Insula Functional Connectivity in Schizophrenia: Subregions, Gradients, and Symptoms

The insular cortex is connected to a diverse network of cortical and subcortical areas. This study aimed to investigate whether the diversity in functional connectivity across the insula’s topography is altered in individuals with schizophrenia and relates to the clinical symptoms of the disorder. Insula-to-whole-brain functional connectivity was mapped using resting-state functional magnetic resonance imaging at the resolution of voxels in individuals with schizophrenia (n = 49) and healthy comparison individuals (n = 52). Diversity in functional connectivity across the insula’s topography was represented as discrete subregions and gradients of continuous variation. Canonical correlation analysis was used to relate interindividual variation in insula connectivity to clinical symptoms. Insula connectional diversity was parcellated into two subregions: dorsoanterior and ventroposterior. Compared with the healthy comparison group, subjects with schizophrenia were associated with an overall reduction in insula functional connectivity as well as reduced differentiation in connectivity profiles between these subregions. A significant interaction effect between diagnosis and insula subregion indicated that the anterior subregion in schizophrenia was connected with increased strength to the somatosensory, motor, occipital, and parietal cortices, whereas the posterior subregion showed increased connectivity with the thalamus and prefrontal cortex. Insula connectivity with the anterior cingulate and auditory cortices was significantly associated with cognitive impairment, negative symptoms, poor psychosocial functioning, and longer duration of illness (r = .64, p = .03). Diversity in functional connectivity across the insula’s rostrocaudal axis is reduced in schizophrenia, resulting in reduced differentiation between anterior and posterior insula. Interindividual variation in insula connectivity explains variability in some of the clinical symptoms of schizophrenia.