The Role of Occipitotemporal Network for Speed-Reading: An fMRI Study.

The activity of occipitotemporal regions involved in linguistic reading processes, such as the ventral occipitotemporal cortex (vOT), is believed to exhibit strong interactions during higher-order language processing, specifically in the connectivity between the occipital gyrus and the temporal gyrus. In this study, we utilized functional magnetic resonance imaging (fMRI) with psychophysiological interaction (PPI) and dynamic causal modeling (DCM) to investigate the functional and effective connectivity in the occipitotemporal network during speed reading. We conducted the experiment with native Japanese speakers who underwent and without speed-reading training and subsequently performed established reading tasks at different speeds (slow, medium, and fast) while undergoing 3-Tesla Siemens fMRI. Our activation analyses revealed significant changes in occipital and temporal regions as reading speed increased, indicating functional connectivity within the occipitotemporal network. DCM results further demonstrated more intricate effective connections and high involvement within the occipitotemporal pathway: (1) reading signals originated from the inferior occipital gyrus (iO), distributed to the vOT and the posterior superior temporal sulcus (pSTS), and then gathered in the anterior superior temporal sulcus (aSTS); (2) reading speed loads had modulation effects on the pathways from the aSTS to vOT and from the iO to vOT. These findings highlight the complex connectivity and dynamic interactions within the occipitotemporal network during speed-reading processes.

National burden of gambling in Japan: an estimation from an online-based cross-sectional investigation and national epidemiological survey.

BACKGROUND: Gambling is a popular leisure activity in many countries, often expected to boost regional economies. Nevertheless, its negative impacts remain a significant concern. Gambling disorder is recognized as the most severe consequence; however, even non- or low-risk gamblers may also face negative impacts. This study aimed to estimate the number of Japanese gamblers experiencing gambling-related harm (GRH) and its distribution across six life domains, financial, relational, emotional, health, social and other aspects, based on the severity of their problem gambling risk. METHODS: This cross-sectional study relied on an online survey conducted between August 5 and 11, 2020. Participants aged 20 years and above, who engaged in gambling during 2019 were recruited via a market research company. The survey assessed the prevalence of GRH 72 items among four gambler risk groups (non-problem, low-, moderate-, and high-risk), as categorized by the Problem Gambling Severity Index. The data was adjusted for population weighting using representative national survey data: the 2017 Comprehensive Survey of Living Conditions and the 2017 Epidemiological Survey on Gambling Addictions. RESULTS: Out of the 28,016 individuals invited to the survey, 6,124 participated in the screening, 3,113 in the main survey, and 3,063 provided valid responses. After adjusting the survey data, it was estimated that 39.0 million (30.8%) of Japan's 126.8 million citizens gambled in 2019. Among them, 4.44 million (11.4%) experienced financial harm, 2.70 million (6.9%) health harm, 2.54 million (6.5%) emotional harm, 1.31 million (3.4%) work/study harm, 1.28 million (3.3%) relationship harm, and 0.46 million (1.2%) other harm. Although high-risk gamblers experienced severe harm at the individual level, over 60% of gamblers who experienced GRHs were non- and low-risk gamblers, with the exception of other harm, at the population level. CONCLUSIONS: The study highlighted the prevention paradox of gambling in Japan. While national gambling policies primarily focus on the prevention and intervention for high-risk gamblers, a more effective approach would involve minimizing GRH across the entire population.

Segmentation and Volume Estimation of the Habenula Using Deep Learning in Patients With Depression.

