Recent MRI studies have shown that schizophrenia is characterized by reductions in brain gray matter, which progress in the acute state of the disease. Cortical circuitry abnormalities in gamma oscillations, such as deficits in the auditory steady state response (ASSR) to gamma frequency (>30-Hz) stimulation, have also been reported in schizophrenia patients. In the current study, we investigated neural responses during click stimulation by BOLD signals. We acquired BOLD responses elicited by click trains of 20, 30, 40 and 80-Hz frequencies from 15 patients with acute episode schizophrenia (AESZ), 14 symptom-severity-matched patients with non-acute episode schizophrenia (NASZ), and 24 healthy controls (HC), assessed via a standard general linear-model-based analysis. The AESZ group showed significantly increased ASSR-BOLD signals to 80-Hz stimuli in the left auditory cortex compared with the HC and NASZ groups. In addition, enhanced 80-Hz ASSR-BOLD signals were associated with more severe auditory hallucination experiences in AESZ participants. The present results indicate that neural over activation occurs during 80-Hz auditory stimulation of the left auditory cortex in individuals with acute state schizophrenia. Given the possible association between abnormal gamma activity and increased glutamate levels, our data may reflect glutamate toxicity in the auditory cortex in the acute state of schizophrenia, which might lead to progressive changes in the left transverse temporal gyrus.

Uncertainty still surrounds the association between metabolic syndrome (MetS) and depression. We aimed to evaluate the association between MetS and elevated depressive symptoms in a general Japanese population.

Nanoparticulate imaging probes have become an increasingly important arsenal in the visualization of molecular markers for early diagnosis and post-therapy assessment of diseases. Surface functionalization of these nanoparticles has led to the development of a variety of targeted nanoprobes for various imaging modalities (e.g. PET, MRI, optical). Despite these advances, detailed understanding of the nanoparticle targeting kinetics, particularly at the early time points immediately after injection, is still lacking. In this study, we report the combination of a T(2)*-weighted time-resolved-MRI (TR-MRI) method with ultra-sensitive superparamagnetic polymeric micelle (SPPM) nanoprobes to quantify the targeting kinetics of cyclic (RGDfK) (cRGD)-encoded SPPM to angiogenic endothelium in subcutaneous human tumor xenograft models in mice. TR-MRI analyses of the α(v)β(3)-targeted and non-targeted SPPMs allowed for the subtraction of blood volume and extravascular signal components from the cRGD-SPPM data, resulting in a specific measurement of the accumulation kinetics of nanoprobes in lung, breast and brain cancer preclinical models. In all three models, α(v)β(3)-specific accumulation of SPPM nanoprobes was observed in the first 5 mins after intravenous injection (first order rate constants were in the range of 0.22-0.24 min(-1)). Similar α(v)β(3)-targeting kinetics was observed for cRGD-SPPM nanoprobes in different tumor xenograft models, consistent with the targeting of mouse angiogenic endothelium despite tumor inoculation from different human cancer cell lines. Results from this study offer new opportunities in the quantitative characterization of the targeting kinetics of cancer-specific nanoparticles to their intended biological targets in an intact animal, which provides fundamental insights on molecular recognition processes in vivo for further development of these nanoprobes.

Aging may alter the motor functions of the basal ganglia and cerebellum; however, no previous neuroimaging study has investigated the effect of aging on the functional connectivity of the motor loops involving these structures. Recently, using fMRI with a parametric approach and structural equation modeling (SEM), we demonstrated a significant functional interaction within the basal ganglia-thalamo-motor (BGTM) loop during self-initiated (SI) finger movement in young normal subjects, whereas cerebro-cerebellar (CC) loop was mainly involved during externally triggered (ET) movement. We applied this method to 12 normal aged subjects (53-72 years old) in order to study the effect of age on BGTM and CC loops. Compared with the functional connectivity seen in young subjects, SEM showed decreased connectivity in BGTM loops during SI task, decreased interaction in the CC loop during ET task, and increased connectivity within motor cortices and between hemispheres during both types of tasks. These results suggest an age-related decline of cortico-subcortical connectivity with increased interactions between motor cortices. Aging effects on SI and ET movements are probably caused by functional alterations within BGTM and CC loops.

Diffusion-weighted imaging (DWI) plays an important role in the preoperative assessment of gliomas; however, the diagnostic performance of histogram-derived parameters from mono-, bi-, and stretched-exponential DWI models in the grading of gliomas has not been fully investigated. Therefore, we compared these models' ability to differentiate between high-grade and low-grade gliomas.

