Temporal-thalamic and cingulo-opercular connectivity in people with schizophrenia

A growing body of research has suggested that people with schizophrenia (SZ) exhibit altered patterns of functional and anatomical brain connectivity. For example, many previous resting state functional connectivity (rsFC) studies have shown that, compared to healthy controls (HC), people with SZ demonstrate hyperconnectivity between subregions of the thalamus and sensory cortices, as well as hypoconnectivity between subregions of the thalamus and prefrontal cortex. In addition to thalamic findings, hypoconnectivity between cingulo-opercular brain regions thought to be involved in salience detection has also been commonly reported in people with SZ. However, previous studies have largely relied on seed-based analyses. Seed-based approaches require researchers to define a single a priori brain region, which is then used to create a rsFC map across the entire brain. While useful for testing specific hypotheses, these analyses are limited in that only a subset of connections across the brain are explored. In the current manuscript, we leverage novel network statistical techniques in order to detect latent functional connectivity networks with organized topology that successfully differentiate people with SZ from HCs. Importantly, these techniques do not require a priori seed selection and allow for whole brain investigation, representing a comprehensive, data-driven approach to determining differential connectivity between diagnostic groups. Across two samples, (Sample 1: 35 SZ, 44 HC; Sample 2: 65 SZ, 79 HC), we found evidence for differential rsFC within a network including temporal and thalamic regions. Connectivity in this network was greater for people with SZ compared to HCs. In the second sample, we also found evidence for hypoconnectivity within a cingulo-opercular network of brain regions in people with SZ compared to HCs. In summary, our results replicate and extend previous studies suggesting hyperconnectivity between the thalamus and sensory cortices and hypoconnectivity between cingulo-opercular regions in people with SZ using data-driven statistical and graph theoretical techniques.