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The aim of this study is to investigate whether mismatch negativity (MMN) is associated with functional status or is a state-independent trait for schizophrenia. We assessed MMN in 26 patients with schizophrenia, 20 healthy subjects with high genetic loading, and 48 healthy controls. Repeated measures analysis of variance and Pearson׳s correlations were used to test the hypothesis that MMN is not state-independent. We found a significant main effect of group, indicating differences in the peak amplitudes of the MMN among the three groups. Post-hoc analyses revealed that schizophrenia patients showed a significant reduction in the peak amplitude of MMN, but subjects at high genetic risk and healthy controls did not. Additionally, significant correlations between Global Assessment of Functioning scores and MMN peak amplitude at Fz and Cz were found in patients with schizophrenia. These findings suggest that MMN may reflect current functional status rather than a genetic risk for schizophrenia., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

The anterior limb of the internal capsule (ALIC), which interconnects with the frontal cortex and thalamus, is volumetrically altered in schizophrenia patients. However, it is unclear whether an abnormal ALIC volume is apparent prior to the onset of schizophrenia and whether this aberrant ALIC volume is related to the frontal gray matter in individuals at ultra-high risk (UHR) for psychosis. We used magnetic resonance imaging of 43 UHR subjects, 36 schizophrenia patients, and 42 healthy controls to investigate manually traced ALIC volumes. Additionally, we evaluated the correlation between the ALIC volume and the frontal gray matter. Significantly reduced ALIC volumes were observed in the UHR and schizophrenia groups compared to the healthy controls. However, the volume of the frontal gray matter was decreased only in the schizophrenia group. A positive correlation between the volumes in the ALIC and frontal gray matter found in healthy controls was maintained only in UHR subjects. In addition, a negative correlation between the total scores on the Positive and Negative Syndrome Scale and the ALIC volumes was observed only in schizophrenia patients. An aberrant ALIC volume but its maintained correlation with the interconnecting frontal lobe was present prior to the onset of full psychosis, indicating the prodromal phase of psychosis., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Neurobiological abnormalities in various brain regions, including the orbitofrontal cortex, basal ganglia, and thalamus, have been found in patients with obsessive-compulsive disorder (OCD), and impairment in white matter connectivity in these regions has recently been suggested. To investigate structural connectivity in OCD, we used the midsagittal area and thickness to assess the morphology of the corpus callosum (CC), the largest connecting fiber tract in the human brain. Midsagittal magnetic resonance images of the CC were acquired from 69 adult patients with OCD and 69 matched normal controls. We calculated and compared the total area and the areas of five subregions of the CC as well as the distances between 200 equidistant points on the top and bottom of lines on the surface of the CC in the two groups. The absolute total area of the CC was significantly larger in OCD patients than in controls when brain size, age, gender, and IQ were controlled. Significant enlargements in CC1, CC2, and CC5 were seen in OCD patients before correction for multiple comparisons. The thickness of the caudal part of the splenium was greater in OCD patients than in controls. The analysis according to gender showed that only male OCD patients differed from male controls with respect to the area of the CC. These findings reflect structural abnormalities in the CC, and especially in the splenium, in adult patients with OCD. Abnormal interhemispheric connectivity, including the parietotemporal and occipital areas, may affect the pathophysiology of OCD. Sexual dimorphism in the CC of OCD patients should be considered., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Empathy deficits might play a role in social dysfunction in schizophrenia. However, few studies have investigated the neuroanatomical underpinnings of the subcomponents of empathy in schizophrenia. This study investigated the hemodynamic responses to three subcomponents of empathy in patients with schizophrenia (N=15) and healthy volunteers (N=18), performing an empathy cartoon task during functional magnetic resonance imaging. The experiment used a block design with four conditions: cognitive, emotional, and inhibitory empathy, and physical causality control. Data were analyzed by comparing the blood-oxygen-level-dependent (BOLD) signal activation between the two groups. The cognitive empathy condition activated the right temporal pole to a lesser extent in the patient group than in comparison subjects. In the emotional and inhibitory conditions, the patients showed greater activation in the left insula and in the right middle/inferior frontal cortex, respectively. These findings add to our understanding of the impaired empathy in patients with schizophrenia by identifying a multi-level cortical dysfunction that underlies a deficit in each subcomponent of empathy and highlighting the importance of the fronto-temporal cortical network in ability to empathize., (Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.)

Although structural and functional neuroimaging studies of schizophrenia have suggested that impaired connectivity in the extensive network of cortical and subcortical areas is involved in its pathophysiology, there were no studies have investigated the structural integrity of the lower sensory brain areas including the inferior (IC) and the superior (SC) colliculus. The IC plays an important role in mediating auditory gating processes and inhibitory neural transmission, while the SC is a key structure in a distributed network mediating saccadic eye movements and shifts of attention, both of which have been linked to the pathophysiology of schizophrenia. We compared the morphologies of the IC and SC, which are involved in the early stage processing of visual and auditory stimuli, in patients with schizophrenia (N=28) and healthy controls (N=34) using high-resolution magnetic resonance imaging. Subjects with schizophrenia had a significantly smaller right IC, compared with controls. The reduced IC volume suggests that a structural abnormality of the IC in patients with schizophrenia may be involved in the auditory cognitive dysfunction of schizophrenia.

