Thalamic-insular dysconnectivity in schizophrenia: evidence from structural equation modeling

Abstract

Structural and functional studies have shown that schizophrenia is often associated with frontolimbic abnormalities in the prefrontal and mediotemporal regions. It is still unclear, however, if such dysfunctional interaction extends as well to relay regions such as the thalamus and the anterior insula. Here, we measured gray matter volumes of five right-hemisphere regions in 68 patients with schizophrenia and 77 matched healthy subjects. The regions were amygdala, thalamus, and entorhinal cortex (identified as anomalous by prior studies on the same population) and dorsolateral prefrontal cortex and anterior insula (isolated by voxel-based morphometry analysis). We used structural equation modeling and found altered path coefficients connecting the thalamus to the anterior insula, the amygdala to the DLPFC, and the entorhinal cortex to the DLPFC. In particular, patients exhibited a stronger thalamus-insular connection than healthy controls. Instead, controls showed positive entorhinal-DLPFC and negative amygdalar-DLPFC connections, both of which were absent in the clinical population. Our data provide evidence that schizophrenia is characterized by an impaired right-hemisphere network, in which intrahemispheric communication involving relay structures may play a major role in sustaining the pathophysiology of the disease.

Figure 1

Surface renderings of the contrasts testing significant decrease of gray matter volume in patients as opposed to controls. (A, B) Significant decrease of gray matter volume at the level of the prefrontal cortex. (C) Significant decrease of gray matter volume at the level of the insula. The surface rendering was obtained from an MNI‐normalized single‐subject brain in which the most lateral regions were removed, thus allowing free vision of the surface of the insular cortex.

Figure 2

Path modeling. Line drawing of a sagittal brain section displaying, for each group, the five regions subtending the network used in the present analysis and the strength of their connection. Black arrows refer to positive path coefficients, whereas gray arrows refer to negative path coefficients. Thickness of each arrow is proportional with the absolute magnitude of the coefficient. Am, amygdala; Tha, thalamus; Ins, anterior insula; EC, entorhinal cortex; dPF, dorsolateral prefrontal cortex.

Figure 3

Barplot displaying path coefficients connecting the amygdala to the dorsolateral prefrontal cortex, the entorhinal cortex to the dorsolateral prefrontal cortex, and the anterior insula to the thalamus. Light gray bars refer to path coefficients estimated in the patient population, whereas dark gray bars refer to path coefficients estimated in the healthy/control population. Significances associated with t‐test based on bootstrap standard errors are also reported. “*” refers to t ₍₁₄₃₎ > 1.98 (corresponding to P < 0.05), whereas “**” refers to t ₍₁₄₃₎ > 2.61 (corresponding to P < 0.01).