophrenia (FES) compared to twenty-five matched controls performing the Human Connectome Project (HCP) social cognition paradigm. Patients had not received regular therapeutic antipsychotics, but were not completely drug naïve. Whilst patients were less accurate than controls in judging social stimuli from non-social stimuli, our results revealed an increase in feedforward connectivity from motion-sensitive V5 to posterior superior temporal sulcus (pSTS) in patients compared to matched controls. At the same time, patients with a higher degree of positive symptoms had more disinhibition within pSTS, a region computationally involved in social cognition. We interpret these findings the framework of active inference, where increased feedforward connectivity may encode aberrant prediction errors from V5 to pSTS and local disinhibition within pSTS may reflect aberrant encoding of the precision of cortical representations about social stimuli.

Keywords: Brain-symptom mapping; Dynamic causal modelling (DCM); Parametric empirical Bayes (PEB); Schizophrenia; Social cognition.