Wataru Gonoi

Reduced Frontal Glutamate + Glutamine and N-Acetylaspartate Levels in Patients With Chronic Schizophrenia but not in Those at Clinical High Risk for Psychosis or With First-Episode Schizophrenia

Changes in brain pathology as schizophrenia progresses have been repeatedly suggested by previous studies. Meta-analyses of previous proton magnetic resonance spectroscopy ((1)H MRS) studies at each clinical stage of schizophrenia indicate that the abnormalities of N-acetylaspartate (NAA) and glutamatergic metabolites change progressively. However, to our knowledge, no single study has addressed the possible differences in (1)H MRS abnormalities in subjects at 3 different stages of disease, including those at ultrahigh risk for psychosis (UHR), with first-episode schizophrenia (FES), and with chronic schizophrenia (ChSz). In the current study, 24 patients with UHR, 19 FES, 25 ChSz, and their demographically matched 3 independent control groups (n = 26/19/28 for the UHR, FES, and ChSz control groups, respectively) underwent (1)H MRS in a 3-Tesla scanner to examine metabolites in medial prefrontal cortex. The analysis revealed significant decreases in the medial prefrontal NAA and glutamate + glutamine (Glx) levels, specifically in the ChSz group as indexed by a significant interaction between stage (UHR/FES/ChSz) and clinical status (patients/controls) (P = .008). Furthermore, the specificity of NAA and Glx reductions compared with the other metabolites in the patients with ChSz was also supported by a significant interaction between the clinical status and types of metabolites that only occurred at the ChSz stage (P = .001 for NAA, P = .004 for Glx). The present study demonstrates significant differences in (1)H MRS abnormalities at different stages of schizophrenia, which potentially correspond to changes in glutamatergic neurotransmission, plasticity, and/or excitotoxicity and regional neuronal integrity with relevance for the progression of schizophrenia.

Voxel-based analysis of the diffusion tensor

IntroductionDiffusion tensor imaging (DTI) has provided important insights into the neurobiological basis for normal development and aging and various disease processes in the central nervous system. The aim of this article is to review the current protocols for DTI acquisition and preprocessing and statistical testing for a voxelwise analysis of DTI, focused on statistical parametric mapping (SPM) and tract-based spatial statistics (TBSS).MethodsWe tested the effects of distortion correction induced by gradient nonlinearity on fractional anisotropy (FA) maps or FA skeletons processed via two SPM-based methods (coregistration and FA template methods), or TBSS-based method, respectively.ResultsWith two SPM-based methods, we found similar results in some points (e.g., significant FA elevation for uncorrected images in anterior-dominant white matter and for corrected images in bilateral middle cerebellar peduncles) and different results in other points (e.g., significantly larger FA for corrected images with coregistration method, but significantly smaller with FA template method in bilateral internal capsules, extending to corona radiata, and semioval centers). In contrast, there was no area with significant difference between uncorrected and corrected FA skeletons with TBSS-based method.ConclusionThe discrepancy among these results was not explained in full, but possible explanations were misregistration and smoothing for the SPM-based methods and insensitivity to FA changes outside the local centers of white matter bundles for TBSS-based method.

Pancreas divisum as a predisposing factor for chronic and recurrent idiopathic pancreatitis: initial in vivo survey

