Language network self-inhibition and semantic similarity in first-episode schizophrenia: A computational-linguistic and effective connectivity approach

Introduction: A central feature of schizophrenia is the disorganization and impoverishment of language. Recently, we observed higher semantic similarity in first-episode-schizophrenia (FES) patients. In this study, we investigate if this aberrant similarity relates to the 'causal' connectivity between two key nodes of the word production system: inferior frontal gyrus (IFG) and the semantic-hub at the ventral anterior temporal lobe (vATL). Methods: Resting-state fMRI scans were collected from 60 participants (30 untreated FES and 30 healthy controls). The semantic distance was measured with the CoVec semantic tool based on GloVe. A spectral dynamic causal model with Parametrical Empirical Bayes was constructed modelling the intrinsic self-inhibitory and extrinsic-excitatory connections within the brain regions. We estimated the parameters of a fully connected model with the semantic distance as a covariate. Results: FES patients chose words with higher semantic similarity when describing the pictures compared to the HC group. Among patients, an increased semantic similarity was related with an increase in intrinsic connections within both the vATL and IFG, suggesting that reduced 'synaptic gain' in these regions likely contribute to aberrant sampling of the semantic space during discourse in schizophrenia. Conclusions: Lexical impoverishment relates to increased self-inhibition in both the IFG and vATL. The associated reduction in synaptic gain may relate to reduced precision of locally generated neural activity, forcing the choice of words that are already 'activated' in a lexical network. One approach to improve word sampling may be via promoting synaptic gain via supra-physiological stimulation within the Broca's-vATL network; this proposal needs verification.