Background: The habenula is involved in the pathophysiology of depression. However, its small structure limits the accuracy of segmentation methods, and the findings regarding its volume have been inconsistent. This study aimed to create a highly accurate habenula segmentation model using deep learning, test its generalizability to clinical magnetic resonance imaging, and examine differences between healthy participants and patients with depression. Methods: This multicenter study included 382 participants (patients with depression: N = 234, women 47.0%; healthy participants: N = 148, women 37.8%). A 3-dimensional residual U-Net was used to create a habenula segmentation model on 3T magnetic resonance images. The reproducibility and generalizability of the predictive model were tested on various validation cohorts. Thereafter, differences between the habenula volume of healthy participants and that of patients with depression were examined. Results: A Dice coefficient of 86.6% was achieved in the derivation cohort. The test-retest dataset showed a mean absolute percentage error of 6.66, indicating sufficiently high reproducibility. A Dice coefficient of >80% was achieved for datasets with different imaging conditions, such as magnetic field strengths, spatial resolutions, and imaging sequences, by adjusting the threshold. A significant negative correlation with age was observed in the general population, and this correlation was more pronounced in patients with depression (p < 10-7, r = -0.59). Habenula volume decreased with depression severity in women even when the effects of age and scanner were excluded (p = .019, η2 = 0.099). Conclusions: Habenula volume could be a pathophysiologically relevant factor and diagnostic and therapeutic marker for depression, particularly in women.

Accurate segmentation of the habenula, a brain region implicated in depression, is challenging. In this study, we developed an automated human habenula segmentation model using deep learning techniques. The model was confirmed to be reproducible and generalizable at various spatial resolutions. Application of this model to a multicenter dataset confirmed that habenula volume decreased with age in healthy volunteers, an association that was more pronounced in individuals with depression. In addition, habenula volume decreased with the severity of depression in women. This novel model for habenula segmentation enables further study of the role of the habenula in depression.

Is P3 amplitude associated with greater gaze distraction effect in schizotypy?

A recently proposed "Hyperfocusing hypothesis" suggests that schizotypy is associated with a more narrow but more intense way of allocating attention. The current study aims to test a vital prediction of this hypothesis in a social context, that schizotypy may be related to greater difficulty overcoming the distracting effects of gaze. This could cause a longer time to respond to targets that are invalidly cued by gaze. The current study tested this prediction in a modified Posner cueing paradigm by using P3 as an indicator for attentional resources. Seventy-four young healthy individuals with different levels of schizotypy were included, they were asked to detect the location of a target that was cued validly or invalidly by the gaze and head orientation. The results revealed that (a) schizotypy is associated with hyperfocusing on gaze direction, leading to greater difficulty overcoming the distracting effect of gaze. The higher the trait-schizotypy score, the more time needed to respond to targets that were invalidly cued by gaze (b) schizotypy is associated with reduced P3 which is directed by social communicative stimuli. The higher the trait-schizotypy score, the smaller the amplitude of P3 (c) the relationship between schizotypal traits and response times of the gaze-invalid condition is fully intermediated by P3. The findings of the current study suggest the P3 component may be a crucial neural mechanism underlying joint attention deficits in schizophrenia.

Harmonizing multisite data with the ComBat method for enhanced Parkinson's disease diagnosis via DAT-SPECT.

Background: Dopamine transporter single-photon emission computed tomography (DAT-SPECT) is a crucial tool for evaluating patients with Parkinson's disease (PD). However, its implication is limited by inter-site variability in large multisite clinical trials. To overcome the limitation, a conventional prospective correction method employs linear regression with phantom scanning, which is effective yet available only in a prospective manner. An alternative, although relatively underexplored, involves retrospective modeling using a statistical method known as "combatting batch effects when combining batches of gene expression microarray data" (ComBat). Methods: We analyzed DAT-SPECT-specific binding ratios (SBRs) derived from 72 healthy older adults and 81 patients with PD registered in four clinical sites. We applied both the prospective correction and the retrospective ComBat correction to the original SBRs. Next, we compared the performance of the original and two corrected SBRs to differentiate the PD patients from the healthy controls. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC). Results: The original SBRs were 6.13 ± 1.54 (mean ± standard deviation) and 2.03 ± 1.41 in the control and PD groups, respectively. After the prospective correction, the mean SBRs were 6.52 ± 1.06 and 2.40 ± 0.99 in the control and PD groups, respectively. After the retrospective ComBat correction, the SBRs were 5.25 ± 0.89 and 2.01 ± 0.73 in the control and PD groups, respectively, resulting in substantial changes in mean values with fewer variances. The original SBRs demonstrated fair performance in differentiating PD from controls (Hedges's g = 2.76; AUC-ROC = 0.936). Both correction methods improved discrimination performance. The ComBat-corrected SBR demonstrated comparable performance (g = 3.99 and AUC-ROC = 0.987) to the prospectively corrected SBR (g = 4.32 and AUC-ROC = 0.992) for discrimination. Conclusion: Although we confirmed that SBRs fairly discriminated PD from healthy older adults without any correction, the correction methods improved their discrimination performance in a multisite setting. Our results support the utility of harmonization methods with ComBat for consolidating SBR-based diagnosis or stratification of PD in multisite studies. Nonetheless, given the substantial changes in the mean values of ComBat-corrected SBRs, caution is advised when interpreting them.

