Functional deficit of the medial prefrontal cortex during emotional sentence attribution in schizophrenia

Abstract

Background

Functional brain imaging research has already demonstrated that patients with schizophrenia had difficulties with emotion processing, namely in facial emotion perception and emotional prosody. However, the moderating effect of social context and the boundary of perceptual categories of emotion attribution remain unclear. This study investigated the neural bases of emotional sentence attribution in schizophrenia.

Methods

Twenty-one schizophrenia patients and 25 healthy subjects underwent an event-related functional magnetic resonance imaging paradigm including two tasks: one to classify sentences according to their emotional content, and the other to classify neutral sentences according to their grammatical person.

Results

First, patients showed longer response times as compared to controls only during the emotion attribution task. Second, patients with schizophrenia showed reduction of activation in bilateral auditory areas irrespective of the presence of emotions. Lastly, during emotional sentences attribution, patients displayed less activation than controls in the medial prefrontal cortex (mPFC).

Conclusions

We suggest that the functional abnormality observed in the mPFC during the emotion attribution task could provide a biological basis for social cognition deficits in patients with schizophrenia.

Introduction

In the last decade a growing body of research demonstrated deficits in social information processing in schizophrenia (Pinkham et al., 2003, Brunet-Gouet and Decety, 2006, Green et al., 2008, Wible, 2012, Green et al., 2015), contributing to impaired verbal communication and social interactions. The mental operations underlying social interactions include processes involved in perceiving, interpreting, and generating responses to the intentions and emotions of other persons (Adolphs, 2003). One of the key aspects of successful social interactions lies in the capacity to accurately recognise the often-subtle emotional cues that are expressed during conversations. Speech can convey emotions through different channels: linguistic and pragmatic information. Linguistic processing involves the semantic integration of words and sentences in order to reconstruct a coherent message, and also relies on phonological and syntactic analysis. The pragmatic information concerns the processing of gestures, facial expressions, and emotional prosody (the melody of speech) that accompanies the oral expression of language. Moreover, schizophrenia is characterized by both emotional and language abnormalities.

Functional brain imaging researches on emotional processing in schizophrenia have already been investigated, with a majority of experiments using basic facial emotion recognition paradigms. Compared with healthy controls, patients had difficulties with emotion perception and showed lower activation in the bilateral amygdala, parahippocampal gyrus and fusiform gyrus, right superior frontal gyrus and right lentiform nucleus (Hempel et al., 2003, Holt et al., 2005, Das et al., 2007, Gur et al., 2007, Li et al., 2010, Satterthwaite et al., 2010, Anticevic et al., 2012). Facial emotion perception is an important domain of social cognition (Green et al., 2005) and impairment in perceiving facial emotion contributes to problems in interpersonal relationships among patients with schizophrenia (Poole et al., 2000). Besides, another research focused on speech prosody recognition (Grandjean et al., 2006). Patients with schizophrenia are often impaired in their capacity to extract non-verbal emotional information from language (Bach et al., 2009b, Bach et al., 2009a, Edwards et al., 2002, Kucharska-Pietura et al., 2005, Leitman et al., 2005, Mitchell et al., 2004, Brazo et al., 2014).

However few studies have investigated the neural bases of emotion recognition during emotional speech attribution in schizophrenia (Mitchell et al., 2004, Regenbogen et al., 2015). Mitchell et al. (2004) demonstrated that patients with schizophrenia activated the left insula to a greater extent than did healthy controls during a sentence auditory task of attending to emotional prosody. The other functional study evaluated the neural responses of emotional expression using video clips and showed aberrant activation in regions implicated in semantic processing in schizophrenia patients during the neutral speech content (Regenbogen et al., 2015). These studies suggested abnormal neural patterns of language areas during emotional speech and need further investigations.

Besides emotional processing abnormalities, disturbance of language processes has long been reported in schizophrenia. Functional brain imaging studies have demonstrated reduced left and increased right prefrontal cortex (PFC) activation during language tasks in schizophrenia patients, relative to healthy controls (Kircher et al., 2002, Boksman et al., 2005, Dollfus et al., 2005, Dollfus et al., 2008) though some have demonstrated only increased right hemisphere activation with no difference in the activation of the left hemisphere (Sommer et al., 2001). Abnormalities were also found in the brain network involved in semantic processing (Kubicki et al., 2003). These semantic processing deficits do not seem to be dependent on grammatical category of a word, such as nouns, verbs, or adjectives (Rossell and Batty, 2008). However, it is less clear how individuals with schizophrenia process verbal material with emotional valence.

Moreover, abundant research has shown that patients with schizophrenia have specific difficulty in inferring what others intend, think, or pretend (Green et al., 2008) and this theory of mind (ToM) impairment probably influences the way schizophrenia patients use language and interpret speech (Brune, 2005). Functional brain imaging research on ToM abilities evidenced lower activation in patients with schizophrenia localized in the cingulate and insular cortex, in the medial PFC (mPFC), and in the left middle/inferior frontal gyrus (Russell et al., 2000, Brunet et al., 2003, Lee et al., 2006). The relationship between emotion processing and ToM has recently been investigated, with some data indicating that these are closely interrelated phenomena (Ochsner, 2008). Decoding of emotions during language communication is thus intermingled with ToM processing.

In this study, the neural bases of emotional sentence attribution were assessed in schizophrenia patients. An auditory task, which has already been validated in healthy volunteers (Hervé et al., 2012), investigated the functional network of emotional processing including verbal information and mental state inference. We hypothesized a functional deficit in a key region, the median prefrontal cortex (mPFC), involved in multiple cognitive processes such as language comprehension, emotion and ToM (Hervé et al., 2012, Beaucousin et al., 2007), in patients with schizophrenia compared to healthy controls during the emotional sentence attribution.