Irony comprehension and context processing in schizophrenia during remission – A functional MRI study

Brain & Language 126 (2013) 231–242

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Irony comprehension and context processing in schizophrenia during remission – A functional MRI study E. Varga a,1, M. Simon a,1, T. Tényi a, Zs. Schnell c, A. Hajnal a, G. Orsi b,f, T. Dóczi d,f, S. Komoly e, J. Janszky b,e,f, R. Füredi a, E. Hamvas a, S. Fekete a, R. Herold a,⇑ a

Department of Psychiatry and Psychotherapy, Medical Faculty, University of Pécs, Hungary Neuro CT Diagnostic Center, Hungary Department of Linguistics and Institute of Psychology, University of Pécs, Hungary d Department of Neurosurgery, Medical Faculty, University of Pécs, Hungary e Department of Neurology, Medical Faculty, University of Pécs, Hungary f MTA-PTE Clinical Neuroscience MR Research Group, Hungary b c

a r t i c l e

i n f o

Article history: Accepted 26 May 2013 Available online 15 July 2013 Keywords: Irony Theory of Mind Schizophrenia Functional MRI Context processing

a b s t r a c t Schizophrenic patients have Theory of Mind (ToM) deficits even during remission, but it is yet unknown whether this could be influenced. We examined the neural correlates of irony understanding in schizophrenic patients, as an indicator of ToM capacity, and evaluated how linguistic help inserted into the context phase could affect irony comprehension. Schizophrenic patients in remission and healthy controls were subjected to event-related functional MRI scanning while performing irony, ‘irony with linguistic help’, and control tasks. Patients understood irony significantly worse than healthy controls. The patients showed stronger brain activity in the parietal and frontal areas in the early phase of irony task, however the healthy controls exhibited higher activation in frontal, temporal and parietal regions in the latter phase of the irony task. Interestingly the linguistic help not only improved the patients’ ToM performance, but it also evoked similar activation pattern to healthy controls. Ó 2013 Elsevier Inc. All rights reserved.

1. Introduction Patients with schizophrenia have deficits in their social cognition even during remission. Theory of Mind (ToM) is an important core component of social cognition. ToM (often referred to as ‘mentalizing’ capacity) is defined as the ability to attribute mental states (such as beliefs, knowledge, intentions) to the self and others (Dennett, 1989; Frith & Frith, 1999; Woodruff & Premack, 1978). In schizophrenia, ToM deficits significantly contribute to the poor overall community functioning (Brüne, 2005; Brüne, Abdel-Hamid, Lehmkämper, & Sonntag, 2007; Lysaker et al., 2005; Pinkham & Penn, 2006; Roncone et al., 2002; Sprong, Schothorst, Vos, Hox, & van Engeland, 2007); and they are superior to neurocognition or clinical symptoms in predicting social functioning (Pijnenborg et al., 2009). While ToM deficits are most pronounced during relapses, deficits of higher order ToM capacities, such as irony (Herold, Tényi, Lénárd, & Trixler, 2002), are apparent during the remission phase as well (Drury, Robinson, & Birchwood, ⇑ Corresponding author. Address: Department of Psychiatry and Psychotherapy, Medical School, University of Pécs, Rét utca 2., Pécs 7623, Hungary. Fax: +36 72 535951. E-mail address: [email protected] (R. Herold). 1 These authors contributed equally to this work. 0093-934X/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.bandl.2013.05.017

1998; Bora, Gökçen, Kayahan, & Veznedaroglu, 2008; Frith & Corcoran, 1996; Herold et al., 2002; Inoue et al., 2006; Janssen, Krabbendam, Jolles, & van Os, 2003). Irony involves implicit communicative intent, where the implicit meaning is the opposite of what is explicitly expressed. Irony comprehension is a non-literal language use that requires not only semantic and syntactic decoding, but also the decoding of the speaker’s non-linguistic inference (Sperber & Wilson, 1995; Sperber & Wilson, 2002). The integration of the literal meaning and social context (Sperber & Wilson, 1995) is essential for irony comprehension, in order to be able to represent the speaker’s mind, and to recognize that the actual intention expressed by the speaker is exactly contrary to the literal meaning of the ironic statement. Thus, irony understanding requires not only the correct interpretation of communicative intentions, but also the ability to construct a coherent narrative based on contradictory information. Several studies detected a connection between irony comprehension and ToM capacities (Frith & Frith, 2003; Happé, 1993; Wimmer, Gruber, & Perner, 1985; Winner, 1988). Schizophrenic patients demonstrated impaired capacities of irony processing associated with poor ToM skills (Gavilán & García-Albea, 2011; Sprong et al., 2007). Since irony is a complex linguistic phenomenon, impairment of irony processing might arise from language disturbances in schizophrenia. Pragmatic language skills

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(Tényi, Herold, Szili, & Trixler, 2002), discourse level processing (Marini et al., 2008), and comprehension of figurative language, among others, were found to be impaired in schizophrenia patients (Herold et al., 2002; Mo, Su, Chan, & Liu, 2008). However, (Gavilán & García-Albea, 2011) demonstrated that schizophrenic patients’ impaired understanding of non-literal language use, such as irony, is based on their ToM deficits. Furthermore, ToM deficits in schizophrenia patients were found to be caused by context processing difficulties, i.e. they are related to a difficulty in utilizing contextual data while assessing the mental states of others (Sarfati, HardyBaylé, Brunet, & Widlöcher, 1999; Schenkel, Spaulding, & Silverstein, 2005). In healthy individuals, brain imaging studies demonstrated that ToM engages a set of brain regions including the medial prefrontal cortex (MPFC) and adjacent paracingulate cortex and anterior cingulate, the temporo-parietal junction (TPJ), superior temporal sulcus (STS) and inferior parietal lobule (IPL), and posterior cingulate cortex/precuneus, as well as the temporal pole and the amygdala (Amodio & Frith, 2006; Ciaramidaro et al., 2007; Gallagher & Frith, 2003; Saxe, 2006; Saxe & Powell, 2006; Abu-Akel & Shamay-Tsoory, 2011; Frith & Frith, 2006). However, dysfunctional neuronal networks form the basis of ToM deficits in schizophrenia. Growing number of functional brain imaging studies applying various types of ToM tasks found that the poor ToM performance of schizophrenia patients is associated with an atypical brain activation pattern that includes both under- and over-activated brain areas. Increased activation was reported in such brain areas as the parietal cortex, middle and superior areas of the temporal cortex, certain prefrontal regions, the thalamus and cerebellar regions, while decreased activation was detected in the inferior areas of the lateral and medial temporal lobe, inferior occipital cortex, medial prefrontal cortex, and the lateral part of the prefrontal cortex near to the insula (Russell et al., 2000; Brunet, Sarfati, Hardy-Baylé, & Decety, 2003; Brüne et al., 2008; Andreasen, Calage, & O’Leary, 2008; Benedetti et al., 2009; Dollfus et al., 2008; Lee et al., 2006; Walter et al., 2009). A most recent study reported an altered time course of ToM processing in schizophrenia detected mainly in the temporopatietal region during the early stages of ToM processing (Vistoli, Brunet-Gouet, Lemoalle, Hardy-Baylé, & Passerieux, 2011). To date, only a few brain imaging studies have examined the neural basis of irony comprehension. During irony understanding, healthy subjects recruited some typical regions of the ToM network, such as the MPFC (Eviatar & Just, 2006; Shamay-Tsoory, Aharon-Peretz, & Levkovitz, 2007; Wakusawa et al., 2007; Wang, Lee, Sigman, & Dapretto, 2006b; Rapp et al., 2010), the temporal pole (Wakusawa et al., 2007; Wang et al., 2006b), IPL (Rapp et al., 2010), as well as the STS (Shibata, Toyomura, Itoh, & Abe, 2010; Uchiyama et al., 2006). However, so far no fMRI study has investigated the neural correlates of irony comprehension in schizophrenia. Functional MRI studies investigating the activity of the ToM network found that activation of the network fluctuates throughout the course of schizophrenia. Individuals with high psychosis proneness presented an over-activation in medial prefrontal areas in contrast to patients with schizophrenia, probably as a compensatory mechanism (Marjoram et al., 2006; Modinos, Renken, Shamay-Tsoory, Ormel, & Aleman, 2010). A recent fMRI study (Brüne et al., 2011) found that subjects at risk of psychosis exhibited a strong BOLD response in the prefrontal cortex, the posterior cingulate, and the temporo-parietal cortex, stronger than patients with manifest schizophrenia and, interestingly, even stronger than healthy controls. However, fluctuations in the activation of the mentalizing network (especially that of the MPFC) can also be detected during the later course of the illness progression (K.-H. Lee et al., 2006). A possible remediation of ToM deficits was reported in an early study with schizophrenic patients (Sarfati, Passerieux, &

