Mentalizing in male schizophrenia patients is compromised by virtue of dysfunctional connectivity between task-positive and task-negative networks

Abstract

Schizophrenia can be conceptualized as a disorder of functional connectivity within the fronto-temporal (FT) and/or default-mode (DM) networks. Recent evidence suggests that dysfunctional integration between these large neural networks may also contribute to the illness, and that the ability to mentalize or have a ‘theory of mind’ (ToM) is discernibly impaired in patients with schizophrenia. Hence in this study, we examined whether impaired functional network connectivity (FNC) contributes to a compromise in the ability to mentalize in patients with schizophrenia. Functional magnetic resonance imaging data were acquired from 20 male schizophrenia patients and 19 matched healthy controls whilst performing a well-known ToM task. The study revealed that relative to non-ToM the engagement of ToM produced reduced neural activity in the lateral FT and insula networks in patients, as compared to healthy subjects. The findings also indicated that in comparison to healthy subjects the DM and medial FT networks are less suppressed in patients irrespective of the task (ToM/non-ToM). Further, FNC analyses showed that the degree of functional connectivity between task-positive (lateral FT and insula) and task-negative (medial FT, posterior DM) networks was significantly reduced in patients as compared to controls. Of note, a significant correlation between the functional connectivity strength of the lateral FT network with the medial FT and the degree to which this is modulated by the ToM task, suggest that mentalizing deficits in male schizophrenia patients may stem from impaired communication between neural networks that comprehend the mental states of self (medial FT) and others (lateral FT).

Mentalizing in schizophrenia: A multivariate functional MRI study

“…While the connectivity pattern for the healthy controls remained relatively consistent across conditions, patients showed additional connectivity with the left iFG and left caudate nucleus during the physical and mental animations. The increased functional connectivity between the left iFG and other frontal regions during the mental animations in patients with schizophrenia is consistent with previous reports (Das, Calhoun, et al, 2012;Jeong, Wible, Hashimoto, & Kubicki, 2009) and suggests inefficient frontal network segregation may explain difficulties on mental judgment tasks. This is further evidenced by the association between accuracy on the mental animations and functional connectivity primarily between the left and right inferior frontal gyri, but also involving the left temporal lobe.…”

“…Regions activated during the physical animations (and random in SZ patients) included the right medial frontal gyrus and the left superior frontal gyrus. The inferior frontal gyri and left superior temporal gyrus involvement supports previous studies employing the Triangles Task (Das, Calhoun, et al, 2012;Das, Lagopoulos, et al, 2012) as well as results from a meta-analysis into similar mentalizing tasks (Schurz, Radua, Aichhorn, Richlan, & Perner, 2014).…”

“…The Triangles Task (Castelli, et al, 2000) is a measure of mentalizing used in previous fMRI studies with patients with schizophrenia (Das, Calhoun, et al, 2012;Das, Lagopoulos, et al, 2012;Pedersen, et al, 2012). It involves viewing animations consisting of a large and small triangle interacting on a screen for a period of 36 seconds.…”

“…As ToM is a complex higher order cognitive ability subserved by a dynamic network of inter-related regions (Adolphs, 2009;Das, Calhoun, et al, 2012;Mohnke, et al, 2015), this approach may further the identification of structurefunction correlates in healthy and clinical groups such as schizophrenia. Previous studies have not incorporated all conditions of the Triangles Task into the fMRI analyses (Das, Calhoun, et al, 2012;Das, Lagopoulos, Coulston, Henderson, & Malhi, 2012).…”

“…Previous studies have not incorporated all conditions of the Triangles Task into the fMRI analyses (Das, Calhoun, et al, 2012;Das, Lagopoulos, Coulston, Henderson, & Malhi, 2012). Although contrasting the mental condition with the random condition may provide hints at the social brain network important for mentalizing, a more nuanced analysis should include the physical (or goaldirected) condition, as this controls for patterned or complex interaction without a mental component.…”