Association of homocysteine with white matter dysconnectivity in schizophrenia.

Several studies have shown white matter (WM) dysconnectivity in people with schizophrenia (SZ). However, the underlying mechanism remains unclear. We investigated the relationship between plasma homocysteine (Hcy) levels and WM microstructure in people with SZ using diffusion tensor imaging (DTI). Fifty-three people with SZ and 83 healthy controls (HC) were included in this retrospective observational study. Tract-Based Spatial Statistics (TBSS) were used to evaluate group differences in WM microstructure. A significant negative correlation between plasma Hcy levels and WM microstructural disruption was noted in the SZ group (Spearman's ρ = -.330, P = 0.016) but not in the HC group (Spearman's ρ = .041, P = 0.712). These results suggest that increased Hcy may be associated with WM dysconnectivity in SZ, and the interaction between Hcy and WM dysconnectivity could be a potential mechanism of the pathophysiology of SZ. Further, longitudinal studies are required to investigate whether high Hcy levels subsequently cause WM microstructural disruption in people with SZ.

Relationship between personal recovery, autobiographical memory, and clinical recovery in people with mental illness in the acute phase.

Aim: Narratives are important in psychiatric rehabilitation. People with a psychiatric diagnosis find it difficult to recall specific autobiographical memories of events that lasted less than a day. Although personal narratives play a central role in personal recovery, the factors influencing personal and clinical recovery, such as psychiatric symptoms and cognitive function, have not been fully explored. Therefore, this study examined the associations between personal recovery and autobiographical memory, age, psychiatric symptoms, and neurocognitive function. Method: The Self-Identified Stage of Recovery, Parts A and B (SISR-A, SISR-B), Autobiographical Memory Test (AMT), Japanese version of the Brief Assessment Scale of Schizophrenia Cognitive Function, and Brief Psychiatric Symptom Rating Scale were administered to 40 individuals with psychiatric disorders who were undergoing psychiatric rehabilitation. Results: A significant positive correlation was found between the total number of specific memories in the AMT and total SISR-B scores. A binary logistic regression analysis revealed that the total number of specific memories, especially high responsiveness to negative cue words, significantly predicted greater personal recovery. Age, psychiatric symptoms, and neurocognitive function did not significantly predict higher personal recovery. Conclusion: In psychiatric rehabilitation, negative episodes should be treated with caution; however, they may also facilitate personal recovery.

Sustained antidepressant effects of ketamine metabolite involve GABAergic inhibition-mediated molecular dynamics in aPVT glutamatergic neurons.

Despite the rapid and sustained antidepressant effects of ketamine and its metabolites, their underlying cellular and molecular mechanisms are not fully understood. Here, we demonstrate that the sustained antidepressant-like behavioral effects of (2S,6S)-hydroxynorketamine (HNK) in repeatedly stressed animal models involve neurobiological changes in the anterior paraventricular nucleus of the thalamus (aPVT). Mechanistically, (2S,6S)-HNK induces mRNA expression of extrasynaptic GABAA receptors and subsequently enhances GABAA-receptor-mediated tonic currents, leading to the nuclear export of histone demethylase KDM6 and its replacement by histone methyltransferase EZH2. This process increases H3K27me3 levels, which in turn suppresses the transcription of genes associated with G-protein-coupled receptor signaling. Thus, our findings shed light on the comprehensive cellular and molecular mechanisms in aPVT underlying the sustained antidepressant behavioral effects of ketamine metabolites. This study may support the development of potentially effective next-generation pharmacotherapies to promote sustained remission of stress-related psychiatric disorders.