Hardy-Baylé, 2000), as their ToM performance in non-verbal ToM tasks improved when verbal support was given. Wang, Lee, Sigman, and Dapretto (2007) observed that children with autism spectrum disorders activated similar brain regions as healthy controls, after they had been explicitly instructed to focus on available contextual social cues in the ironic scenarios (i.e. facial expression, tone voice). Similarly, linguistic cues improved the understanding }ri, Lukács, & Pléh, 2004). of irony in autism spectrum disorders (Gyo 1.1. Aim of the study Our aim was to investigate irony comprehension and the underlying brain activity in patients with schizophrenia during remission. To decrease the heterogeneity of the experimental group we decided to examine a clinically homogenous group of patients with paranoid type of schizophrenia. We examined various phases of irony comprehension separately (such as context phase, statement phase, as well as question on comprehension and answer phase). We also evaluated whether providing more explicit contextual information (by insertion of a short linguistic cue that described the speakers’ emotional state) could modify the patients’ performance in irony comprehension and the related brain activities. We hypothesized that patients with schizophrenia would perform worse and exhibit an abnormal brain activation pattern during irony comprehension. We assumed that linguistic cues depicting the speaker’s emotional state would improve patients’ performance, and modify the network activation. To model complex, real life situations, when irony is applied in conversational situations, we used short social scenarios presented as auditory stimuli in an event related design, and examined the differences in irony processing at various stages of the paradigm in patients and controls. 2. Material and methods 2.1. Participants The schizophrenia group (SG) comprised 21 (9 male and 12 female) patients with paranoid type of schizophrenia fulfilling the diagnostic criteria of DSM-IV. Patients were recruited from the psychosis unit of the Department of Psychiatry and Psychotherapy, University of Pécs. All of them were in remission according to the remission criteria of schizophrenia (Andreasen et al., 2005), namely the key items of Positive and Negative Syndrome Scale (delusions, unusual thought content, hallucinatory behavior, conceptual disorganization, mannerism/posturing, blunted affect, social withdrawal, lack of spontaneity) were mild or less (63) at least for 6 months before entering the study. Subjects were rated using the Schedule for Affective and Schizophrenic Disorders – Lifetime Version to confirm their diagnoses (Endicott & Spitzer, 1978). Patients with history of substance abuse, neurological disorder, and mental retardation or cognitive deficits unrelated with schizophrenia were excluded. Patients were on maintenance antipsychotic medication (amisulpiride n = 1, aripiprazole n = 1, clozapine n = 4, olanzapine n = 2, quetiapine n = 2, risperidone n = 2, sertindole n = 1, ziprazidone n = 1, flupentixol n = 3, haloperidol n = 1), except three who were on combination of quetiapine + flupenthixol, amisulpiride + haloperidol, and clozapine + risperidone. The control group (CG) consisted of 24 healthy individuals (10 male and 14 female) recruited from various sources. They were invited to the study by newspaper advertisements or were recruited from a local center for unemployed individuals. They had no record of psychiatric (personal or family) and neurological morbidity, presence of dependence on psychoactive substances (excluding caffeine and tobacco). The age, the socioeconomic and the occupational status were matched to the characteristics of the patients group (Table 1).

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The general intelligence was measured by the Hungarian version of Wechsler Adult Intelligence Scale (WAIS; (Wechsler, 2007)). The psychopathology was assessed using Positive and Negative Syndrome Scale (PANSS; (Kay & Opler, 1987)). As depression can have an impact on ToM performance (Lee, Harkness, Sabbagh, & Jacobson, 2005), depressive symptoms were also assessed with PANSS Depression subscale ((Lindenmayer, Grochowski, & Hyman, 1995) items: depression, guilt feelings, anxiety and somatic concern). A trained psychiatrist blinded with respect to the testing results rated the patients. All subjects were right-handed estimated by Edinburgh handedness inventory (Oldfield, 1971). A recent meta-analysis of ToM skills in patients with schizophrenia suggested that ToM is not influenced by gender (Sprong et al., 2007), so we used mixed gender groups, the male/ female proportion did not significantly differ in two experimental groups. After complete description of the study to the participants, written informed consent was obtained. The investigation was done following institutional guidelines. Ethical perspectives were established in accordance with the latest version of the Declaration of Helsinki. The Committee on Medical Ethics of University of Pécs approved this study design. 2.2. Stimuli We used three experimental conditions (see examples in Appendix): irony (I), irony with linguistic help (IH) and a control (C) condition. During scanning participants listened to short tasks (i.e. scenarios). We used auditory stimuli – as opposed to reading – to minimize individual differences in the processing of the stimuli. We presented 15 scenarios in each condition summing up to a total of 45 tasks. Each scenario was matched in syntactic structure, semantic complexity and length. In our study, we used a challenging paradigm, i.e. participants had to answer a Y/N question at the end of each task. All of them started with a two-sentence context phase followed by a statement and a yes/no comprehension question testing if the statement was correctly understood. ‘‘Yes’’ was the adequate response if the comment was true, and ‘‘no’’ if it was false. In irony condition (I) the tasks consisted of a short context phase describing a social situation with two participants, this was followed by an ironic statement, i.e. one of the participants’ ironic remark the literal meaning of which was the opposite of the intended one. In the irony with linguistic help condition (IH),