White matter (WM) abnormalities in schizophrenia may offer important clues to a better understanding of the disconnectivity associated with the disorder. The aim of this study was to elucidate a WM basis of auditory hallucinations in schizophrenia through the simultaneous investigation of WM tract integrity and WM density. Diffusion tensor images (DTIs) and structural T1 magnetic resonance images (MRIs) were taken from 15 hallucinating schizophrenic patients, 15 non-hallucinating schizophrenic patients and 22 normal controls. Voxel-based analyses and post-hoc region of interest analyses were obtained to compare the three groups on fractional anisotropy (FA) derived from DTI as well as WM density derived from structural MRIs. In both the hallucinating and non-hallucinating groups, FA of the WM regions was significantly decreased in the left superior longitudinal fasciculus (SLF), whereas WM density was significantly increased in the left inferior longitudinal fasciculus (ILF). The mean FA value of the left frontal part of the SLF was positively correlated with the severity score of auditory hallucinations in the hallucinating patient group. Our findings show that WM changes were mainly observed in the frontal and temporal areas, suggesting that disconnectivity in the left fronto-temporal area may contribute to the pathophysiology of schizophrenia. In addition, pathologic WM changes in this region may be an important step in the development of auditory hallucinations in schizophrenia.

Volumetric changes of striatal structures based on magnetic resonance imaging (MRI) have been inconsistent in patients with obsessive-compulsive disorder (OCD) due to methodological limitations. The purpose of this study was to investigate shape deformities of the corpus striatum in patients with OCD. We performed 3-D shape deformation analysis of the caudate nucleus, the putamen, and the globus pallidus in 36 patients with OCD and 36 healthy normal subjects. Shape analysis showed deformity of the striatal structures, especially the caudate nucleus. Outward deformities in the superior, anterior portion of the bilateral caudate were observed in patients with OCD. In addition, an outward deformity in the inferior, lateral portion of the left putamen was also detected. These results suggest that patients with OCD have shape deformities of the corpus striatum, especially the caudate nucleus, compared with healthy normal subjects, and that shape analysis may provide an important complement to volumetric MRI studies in investigating the pathophysiology of OCD.

Magnetic resonance imaging (MRI) has an important role in investigating the changes in brain structure that are associated with schizophrenia. In this study, MRI scans of patients diagnosed with schizophrenia (37 males; 19 females; 17-42 years of age) were compared with those of an age- and sex-matched group of normal subjects (37 males; 19 females; 18-40 years of age). Based on the images of the healthy control subjects, we constructed a representative average brain template. Automated image analysis techniques were used to measure differences in the regional nonlinear deformation fields between the two groups. A deformation field, which measures the spatial transformation to deform a template of brain anatomy to each individual data, was obtained as a three-dimensional displacement vector in each voxel. There was a significantly greater magnitude of the deformation fields in the superior frontal and parietal lobes as well as in the cingulate gyrus connecting both lobes of the patients with schizophrenia than in those of healthy controls, suggesting that these cerebral regions have a significantly higher structural variability in schizophrenia.

The anterior cingulate gyrus is a heterogeneous region that has specialized subdivisions with respect to its cytoarchitecture, function and connectivity. The aim of this study was to examine the morphological changes of the caudal subdivision of the anterior cingulate gyrus in the context of the cortico-striatal-thalamo-cortical circuitry of schizophrenia and their relationship to clinical symptoms. Accordingly, we measured the volumes of the caudal and rostral anterior cingulate gyrus, the orbitofrontal cortex, the caudate and the thalamus by magnetic resonance imaging in age- and sex-matched groups, which consisted of 22 patients with schizophrenia and 22 normal volunteers. The clinical symptoms of schizophrenia patients were obtained using the Positive and Negative Syndrome Scale. Volumetric reduction of the right caudal anterior cingulate gyrus was observed in patients with schizophrenia as compared with the normal controls. Furthermore, a smaller volume of the caudal anterior cingulate gyrus was significantly correlated with more severe positive symptoms of schizophrenia. Thus, these findings suggest that a volumetric abnormality of the caudal anterior cingulate gyrus in schizophrenia may be related to positive symptoms and possibly involved in the pathophysiology of schizophrenia.