Background It is a controversial issue whether pancreas divisum (PD) induces pancreatitis. All previous studies have investigated this issue based on endoscopic procedures, which inevitably involve a selection bias. Objectives To determine the unbiased prevalence rate of PD in a community population and to investigate the effect of PD on idiopathic pancreatitis using a non-invasive magnetic resonance (MR) technique. Design Cross-sectional study. Patients The study enrolled 504 subjects from the community who participated in the medical check-up programme and 46 patients with idiopathic pancreatitis (8 acute, 23 chronic, 15 recurrent) extracted from 70 122 consecutive MR studies performed at an academic tertiary care hospital. Interventions All subjects underwent magnetic resonance (MR) scanning and medical examination. Main outcome measures Statistical comparison between subjects from the community and patients with idiopathic pancreatitis was made for the rate of PD (and its subtypes: classical PD, PD with absent ventral duct, and incomplete PD), MR findings, and clinical features. Results Multiple logistic regression analysis revealed PD as a significant factor that induces pancreatitis (OR 23.4; p<0.0001). The PD rate was significantly higher for all/chronic/recurrent idiopathic pancreatitis patients (35%/43%/33%; p<0.001 for all) than for subjects in the community group (2.6%), but was not higher for acute pancreatitis (13%; p=0.357). All PD subtypes were indicated to induce idiopathic pancreatitis but showed different associations with each onset type of pancreatitis. Conclusions This is the first study to describe the prevalence of PD and PD subtypes in a community population and their association with idiopathic pancreatitis in vivo based on the findings of non-invasive MR and with minimal selection bias. It is concluded that PD should be considered a predisposing factor for chronic and recurrent pancreatitis.

Diminished Medial Prefrontal Activity behind Autistic Social Judgments of Incongruent Information

Individuals with autism spectrum disorders (ASD) tend to make inadequate social judgments, particularly when the nonverbal and verbal emotional expressions of other people are incongruent. Although previous behavioral studies have suggested that ASD individuals have difficulty in using nonverbal cues when presented with incongruent verbal-nonverbal information, the neural mechanisms underlying this symptom of ASD remain unclear. In the present functional magnetic resonance imaging study, we compared brain activity in 15 non-medicated adult males with high-functioning ASD to that of 17 age-, parental-background-, socioeconomic-, and intelligence-quotient-matched typically-developed (TD) male participants. Brain activity was measured while each participant made friend or foe judgments of realistic movies in which professional actors spoke with conflicting nonverbal facial expressions and voice prosody. We found that the ASD group made significantly less judgments primarily based on the nonverbal information than the TD group, and they exhibited significantly less brain activity in the right inferior frontal gyrus, bilateral anterior insula, anterior cingulate cortex/ventral medial prefrontal cortex (ACC/vmPFC), and dorsal medial prefrontal cortex (dmPFC) than the TD group. Among these five regions, the ACC/vmPFC and dmPFC were most involved in nonverbal-information-biased judgments in the TD group. Furthermore, the degree of decrease of the brain activity in these two brain regions predicted the severity of autistic communication deficits. The findings indicate that diminished activity in the ACC/vmPFC and dmPFC underlies the impaired abilities of individuals with ASD to use nonverbal content when making judgments regarding other people based on incongruent social information.

Localized gray matter volume reductions in the pars triangularis of the inferior frontal gyrus in individuals at clinical high-risk for psychosis and first episode for schizophrenia

Recent studies have suggested an important role for Brocas region and its right hemisphere counterpart in the pathophysiology of schizophrenia, owing to its roles in language and interpersonal information processing. Brocas region consists of the pars opercularis (PO) and the pars triangularis (PT). Neuroimaging studies have suggested that they have differential functional roles in healthy individuals and contribute differentially to the pathogenesis of schizophrenic symptoms. However, volume changes in these regions in subjects with ultra-high risk for psychosis (UHR) or first-episode schizophrenia (FES) have not been clarified. In the present 3 Tesla magnetic resonance imaging study, we separately measured the gray matter volumes of the PO and PT using a reliable manual-tracing volumetry in 80 participants (20 with UHR, 20 with FES, and 40 matched controls). The controls constituted two groups: the first group was matched for age, sex, parental socioeconomic background, and intelligence quotient to UHR (n=20); the second was matched for those to FES (n=20). Compared with matched controls, the volume of the bilateral PT, but not that of the PO, was significantly reduced in the subjects with UHR and FES. The reduced right PT volume, which showed the largest effect size among regions-of-interest in the both UHR and FES groups, correlated with the severity of the positive symptoms also in the both groups. These results suggest that localized gray matter volume reductions of the bilateral PT represent a vulnerability to schizophrenia in contrast to the PO volume, which was previously found to be reduced in patients with chronic schizophrenia. The right PT might preferentially contribute to the pathogenesis of psychotic symptoms.