the context part contained one additional word as a linguistic help describing the speaker’s emotional state. The control condition (C) contained tasks based on physical causality, which entailed the representation of non-intentional causal links from the part of the participants. The length of each scenario across the different conditions (I, IH, C) and also the length of the different phases of the scenarios (context phase, statement phase and question–answer–phase) were strictly matched; hence there was no significant difference between the length of them. The average length was 14.62 s (1.01SD). It was 14.85 s (1.07SD) for the I, 14.62 s (0.98SD) for the IH and 14.38 s (1.03SD) for the C. The average duration of the context phase was 8.5 s (1.01SD). It was 8.9 s (1.78SD) in the I, 9.17 s (0.55SD) in the IH and 7.43 s (0.64SD) in the C. The duration of the statement phase was 3.24 s (0.68SD) in average and it was 2.97 s (0.3SD) in the I, 2.75 s (0.3SD) in the IH and 3.99 s (0.6SD) in the C. The average length of the question–answer part was 2.85 s (0.45SD). It was 2.9 s (0.43SD) in the I, 2.69 s (0.41SD) in the IH and 2.96 s (0.5SD) in the C. Participants had 5–7 s between the trials to answer the questions. All of them were able to respond within the given time. Otherwise they would have been excluded from the data analysis. Before scanning, participants were made familiar with examples of scenarios similar with those used during scanning and all demonstrated understanding of task requirements. Understanding was confirmed if the participants were able to complete a practicing series of tasks, and their reactions revealed appropriate use of task controls. Additionally, two of the authors also explored the participants verbally if they understood the tasks properly. 2.3. Activation paradigm We used an event-related design mainly because of the challenging paradigm (Friston et al., 1999). Also, we used an event-related design to minimize habituation effects. The activation paradigm was constructed according to the most recent literature on fMRI research of irony and ToM (Shibata et al. 2010; Uchiyama et al. 2006; Walter et al. 2009). Each task started with a context phase (1), followed by a 2–4 s (jittered) inter-stimulus interval. The ironic statement phase (2) appeared next, and finally a comprehensive question (3) followed. Between tasks, inter-trial intervals

Table 1 Demographic, data, and clinical variables, and task performances in schizophrenia and control groups. Variable

Gender (% female) Handedness (% right) Age (years) Education (years) Full Scale IQd PANSS total score PANSS Positive scale PANSS Negative scale PANSS Depression subscale PANSS General Psychopathology scale Age at onset (years)e Duration of illness (years) Response accuracy in tasks during scanningf Irony tasks Irony with linguistic help tasks Control tasks a b c d e f

Control group (n = 24)

Schizophrenia group (n = 21)

Percentage

Percentage

Mean ± SD (range)

63.63 100

13 (7–15) 14 (8–15) 14 (11–15)

0.3857a

57.14 100 33.96 ± 8.51 (23–55) 15.21 ± 2.4 (11–18) 119.29 ± 9.46 (97–133)

p Value

Mean ± SD (range)

37.95 ± 9.06 (21–55) 13.43 ± 2.36 (11–18) 106.04 ± 13.22 (81–127) 66.57 ± 13.83 (33–91) 13.81 ± 3.23 (7–21) 17.00 ± 5.43 (8–25) 9.05 ± 2.99 (4–15) 34.00 ± 7.03 (18–44) 26.76 ± 6.06 (17–39) 11.95 ± 8.45 (1–31) 15 (10–15) 15 (13–15) 15 (14–15)

Chi-squared test was used for comparing gender proportions. Independent sample t-test was used to compare group means. Statistically significant differences, two-tailed p < 0.05, uncorrected. IQ, general IQ obtained from the Wechsler Adult Intelligence Scale. Age of onset was defined as the presentation of psychotic symptoms in the context of functional decline. As there was no normal distribution in most of the datasets, the medians (ranges) of the number of correct answers are presented.

0.14b 0.02b,c 0.0003b,c

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of 5–7 s (jittered) were used (Fig. 1). After the question, yes/no judgments were given by pressing a button with the thumb (yes) or index finger (no), as quickly as possible. The third phase of the tasks (question–answer phase) continued until participants pressed the answer button. The experimental protocol was administered in one session of 45 tasks; the whole scanning time lasted approximately 30 min. During fMRI data analysis each phase of the tasks were analyzed as a separated event, so we had a total of 135 (=45  3) events. All of the 45 scenarios were presented in randomized order. We tried to model the real life where ironic remarks emerge unexpectedly in social situations. The order of the tasks was the same across subjects. Stimuli were presented with NordicNeuroLab fMRI Hardware (VisualSystem, AudioSystem, ResponseGrip, SyncBox). During scanning, participants’ Y/N responses were registered and saved; response accuracy was evaluated after scanning. Response accuracies were regarded as scores presenting the performance in irony (I score), irony with linguistic help (IH score), as well as control tasks (C score). 2.4. Functional MRI data acquisition Functional magnetic resonance (MR) imaging was performed on a 3T MR scanner (Siemens Magnetom Trio, Siemens AG, Erlangen, Germany) with 12-channel phased array TIM head coil for radio frequency reception. We used a standard EPI sequence to obtain functional MR images with the following parameters: TR (repetition time): 2000 ms; TE (echo time): 36 ms; voxel size: 2 mm  2 mm  3 mm, field of view: 192 mm  192 mm; 23 axial slices with a thickness of 4-mm (no gap), interleaved slice order to avoid crosstalk; 76° flip angle; 1360-Hz receiver bandwidth. We acquired 567 volumes per session. Anatomical images were acquired using a magnetization prepared rapid gradient echo (MPRAGE) sequence (TR: 1900 ms; TE: 3.44 ms, 9° flip angle, 180-Hz receiver bandwidth, 0.9  0.9  0.9 mm3 isotropic voxel size). 2.5. Demographic, clinical, and behavioral data analysis The Statistical Package for the Social Sciences (spss; SPSS Inc., Chicago, IL, USA (Nie, 1975)) version 15 for Windows was used for statistical analysis of demographic and clinical data, as well as full scale IQ and ToM task performance. We used independent sample t-test for parametric, as well as chi-squared test for non-parametric