Associations of conservatism and jumping to conclusions biases with aberrant salience and default mode network.

AIM: While conservatism bias refers to the human need for more evidence for decision-making than rational thinking expects, the jumping to conclusions (JTC) bias refers to the need for less evidence among individuals with schizophrenia/delusion compared to healthy people. Although the hippocampus-midbrain-striatal aberrant salience system and the salience, default mode (DMN), and frontoparietal networks ("triple networks") are implicated in delusion/schizophrenia pathophysiology, the associations between conservatism/JTC and these systems/networks are unclear. METHODS: Thirty-seven patients with schizophrenia and 33 healthy controls performed the beads task, with large and small numbers of bead draws to decision (DTD) indicating conservatism and JTC, respectively. We performed independent component analysis (ICA) of resting functional magnetic resonance imaging (fMRI) data. For systems/networks above, we investigated interactions between diagnosis and DTD, and main effects of DTD. We similarly applied ICA to structural and diffusion MRI to explore the associations between DTD and gray/white matter. RESULTS: We identified a significant main effect of DTD with functional connectivity between the striatum and DMN, which was negatively correlated with delusion severity in patients, indicating that the greater the anti-correlation between these networks, the stronger the JTC and delusion. We further observed the main effects of DTD on a gray matter network resembling the DMN, and a white matter network connecting the functional and gray matter networks (all P < 0.05, family-wise error [FWE] correction). Function and gray/white matter showed no significant interactions. CONCLUSION: Our results support the novel association of conservatism and JTC biases with aberrant salience and default brain mode.

Revisiting Emil Kraepelin's eugenic arguments.

It is widely recognized that Emil Kraepelin explicitly advocated for eugenic ideas in his academic works. Given the renewed interest in related concepts such as self-domestication and neo-Lamarckism in different contexts, this article revisits his eugenic arguments by scrutinizing a section of his seminal work, the 8th edition of his textbook published in 1909. Our analysis reveals that Kraepelin's arguments consisted of multiple theories and ideas prevalent at the time (i.e. self-domestication hypothesis, neo-Lamarckism, degeneration theory, social Darwinism, racism and ethnic nationalism), each of which presented individual fundamental claims. Nevertheless, Kraepelin amalgamated them into one combined narrative, which crystallized into an anti-humanistic psychiatry in the next generation. This paper cautions that a similar 'packaging of ideas' might be emerging now.

Systematic reduction of gray matter volume in anorexia nervosa, but relative enlargement with clinical symptoms in the prefrontal and posterior insular cortices: a multicenter neuroimaging study.

Although brain morphological abnormalities have been reported in anorexia nervosa (AN), the reliability and reproducibility of previous studies were limited due to insufficient sample sizes, which prevented exploratory analysis of the whole brain as opposed to regions of interest (ROIs). Objective was to identify brain morphological abnormalities in AN and the association with severity of AN by brain structural magnetic resonance imaging (MRI) in a multicenter study, and to conduct exploratory analysis of the whole brain. Here, we conducted a cross-sectional multicenter study using T1-weighted imaging (T1WI) data collected between May 2014 and February 2019 in Japan. We analyzed MRI data from 103 female AN patients (58 anorexia nervosa restricting type [ANR] and 45 anorexia nervosa binge-purging type [ANBP]) and 102 age-matched female healthy controls (HC). MRI data from five centers were preprocessed using the latest harmonization method to correct for intercenter differences. Gray matter volume (GMV) was calculated from T1WI data of all participants. Of the 205 participants, we obtained severity of eating disorder symptom scores from 179 participants, including 87 in the AN group (51 ANR, 36 ANBP) and 92 HC using the Eating Disorder Examination Questionnaire (EDE-Q) 6.0. GMV reduction were observed in the AN brain, including the bilateral cerebellum, middle and posterior cingulate gyrus, supplementary motor cortex, precentral gyrus medial segment, and thalamus. In addition, the orbitofrontal cortex (OFC), ventromedial prefrontal cortex (vmPFC), rostral anterior cingulate cortex (ACC), and posterior insula volumes showed positive correlations with severity of symptoms. This multicenter study was conducted with a large sample size to identify brain morphological abnormalities in AN. The findings provide a better understanding of the pathogenesis of AN and have potential for the development of brain imaging biomarkers of AN. Trial Registration: UMIN000017456. https://center6.umin.ac.jp/cgi-open-bin/icdr/ctr_view.cgi?recptno=R000019303 .

