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Background It has been theorized that hallucinations, a common symptom of schizophrenia, are caused by failures in reality monitoring. The paracingulate sulcus (PCS) has been implicated as a brain structure supporting reality monitoring with the absence or shorter length of PCS associated with an occurrence of hallucinations in schizophrenia. The absence or shorter length of PCS has been associated with an occurrence of hallucinations. There are inconsistent findings in the literature regarding the role of the asymmetry of this structure for hallucinations. Here, we investigated the length of the PCS and cortical thickness of surrounding structures in patients with a lifetime history of auditory verbal hallucinations (AVH). Design Seventy-seven patients and twenty-eight healthy controls (HC) underwent an anatomical MRI scan. PCS length and cortical thickness were estimated using Mango brain visualization and FreeSurfer, respectively. Patients with AVH (n = 45) and patients without AVH were compared (n = 32) to the controls. Results PCS length significantly differed between HC and patient groups (F(2,102) = 3.57, P = .032) in the left but not in the right sulcus. We found significantly longer PCS between HC and AVH group but no difference between patient groups. Similarly, we found significant thinning of cortical structures including structures surrounding anterior parts of PCS between HC and patients either in general or per group, but no significant differences were observed between patient groups. Conclusions PCS length in the left hemisphere is shorter in schizophrenia patients with hallucinations as compared to HC subjects. The patient group without hallucinations was in between those 2 groups. Cortical thickness of neighboring areas of PCS is diminished in patient groups relative to the healthy comparison subjects. The role of lateralization and functional involvement of the PCS region in processes underlying hallucinations, such as reality monitoring, needs further clarification.

Background Apathy is a quantitative reduction in motivation and goal-directed behaviors, not only observed in neuropsychiatric disorders, but also present in healthy populations. Although brain abnormalities associated with apathy in clinical disorders have been studied, the organization of brain networks in healthy individuals has yet to be identified. Method We examined properties of intrinsic brain networks in healthy individuals with varied levels of apathy. By using functional magnetic resonance imaging in combination with graph theory analysis and dynamic causal modeling analysis, we tested communications among nodes and modules as well as effective connectivity among brain networks. Results We found that the average participation coefficient of the subcortical network, especially the amygdala, was lower in individuals with high than low apathy. Importantly, we observed weaker effective connectivity fromthe hippocampus and parahippocampal gyrus to the amygdala, and from the amygdala to the parahippocampal gyrus and medial frontal cortex in individuals with apathy. Conclusion These findings suggest that individuals with high apathy exhibit aberrant communication within the cortical-to-subcortical network, characterized by differences in amygdala-related effective connectivity. Our work sheds light on the neural basis of apathy in subclinical populations and may have implications for understanding the development of clinical conditions that feature apathy.

Anxiety-related illnesses are highly prevalent in human society. Being able to identify neurobiological markers signaling high trait anxiety could aid the assessment of individuals with high risk for mental illness. Here, we applied connectome-based predictive modeling (CPM) to whole-brain resting-state functional connectivity (rsFC) data to predict the degree of anxiety in 76 healthy participants. Using a computational “lesion” method in CPM, we then examined the weights of the identified main brain areas as well as their connectivity. Results showed that the CPM could predict individual anxiety from whole-brain rsFC, especially from limbic areas-whole brain and prefrontal cortex-whole brain. The prediction power of the model significantly decreased from (simulated) lesions of limbic areas, lesions of the connectivity within the limbic system, and lesions of the connectivity between limbic regions and the prefrontal cortex.Although the same model also predicted depression, anxiety-specific networks could be identified independently, centered at the prefrontal cortex. These findings highlight the important role of the limbic system and the prefrontal cortex in the prediction of anxiety. Our work provides evidence for the usefulness of connectome-based modeling of rsFC in predicting individual personality differences and indicates its potential for identifying personality structures at risk of developing psychopathology.