data to determine between-group differences. As distributions proved not to be normal, Kruskall-Wallis one-way analysis of variance (ANOVA) by ranks was performed to compare group medians across the experimental conditions. Spearman’s rank correlation coefficients (q) were calculated to assess the relation between I, IH and C task scores and clinical symptom scores (PANSS total score and subscales in the SG), WAIS scores (IQ values), as well as demographic data. 2.6. Functional MRI data analysis Functional data sets were analyzed using FSL 4.1.3. (FMRIB’s Software Library, http://www.fmrib.ox.ac.uk/fsl). FMRI data processing was carried out using FEAT (FMRI Expert Analysis Tool) Version 5.98, part of FSL. The following pre-statistics processing was applied; nonbrain removal using BET (Brain Extraction Tool) (Smith, 2002) motion correction using MCFLIRT (Motion Correction using FMRIB’s Linear Image Registration Tool) (Jenkinson, Bannister, Brady, & Smith, 2002); spatial smoothing using a Gaussian kernel of FWHM 5 mm; grand-mean intensity normalization of the entire 4D dataset by a single multiplicative factor; highpass temporal filtering (cut-off at 50s). After preprocessing time-series statistical analysis was carried out using FILM (FMRIB’s Improved Linear Model) with local autocorrelation correction (Woolrich, Ripley, Brady, & Smith, 2001). Blood oxygenation level-dependent (BOLD) changes during the different phases of the tasks were modelled using separate regressors during context phase for I, C and IH conditions, during statement phase for I, C and IH conditions; as well as during question–answer phase for IH conditions. Questions (such as ‘‘where is the BOLD response to the ironic statement greater than the BOLD response to the control statement?’’) were answered by defining contrasts of regressors: context phase: I > C, IH > C, statement phase: I > C, IH > C, question–answer phase: I > C, IH > C. Note, that we defined I > C, as well as IH > C contrasts of regressors, in order to eliminate the confounding factor of basic semantic processing. Moreover, significant activations in the I > IH, as well as in the IH > I contrasts were also calculated during each phase of the tasks. The resulting first-level contrast images were entered into higherlevel analyses to test for differences in activation within- and between study groups. The single session data sets were registered into standard space using FLIRT (FMRIB’s Linear Image Registration Tool) (Jenkinson & Smith, 2001) (Jenkinson, Bannister, Brady, & Smith, 2002). For multivariate analysis, all functional scans were registered to the MNI152 standard space using the affine registration matrices derived by FLIRT. Higher-level analysis was carried out using FLAME (FMRIB’s Local Analysis of Mixed Effects) stage 1 and stage 2 (Beckmann, Jenkinson, & Smith, 2003) (Woolrich, Behrens, Beckmann, Jenkinson, & Smith, 2004) (Woolrich, 2008). Z (Gaussianised T/F) statistic images were threshold using clusters determined by Z > 2.3 and a (corrected) cluster significance threshold of P = 0.05 (Worsley, 2001). Images were rendered on a mean anatomical brain volume of all subjects in standard space for display purposes. As patients’ full scale IQ was found significantly lower than healthy subjects’ IQ (stat: t = 3.9, P < 0.001), our group-level general linear model included full scale IQ as an additional covariate modeling general intelligence scores for the schizophrenic and control groups (demeaned separately for each group). Thus, we modeled full-scale IQ scores as covariates of no interest to remove any potential contributions of general intelligence to the brain activations during task performance. 3. Results

Fig. 1. Forty-five task trials were presented in event-related functional magnetic resonance imaging paradigm. Each task trial started with a context part (1), followed by a 2–4 s (jittered) inter-stimulus interval, the (ironic) statement (2) appeared next, and finally a question (3) followed. Between trials an inter-trial interval of 5–7 s (jittered) was used.

Demographic data, WAIS scores, PANSS and response accuracy in the tasks are summarized in Table 1. There was no significant difference in age (t = 1.53, n.s. [not significant]) and gender

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(v2 = 0.3, df = 1, n.s.), but we found a statistically significant between-group difference in the years of education (t = 2.51, P = 0.02). Full scale IQ was significantly lower in the SG (t = 3.9, P < 0.001) (Table 1). 3.1. Behavioral results The CG performed significantly more accurate in the irony (I) condition (Kruskal–Wallis ANOVA, P < 0.0001, Kruskal–Wallis statistic = 37.14; Dunn’s Multiple Comparison Test: difference in rank sum = 39.82, P < 0.01; medianCG = 15, rangeCG = 10–15; medianSG = 13, rangeSG = 7–15) than the SG; however, this between-group difference disappeared in the IH, as well as in the C condition (Dunn’s Multiple Comparison Test: difference in rank sum = 29.98; and 26, respectively, n.s.; IH condition: medianCG = 15, rangeCG = 13–15, medianSG = 14, rangeSG = 8–15; C condition: medianCG = 15, rangeCG = 14–15, medianSG = 14, rangeSG = 11–15). In the SG, there was no significant correlation between PANSS scores and I and IH task scores, between the PANSS Positive scale and C task scores, and between the PANSS Depression subscale and C task scores. Interestingly, significant correlation was found between PANSS Negative scale and C task scores (q = 0.6765, P < 0.001), PANSS General Psychopathology scale and C task scores (q = 0.6427, P < 0.01) and between PANSS total scores and C task scores (q = 0.7297, P < 0.01). Moreover, in the SG, general IQ significantly correlated with I and IH task scores (q = 0.5108, P < 0.05, and q = 0.5584, P < 0.05, respectively); however, it was not significant after Bonferroni correction, and there was no correlation between IQ and C task scores. In the SG, demographic variables, the age at the onset of the illness, the number of the episodes, and the length of the illness did not correlate with the performance in I, IH, and C tasks. The only significant correlation was found between C task scores and years of education (q = 0.4864, P < 0.05). Table 2 presents Spearman’s correlation coefficients and significance levels in all comparisons. However, there was no significant correlation between demographic data and task performances in the CG: correlation between performance in I condition and IQ: q = 0.2415, n.s., age: q = 0.059, n.s., years of education: q = 0.155, n.s.; correlation between performance in IH condition and IQ: q = 0.0534, n.s., age: q = 0.2067, n.s. years of education: 0.143, n.s.; as well as correlation between performance in C condition and IQ: q = 0.0822, n.s., age: q = 0.219, n.s., years of education: q = 0.3613, n.s.

