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

Abstract

Schizophrenia is a tenacious psychiatric disorder thought to result from synaptic dysfunction. 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 how aberrant synaptic connectivity is expressed in schizophrenia during social perception and how it relates to positive and negative symptomatology. We used fMRI and dynamic causal modelling (DCM) to test for abnormalities in synaptic efficacy 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. Our data reveal an increase in excitatory feedforward connectivity from motion-sensitive V5 to posterior superior temporal sulcus (pSTS) in patients compared to matched controls. At the same time, were less accurate than controls in judging social stimuli from non-social stimuli. Crucially, patients with a higher degree of positive symptoms had more disinhibition within pSTS, a region computationally involved in Theory of Mind. We interpret these within a predictive coding framework where increased feedforward connectivity may encode aberrant prediction errors from V5 to hierarchically higher pSTS and local disinhibition within pSTS may reflect aberrant encoding of the precision of cortical representations about social stimuli.

A fundamental distinction in early neural processing of implicit social interpretation in schizophrenia and bipolar disorder

“…Studies focusing on connectivity analysis could bring further detail to the biological processes underlying these findings, and specific disease trajectories occurring in BPD and SCZ ( Jimenez, 2019 ). Developmental synaptic dysfunction has been proposed as a likely mechanism of psychotic symptoms, and aberrant connectivity to the TPJ, namely the pSTS, has been reported in first-episode SCZ ( Dietz, 2020 ). Models derived from extrinsic and intrinsic connections to the TPJ, personalized for specific dysfunctions found in SCZ and BPD patients, could identify ideal anatomical targets for differential therapeutic neuromodulation (e.g.…”

Sub-optimal modulation of gain by the cognitive control system in young adults with early psychosis

“…In all, 30 EP participants and 30 aged and gender-matched controls with no family history of mental health disorders were recruited from October 2017 to July 2019. The sample size for adequate power to detect differences in behavior and functional magnetic resonance imaging (fMRI) was based on similar studies examining EP populations [9][10][11][12][13][14]. All participants were 17-25 years old.…”

“…Studies assessing hierarchical interactions between cortical regions in EP have shown that functional changes may occur in the absence of poor performance in simple tasks [9][10][11][12][13][14]. These findings suggest that hierarchical systems only falter under high levels of task difficulty, such as that engendered by stimulus conflict.…”