Background Proton Magnetic Resonance Spectroscopy (1H-MRS) studies indicate that altered brain glutamate signalling contributes to the pathophysiology of schizophrenia and treatment response. However it is unclear whether clinical and demographic factors affect glutamate levels in the brain. Here we aim to determine the effects of age, antipsychotic medication, symptom severity and duration of illness on levels of glutamatergic metabolites and creatine, in a large multicentre dataset of patients with schizophrenia and healthy volunteers. Methods Authors of 1H-MRS studies in schizophrenia were contacted between January 2014 and August 2017 and asked to provide individual glutamate, Glx, glutamine and creatine values alongside demographic and clinical data. Forty-five 1H-MRS studies contributed data to the multicentre dataset, and data was available from 1194 healthy volunteers and 1526 patients with schizophrenia and those at high risk of developing psychosis. Results Age was associated with reduced glutamate levels in the medial frontal cortex, but the effect of aging was not accelerated in patients compared to healthy volunteers. Higher glutamate and Glx in the medial frontal and temporal lobes were associated with more severe symptoms, whereas Glx in subcortical regions, specifically the thalamus and striatum, did not relate to symptom severity. In the medial frontal cortex and striatum, exposure to antipsychotic medication was associated with lower levels of glutamatergic metabolites. Duration of illness was not associated with glutamatergic metabolites. Lastly, creatine in the medial frontal cortex and thalamus increased with age. Discussion These data suggest that future 1H-MRS studies should control for the effects of age, symptom severity, and antipsychotic medication exposure. Caution is needed when using creatine as a reference to scale metabolites.

Background Negative symptoms can be seen to represent a continuum from subclinical manifestations in the general population to severe symptoms in schizophrenia. Neuroanatomical studies show evidence of fronto-striatal structural abnormalities linked to negative symptoms in patients with schizophrenia (Walton et al. 2018). However, it remains an open question whether these structural associations are also observed in ostensibly healthy individuals reporting subclinical negative symptoms. The present study used structural T1-weighted brain imaging data from the ENIGMA Schizotypy Working Group to investigate the relationship between subclinical negative symptoms and fronto-striatal structural measures. Methods We included 2,235 healthy unmedicated individuals with varying levels of schizotypy from 17 centers around the world. The complete sample had a weighted mean (range) age of 29.2 (15.9–39.6) and 59.4% (51–100) were male. Subclinical negative symptoms were assessed at each site separately using factor scores from self-report schizotypy questionnaires (i.e., the Community Assessment of Psychic Experiences, the Oxford-Liverpool Inventory of Feelings and Experiences, or the Schizotypal Personality Questionnaire). Based on prior studies in schizophrenia, we obtained cortical thickness from 22 frontal regions-of-interest (ROIs) and subcortical volumes from 6 striatal ROIs using FreeSurfer. We performed meta-analyses of effect sizes (standardized regression coefficients) from a model predicting mean cortical thickness by subclinical negative symptom scores, adjusting for age, sex, and site. The same analysis was repeated for subcortical volumes including intracranial volume as additional covariate. Results Meta-analyses revealed significant positive associations between subclinical negative symptoms and cortical thickness of the left frontal pole (βstd=0.091; pFDR=0.009), right medial orbitofrontal cortex (βstd=0.083; pFDR=0.009) and right anterior cingulate cortex (βstd=0.07; pFDR=0.011). Discussion Using a large sample of healthy unmedicated individuals with varying levels of schizotypal personality traits, this ENIGMA meta-analysis showed that subclinical negative symptoms are associated with thicker prefrontal cortex. The present data are contrary to previous findings in schizophrenia, which demonstrates a relationship between negative symptoms and lower prefrontal cortical thickness (Walton et al. 2018). These divergent neural correlates suggest that thicker cortex could be a potential compensatory mechanism preventing individuals with schizotypy from the clinical manifestation of severe negative symptoms. Alternatively, greater prefrontal cortical thickness could also be associated with pathological processes along the negative symptom continuum prior to clinical manifestation.