the I > C contrast. However, the SG recruited highly widespread areas encompassing not only the left IPL (reaching the TPJ), but also several prefrontal and temporo-parietal, as well as subcortical regions in the I > C contrast. In the IH > C contrast, the CG exhibited significant brain activations in the left TPJ (BA 39), in the posterior division of left middle temporal gyrus (MTG, BA 21), in the right cuneus (BA 18), in the left precuneus/ posterior cingulate cortex (PCC; BA 7/23), as well as in two lateral prefrontal regions: in the left superior frontal gyrus (SFG, BA 10), and in the pars triangularis of the left inferior frontal gyrus (IFG, BA 45). In the SG, the IH > C contrast revealed activations markedly similar to those in the control group: significant activations were registered in the temporooccipital part of the left MTG (BA 37), in the right cuneus (BA 17), in the left precuneus (BA 7), in the bilateral middle frontal gyrus (MFG, BA 6), in the left SFG (BA 10), and in the pars triangularis of the left IFG (BA 45). 3.2.1.2. Between-group comparisons (Table 3, Fig. 2A). Between group comparison of the I > C contrasts reveled significantly stronger activation in the SG in the left IPL (BA 39) and in the left IFG (pars opercularis, BA 44). Remarkably, comparison of the IH > C contrasts yielded no significant between-group differences. 3.2.2. Significant brain activations during the statement phase of the tasks (Table 4) 3.2.2.1. Within-group activations. In the I > C contrast, activity in the left temporal lobe with a local maximum in the left posterior sulcus temporalis superior (STS), in the medial prefrontal and in the medial parietal areas, in the dorsolateral PFC (DLPFC), and in the right MTG was found in the CG. The SG activated the left IFG (BA 45), right STG (involving the Heschl gyrus), as well as the left MTG, right superior temporal gyrus (STG, BA 22). In the IH > C contrast, the CG showed significantly greater brain activation in the left and the right STS (BA 21), in the left PCC/precuneus (BA 23/7), in the left thalamus, and in the left anterior MPFC (SFG, BA 10). In the SG, significant activations were seen in the left PCC/precuneus (BA 31/7), and in the right anterior MPFC (SFG, BA 10). 3.2.2.2. Between-group comparisons. (Table 4, Fig. 2B) of the I > C contrast: the CG showed significantly stronger activation in the right IPL (BA 40), in the right temporal pole (TP, BA 38), and in the right MFG (BA 10). Notably, there were no significant between-group differences when comparing the IH > C contrasts.

3.2. Functional MRI results 3.2.1. Significant brain activations during the context phase of the tasks (Table 3) 3.2.1.1. Within-group activations. The CG had significantly greater activation in the left temporo-parietal junction (TPJ, BA 39) in

3.2.3. Activation patterns during the question–answerphase of the tasks There were no significant within- or between-group differences between the I > C, as well as IH > C contrasts in the question–answer phase.

Table 2 Correlations between demographic data, clinical symptom scores and response accuracy in ToM tasks in schizophrenia group. Correlation coefficients (Spearman r) are presented. PANSS positive I IH C

0.0889 0.1652 0.1823

PANSS negative 0.0017 0.1597 0.6765***

PANSS general 0.1611 0.1645 0.6427**

PANSS depr 0.1642 0.2109 0.3463

PANSS total 0.0814 0.1121 0.7297***

IQ

Age *

0.5108 0.5584* 0.3038

0.2383 0.1652 0.1651

Edu 0.2195 0.2374 0.4864*

Age at onset 0.068 0.1963 0.1564

Episodes 0.2986 0.1763 0.3662

Duration of illness 0.2274 0.1892 0.3086

I, irony condition; IH, irony with help condition; C, control condition. PANSS positive, positive symptom score; PANSS negative, negative symptom score, PANSS general, general symptom score; PANSS total, total symptom score. IQ, general IQ measured with WAIS; Edu, years of education; Episodes, number of episodes. Age, age at onset, number of episodes, and duration of illness are expressed in years. Values in bold present correlations significant after Bonferroni correction. * p < 0.05, uncorrected. ** p < 0.01, uncorrected. *** p < 0.001, uncorrected.

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Table 3 Significant activations in patients with schizophrenia and in control subjects during the context phase of the tasks. During the context phase, we found significant between-group activations only in the schizophrenia group > control group contrast. x, y, z Coordinates are in millimeters, Montreal Neurological Institute (MNI) system. Selected local maxima are shown. Z (Gaussianised T/F) statistic images were threshold using clusters determined by Z > 2.3 and a (corrected) cluster significance threshold of P = 0.05. In case of the larger clusters (5000–12,000 voxels) we listed the output of the cluster breakdown as well.. Region (BA)

Control group Hem

I > C contrast activations SFG (9) SFG (10) IFG pars opercularis (44) IFG pars opercularis (44) Paracingulate Gyrus/ACC (32) Anterior Insula (48) SPL(7) TPJ (39) Precuneus (7) TPJ (39) IPL (39) IPL (40) TPJ (39) MTG tempoccipit. part (37) Putamen IH > C contrast activations SFG (10) MFG (6) IFG pars triangularis (45) MTG posterior division (21) MTG temporooccipit.part (37) TPJ (39) Cuneus (18) Cuneus (17) Precuneus (7)

L L L

x

Schizophrenia group y

64 2 64

z

50 58 50

Zmax

18 40 22

4.49 4.42 4.31

Voxel

Hem

x

y

Schizophrenia group > control group z

Zmax

Voxel

R L R

36 12 38

44 58 8

36 30 34

4.34 4.07 4.97

654 518 2028

L L R

4 30 28

18 24 54

48 0 56

4.87 5.46 4.47

1290 4450 2050

L L L R

38 60 44 18

34 48 60 10

38 10 14 8

5.25 5.09 5.02 4.22

12026

L L R L

14 38 48 56

56 2 6 22

30 52 42 8

4.66 4.07 4.34 4.25

1111 1462 1183 669

L

50

50

10

4.52

1885

R L

16 8

78 60

8 36

4.20 3.95

1550 467

Hem

x

L

44

L

40

y

z

Zmax

Voxel

8

28

4.92

2694

40

4.24

1269

9115

L

18

60

26

5.46

2641

L L

52 56

26 24

0 8

4.61 4.98

663 3016

L R

58 12

54 84

24 26

6.13 3.44

3094 690

L

4

58

36

4.33

565

50

1413

BA Brodmann area, Hem hemisphere, Voxel number of voxels, L left, R right, SFG Superior Frontal Gyrus, MFG Middle Frontal Gyrus, IFG Inferior Frontal Gyrus, ACC Anterior Cingulate Cortex, SPL Superior Parietal Lobule, IPL Inferior Parietal Lobule, TPJ Temporo-parietal Junction, MTG Middle Temporal Gyrus, STG Superior Temporal Gyrus.

In addition, we found no relevant brain activation in the I > IH and IH > I contrasts, as well as no between group differences of them. 4. Discussion In line with previous studies, schizophrenic patients performed significantly worse in the irony comprehension task than healthy controls (Gavilán & García-Albea, 2011; Herold et al., 2002; Mo et al., 2008; Sprong et al., 2007). During the sequential analysis of fMRI data, we found that the two groups had markedly different brain activation patterns. After the insertion of a short linguistic help, which had reduced the implicit information content of the context, response accuracy of schizophrenic patients improved, and the statistically significant differences between the groups disappeared. Notably, there were no significant differences in the BOLD responses between the groups, when linguistic help was added to the context. 4.1. BOLD response differences between the SG and the CG during the context phase (Irony versus Control task contrasts) The context phase of the irony tasks delineated the social scenario. During the context phase subjects had to take the characters’ perspective, acknowledge the implicit emotional state and communicative intent in the scenarios. During the context phase the CG presented activity in the left TPJ and precuneus. Activation of the TPJ/STS is one of the most widely replicated findings in functional brain imaging studies on ToM (Decety & Lamm, 2007; Saxe & Wexler, 2005). More specifically, the left TPJ has been found to be activated for understanding of communicative intentions and