Discrete prefrontal neuronal circuits determine repeated stress-induced behavioral phenotypes in male mice.

Chronic stress is a major risk factor for psychiatric disorders, including depression. Although depression is a highly heterogeneous syndrome, it remains unclear how chronic stress drives individual differences in behavioral responses. In this study, we developed a subtyping-based approach wherein stressed male mice were divided into four subtypes based on their behavioral patterns of social interaction deficits and anhedonia, the core symptoms of psychiatric disorders. We identified three prefrontal cortical neuronal projections that regulate repeated stress-induced behavioral phenotypes. Among them, the medial prefrontal cortex (mPFC)→anterior paraventricular thalamus (aPVT) pathway determines the specific behavioral subtype that exhibits both social deficits and anhedonia. Additionally, we identified the circuit-level molecular mechanism underlying this subtype: KDM5C-mediated epigenetic repression of Shisa2 transcription in aPVT projectors in the mPFC led to social deficits and anhedonia. Thus, we provide a set of biological aspects at the cellular, molecular, and epigenetic levels that determine distinctive stress-induced behavioral phenotypes.

Differences between subclinical attention-deficit/hyperactivity and autistic traits in default mode, salience, and frontoparietal network connectivities in young adult Japanese.

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are associated with attentional impairments, with both commonalities and differences in the nature of their attention deficits. This study aimed to investigate the neural correlates of ADHD and ASD traits in healthy individuals, focusing on the functional connectivity (FC) of attention-related large-scale brain networks (LSBNs). The participants were 61 healthy individuals (30 men; age, 21.9 ± 1.9 years). The Adult ADHD Self-Report Scale (ASRS) and Autism Spectrum Quotient (AQ) were administered as indicators of ADHD and ASD traits, respectively. Performance in the continuous performance test (CPT) was used as a behavioural measure of sustained attentional function. Functional magnetic resonance imaging scans were performed during the resting state (Rest) and auditory oddball task (Odd). Considering the critical role in attention processing, we focused our analyses on the default mode (DMN), frontoparietal (FPN), and salience (SN) networks. Region of interest (ROI)-to-ROI analyses (false discovery rate < 0.05) were performed to determine relationships between psychological measures with within-network FC (DMN, FPN, and SN) as well as with between-network FC (DMN-FPN, DMN-SN, and FPN-SN). ASRS scores, but not AQ scores, were correlated with less frequent commission errors and shorter reaction times in the CPT. During Odd, significant positive correlations with ASRS were demonstrated in multiple FCs within DMN, while significant positive correlations with AQ were demonstrated in multiple FCs within FPN. AQs were negatively correlated with FPN-SN FCs. During Rest, AQs were negatively and positively correlated with one FC within the SN and multiple FCs between the DMN and SN, respectively. These findings of the ROI-to-ROI analysis were only partially replicated in a split-half replication analysis, a replication analysis with open-access data sets, and a replication analysis with a structure-based atlas. The better CPT performance by individuals with subclinical ADHD traits suggests positive effects of these traits on sustained attention. Differential associations between LSBN FCs and ASD/ADHD traits corroborate the notion of differences in sustained and selective attention between clinical ADHD and ASD.

Compact magneto-optical isolator by µ-transfer printing of magneto-optical single-crystal film on silicon waveguides.

Optical isolators provide one-way propagation and are necessary to protect laser diodes from damage and unstable operation caused by reflected light. Although magneto-optical (MO) devices can operate as isolators, achieving high-density integration using conventional direct bonding methods is difficult because a large and thick growth substrate remains on the circuits. We experimentally demonstrated a compact Mach-Zehnder interferometer-based MO isolator with Si waveguides by the µ-transfer printing of a Ce:YIG/SGGG coupon. The isolator has a footprint of 0.25 mm2 with a Ce:YIG/SGGG coupon of 50 × 800 µm2 and ∼ 1-µm thickness and achieved a maximum isolation ratio of 14 dB in telecom bands.