Cell detachment is essential in culturing adherent cells. Trypsinization is the most popular detachment technique, even though it reduces viability due to the damage to the membrane and extracellular matrix. Avoiding such damage would improve cell culture efficiency. Here we propose an enzyme-free cell detachment method that employs the acoustic pressure, sloshing in serum-free medium from intermittent traveling wave. This method detaches 96.2% of the cells, and increases its transfer yield to 130% of conventional methods for 48 h, compared to the number of cells detached by trypsinization. We show the elimination of trypsinization reduces cell damage, improving the survival of the detached cells. Acoustic pressure applied to the cells and media sloshing from the intermittent traveling wave were identified as the most important factors leading to cell detachment. This proposed method will improve biopharmaceutical production by expediting the amplification of tissue-cultured cells through a more efficient transfer process.

To identify abnormalities of regional cerebral blood flow (rCBF) in individuals with obsessive-compulsive disorder (OCD) by conducting a voxel-based analysis of pseudo-continuous arterial spin labeling (pCASL) perfusion images.

Background: Although abnormality of cerebellar-cerebral functional connectivity at rest in obsessive-compulsive disorder (OCD) has been hypothesized, only a few studies have investigated the neural mechanism. To verify the findings of previous studies, a large sample of patients with OCD was studied because OCD shows possible heterogeneity. Methods: Forty-seven medication-free patients with OCD and 62 healthy controls (HCs) underwent resting-state functional magnetic imaging scans. Seed-based connectivity was examined to investigate differences in cerebellar-cerebral functional connectivity in OCD patients compared with HCs. Correlations between functional connectivity and the severity of obsessive-compulsive symptoms were analyzed. Results: In OCD, we found significantly increased functional connectivity between the right lobule VI and the left precuneus, which is a component of the default mode network (DMN), compared to HCs. However, there was no correlation between the connectivity of the right lobule VI-left precuneus and obsessive-compulsive severity. Conclusions: These findings suggest that altered functional connectivity between the cerebellum and DMN might cause changes in intrinsic large-scale brain networks related to the traits of OCD.

Alexithymia, a personality trait characterized by difficulties in identifying and expressing their emotions despite having a range of emotional experiences, can impact individuals' stress coping mechanisms. While many studies have investigated brain functions associated with specific tasks in relation to emotion processing, research focusing on resting-state brain functions has been limited. Thus, the aim of this study was to investigate the relationship between alexithymia and brain function by analyzing arterial spin labeling (ASL) data obtained during the resting state.

To assess the reproducibility of ADC, T1, T2, and proton density (PD) measurements on the cortex across the entire brain using high-resolution pseudo-3D diffusion-weighted imaging using echo-planar imaging with compressed SENSE (EPICS-DWI) and 3D quantification with an interleaved Look-Locker acquisition sequence with T2 preparation pulse (3D-QALAS) in normal healthy adults.

This study aimed to compare assessments by radiologists, artificial intelligence (AI), and quantitative measurement using synthetic MRI (SyMRI) for differential diagnosis between astrocytoma, IDH-mutant and oligodendroglioma, and IDH-mutant and 1p/19q-codeleted and to identify the superior method.

Whole-exome sequencing using next-generation technologies has been previously demonstrated to be able to detect rare disease-causing variants. Progressive external ophthalmoplegia (PEO) is an inherited mitochondrial disease that follows either autosomal dominant or recessive forms of inheritance (adPEO or arPEO). AdPEO is a genetically heterogeneous disease and several genes, including POLG1 and C10orf2/Twinkle, have been identified as responsible genes. On the other hand, POLG1 was the only established gene causing arPEO with mitochondrial DNA deletions. We previously reported a case of PEO with unidentified genetic etiology. The patient was born of a first-cousin marriage. Therefore, the recessive form of inheritance was suspected.

The basal ganglia and cerebellar loops are known to participate differently in self-initiated (SI) and externally triggered (ET) movements. However, no previous neuroimaging studies have illustrated functional organization of these loops in vivo. Here, we aimed to functionally visualize these loops during motor execution using functional magnetic resonance imaging (fMRI) with structural equation modeling (SEM). Twelve normal subjects (24-29 years old) were scanned while performing five different frequencies of sequential left finger movements using either SI or ET movements. Random effect analysis combined with a parametric approach revealed a significant positive linear dependence of cerebral activation upon movement rate in the right Put, GPi, VL, SMC and SMA during SI tasks. During ET tasks, significant positive linear relationships were found in the right SMC, VPL, left CB and DN, whereas tendency for linear relationships was seen in the right PMv. SEM further showed significant interactions within the right basal ganglia-thalamo-motor loop during SI tasks. In contrast, there were significant interactions within the entire right cerebral hemisphere-left cerebellar loop involving CB, DN, VPL, PMv and SMC during ET tasks. Therefore, our modeling approach enabled identification of different contributions of the motor loops of basal ganglia and cerebellum to SI and ET tasks during motor execution.

In an 8-week, randomized, placebo-controlled, double-blind study, an extended-release formulation of quetiapine, quetiapine XR, demonstrated efficacy and safety in Japanese patients with bipolar depression. Bipolar disorder is a chronic disease requiring continuous treatment.