seems to be specific to the attribution of shared social intention (Ciaramidaro et al., 2007; Saxe & Wexler, 2005; Walter et al., 2004). On the other hand, precuneus was also found to be a part of the ToM network, and associated with self-reflection and autobiographic memory (Cavanna & Trimble, 2006). All these are capacities of key importance to process a complex social context. Remarkably, processing of the complex social context of the scenarios appeared to be a substantial linguistic, cognitive, and emotional load to the schizophrenic patients, as the SG recruited highly widespread areas encompassing not only the left IPL (reaching the TPJ), but also several prefrontal and temporo-parietal, as well as subcortical regions in the I > C contrast. Between-group comparison: the SG exhibited significantly stronger activations in the left IFG (with a local maximum in pars opercularis, BA 44), and in the left IPL (with a local maximum in the anterior intraparietal sulcus [aIPS]) during the context phase. Increased activity of the left BA 44 was associated with schizotypal personality traits, with high risk for psychosis, as well as with established schizophrenia in various linguistic paradigms, such as metaphor and irony tasks (Kircher, Leube, Erb, Grodd, & Rapp, 2007; Rapp et al., 2010; Sabb et al., 2010). Nevertheless, unlike previous studies, we analyzed the context phase separately from the statement phase. Patients’ over-activation of the left IFG appeared during processing of contextual information, which can also be a related with schizophrenic patients’ impaired capacity for context processing (Hemsley, 2005), and could substantially account for schizophrenic patients’ difficulties in social cognition (Green, Uhlhaas, & Coltheart, 2005) that required the compensatory activation of the IFG. Moreover, both the IFG and the IPL/aIPS are considered to be parts of the human ‘mirror neuron system’ (MNS, (Molenberghs, Cunnington, & Mattingley, 2012; Rizzolatti & Craighero, 2004)

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Table 4 Significant brain activations in patients with schizophrenia and control subjects during the ironic statement phase of the task. During the context phase, we found significant between group-activations only in the schizophrenia group < control group contrast. x, y, z Coordinates are in millimeters, Montreal Neurological Institute (MNI) system. Selected local maxima are shown. Z (Gaussianised T/F) statistic images were threshold using clusters determined by Z > 2.3 and a (corrected) cluster significance threshold of P = 0.05. In case of the larger clusters (5000–12,000 voxels) we listed the output of the cluster breakdown as well. Region (BA)

Control group Hem

I > C contrast activations SFG (10) MFG (6) MFG (10) IFG pars triangularis (45) STG posterior division (22) STS (21) IFG pars orbitalis (47) STG (21) TPJ (39) MTG temporooccipital part (37) MTG posterior division (21) IFG pars triangularis (45) STG posterior division (22) Temporal pole (38) ACC (24) PCC/Precuneus (23/7) IPL (39) IPL (40) IH > C contrast activations SFG (10) STS (21) PCC/Precuneus (23/7) PCC/ Precuneus (31/7) Thalamus

L L

x

Schizophrenia group y

22 48

z 56 0

20 36

Zmax

Voxel

4.55 3.54

474 460

L L L L L

56 48 56 58 56

2 22 2 54 50

16 8 20 18 2

6.65 6.64 5.91 5.73 5.66

9510

R

52 54 50

26 32 32

8 8 0

6.30 5.07 4.80

5757

R L R

2 6 40

22 50 56

34 28 58

4.78 4.40 3.51

2271 2237 462

L R L L

4 56 54 8

56 8 2 48

24 12 20 34

4.31 4.40 5.49 3.85

1057 1767 4605 1046

L

0

20

8

4.06

574

Hem

x

y

Schizophrenia group
Zmax

Voxel

L R

54 58

32 36

8 8

4.08 4.23

947 1850

L

56

38

4

5.08

2363

R

4

62

20

3.36

399

L

8

56

26

5.46

1901

Hem

x

y

z

Zmax

Voxel

R

42

42

20

3.89

986

R

54

20

10

3.29

414

R

52

30

52

3.65

799

BA Brodmann area; L left, R right, Hem hemisphere, Voxel number of voxels, SFG Superior Frontal Gyrus, MFG Middle Frontal Gyrus, IFG Inferior Frontal Gyrus, SPL Superior Parietal Lobule, IPL Inferior Parietal Lobule, MTG Middle Temporal Gyrus, STG Superior Temporal Gyrus, STS Superior Temporal Sulcus, ACC Anterior Cigulate Cortex, PCC Posterior Cingulate Cortex.

and may contribute to mentalizing. However, the human MNS plays a role in the ‘lower-level’ mental state attribution, but not in the ‘higher-level’ inference making (Van Overwalle & Baetens, 2009). Considering the simulation theory of social cognition (Gallese, 2007), schizophrenic patients’ over-activation of the MNS regions can be related with the attempt to simulate complex social contexts based on their previous social experiences as an intrinsic, ‘automatic resonance to others’ (Gallese, 2007). However, simulation of goal directed actions is not sufficient for an appropriate ToM performance (U. Frith & Frith, 2001). Furthermore, our result is consistent with the strong functional lateralization of the inferior parietal lobule: the right IPL was found to be engaged in conscious representation of other’s mind, since first person perspective activated predominantly the left IPL (Decety & Chaminade, 2003; Ruby & Decety, 2001). In our present study, stronger between-group activation of the left IFG and the left IPL in the SG can be interpreted as a compensatory activity for vanquishing ToM and language deficits in schizophrenia. All these correspond with schizophrenic patients’ difficulties in context processing. 4.2. BOLD response differences between the SG and the CG during the ironic statement phase (Irony versus Control task contrasts) In line with previous neuroimaging studies on irony, understanding, we registered activations of several regions of the ToM network: we found a widespread left temporal lobe activation with a local maximum in the left posterior STS (Uchiyama et al., 2006) (Shibata et al., 2010), activation in the PCC/precuneus, in the ACC extending into the right paracingulate cortex and the anterior MPFC (BA 10) (Wang, Lee, Sigman, & Dapretto, 2006a, 2006b;