It remains controversial as to what determines the neurodegenerative course in schizophrenia. This study administered a modified version of the Stroop task and investigated the relationship between functional magnetic resonance imaging (fMRI) signal changes in dysfunctioned task-related regions and clinical course variables. Functional MRI data during task performance were acquired from 10 right-handed schizophrenic patients (mean+/-SD age=29.2+/-10.3 years, range of illness duration=0.8-14 years, number of episodes=1-5) and 10 healthy controls (mean+/-SD age=30.3+/-6.4). Imaging data were investigated on a voxel-by-voxel basis for single group analysis and for between-group analysis according to the random effect model using Statistical Parametric Mapping (SPM 99b). Correlation analysis with age as a covariate identified those brain regions whose fMRI signal changes were significantly related to clinical course variables in schizophrenia. The number of psychotic episodes was negatively correlated with the fMRI signal change in the right inferior frontal and the right frontal precentral gyri among the activated regions during the Stroop task in schizophrenia, whereas the length of illness was not so correlated. The number of psychotic episodes was also negatively correlated with the fMRI signal change in the left paracingulate in which functional activity was diminished in the patients relative to the controls. Our results indicate that recurrent psychotic episodes are related to the neurodegenerative course in some dysfunctional brain regions in schizophrenia.

Numerous imaging studies have shown structural brain abnormalities in schizophrenia. Recently, voxel-based morphometry enabled whole brain analysis beyond the regions of interest (ROI). Regional gray matter concentrations of magnetic resonance (MR) images from 35 patients with paranoid schizophrenia were compared with those from 35 age- and sex-matched controls, and their clinical correlations were explored using voxel-based morphometry. Gray matter concentrations in the patients were significantly reduced in the left insular and dorsolateral prefrontal regions, and bilaterally in the medial frontal, anterior cingulate, inferior frontal and superior temporal regions. On the other hand, gray matter concentrations in the bilateral cerebellum and right striatum were significantly increased in the patients compared with controls. A negative correlation between the score for the severity of 'lack of insight and judgment' and gray matter concentrations in the left posterior and right anterior cingulate and bilateral inferior temporal regions including the lateral fusiform gyri was found. These results suggest the important roles of the paralimbic structures in the pathophysiology of schizophrenia and the involvement of the perceptual and monitoring systems in the mechanism of insight.

The cognitive significance of P300 abnormalities in schizophrenia and obsessive-compulsive disorder (OCD) was investigated. P300 was measured by an auditory oddball paradigm, in which a series of standard tones (1000 Hz) and target tones (1500 Hz) were presented. The subject's task was to count the number of the presented target tones. Cognitive functions were evaluated by neuropsychological tests, which were chosen to be sensitive to frontal and temporal dysfunction. Twenty-two schizophrenic patients, 19 OCD patients and 21 healthy controls participated. Event-related potentials measured at 15 electrode sites, which consisted of five levels on the left-right dimension and three levels on the anterior-posterior dimension, were included in the statistical analysis. P300 amplitudes on all 15 electrode sites were significantly smaller in schizophrenic and OCD patients than in the controls. Schizophrenic patients performed poorly on almost all neuropsychological tests, while OCD patients showed impaired performance on the Rey-Osterrieth Complex Figure Test and on a controlled oral word association test. In schizophrenic patients, P300 amplitude was associated with performance on verbal memory and learning by the Luria-Nebraska Neuropsychological Battery, while for OCD patients, P300 amplitude was related to the Trail Making Test, Part B response time. These results indicate that schizophrenic patients have generalized cognitive impairments, which are substrated by a wide range of cortical dysfunctions. The major cognitive deficits observed in OCD patients were impairments of controlled attention and self-guided, flexible behavior, which are mediated by the fronto-striatal system. The neurophysiological mechanisms underlying P300 abnormalities observed in schizophrenic and OCD patients are discussed.

Although results from neuropsychological and neuroimaging studies have postulated the involvement of the frontal lobe and the subcortical brain regions in the pathophysiology of obsessive-compulsive disorder (OCD), neuroimaging studies have provided little evidence that cognitive abnormalities in patients with OCD are related to dysfunctions in these areas. This study was designed to determine whether the clinical features and cognitive deficits of OCD might be taken to reflect frontal-subcortical dysfunction. Fourteen patients with OCD and 14 case-matched normal subjects completed clinical and cognitive evaluation, including four sets of neuropsychological tests that assessed the executive functions and visual memory. Cerebral glucose metabolic rates were measured by using positron emission tomography (PET) with 18F-fluorodeoxyglucose. Behavioral and PET data were analyzed using statistical parametric mapping for group differences and behavioral-metabolic correlates. The right orbitofrontal cortex showed increased metabolic activity and the left parieto-occipital junction showed decreased metabolic activity in patients. Metabolism in the right hippocampus, the left putamen and the right parietal region was associated with the severity of obsessive-compulsive symptoms. Correlations between metabolic rates and neuropsychological test scores in the prefrontal cortex and the putamen occurred only in the patient group. These results suggest that patients with OCD have distinct features of brain metabolic activities for performing cognitive tasks as well as presenting obsessive-compulsive symptoms. In particular, the frontal-subcortical circuits might mediate not only symptomatic expression but also cognitive expression in patients with OCD., (Copyright 2002 Elsevier Science Ireland Ltd.)