Impaired cognitive flexibility has been implicated in the genetic basis of obsessive-compulsive disorder (OCD). Recent endophenotype studies of OCD showed neural inefficiency in the cognitive control network and interference by the limbic network of the cognitive control network. Exploring the relationship between the functional brain network and impaired cognitive flexibility may provide novel information about the neurobiological basis of OCD.

There may be different neural bases between subjects with epilepsy only (EP) and interictal chronic epilepsy psychosis (EPS). However, there have been few structural MRI studies of EPS. The current study was conducted to investigate the neural substrate of EPS. T1-weighted images were analyzed in 14 patients with EPS and 14 strictly-matched patients with EP. We conducted volume comparison in the whole brain using voxel-based morphometry (VBM). The VBM method revealed that EPS patients exhibited significantly reduced gray matter volumes in the left postcentral gyrus and the left supra marginal gyrus compared with EP patients (adjusted p = 0.029, FDR corrected q; k = 319 voxels). For clinical correlations, there were no significant associations between psychotic symptoms and gray matter volumes in the left postcentral gyrus and the left supra marginal gyrus. VBM analysis revealed that reduced gray matter volumes in the left postcentral gyrus and the left supra marginal gyrus may be crucial regions for EPS.

Several studies have revealed that neuregulins (NRGs) are involved in brain function and psychiatric disorders. While NRGs have been regarded as neuron- or astrocyte-derived molecules, our research has revealed that microglia also express NRGs, levels of which are markedly increased in activated microglia. Previous studies have indicated that microglia are activated in the brains of individuals with autism spectrum disorder (ASD). Therefore, we investigated microglial NRG mRNA expression in multiple lines of mice considered models of ASD. Intriguingly, microglial NRG expression significantly increased in BTBR and socially-isolated mice, while maternal immune activation (MIA) mice exhibited identical NRG expression to controls. Furthermore, we observed a positive correlation between NRG expression in microglia and peripheral blood mononuclear cells (PBMCs) in mice, suggesting that NRG expression in human PBMCs may mirror microglia-derived NRG expression in the human brain. To translate these findings for application in clinical psychiatry, we measured levels of NRG1 splice-variant expression in clinically available PBMCs of patients with ASD. Levels of NRG1 type III expression in PBMCs were positively correlated with impairments in social interaction in children with ASD (as assessed using the Autistic Diagnostic Interview-Revised test: ADI-R). These findings suggest that immune cell-derived NRGs may be implicated in the pathobiology of psychiatric disorders such as ASD.

In this study, we evaluated the efficacy of intravoxel incoherent motion (IVIM)-derived parameters calculated with three b-values in differentiating high-grade gliomas (HGGs) from low-grade gliomas (LGGs) by comparing those calculated with multiple b-values. Ten patients with LGG (ages 35.1±12.1 yrs; 4 males, 6 females) and 21 patients with HGG (ages 60.6±19.1 yrs; 10 males, 11 females) who underwent subsequent surgical resections were examined with both IVIM imaging and histopathological analysis. The IVIM diffusion-weighted imaging was conducted using a single-shot echo planar sequence with 13 b-factors (0, 10, 20, 30, 50, 80, 100, 200, 300, 400, 600, 800, and 1000 sec/mm2) at 3T. In the conventional IVIM analysis, the perfusion fraction (f) and true diffusion coefficient (D) were calculated by biexponential fitting model with 13 b-values. In the simplified method with the selected three b-values (0, 300, and 1000 sec/mm2), D simply corresponds to the slope of a straight line passing through two logarithmic signal intensities (SIs) at the b-values of 300 and 1000 s/mm2, and f corresponds to the difference between the intercept of this line and SI at the b-value of 0 sec/mm2. The maximum f (f-max) and minimum D (D-min) was measured in each tumor. The f-max values calculated with three b-values (12.8±5.9%) were significantly lower than those with 13 b-values (17.3±7.5%, p<0.0001), but a good correlation and agreement were observed between these sets of f-max values (r = 0.79, ICC = 0.87). In the IVIM imaging with both three and 13 b-values, the HGGs showed significantly higher f-max values compared to the LGGs (p<0.001, respectively). The D-min values calculated with three b-values (1.06±0.31 ×10-3 mm2/sec) was not different from those with 13 b-values (1.07±0.33 ×10-3 mm2/sec), and an excellent correlation and agreement were found between them (r = 0.99, ICC = 0.99). The simplified IVIM imaging using three b-values can efficiently differentiate HGGs and LGGs.

The burden of dementia is growing rapidly and has become a medical and social problem in Japan. Prospective cohort studies have been considered an effective methodology to clarify the risk factors and the etiology of dementia. We aimed to perform a large-scale dementia cohort study to elucidate environmental and genetic risk factors for dementia, as well as their interaction.

To investigate the binding potential of newly developed Annexin V-conjugated ultrasmall superparamagnetic iron oxide (V-USPIO) for detection of drug-induced apoptosis in vitro and in vivo.