Toshiya Murai

Age-related cortical thinning in schizophrenia

Although the effects of aging on the neural correlates of schizophrenia have been researched for many years, no clear conclusion has been reached. While some studies have demonstrated progressive age-related gray matter reductions in schizophrenia, other studies have not found evidence of progression. Moreover, it remains unclear whether the influence of aging on global or regional cortical thickness differs between schizophrenia patients and healthy controls. This study aimed to confirm previous reports of reduced cortical thickness in schizophrenia, and to investigate the effects of age on global and regional cortical thickness. Eighty-three patients with schizophrenia (six first-episode patients and 77 chronic patients; age range=18-55 years) and 90 age-, gender- and education-matched healthy controls (age range=19-56 years) underwent structural magnetic resonance imaging (MRI) using a 3-Tesla scanner. Surface-based analysis was applied to assess cortical thickness in the whole brain. The patient group exhibited both global and regional cortical thinning in regions including the prefrontal and temporal cortices. The correlation between age and cortical thickness showed a similar pattern in patients and controls, both globally and regionally. These results suggest that the reduction of cortical thickness in schizophrenia might not be progressive over the course of the illness, indicating that pathological processes occur in a relatively limited period of time around the onset of illness.

Reduced white matter integrity correlated with cortico-subcortical gray matter deficits in schizophrenia.

BACKGROUNDnThe pathology of schizophrenia is thought to involve multiple brain regions and the connections among them. Although a number of MRI studies have demonstrated gray matter reductions and abnormal white matter integrity in schizophrenia, to date no study has investigated their association in the whole brain.nnnMETHODSnTwenty-seven schizophrenia patients and 33 healthy controls were recruited. Voxelwise group comparison of white matter fractional anisotropy (FA) was performed using tract-based spatial statistics (TBSS). Comparison of gray matter concentration (GMC) was performed using voxel-based morphometry (VBM). Voxelwise correlational analyses were performed for patients inside a significant GMC reduction mask created by VBM, using simple regression models with mean FA values of each significant TBSS cluster as explanatory variables.nnnRESULTSnTBSS revealed FA reduction in left prefrontal and occipital regions in the patients. Mean FA values of both areas revealed significant correlation with gray matter reduction in multiple cortical and subcortical areas, with overlapping but different patterns.nnnCONCLUSIONSnVoxelwise correlational analysis of white and gray matter pathology, as performed here, further elucidated the pathophysiology of schizophrenia, and provided a novel view of the disconnection hypothesis of schizophrenia.

Brain volume and dysexecutive behavior in schizophrenia

OBJECTIVEnBehaviors associated with frontal/executive impairments are common in patients with schizophrenia. Our aim was to reconfirm that morphological brain abnormalities in schizophrenia patients would overlap the areas underpinning frontal systems behavior, and examine whether any specific association exists between abnormalities of brain structures and frontal behavioral deficits in schizophrenia patients.nnnMETHODnTwenty-six schizophrenia patients and 26 matched healthy controls underwent structural magnetic resonance imaging and their frontal function was assessed by a self-rating questionnaire, Frontal Systems Behavior Scale (FrSBe). We applied voxel-based morphometry (VBM) to investigate regional brain volume alternations.nnnRESULTnCompared with healthy controls, schizophrenia patients showed reduced gray matter volume in multiple frontal and temporal structures, namely, the bilateral dorsolateral prefrontal cortices (DLPFC), bilateral medial prefrontal cortices, left ventrolateral prefrontal cortex, bilateral anterior cingulate cortices, and bilateral superior temporal gyri. The scores on the executive dysfunction subscale of the FrSBe were correlated with volume reduction in the bilateral DLPFC in the patient group.nnnCONCLUSIONnOur result suggests that pathology of the DLPFC could be the neural basis of real-life dysexecutive behaviors in schizophrenia patients.

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

BACKGROUNDnThe 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.nnnMETHODSnTwenty-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.nnnRESULTSnSchizophrenia 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.nnnCONCLUSIONSnOur voxelwise correlational analysis of white matter provided a potential neural basis for the social cognition impairments in schizophrenia, in support of the disconnection hypothesis.

Abnormal asymmetry of white matter integrity in schizophrenia revealed by voxelwise diffusion tensor imaging.

A number of magnetic resonance imaging (MRI) studies have revealed morphological cortical asymmetry in the normal human brain, and reduction or inversion of such hemispheric asymmetry has been reported in schizophrenia. On the other hand, diffusion tensor imaging (DTI) studies have reported inconsistent findings concerning abnormal asymmetry of white matter integrity in schizophrenia. Our aim was to confirm whether there is reduced or inverted asymmetry of white matter integrity in the whole brain in schizophrenia. For this study, 26 right‐handed schizophrenia patients, and 32 matched healthy control subjects were investigated. Voxelwise analysis of DTI data was performed using the tract‐based spatial statistics. The fractional anisotropy (FA) images were normalized and projected onto the symmetrical white matter skeleton, and the laterality index (LI) of FA, determined by 2 × (left ‐ right)/(left + right), was calculated. The results reveal that schizophrenia patients and healthy controls showed similar patterns of overall FA asymmetries. In the group comparison, patients showed significant reduction of LI in the external capsule (EC), and posterior limb of the internal capsule (PLIC). The EC cluster revealed increased rightward asymmetry, and the PLIC cluster showed reduced leftward asymmetry. Rightward‐shift of FA in the EC cluster correlated with negative symptom severity. Considering that the EC cluster includes the uncinate and inferior occipitofrontal fasciculi, which have connections to the orbitofrontal cortex, abnormal asymmetry of white matter integrity in schizophrenia may play a crucial role in the pathogenesis of schizophrenia, through the altered connectivity to the orbitofrontal cortex. Hum Brain Mapp, 2011.

