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

To identify the brain regions involved in the interpretation of intentional movement by patients with schizophrenia, we investigated the association between cerebral gray matter (GM) volumes and performance on a theory of mind (ToM) task using voxel-based morphometry. Eighteen patients with schizophrenia and thirty healthy controls participated in the study. Participants were given a moving shapes task that employs the interpretation of intentional movement. Verbal descriptions were rated according to intentionality. ToM performance deficits in patients were found to be positively correlated with GM volume reductions in the superior temporal sulcus and medial prefrontal cortex. Our findings confirm that divergent brain regions contribute to mentalizing abilities and that GM volume reductions impact behavioral deficits in patients with schizophrenia.

Transcultural differences in brain activation patterns during theory of mind (ToM) task performance in Japanese and Caucasian participants.

BACKGROUND: Theory of mind (ToM) functioning develops during certain phases of childhood. Factors such as language development and educational style seem to influence its development. Some studies that have focused on transcultural aspects of ToM development have found differences between Asian and Western cultures. To date, however, little is known about transcultural differences in neural activation patterns as they relate to ToM functioning. EXPERIMENTAL METHODS: The aim of our study was to observe ToM functioning and differences in brain activation patterns, as assessed by functional magnetic resonance imaging (fMRI). This study included a sample of 18 healthy Japanese and 15 healthy Caucasian subjects living in Japan. We presented a ToM task depicting geometrical shapes moving in social patterns. We also administered questionnaires to examine empathy abilities and cultural background factors. RESULTS: Behavioral data showed no significant group differences in the subjects' post-scan descriptions of the movies. The imaging results displayed stronger activation in the medial prefrontal cortex (MPFC) in the Caucasian sample during the presentation of ToM videos. Furthermore, the task-associated activation of the MPFC was positively correlated with autistic and alexithymic features in the Japanese sample. DISCUSSION: In summary, our results showed evidence of culturally dependent sociobehavioral trait patterns, which suggests that they have an impact on brain activation patterns during information processing involving ToM.

Reduced white matter integrity as a neural correlate of social cognition deficits in schizophrenia.

BACKGROUND: The pathology of schizophrenia is thought to involve multiple gray and white matter regions. A number of studies have revealed impaired social cognition in schizophrenia. Some evidence suggests an association of this social cognition deficit with gray matter reductions in 'social brain' areas. However, no study has yet revealed the association between social cognition abilities and white matter abnormalities in schizophrenia patients. METHODS: Twenty-six schizophrenia patients and 27 healthy controls underwent the Perception of Affect Task (PAT), which consisted of four subtasks measuring different aspects of emotion attribution. Voxelwise group comparison of white matter fractional anisotropy (FA) was performed using tract-based spatial statistics (TBSS). The relation between impaired social cognition ability and FA reduction was examined in patients for each subtask, using simple regression analysis within brain areas that showed a significant FA reduction in patients compared with controls. The same correlational analysis was also performed for healthy controls in the whole brain. RESULTS: Schizophrenia patients showed reduced emotion attribution ability compared with controls in all four subtasks. The facial emotion perception subtask showed a significant correlation with FA reductions in the left occipital white matter region and left posterior callosal region. The correlational analyses in healthy controls revealed no significant correlation of FA with any of the PAT subtasks. CONCLUSIONS: Our voxelwise correlational analysis of white matter provided a potential neural basis for the social cognition impairments in schizophrenia, in support of the disconnection hypothesis.

Investigating association of brain volumes with intracranial capacity in schizophrenia.

Intracranial volume (ICV) is usually treated as a global or nuisance covariate in almost all volumetric studies of schizophrenia. However, validation for this analytic method has seldom been accomplished. In this study, we aimed to determine the effects of ICV on gray matter (GM) and white matter (WM) volumes. Sixty-three patients with schizophrenia and sixty normal controls were recruited; and high resolution T1 weighted images were obtained by 3T-MRI. After segmentation and normalization of the images into GM, WM, and cerebrospinal fluid (CSF), multiple regression analyses of global GM and WM volumes were performed using explanatory variables such as diagnosis, ICV, and diagnosis-ICV interaction. In addition, associations between regional GM and WM volumes with ICV were also investigated using voxel-based morphometry (VBM). No significant interaction between diagnosis and ICV was found for global GM volume, whereas interactions were detected in restricted GM areas using VBM. On the other hand, an interaction between ICV and diagnosis was found in WM not only for regional volumes, but also for global WM volume. The regression slope of global WM volumes against ICV was steeper in patients with schizophrenia than in healthy controls. These results imply that ICV should be carefully evaluated in the analyses of volumetric studies of schizophrenia, especially when analyzing WM volumes.

Insular volume reduction in schizophrenia.

Structural and functional abnormalities of the insular cortex have been reported in patients with schizophrenia. Most studies have shown that the insular volumes in schizophrenia patients are smaller than those of healthy people. As the insular cortex is functio-anatomically divided into anterior and posterior subdivisons, recent research is focused on uncovering a specific subdivisional abnormality of the insula in patients with schizophrenia. A recent ROI-based volumetric MRI study demonstrated specific left anterior insular volume reduction in chronic schizophrenia patients (Makris N, Goldstein J, Kennedy D, Hodge S, Caviness V, Faraone S, Tsuang M, Seidman L (2006) Decreased volume of left and total anterior insular lobule in schizophrenia. Schizophr Res 83:155-171). On the other hand, our VBM-based volumetric study revealed a reduction in right posterior insular volume (Yamada M, Hirao K, Namiki C, Hanakawa T, Fukuyama H, Hayashi T, Murai T (2007) Social cognition and frontal lobe pathology in schizophrenia: a voxel-based morphometric study. NeuroImage 35:292-298). In order to address these controversial results, ROI-based subdivisional volumetry was performed using the MRI images from the same population we analyzed in our previous VBM-study. The sample group comprised 20 schizophrenia patients and 20 matched healthy controls. Patients with schizophrenia showed a global reduction in insular gray matter volumes relative to healthy comparison subjects. In a simple comparison of the volumes of each subdivision between the groups, a statistically significant volume reduction in patients with schizophrenia was demonstrated only in the right posterior insula. This study suggests that insular abnormalities in schizophrenia would include anterior as well as posterior parts. Each subdivisional abnormality may impact on different aspects of the pathophysiology and psychopathology of schizophrenia; these relationships should be the focus of future research.