Two-sample t-test comparing insula activation in patients and controls.

<p>In comparison with controls, schizophrenia patients show reduced bilateral insula activation in response to masked facial expressions of disgust (Axial view, z = 1, color bar Z-score). Visualization was performed using a standard anatomical template from the MRIcron toolbox (<a href="http://www.mricro.com/mricron" target="_blank">www.mricro.com/mricron</a>).</p

Social Alienation in Schizophrenia Patients: Association with Insula Responsiveness to Facial Expressions of Disgust

<div><p>Introduction</p><p>Among the functional neuroimaging studies on emotional face processing in schizophrenia, few have used paradigms with facial expressions of disgust. In this study, we investigated whether schizophrenia patients show less insula activation to macro-expressions (overt, clearly visible expressions) and micro-expressions (covert, very brief expressions) of disgust than healthy controls. Furthermore, departing from the assumption that disgust faces signal social rejection, we examined whether perceptual sensitivity to disgust is related to social alienation in patients and controls. We hypothesized that high insula responsiveness to facial disgust predicts social alienation.</p><p>Methods</p><p>We used functional magnetic resonance imaging to measure insula activation in 36 schizophrenia patients and 40 healthy controls. During scanning, subjects passively viewed covert and overt presentations of disgust and neutral faces. To measure social alienation, a social loneliness scale and an agreeableness scale were administered.</p><p>Results</p><p>Schizophrenia patients exhibited reduced insula activation in response to covert facial expressions of disgust. With respect to macro-expressions of disgust, no between-group differences emerged. In patients, insula responsiveness to covert faces of disgust was positively correlated with social loneliness. Furthermore, patients' insula responsiveness to covert and overt faces of disgust was negatively correlated with agreeableness. In controls, insula responsiveness to covert expressions of disgust correlated negatively with agreeableness.</p><p>Discussion</p><p>Schizophrenia patients show reduced insula responsiveness to micro-expressions but not macro-expressions of disgust compared to healthy controls. In patients, low agreeableness was associated with stronger insula response to micro- and macro-expressions of disgust. Patients with a strong tendency to feel uncomfortable with social interactions appear to be characterized by a high sensitivity for facial expression signaling social rejection. Given the associations of insula responsiveness to covert disgust expression with low agreeableness in healthy individuals, insula responsiveness to expressions of disgust might be in general a neural marker of the personality trait of agreeableness.</p></div

Correlation between insula activation and social loneliness in patients.

<p>In schizophrenia patients, right insula responsiveness to masked expressions of disgust is positively correlated with social loneliness (Axial view, z = 0, color bar correlation coefficient r). The scatter plot displays the correlation between the social loneliness scale scores and the mean cluster activation values (r = 0.45). Visualization was performed using a standard anatomical template from the MRIcron toolbox (<a href="http://www.mricro.com/mricron" target="_blank">www.mricro.com/mricron</a>).</p

Sociodemographic and clinical data.

<p>Sociodemographic and clinical data of patients and controls (patients: N = 36; controls: N = 40) and clinical data of patients; mean ± SE (range); p: significance of two sample t-test/chi-square-test between patients and controls.</p><p>¹ Education years of parent with the highest degree. Data missing for one patient.</p><p>² Assessed with the Mehrfachwahl-Wortschatz-Intelligenztest (MWT-B <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0085014#pone.0085014-Lehrl1" target="_blank">[36]</a>).</p><p>³ All SANS and SAPS scores represent global ratings of the symptom.</p

Correlation between insula activation and agreeableness in patients.

<p>In schizophrenia patients, bilateral insula responsiveness to masked expressions of disgust is negatively correlated with agreeableness (Axial view, z = 0, color bar correlation coefficient r). The scatter plot displays the correlation between the agreeableness scale scores and the mean cluster activation values for the left insula (r = −0.55). Visualization was performed using a standard anatomical template from the MRIcron toolbox (<a href="http://www.mricro.com/mricron" target="_blank">www.mricro.com/mricron</a>).</p

Illustration of paradigm.

<p>In the micro-expressions sequence displayed here, emotional expressions were masked by neutral expressions. In the macro-expressions sequence, facial expressions were presented for 533 ms. Both sequences consisted of alternating blocks of face stimuli and no-face stimuli. In each block, facial stimuli were presented in a randomized order.</p

Boxplot illustrating the distribution of left insula activation values in patients and controls.

<p>Schizophrenia patients show overall reduced insula activation levels in comparison with the control group. The distribution is similar for the right insula.</p

Masked expressions sequence: task effects on bilateral insula and amygdala activation.

<p>Task effects of the masked expressions paradigm on insula and amygdala activation in patients and controls as assessed by the effects-of-interest F-contrast (Family wise error correction: p = 0.05; k = 50 voxels).</p