BACKGROUND: Neuroanatomical studies have provided some evidence for a neurobiological continuity between psychotic symptoms in patients with schizophrenia and subclinical psychotic-like experiences as identified via self-report questionnaires (or schizotypy) in otherwise healthy individuals. Despite a number of structural brain imaging studies published in subjects with schizotypy, these have often been limited by relatively small sample sizes. This study represents the first meta-analysis of structural MRI scans in schizotypy assessed with standardized methods at 17 centres worldwide. METHODS: The total sample included in the case-control meta-analysis involved 496 subjects with high schizotypy and 588 comparison subjects with low schizotypy as identified with validated self-report schizotypy questionnaires (i.e., the Community Assessment of Psychic Experiences, the Oxford-Liverpool Inventory of Feelings and Experiences, or the Schizotypal Personality Questionnaire). Left and right lateral ventricle, thalamus, caudate, putamen, pallidum, accumbens, hippocampus and amygdala volumes, as well as intracranial volumes (ICV), were obtained with FreeSurfer from high-resolution T1-weighted structural brain scans locally by each site. Analyses of individual subject data were also performed by the site that contributed the sample, using code created within the ENIGMA collaboration. Group differences for each ROI within each sample were examined using univariate linear regression analysis in R predicting the left, right and mean subcortical volumes with group (low or high schizotypy) controlling for age, sex, site and ICV. For each sample, Cohen’s d effect sizes for each ROI were computed based on the group contrast t-statistics. Random-effects meta-analyses of Cohen’s d effect sizes for each ROI were performed using R’s metafor package. RESULTS: For the case-control meta-analysis, mean (range) age across samples was 29.2 (19.2–44.9) years for subjects with high schizotypy and 28.5 (19.4–42.5) years for subjects with low schizotypy. High and low schizotypy samples were on average 48.6% (25–100) and 49.0% (8–100) male. Compared to low schizotypy, people with high schizotypy had smaller left nucleus accumbens volumes (Cohen’s d = -0.13, p = 0.04). No other significant meta-analytical effects were identified. DISCUSSION: Worldwide cooperative analyses of brain imaging data support a profile of subcortical abnormalities involving the ventral striatum in healthy individuals with subclinical psychotic-like experiences. Though the effect size is small, the result is consistent with findings in schizophrenia patients and suggesting that these effects are not secondary to potential influences of disease chronicity or antipsychotic medication. The lack of significant effects in other reported regions in schizophrenia research may indicate that further subcortical abnormalities may not be present or detectable in schizotypy samples and could reflect mechanisms of resilience in this population.

Alexithymia is a psychological construct that can be divided into a cognitive and affective dimension. The cognitive dimension is characterized by difficulties in identifying, verbalizing and analysing feelings. The affective dimension comprises reduced levels of emotional experience and imagination. Alexithymia is widely regarded to arise from an impairment of emotion regulation. This is the first functional magnetic resonance imaging (fMRI) study to critically evaluate this by investigating the neural correlates of emotion regulation as a function of alexithymia levels. The aim of the current study was to investigate the neural correlates underlying the two alexithymia dimensions during emotion perception and emotion regulation. Using fMRI, we scanned 51 healthy subjects while viewing, reappraising or suppressing negative emotional pictures. The results support the idea that cognitive alexithymia, but not affective alexithymia, is associated with lower activation in emotional attention and recognition networks during emotion perception. However, in contrast with several theories, no alexithymia-related differences were found during emotion regulation (neither reappraisal nor suppression). These findings suggest that alexithymia may result from an early emotion processing deficit rather than compromised frontal circuits subserving higher-order emotion regulation processes.