Absence of age-related prefrontal NAA change in adults with autism spectrum disorders.

Atypical trajectory of brain growth in autism spectrum disorders (ASDs) has been recognized as a potential etiology of an atypical course of behavioral development. Numerous neuroimaging studies have focused on childhood to investigate atypical age-related change of brain structure and function, because it is a period of neuron and synapse maturation. Recent studies, however, have shown that the atypical age-related structural change of autistic brain expands beyond childhood and constitutes neural underpinnings for lifelong difficulty to behavioral adaptation. Thus, we examined effects of aging on neurochemical aspects of brain maturation using 3-T proton magnetic resonance spectroscopy (1H-MRS) with single voxel in the medial prefrontal cortex (PFC) in 24 adult men with non-medicated high-functioning ASDs and 25 age-, IQ- and parental-socioeconomic-background-matched men with typical development (TD). Multivariate analyses of covariance demonstrated significantly high N-acetylaspartate (NAA) level in the ASD subjects compared with the TD subjects (F=4.83, P=0.033). The low NAA level showed a significant positive correlation with advanced age in the TD group (r=−0.618, P=0.001), but was not evident among the ASD individuals (r=0.258, P=0.223). Fisher’s r-to-z transformation showed a significant difference in the correlations between the ASD and TD groups (Z=−3.23, P=0.001), which indicated that the age–NAA relationship was significantly specific to people with TD. The current 1H-MRS study provided new evidence that atypical age-related change of neurochemical aspects of brain maturation in ASD individuals expands beyond childhood and persists during adulthood.

Intravascular gas distribution in the upper abdomen of non-traumatic in-hospital death cases on postmortem computed tomography.

OBJECTIVES To investigate the occurrence of intravascular gas in the liver, kidneys, spleen, and pancreas by postmortem computed tomography (PMCT) in cases of non-traumatic in-hospital deaths and elucidate the relationship between the PMCT data and clinical information or autopsy results. METHODS The study included 45 cadavers of patients who died while receiving treatment in our academic tertiary-care hospital between April and December 2009. All subjects underwent PMCT and conventional autopsy. The appearance of postmortem gas in the liver, kidney, spleen, and pancreas was assessed using PMCT and scored using a subjective scale (liver, L0-L3; kidney, K0-K2; spleen, S0-S1; and pancreas, P0-P1), and the distribution of gases in the vessels of the liver (arteries, veins, and portal veins) was analyzed. The relationship between the gas score and time elapsed since death, cardiopulmonary resuscitation (CPR), administration of antibiotics, a history of bacteremia, or cause of death was assessed statistically. RESULTS Positive correlations were found between administration of CPR and liver and kidney gas scores (P=0.008 and 0.002, respectively), but not with spleen and pancreas gas (P=0.291 and 0.535, respectively). No significant relationship between distribution of gas in the vessels of the liver and CPR was found. No other significant correlations between gas and any of the other parameters described above were found. While significant correlations were detected in no-CPR cases between liver gas, kidney gas, spleen gas, and pancreas gas (P<0.001 for all six combinations), no correlation between these parameters was detected in the CPR cases. CONCLUSIONS The present study was the first statistical analysis of intravascular gas in the liver, kidneys, spleen, and pancreas by using PMCT in non-traumatic in-hospital death cases. The results showed that PMCT in the presence and absence of CPR reveals differences in intraorgan gas distribution. In addition, the detection of intraorgan gas on PMCT cannot be used to predict time elapsed since death, and it is not affected by the administration of antibiotics, a history of bacteremia, and cause of death. Awareness of these postmortem changes is important for the accurate interpretation of PMCT results.