Shibata et al., 2010; Uchiyama et al., 2006; Wakusawa et al., 2007), as well as in the right IPL (Lauro, Tettamanti, Cappa, & Papagno, 2008; Rapp et al., 2010; Stringaris, Medford, Giampietro, Brammer, & David, 2007) in the CG. The CG also recruited the anterior part of the left DLPFC (BA10) which is associated with working memory and episodic memory retrieval (Gilbert et al., 2006). Similarly to other studies on understanding irony and other types of non-literal language use, the left premotor cortex (BA 6, (Ahrens et al., 2007; Boulenger, Hauk, & Pulvermüller, 2009; Shibata et al., 2010)) was also activated. Unlike previous studies on irony understanding, we used auditory stimuli in the fMRI paradigm: a professional actress read the scenarios for recording. The auditory stimuli amplified the impact of prosody and added a special realistic feature to the experimental situation. Consequently, both the ToM network and the regions processing non-verbal communication cues were activated beside areas of language processing. Also, right MTG (BA 21) activations were found in several studies on irony comprehension, which corresponds with the crucial role of this region in non-literal language processing (Eviatar & Just, 2006; Wakusawa et al., 2007; Wang et al., 2006b), as well as in encoding the prosodic information (Friederici, 2011). While the CG presented activations mainly in ToM related brain areas, and in regions associated with the non-literal language processing, the SG activated regions associated with linguistic and auditory processing. In the between-group comparison, the CG exhibited significantly greater BOLD responses than the SG in three brain areas, right anterior DLPFC, right TP, and right IPL, during the ironic statement phase. Considering schizophrenic patients’ weaker activation of the anterior DLPFC, we can speculate that this between-group difference may be a part of the ‘‘hyporfontality’’ phenomenon in

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schizophrenia (Weinberger & Berman, 1996). The anterior DLPFC (MFG, BA 10) has been associated with working memory and episodic memory retrieval (Gilbert et al., 2006), but in an fMRI study of semantic integration in schizophrenia patients failed to recruit the right anterior DLPFC during processing abstract and incongruous sentences (Kuperberg, West, Lakshmanan, & Goff, 2008). Moreover, an fMRI study reported that schizophrenic patients’ context processing difficulties were specifically associated with their MFG dysfunction (MacDonald et al., 2005). The activation of the temporal pole (BA 38) was reported not only in several functional brain imaging studies on irony comprehension in healthy individuals (Uchiyama et al., 2006; Wakusawa et al., 2007; Wang et al., 2006b), but it is also a region that stores ‘‘social scripts’’, which are built up through past experiences of the self and can be applied as fast solutions in social situations (Grabowski et al., 2001; Olson, Plotzker, & Ezzyat, 2007). Activation of the TP, especially in the right hemisphere, has also been linked with social semantic processing and formation of narrative (Ross & Olson, 2010). In schizophrenic patients, a significant grey matter reduction of TP was reported (Kasai et al., 2003; Wright et al., 1999). A recent fMRI study in patients with schizophrenia revealed reduced activation in the right TP during cognitive empathy tasks compared with controls (S. J. Lee et al., 2010). In a voxel based morphometric study, schizophrenic patients’ reduced grey matter density in the right TP area was associated with ToM deficits (emotional ToM: Faux pas task; (Herold et al., 2009)). The right IPL is a part of the right fronto-temporal network, and plays an essential role in self-other discrimination (Decety & Sommerville, 2003; Uddin, Molnar-Szakacs, Zaidel, & Iacoboni, 2006). IPL abnormalities are one of the most frequently replicated findings in schizophrenia; and IPL is believed to be an important part of the schizophrenia network disorder. At least 4 main functional deficits have been associated with the IPL: executive functions, sensory integration, body image, and concept of self (see (Torrey, 2007) for review), among which the latter seems to be the most relevant in irony understanding. Since impairment of the concept of the self has not only an impact on the self-awareness, it is

related with the person’s ability to infer mental states in others. The role of the IPL is widely reported in the ToM literature (Brüne & Brüne-Cohrs, 2006) and IPL dysfunctions related to difficulties in self-other distinction have been often found to be related with social brain impairments in schizophrenia (see (Brunet-Gouet & Decety, 2006) for a review). In conclusion, while the CG showed widespread activations in several ToM related areas, and also language areas during ironic statement, the SG’s activation pattern was poorer and localized mainly in brain areas associated with semantic processing. Between-group differences of brain activation during ironic statement are in line with studies on structural and functional brain imaging studies in schizophrenia and ToM. 4.3. The effect of linguistic help (Irony with Help versus Control task contrasts) In the IH condition, a short linguistic cue made explicit the speaker’s emotional state during the context which decreased the context processing demand of the task. Due to this, neither the response accuracy, nor the registered BOLD responses differed statistically between the groups. Similarly to the I > C contrasts, a significant activation of the left TPJ and precuneus could be found in the CG. However, due to the inserted linguistic help the SG also activated these regions. Furthermore, we suggest that linguistic help served as a cue activating higher-order cognitive functions such as working memory (DLPFC activation) in both groups. Moreover, the CG showed an additional activation in the left MTG, while the SG had right and left MFG activations. BOLD responses in the left IFG (BA 45) and in the left MTG (BA 21) are typically detected during the comprehension of linguistic cues (Giora, Zaidel, Soroker, Batori, & Kasher, 2000; ShamayTsoory & Aharon-Peretz, 2007; Uchiyama et al., 2006; Wang et al., 2006b). Importantly, during the statement phase of the IH tasks both group activated two key regions of the ToM network (the anterior MPFC (BA 10) and the PCC/precuneus (BA 23/7)). In addition, the

Fig. 2. Panel A: Context phase, between-group comparison of I > C contrasts. Brain areas show significantly greater activity in schizophrenic patients than in healthy control subjects. Panel B: Ironic statement phase, between-group comparison of I > C contrasts. Brain areas show significantly greater activity in healthy control subjects than in schizophrenic patients. Z statistic images were threshold using clusters determined by Z > 2.3 and a corrected cluster significance threshold of P = 0.05. Color bars indicate z scores. L left, R right, IFG inferior frontal gyrus, IPLinferior parietal lobule, MFG middle frontal gyrus, TP temporal pole.

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CG showed activations in the right STS, in the left MTG (BA 21) as well as in the left thalamus. Especially the anterior MPFC has been proposed as a key region of mentalizing (Amodio & Frith, 2006; Frith & Frith, 2003), but also the PCC/ precuneus is often found to be activated in ToM studies (Abu-Akel & Shamay-Tsoory, 2011; Cavanna & Trimble, 2006), and regarded as a functional integration zone, where mentalizing and autobiographic memory interact (Spreng & Mar, 2012). The most unique finding of the present study was the SG’s engagement of the mentalizing network during the statement phase in the IH vs C contrasts. Our result is in line with a recent fMRI study investigating children and adolescents with autism spectrum disorder while using short scenarios with irony (Wang et al., 2007). In that study, the explicit intention to attend to relevant social cues (i.e. facial expression, tone voice) resulted in normalization of MPFC activity in children with autism spectrum disorder. We can presume that after having listened to the explicit linguistic help in the context, not only the CG but also the SG was able to mobilize the ToM network in order to adequately represent the speakers’ intention, and understand irony. Finally, we should consider how our results can be utilized in trainings aiming to improve the social cognitive and interactive skills of schizophrenic patients. Research on psychosocial interventions prooved that patients with schizophrenia are able to improve their ToM strategies (Horan et al., 2008; Kayser, Sarfati, Besche, & Hardy-Baylé, 2006; Penn et al., 2005; Roberts & Penn, 2009; Roncone et al., 2004). The Social Cognition an Interaction Training (SCIT) developed by Penn, Roberts, Combs, and Sterne (2007) is probably the most evidence based training program (see Bartholomeusz & Allott, 2012 for a recent review). Furthermore, the Emotion and ToM Imitation Training (ETIT, Mazza et al., 2010) has been found to improve functional outcome in schizophrenia as well. ETIT also increased electroactivity of medial frontal areas (Mazza et al., 2010). Interestingly, both SCIT and ETIT involve a range of approaches (i.e. coaching, role play, etc.), but both of them begin with emotion processing training (i.e. defining emotions, emotion mimicry), and continue with other social cognitive and interaction skills. The efficacy of trainings such as those mentioned above might correspond with our results, as we found that making explicit the speaker’s emotional state (by means of a short linguistic cue) can substantially improve schizophrenic patients’ performance during irony understanding. Thus, the short linguistic help inserted to the context improved the SG’s task performance (i.e. response accuracy). Also, between group differences in brain activations observed in I > C contrasts disappeared in IH > C contrasts.