Background Difficulties in metacognition, or the ability to think about thinking and feeling, form an impediment to daily life functioning for persons with a psychotic disorder. In the past years, our research team has undertaken a multicenter, randomized controlled trial to investigate the efficacy of a new intervention designed to assist persons with a psychotic disorder to improve their metacognitive functioning (Metacognitive Reflection and Insight Therapy; MERIT). Methods After training thirteen therapists from seven mental healthcare institutes in the Netherlands, participants (n=70) with a DSM-IV-TR diagnosis of schizophrenia or schizoaffective disorder were included and randomized into either the MERIT condition or a treatment-as-usual condition. Persons randomized into the MERIT condition received 40 sessions of metacognitive psychotherapy, while persons in the control condition received care as usual. Measures of primary outcome (metacognition), secondary outcomes (empathy, depression, insight, stigma, social functioning, symptoms and quality of life) and control variables (neurocognition, premorbid IQ) were collected at baseline (pre), directly after therapy end (post) and at 6-month follow-up. After the follow-up measurement, research assistants were unblinded in order to conduct an interview with the participants regarding their experience of the therapy. Results Multilevel intention-to-treat and sensitivity analyses demonstrated that in both groups metacognition had improved, with no significant differences between the groups (χ2 (1)=0.435, p=.51). At 6-month follow-up, however, participants in the MERIT condition demonstrated they had continued to improve on metacognition, while scores from the control condition dipped back down (χ2 (1)=3.763, p=.05). Gains mainly seemed to be on metacognitive Self-Reflectivity (χ2 (1)=10.295, p=.001). No effects were found on secondary measures in either condition. Discussion During this presentation, we will discuss our findings and the therapy protocol, including a discussion of the clinical relevance of the current intervention, analysis of post-therapy interviews surrounding the participant’s experiences of the therapy, as well as practical limitations that were encountered during this five-year trial. Note S. de Jong (speaker) and R.J.M van Donkersgoed are early career scientists, expected to defend their dissertations in 2018.

BACKGROUND: Are people who are extraordinarily creative more likely to be mentally ill? Are all mentally ill people more creative? These are questions that have been asked for a very long time by scientists and philosophers. The link between creativity and mental illnesses has been hypothesized in varied ways. However, this link has not been properly established yet. Research from the last two decades has proposed that the problems in establishing such link or relationship is that it may only be present in certain specific mental illnesses, namely those with a psychotic component (e.g. bipolar disorder, schizotypal personality disorder) (Thys, Sabbe, & De Hert, 2014; Barrantes Vidal, 2004). We study this link using musical hallucinations (MH) as these are often being believed to be experienced as less disturbing than other types of hallucinations (e.g. auditory verbal, visual) (Shakenraad et al., 2006; Evers, 2006). Using MH in this study allowed to investigate the creativity-”madness” link in a more positive light. METHODS: 76 participants were measured from a student population, who completed a series of tasks. We introduced a novel approach of measuring creativity (defined as the propensity to detect imaginary music), through a musical Signal Detection Task (SDT). During this SDT, bursts of audible pink noise were being played, sometimes mixed with music, and sometimes without. The participants also completed two questionnaires, related to hallucination proneness (LSHS-R) and schizotypy personality traits (SPQ-BR). Furthermore, the participants performed a series of computer tasks related to different ways of measuring creativity: two classical measures of creativity, namely a biographical questionnaire and an Alternate Uses Task (AUT; Guilford, Dunham, & Hoepfner, 1967). We hypothesized that hearing music when none was being played (false alarm) could be considered to be a form of creativity and that this would positively correlate with proneness to hallucinate. Moreover, we also hypothesized that the included classical creativity measures would be positively associated with SPQ-BR. RESULTS: Correlation and regression analyses showed that in the musical SDT, contrary to our hypothesis, false alarms were negatively correlated to the LSHS-R scores: participants that were more prone to hallucinate reported less false alarms (p=0.040) than those who scored lower on the LSHS-R. Furthermore, more prone individuals reported higher sensitivity scores: they were better able to distinguish noise from music (p=0.004). Additionally, no significant correlation was observed between the classical creativity measures and the musical SDT or with the SPQ-BR scores. DISCUSSION: Further analysis of the sensitivity measures of the SDT revealed that scores of only three subjects could be driving this found correlation, thus caution is needed considering this relatively small, non-clinical, sample. Furthermore, the lack of correlation between the classical creativity measures and the SPQ-BR could be suggesting that there is either no relationship between creativity and schizotypy, or that perhaps, these two classical measures of creativity are measuring a different type of creativity than the one linked to schizotypy in former research. The continuation of this study includes an improved musical SDT and a musical creativity task. In this new experiment, the sample will come from a patient population with psychotic features. By learning more about the relationship of mental illnesses and creativity, and implementing this knowledge, existent treatments can be improved, and new ones may be developed to truly benefit this particular patient population.

