Theory of Mind Skills Are Related to Gray Matter Volume in the Ventromedial Prefrontal Cortex in Schizophrenia

Abstract

Background Among individuals with schizophrenia, deficits in theory of mind (ToM) skills predict poor social functioning. Therefore, identifying the neural basis of ToM may assist the development of treatments that improve social outcomes. Despite growing evidence that the ventromedial prefrontal cortex (VMPFC) facilitates ToM skills among healthy individuals, methodological challenges, such as the influence of general cognitive deficits, have made it difficult to identify the relationship between ToM processing and VMPFC function in schizophrenia. Methods We used voxel-based morphometry (VBM) and a multi-method behavioral assessment of ToM processing, including performance-based (Recognition of Faux Pas Test), self-report (Interpersonal Reactivity Index, Perspective-Taking), and interview-rated (Quality of Life Scale–Empathy score) ToM assessments, to investigate whether ToM skills were related to VMPFC gray matter volume (GMV). Standardized neuropsychological measures were used to assess global cognition. 21 schizophrenia and 17 healthy control subjects participated. Results Between-group behavioral analyses showed that, as compared to healthy participants, schizophrenia participants had worse ToM performance and lower self-reported ToM processing in daily life. The between-group analysis of GMV showed that schizophrenia participants had less VMPFC GMV than healthy participants. Moreover, among schizophrenia participants, all three measures of ToM processing were associated with VMPFC GMV, such that worse ToM skills were related to less VMPFC GMV. This association remained strong for self-reported and interview-rated ToM skills even when controlling for the influence of global cognition. Conclusions The findings suggest that among individuals with schizophrenia, reduced VMPFC GMV is specifically associated with deficits using ToM skills to enhance social relationships.

Impact of gray matter reductions on theory of mind abilities in patients with schizophrenia

“…A study on a faux pas task in schizophrenia found a correlation of behavioral ToM deficits with reductions of GM in the orbitofrontal region (Herold et al, 2009). A correlation with the ventromedial prefrontal cortex (vmPFC) was found in another study using the same task (Hooker, Bruce, Lincoln, Fisher, & Vinogradov, 2011). Volume reductions of the ACC (Fujiwara et al 2007) and the PFC (Hirao et al, 2008;Yamada et al, 2007) have been associated with poor performance in an emotion attribution task.…”

“…However, previous research that correlates ToM functions to GM regions has focused on more controlled, on-line mentalizing tasks (Hooker et al, 2011;Russell et al, 2000).…”

Empathy in schizophrenia: A meta-analysis of the Interpersonal Reactivity Index

“…This finding has been reported in several studies (e.g., see Andrews et al, 2013;Fujiwara et al, 2008;Gizewski et al, 2013;Montag et al, 2012a), but results across studies have yet to be metaanalyzed. Studies examining the fantasy component, on the other hand, report more disparate findings, with some finding significant deficits in schizophrenia samples (Derntl et al, 2012b;Fujiwara et al, 2008;Hooker et al, 2011;Lee et al, 2010) while others find fantasy abilities to be intact or trending toward greater levels in schizophrenia groups (Fischer-Shofty et al, 2013;Matsumoto et al, 2015;McCormick et al, 2012).…”

Neurobiologic Underpinnings of Social Cognition and Metacognition in Schizophrenia Spectrum Disorders

“…In the case of ToM, the MPFC, orbital frontal cortex (OFC), and ACC are the main frontal areas that have been implicated in mental state attribution. Poor performance on cognitive and affective ToM tasks have been associated with reduced gray matter volumes in ventromedial PFC and ventrolateral PFC, respectively (Hirao et al, 2008;Hooker et al, 2011). The studies that have investigated functional activity in patients during different ToM tasks have consistently revealed aberrant activation patterns in the MPFC, but at the same time reflecting contrasting degrees of activation, with some demonstrating a hypoactivation (Brunet et al, 2003;Lee et al, 2006;Walter et al, 2009) and others reporting hyperactivation (Andreasen et al, 2008;Lee et al, 2010;Lee et al, 2011;Pedersen et al, 2012).…”