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. 2020 Jun:220:69-77.
doi: 10.1016/j.schres.2020.03.068. Epub 2020 Apr 16.

Insula functional connectivity in schizophrenia

Julia M Sheffield  1 , Baxter P Rogers  2 , Jennifer Urbano Blackford  3 , Stephan Heckers  4 , Neil D Woodward  4
Affiliations

Insula functional connectivity in schizophrenia

Julia M Sheffield et al. Schizophr Res. 2020 Jun.

Abstract

The insula is structurally abnormal in schizophrenia, demonstrating reductions in volume, cortical thickness, and altered gyrification during prodromal, early and chronic stages of the illness. Despite compelling structural alterations, less is known about its functional connectivity, limited by studies considering the insula as a whole or only within the context of resting-state networks. There is evidence, however, from healthy subjects that the insula is comprised of sub-regions with distinct functional profiles, with dorsal anterior insula (dAI) involved in cognitive processing, ventral anterior insula (vAI) involved in affective processing, and posterior insula (PI) involved in somatosensory processing. The current study builds on this prior work and characterizes insula resting-state functional connectivity sub-region profiles in a large cohort of schizophrenia (N = 191) and healthy (N = 196) participants and hypothesizes specific associations between insula sub-region connectivity abnormalities and clinical characteristics related to their functional profiles. Functional dysconnectivity of the insula in schizophrenia is broadly characterized by reduced connectivity within insula sub-networks and greater connectivity with regions not normally connected with that sub-region, reflected in significantly greater similarity of dAI and PI connectivity profiles and significantly lower similarity of dAI and vAI connectivity profiles (p < .05). In schizophrenia, reduced connectivity of dAI correlates with cognitive function (r = 0.18, p = .014), whereas stronger connectivity between vAI and superior temporal sulcus correlates with negative symptoms (r = 0.27, p < .001). These findings reveal altered insula connectivity in all three sub-regions and converge with recent evidence of reduced differentiation of insula connectivity in schizophrenia, implicating functional dysconnectivity of the insula in cognitive and clinical symptoms.

Keywords: Cognition; Insula; Negative symptoms; Positive symptoms; Resting-state functional connectivity; Schizophrenia.

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Conflict of interest statement

Declaration of competing interest The authors declare no conflicts of interest.

Figures

Fig. 1:
Fig. 1:
Within-group functional connectivity of insula sub-regions projected onto inflated right-hemisphere surfaces to illustrate functional profiles of each sub-region. Results thresholded at whole-brain (FWE) cluster-level corrected p=.05 using a voxel-wise p=.001 (uncorrected) cluster-defining threshold.
Fig. 2:
Fig. 2:
Clusters demonstrating significant group differences for each insula sub-region. Group difference maps were thresholded at cluster-level pFWE <.05 for voxel-wise cluster-defining threshold p=.001 (uncorrected), controlling for head motion, study protocol and gender. Numbers of coronal sections designate MNI-Y position of slice. Bar plots illustrate average functional connectivity within each significant cluster. L SI = Left Substantia Innominata; OFC = Orbitofrontal Cortex; R SI = Right Substantia Innominata; SPL = Superior Parietal Lobe; P. Visual = Primary Visual Cortex; SS = Somatosensory Cortex; dACC = Dorsal Anterior Cingulate Cortex; Hipp. = Hippocampus; STG = Superior Temporal Gyrus; PI = Posterior Insula; PCC = Posterior Cingulate Cortex; SPC = Superior Parietal Cortex; FEF = Frontal Eye Field; Cereb. = Cerebellum; V. PCC = Ventral Posterior Cingulate Cortex; PFC = Prefrontal Cortex.
Fig. 3:
Fig. 3:
A) Average connectivity extracted from the regions that demonstrated reduced connectivity with the dAI in schizophrenia (shown in blue) was associated with better overall cognitive ability (total SCIP z-score) (VOI = volume-of-interest analysis in SPM). B) Whole-brain voxel-wise analysis revealed a positive association between vAI connectivity with right posterior superior temporal gyrus (shown in red) and negative symptoms. Connectivity of vAI with the whole brain in the healthy group is overlaid in blue, demonstrating no significant connectivity between vAI and STS in healthy participants, suggesting that vAI-STS are abnormally connected in schizophrenia, contributing to negative symptom severity.
See this image and copyright information in PMC

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