How we perceive emotional signals from our environment depends on our personality. Alexithymia, a personality trait characterized by difficulties in emotion regulation has been linked to aberrant brain activity for visual emotional processing. Whether alexithymia also affects the brain's perception of emotional speech prosody is currently unknown. We used functional magnetic resonance imaging to investigate the impact of alexithymia on hemodynamic activity of three a priori regions of the prosody network: the superior temporal gyrus (STG), the inferior frontal gyrus and the amygdala. Twenty-two subjects performed an explicit task (emotional prosody categorization) and an implicit task (metrical stress evaluation) on the same prosodic stimuli. Irrespective of task, alexithymia was associated with a blunted response of the right STG and the bilateral amygdalae to angry, surprised and neutral prosody. Individuals with difficulty describing feelings deactivated the left STG and the bilateral amygdalae to a lesser extent in response to angry compared with neutral prosody, suggesting that they perceived angry prosody as relatively more salient than neutral prosody. In conclusion, alexithymia may be associated with a generally blunted neural response to speech prosody. Such restricted prosodic processing may contribute to problems in social communication associated with this personality trait.

Alexithymia is a trait characterized by a diminished capacity to describe and distinguish emotions and to fantasize; it is associated with reduced introspection and problems in emotion processing. The default mode network (DMN) is a network of brain areas that is normally active during rest and involved in emotion processing and self-referential mental activity, including introspection. We hypothesized that connectivity of the DMN might be altered in alexithymia. Twenty alexithymic and 18 non-alexithymic healthy volunteers underwent a resting state fMRI scan. Independent component analysis was used to identify the DMN. Differences in connectivity strength were compared between groups. Within the DMN, alexithymic participants showed lower connectivity within areas of the DMN (medial frontal and temporal areas) as compared to non-alexithymic participants. In contrast, connectivity in the high-alexithymic participants was higher for the sensorimotor cortex, occipital areas and right lateral frontal cortex than in the low-alexithymic participants. These results suggest a diminished connectivity within the DMN of alexithymic participants, in brain areas that may also be involved in emotional awareness and self-referential processing. On the other hand, alexithymia was associated with stronger functional connections of the DMN with brain areas involved in sensory input and control of emotion.

