Aberrant Temporal Connectivity in Persons at Clinical High Risk for Psychosis

Abstract

Background Schizophrenia, a neurodevelopmental disorder, involves abnormalities in functional connectivity (FC) across distributed neural networks, which are thought to antedate the emergence of psychosis. In a cohort of adolescents and young adults at clinical high risk (CHR) for psychosis, we applied data-driven approaches to resting-state fMRI data so as to systematically characterize FC abnormalities during this period and determine whether these abnormalities are associated with psychosis risk and severity of psychotic symptoms. Methods Fifty-one CHR participants and 47 matched healthy controls (HCs) were included in our analyses. Twelve of these CHR participants developed psychosis within 3.9 years. We estimated one multivariate measure of FC and studied its relationship to CHR status, conversion to psychosis and positive symptom severity. Results Multivariate analyses revealed between-group differences in whole-brain connectivity patterns of bilateral temporal areas, mostly affecting their functional connections to the thalamus. Further, more severe positive symptoms were associated with greater connectivity abnormalities in the anterior cingulate and frontal cortex. Conclusions Our study demonstrates that the well-established FC abnormalities of the thalamus and temporal areas observed in schizophrenia are also present in the CHR period, with aberrant connectivity of the temporal cortex most associated with psychosis risk.

Emerging Temporal Lobe Dysfunction in People at Clinical High Risk for Psychosis

“…While the evidence remains equivocal, several imaging studies adopting whole brain analytical approaches support this view [e.g., Refs. (10, 15, 21, 23, 24, 89)] and recent connectivity studies in large CHR data sets show that lateral temporal (28) and prefrontal cortex (88) disconnectivity are particularly associated with conversion to psychosis. Intriguingly, analysis of speech in CHR cohorts (a function strongly related to lateral temporal, frontal, and parietal lobe function) (81) shows that reduced semantic coherence and syntactic complexity predicted later psychosis development with 100% accuracy, outperforming classification from clinical interviews (102).…”

“…Dysfunction in lateral temporal-centered networks in patients with schizophrenia is thought to underlie positive symptoms relating to language, thought, and speech such as auditory verbal hallucinations (10, 84–86) and thought disorder (87). To date, there are a limited number of studies suggesting altered function and connectivity in this network during prodromal stages of illness (22–24, 28). In a cross-sectional study, Crossley et al (22) studied participants with CHR for psychosis, FEP patients, and healthy controls using a working memory task.…”

“…Colibazzi and colleagues (24) also use a prospective design with data-driven approaches to resting-state fMRI data to examine resting functional connectivity in a CHR group. Multivariate analyses revealed between-group differences in whole-brain connectivity patterns in bilateral temporal areas, mostly affecting functional connections to the thalamus.…”

“…(8, 15–20)] and the lateral temporal cortices [e.g., Refs. (21–24)]. Moreover, preclinical models [see Refs.…”

“…Furthermore, guided by work in animal models of schizophrenia (25–27) and findings from neuroimaging studies in patients with established schizophrenia, nascent neuroimaging research in CHR populations has identified the importance of an MTL and subcortical network involving the hippocampus, midbrain, and striatum (8, 9). Meanwhile, a separate body of neuroimaging work in CHR cohorts, again informed to a large extent by research in patients with established schizophrenia, has identified functional and anatomical alterations in the lateral temporal cortex and broader networks involving the frontal and parietal lobes (24, 28).…”