Interindividual variability of functional connectome in schizophrenia.

Schizophrenia is a complex psychiatric disorder that displays an outstanding interindividual variability in clinical manifestation and neurobiological substrates. A better characterization and quantification of this heterogeneity could guide the search for both common abnormalities (linked to lower intersubject variability) and the presence of biological subtypes (leading to a greater heterogeneity across subjects). In the current study, we address interindividual variability in functional connectome by means of resting-state fMRI in a large sample of patients with schizophrenia and healthy controls. Among the different metrics of distance/dissimilarity used to assess variability, geodesic distance showed robust results to head motion. The main findings of the current study point to (i) a higher between subject heterogeneity in the functional connectome of patients, (ii) variable levels of heterogeneity throughout the cortex, with greater variability in frontoparietal and default mode networks, and lower variability in the salience network, and (iii) an association of whole-brain variability with levels of clinical symptom severity and with topological properties of brain networks, suggesting that the average functional connectome overrepresents those patients with lower functional integration and with more severe clinical symptoms. Moreover, after performing a graph theoretical analysis of brain networks, we found that patients with more severe clinical symptoms had decreased connectivity at both whole-brain level and within the salience network, and that patients with higher negative symptoms had large-scale functional integration deficits.

Deficits in nominal reference identify thought disordered speech in a narrative production task.

Formal thought disorder (TD) is a neuropathology manifest in formal language dysfunction, but few behavioural linguistic studies exist. These have highlighted problems in the domain of semantics and more specifically of reference. Here we aimed for a more complete and systematic linguistic model of TD, focused on (i) a more in-depth analysis of anomalies of reference as depending on the grammatical construction type in which they occur, and (ii) measures of formal grammatical complexity and errors. Narrative speech obtained from 40 patients with schizophrenia, 20 with TD and 20 without, and from 14 healthy controls matched on pre-morbid IQ, was rated blindly. Results showed that of 10 linguistic variables annotated, 4 showed significant differences between groups, including the two patient groups. These all concerned mis-uses of noun phrases (NPs) for purposes of reference, but showed sensitivity to how NPs were classed: definite and pronominal forms of reference were more affected than indefinite and non-pronominal (lexical) NPs. None of the measures of formal grammatical complexity and errors distinguished groups. We conclude that TD exhibits a specific and differentiated linguistic profile, which can illuminate TD neuro-cognitively and inform future neuroimaging studies, and can have clinical utility as a linguistic biomarker.