Background: Individuals who have a psychotic disorder often fnd it dif-fcult to recognize emotions, read others' mental states, and assess social situations. These social cognitive defcits are highly predictive of problems in daily life functioning. Meta-analyses show that social cognition can be improved by social cognition training (SCT) approaches; however, long-term effects appear to be limited. Given that training of cognitive functions is best executed in a manner that resembles and is integrated with participants' daily lives as much as possible, a plausible explanation is that the stimuli and techniques that are typically used in SCT do not suffciently resemble real-life social interactions. Several key characteristics of real-world interactions are absent from these stimuli, most notably interaction with the material. Methods: To improve transference of SCT to daily life functioning and interaction, we have therefore developed a SCT which utilizes Virtual Reality (VR). VR is highly realistic, eliciting genuine psychological reac-tions, and highly interactive: the environment and the virtual people (“avatars”) in it react to the actions of the participant. At the same time, VR is customizable and controllable, allowing for training that is tailored to the individual. Results: A new form of SCT, utilizing VR (called “DiSCoVR”), has been developed. DiSCoVR consists of 16 sessions, provided over the course of 8 weeks, in which the following social cognitive domains are trained: (1) Emotion perception; (2) Social perception and Theory of Mind (ie, understanding the context and interdependence of emotions, thoughts and behavior); and (3) Social interaction training (ie, understanding the other person and choosing an adequate response). These domains are trained in VR, supplemented by coaching from a therapist, and homework assignments. DiSCoVR is currently being piloted amongst 25 mental health service clients and 25 healthy controls in the northern Netherlands. In this pilot, we primarily test the acceptability and feasibility of the intervention. Furthermore, effects of the intervention on several domains of social cognition are investigated. Moreover, social behavior in VR is studied using heart rate and eye tracking data, comparing healthy controls and clients. Conclusion: We will present a theoretical framework for DiSCoVR. Moreover, we will demonstrate the intervention and provide preliminary results of the ongoing pilot study.

Theories about auditory hallucinations in schizophrenia suggest that these experiences occur because patients fail to recognize thoughts and mental events as self-generated. Different theoretical models have been proposed about the cognitive mechanisms underlying auditory hallucinations. Regardless of the cognitive model being tested, however, experimental designs are almost identical in that they require a judgment regarding whether an action was self-originated or not. The aim of the current study was to integrate all available literature for a meta-analysis on this topic and reach conclusions about self-recognition performance in (1) patients with schizophrenia compared with healthy controls and (2) patients with auditory hallucinations compared with patients without these symptoms. A comprehensive literature review identified 23 studies that contrasted the performance of schizophrenia patients with healthy controls (1370 participants) and 9 studies that directly compared patients with and without auditory hallucinations (315 participants). We found significantly reduced self-recognition performance in schizophrenia patients, which was more pronounced in patients with auditory hallucinations compared with patients without. In patients with hallucinations, this pattern of performance was specific to self-recognition processes and not to the recognition of new external information. A striking finding was the homogeneity in results across studies regardless of the action modality, timing delay, and design used to measure self-recognition. In summary, this review of studies from the last 30 years substantiates the view that self-recognition is impaired in patients with schizophrenia and particularly those with auditory hallucinations. This suggests an association, perhaps a causal one, between such deficit and hallucinatory experiences in schizophrenia.

Background Apathy is a highly debilitating and frequently occurring behavioral characteristic, present in approximately half of the patients with schizophrenia. Apathy is considered a core negative symptom that relates strongest to lack of initiative and is the strongest predictor of poor functional outcome, poor medication compliance, and high caregiver burden. Notwithstanding, measuring apathy is still a challenge. Therefore, we aimed to investigate whether actigraphy, an objective and continuous measurement of activity levels, could yield an objective quantitative measure of apathy severity in schizophrenia patients. Moreover, we aimed to investigate whether actigraphy related to relevant functional neuroimaging underpinnings of apathy, i.e. self-initiated goal-directed behavior. Methods Quantity, variability, and initiation of motor behavior were studied in relation to apathy severity as measured with clinical measures, and in relation to neural correlates of self-initiated behavior using functional Magnetic Resonance Imaging (fMRI). All patients (N=58) suffered from clinical significant apathy, as measured with the Apathy Evaluation Scale and Scale for the Assessment of Negative Symptoms and wore an actigraph for 48 continuous hours. Physical activity was quantified as the total activity counts over the patients’ ten most active hours of each day, summed over two weekend days (Activity-total, i.e. 20 hours in total). Variability of motor behavior (Activity-variability) was calculated by taking the root of the Mean Squared Successive Difference of the activity counts. For 31 of these patients, fMRI data during a task tapping into self-initiative was available. Results Results showed that quantity, variability, and initiation of motor behavior were associated with negative symptoms, but not specifically with apathy. Motor behavior parameters were associated with brain activation during the self-initiative task in various brain regions including inferior parietal regions. The results were only observed during the condition wherein participants were asked to promptly reply to specific cues and not during the condition where more freedom in timing and selection of behavior was allowed. Discussion Actigraphy can be used to measure quantity as well as variability of motor behavior in patients with schizophrenia and with specific relevance for negative symptoms, and that it correlates with selective neural substrates of action selection and activation of motor programs. However, actigraphy may not capture higher-order motivational processes that contribute to apathy severity.