4.4. Limitations of the study The interpretation of our data is limited by the relatively small number of subjects, the significant difference in IQ between the groups, and by the heterogeneity of the antipsychotic treatment. Full scale IQ was significantly lower in the SG, than in the CG. We found positive correlation between the patients IQ and their performance in the irony and in the irony with linguistic help conditions. Some authors regard ToM deficits in schizophrenia being independent of general intelligence (Harrington, Siegert, & McClure, 2012; Mo et al., 2008; Schenkel et al., 2005), others (Bora, Eryavuz, Kayahan, Sungu, & Veznedaroglu, 2006; Brüne, 2002) found that IQ have an impact on ToM performance. A re-

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cent meta-analysis (Bora, Yücel, & Pantelis, 2009) concluded that deficits of the general intelligence contribute to ToM impairments only in the remission phase of the schizophrenic illness. Although this question is still under debate, our results and previous data (Brüne, 2002; Herold et al., 2009; Pickup & Frith, 2001) suggest that patients with higher IQ might be able to understand irony better and utilize the linguistic help more successfully because they can rely more successfully on an IQ-dependent problem solving skills and analogical reasoning (Andreasen, Calage, & O’Leary, 2008). On the other hand we should also mention that our patients’ IQ values were somewhat higher than in previous studies in ToM research, which could be the result of the matching procedure of the patient selection. However, similarly to previous studies with schizophrenic patients (Andreasen, Calage, & O’Leary, 2008; Brüne et al., 2008; Russell et al., 2000), where the control groups were not matched with the schizophrenia groups in terms of general intelligence either, deemed IQ was included in the design matrix as an additional regressor for each group. Moreover, significant negative correlations were found between patients’ performance in control tasks and PANSS total score, negative symptom score as well as general symptom score. No association with the performance in I or IH tasks was detected. In addition, we investigated chronically ill schizophrenic patients who were recruited from outpatient community services; Patients were not hospitalized at the time of the scanning, and scored relatively low on each symptom scale. The average PANSS score was >2 only in negative symptom scale, but it did not reach 3. This suggests that our sample consisted of patients with a slight but not significant predominance of negative symptoms. However we did not analyze the relationship between symptom scores and brain activation because the ToM performance did not correlate with the symptoms. Nevertheless, we could not rule out the possible effect of hypofrontality associated with negative symptoms in schizophrenia (Weinberger & Berman, 1996). On the other hand, patients were carefully selected and taken exclusively from the paranoid schizophrenia subgroup. All schizophrenic patients in our study received antipsychotic medication. It was not the aim of the study to investigate the effect of medication. The high diversity of the applied antipsychotics made statistically difficult to create homogenous groups. However, Mo et al. (2008) reported no significant correlation between antipsychotic dose and schizophrenic patients’ performance in irony and metaphor understanding. Nevertheless, replication of this study with a higher number of participants, who are more homogeneously medicated, and have more homogenous symptoms, could further validate the present results. Role of funding source This research was supported by ‘‘Save what can be saved’’ – Applied neurological research using high-field magnetic resonance imaging: Grant of the EGT and Norwegian Financing mechanism (0114/NA/2008-3/ÖP-9 VSZ). Tamas Tényi was supported by the ‘‘Developing the South-Transdanubian Regional University Competitiveness’’ Grant (SROP-4.2.1.B-10/2/KONV-2010-0002). Acknowledgments The authors would also like to express their gratitude to Boldizsar Czeh for his constructive comments on the manuscript.

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Appendix A. Examples

Irony condition (I): 1. Context phase: Joe went home from school and told his father that he had failed his maths test. His father said: Ironic statement phase: Oh boy, you just made my day! Question–answer phase: Did Joe’s father think that Joe made his day? 2. Context phase: Tom and Ben are having an argument. Ben does not listen to Tom’s opinion at all. Tom says: Ironic statement phase: I am so glad you always listen to my opinion. Question–answer phase: Does Tom think that Ben does not listen to his opinion? 3. Context phase: John suggests Steven that they should go to the movie theatre. Steve brings the decision to go rather late, and they eventually arrive late for the film. John says: Ironic statement phase: Steve, you are very good at bringing decisions. Question–answer phase: Does John think that Steve is not good at bringing decisions? Irony with linguistic help condition (IH): 1. Context phase: Peter helps Tom repair his car. Peter takes out a screw and it incidentally falls into the service tank. Tom angrily remarks: Ironic statement phase: You really are a great help! Question–answer phase: Does Tom think that Peter isn’t much help? 2. Context phase: Rose orders a cup of coffee in a restaurant. The waiter brings out her coffee, but near the table he accidentally stumbles, and pours it in Rose. Rose disappointedly remarks: Ironic statement phase: I am grateful for the coffee! Question–answer phase: Does Rose think she is grateful for the coffee? 3. Context phase: Sarah asks Paul to cut her hair. Paul cuts it too short on one side. Sarah furiously remarks: Ironic statement phase: You did a pretty haircut! Question–answer phase: Does Sarah think that Paul did not do a pretty haircut? Control condition (C): 1. Context phase: It is raining all day. There is so much water flowing down the water-spout that it floods the whole yard. Statement phase: The huge amount of water renders the entire yard heavily muddy. Question–answer phase: Does the yard stay dry after the daylong rain? 2. Context phase: There are peaches and apricots on the fruit trees in the garden. Suddenly a hail comes so strong that it makes all the fruits fall on the ground. Statement phase: By the time it stops, there are hardly any fruit left on the trees. Question–answer phase: Is there a lot of fruit on the trees after the storm? 3. Context phase: As the wind blows, a yellow and a red balloon float in the air. The red flies way up high, but the yellow hits a thorny bush. Statement phase: It falls on the bush so hard that it bursts. Question–answer phase: Does the yellow balloon fall on the thorny bush so hard that it bursts?

Appendix B. Supplementary material Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.bandl.2013.05. 017.

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