Alexithymia and regional gray matter alterations in schizophrenia

Alexithymia is characterized by deficits in emotional self-awareness. Although alexithymia refers to a deficit in recognizing ones own emotions, some studies have focused on the relation between alexithymia and impaired social cognition. An association between alexithymia and schizophrenia has been previously reported, but the brain structures involved remain unclear. The present study investigated associations between alexithymia and specific brain structures to determine whether these regions overlapped with key structures underlying social cognition. Twenty-one patients with schizophrenia and 24 age-, gender- and education level-matched healthy controls underwent structural magnetic resonance imaging. Alexithymia was assessed using the 20-item Toronto Alexithymia Scale (TAS-20). We applied voxel-based morphometry to investigate the correlation between TAS-20 scores and regional brain alterations. TAS-20 scores were significantly higher in patients than controls. Bilateral ventral striatum and left ventral premotor cortex volumes were negatively correlated with TAS-20 total scores in controls, while left supramarginal gyrus (SMG) volume was negatively correlated with TAS-20 total scores in patients. These results suggest that schizophrenia is associated with alexithymia, and that gray matter alterations of the left SMG constitute a key pathology underlying alexithymia in schizophrenia. This association may be related to deficits in self-other distinction, self-disturbance, and language processing in schizophrenia.

Liberal bias mediates emotion recognition deficits in frontal traumatic brain injury

It is well-known that patients having sustained frontal-lobe traumatic brain injury (TBI) are severely impaired on tests of emotion recognition. Indeed, these patients have significant difficulty recognizing facial expressions of emotion, and such deficits are often associated with decreased social functioning and poor quality of life. As of yet, no studies have examined the response patterns which underlie facial emotion recognition impairment in TBI and which may lend clarity to the interpretation of deficits. Therefore, the present study aimed to characterize response patterns in facial emotion recognition in 14 patients with frontal TBI compared to 22 matched control subjects, using a task which required participants to rate the intensity of each emotion (happiness, sadness, anger, disgust, surprise and fear) of a series of photographs of emotional and neutral faces. Results first confirmed the presence of facial emotion recognition impairment in TBI, and further revealed that patients displayed a liberal bias when rating facial expressions, leading them to associate intense ratings of incorrect emotional labels to sad, disgusted, surprised and fearful facial expressions. These findings are generally in line with prior studies which also report important facial affect recognition deficits in TBI patients, particularly for negative emotions.

Development of a multi-dimensional scale for PDD and ADHD.

A novel assessment scale, the multi-dimensional scale for pervasive developmental disorder (PDD) and attention-deficit/hyperactivity disorder (ADHD) (MSPA), is reported. Existing assessment scales are intended to establish each diagnosis. However, the diagnosis by itself does not always capture individual characteristics or indicate the level of support required, since inter-individual differences are substantial and co-morbidity is common. The MSPA consists of 14 domains and each domain is rated by a nine-point quantitative scale. The clinical and behavioral features are projected onto a radar-chart, which facilitates understanding of the disorders both by the patients themselves and by those in their surroundings. We assessed 179 patients and analyzed features by six diagnostic subgroups, which showed relationships between features and diagnoses. The inter-rater reliability was satisfactory.

Psychological factors influencing donors' decision-making pattern in living-donor liver transplantation.

Background. It has been reported that living liver donors may develop psychological or psychosocial impairments after transplantation, although the majority of them do not develop much difficulties. Their postoperative psychological prognosis may be affected by the way they made their decision to donate. The purpose of this study was to investigate the association of donors preoperative psychological factors with the processes of their individual decision-making to donate and their family-level decision-making to select one donor among themselves. Methods. A total of 165 living liver donor candidates underwent a semistructured interview, several standardized psychological tests, and a quality of life measurement. The results of the tests were compared among the groups classified according to the types of their individual and family decision-making processes. Results. Donor candidates who made a “postponement decision” had higher trait anxiety and higher alexithymia scores than candidates who made a “deliberate decision,” and candidates whose family made a “de facto decision” had higher trait anxiety and higher alexithymia scores than candidates whose family made a “decision of consensus,” which indicates that those who have high trait anxiety or alexithymia may tend to take a “postponement” pattern in the individual decision-making process and a “de facto decision” pattern in the family decision-making process. Conclusions. The results indicate the importance of noting living donors psychological traits for providing them appropriate preoperative psychological support.

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.