The regulation of negative emotion through reappraisal has been shown to induce increased prefrontal activity and decreased amygdala activity. Individual differences in dispositional mindfulness reflect differences in typical recognition, detachment and regulation of current experience, thought to also operate as top-down control mechanism. We sought to investigate whether such individual differences would be associated with brain activity elicited during reappraisal of negative emotion. Eighteen healthy participants completed a functional magnetic resonance imaging task that involved attending to or reappraising negative stimuli, and provided emotion experience ratings after each trial. Dispositional mindfulness was assessed with a self-report questionnaire. Reappraisal induced activity in a brain network involving predominantly dorsal portions of the prefrontal cortex, replicating previous studies. A voxelwise regression analysis showed that individual differences in the tendency to be mindful predicted activity in neural regions underlying reappraisal, with dorsomedial prefrontal cortex activation increasing with more mindfulness traits. Notably, this prefrontal activation was inversely correlated with the amygdala response to negative scenes, further supporting its role in down-regulating emotion-generation regions. These findings suggest that individual differences in dispositional mindfulness, which reflect the tendency to recognize and regulate current states, may modulate activity in neural systems involved in the effective cognitive control of negative emotion.

Sex differences in cognition are consistently reported, men excelling in most visuospatial tasks and women in certain verbal tasks. It has been hypothesized that these sex differences in cognition results from a more bilateral pattern of language representation in women than in men. This bilateral pattern of language representation in women is thought to interfere with visuospatial functions in the right hemisphere. To test whether language representation is indeed more bilateral in the female than in the male brain, a meta-analysis was performed on studies that assessed language activity with functional imaging in healthy men and women. Effect sizes were weighted for sample size and the meta-analytic method was applied to obtain a combined effect size. Fourteen studies were included, providing data on 377 men and 442 women. Meta-analysis yielded a mean weighted effect d of 0.21 with a 95% confidence interval of -0.05 to 0.48, indicating no significant difference in language lateralization between men and women. This implies that the putative sex difference in language lateralization may be absent at the population level, or may be observed only with some, as yet not defined, language tasks. It is therefore not likely that differences in language lateralization underlie the general sex differences in cognitive performance, and the neuronal basis for these cognitive sex differences remains elusive.

Background: The majority of people with schizophrenia show serious cognitive impairments that cause deficits in general and social functioning. Cognitive Adaptation Training (CAT) is a compensatory strategy that aims to bypass the cognitive deficits by creating new routines in the patients’ environment through the use of environmental supports. In this study, we investigated which factors facilitate and hamper the implementation of the intervention in a hospital setting. Furthermore, we examined the relationship between implementation success and effectiveness of the intervention on functional outcomes.

Sir, In their Letter to the Editor, Kitazawa and Kansaku responded to our meta-analysis on sex differences in language lateralization measured with functional imaging techniques (Sommer et al ., 2004). Though Kitazawa and Kansaku gave an interesting interpretation of the data, we do not agree with the alternative calculation of the effect sizes of two studies they suggested. Kitazawa and Kansaku hypothesized that sex differences in language lateralization may be present only when subjects listen to stories, since two studies (Kansaku et al ., 2000; Philips et al …