Cortical thickness, gray matter volume, and white matter anisotropy and diffusivity in schizophrenia.

IntroductionThe study was conducted to evaluate simultaneously gray matter changes and white matter changes in patients with schizophrenia.MethodsCortical thickness, gray matter volume, and white matter anisotropy and diffusivity changes in schizophrenic patients (n = 21) were assessed relative to age-, gender-, and parental socioeconomic status-matched healthy controls (n = 21). We used a newly described semi-automated method (FreeSurfer version 4.5) to determine cortical thickness and gray matter volume and used the tract-based spatial statistics method to evaluate white matter anisotropy and diffusivity.ResultsSchizophrenic patients showed a significant decrease in hippocampal volume compared with healthy controls. No significant thickness deficits or anisotropy and diffusivity changes were found in schizophrenic patients compared with healthy controls. Stepwise multivariate analysis revealed that hippocampal volume was positively related to duration of illness in schizophrenic patients.ConclusionOur results suggest that hippocampal volume is smaller in schizophrenic patients compared with healthy controls and that progressive hippocampal volume loss occurs in the early course of illness in schizophrenic patients but not in the more chronic stages.

Network structure underlying resolution of conflicting non-verbal and verbal social information

Social judgments often require resolution of incongruity in communication contents. Although previous studies revealed that such conflict resolution recruits brain regions including the medial prefrontal cortex (mPFC) and posterior inferior frontal gyrus (pIFG), functional relationships and networks among these regions remain unclear. In this functional magnetic resonance imaging study, we investigated the functional dissociation and networks by measuring human brain activity during resolving incongruity between verbal and non-verbal emotional contents. First, we found that the conflict resolutions biased by the non-verbal contents activated the posterior dorsal mPFC (post-dmPFC), bilateral anterior insula (AI) and right dorsal pIFG, whereas the resolutions biased by the verbal contents activated the bilateral ventral pIFG. In contrast, the anterior dmPFC (ant-dmPFC), bilateral superior temporal sulcus and fusiform gyrus were commonly involved in both of the resolutions. Second, we found that the post-dmPFC and right ventral pIFG were hub regions in networks underlying the non-verbal- and verbal-content-biased resolutions, respectively. Finally, we revealed that these resolution-type-specific networks were bridged by the ant-dmPFC, which was recruited for the conflict resolutions earlier than the two hub regions. These findings suggest that, in social conflict resolutions, the ant-dmPFC selectively recruits one of the resolution-type-specific networks through its interaction with resolution-type-specific hub regions.

Retroportal main pancreatic duct with circumportal pancreas: radiographic visualization.

PURPOSE The aim of this study was to investigate the imaging findings of retroportal main pancreatic duct (RMPD), a rare anomaly of the pancreas, and circumportal pancreas (CP) on computed tomography (CT) and magnetic resonance (MR) imaging. We also reviewed the previous literature and discussed its best imaging method, etiology and clinical importance. METHODS This work is a retrospective study. Two cases of RMPD were enrolled. The imaging findings of RMPD and CP were reviewed among the various CT and MR images obtained. Differences in visualization among the scans were evaluated using a four-stage model. RESULTS RMPD was always accompanied by CP. RMPD was detectable on contrast-enhanced CT but not on noncontrasted CT. RMPD was shown most clearly on arterial, portal and late phases of contrast-enhanced CT, contrast-enhanced fat-suppressed T1-weighted images and fat-suppressed T2-weighted images. CP was much easier to detect than RMPD and could be identified even on noncontrasted images. CONCLUSIONS We described the fourth and the fifth reported cases of RMPD. This is the first study to describe its MR imaging findings. CP was always present in cases of RMPD and was easily detectable on tomographic images. When radiologists or surgeons notice CP, it is necessary to pay attention to the course of the main pancreatic duct, particularly preoperatively to avoid surgical complications. It should be noted that these anomalies are undetectable on projection images.