Association between enhanced carbonyl stress and decreased apparent axonal density in schizophrenia by multimodal white matter imaging.

Carbonyl stress is a condition featuring increased rich reactive carbonyl compounds, which facilitate the formation of advanced glycation end products including pentosidine. We previously reported the relationship between enhanced carbonyl stress and disrupted white matter integrity in schizophrenia, although which microstructural component is disrupted remained unclear. In this study, 32 patients with schizophrenia (SCZ) and 45 age- and gender-matched healthy volunteers (HC) were recruited. We obtained blood samples for carbonyl stress markers (plasma pentosidine and serum pyridoxal) and multi-modal magnetic resonance imaging measures of white matter microstructures including apparent axonal density (intra-cellular volume fraction (ICVF)) and orientation (orientation dispersion index (ODI)), and inflammation (free water (FW)). In SCZ, the plasma pentosidine level was significantly increased. Group comparison revealed that mean white matter values were decreased for ICVF, and increased for FW. We found a significant negative correlation between the plasma pentosidine level and mean ICVF values in SCZ, and a significant negative correlation between the serum pyridoxal level and mean ODI value in HC, regardless of age. Our results suggest an association between enhanced carbonyl stress and axonal abnormality in SCZ.

Sensory processing, autonomic nervous function, and social participation in people with mental illnesses.

Introduction: This study investigated the relationship between sensory processing, respiratory sinus arrhythmia, and social participation in people with psychiatric disorders. Method: This study recruited 30 participants, primarily women, from a psychiatric university hospital with a mental health diagnosis listed in the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (mean age: 37.7 ± 16.0 years). Sensory processing, autonomic nervous function, and social participation were measured using the Adolescent/Adult Sensory Profile®, respiratory sinus arrhythmia, and World Health Organization Disability Assessment Schedule, respectively. Through mediation analysis, a model wherein sensory processing mediated the relationship between respiratory sinus arrhythmia and social participation was developed. Results: Social participation was moderately to highly correlated with Adolescent/Adult Sensory Profile® quadrants (excluding sensory seeking) and respiratory sinus arrhythmia. Furthermore, the mediation analysis revealed that sensory avoiding mediated the relationship between respiratory sinus arrhythmia and social participation, consequently counteracting the direct relationship. Conclusion: A mediation model was constructed, which indicated that individuals with psychiatric disorders and low parasympathetic nervous system activity expressed higher sensory processing quadrant of sensory avoiding. Ultimately, this was associated with reduced social participation.

The unique contribution of handwriting accuracy to literacy skills in Japanese adolescents.

There is widespread concern about declining literacy skills in recent young Japanese. The present study investigated how higher-level reading and writing proficiencies are underpinned by basic literacy skills in Japanese adolescents. From a large database of the most popular literacy exams in Japan, we retrospectively analyzed word- and text-level data for middle and high school students who had taken the exams during the same period in the 2019 academic year using structural equation modeling. We extracted main data for 161 students as well as six independent datasets for validation. Our results validated the three-dimensional view of word-level literacy (reading accuracy, writing accuracy, and semantic comprehension) and demonstrated that writing and semantic skills underpinned text writing and reading, respectively. The semantic comprehension of words affected text writing indirectly via text reading; however, it could not replace the direct effect of word writing accuracy. These findings, which were robustly replicated with multiple independent datasets, provided new evidence of dimension-specific relationships between word- and text-level literacy skills and confirmed the unique contribution of word handwriting acquisition to text literacy proficiency. The replacement of handwriting by digital writing (e.g., typing) is a global trend. However, the dual-pathway model of literacy development identified in this study suggests there are advantages in sustaining early literacy education by handwriting for the growth of higher-level language skills in future generations. Supplementary Information: The online version contains supplementary material available at 10.1007/s11145-023-10433-3.

Commonalities and differences in ECT-induced gray matter volume change between depression and schizophrenia.

BACKGROUND: Electroconvulsive therapy (ECT) is one of the most effective treatments for depression and schizophrenia, particularly in urgent or treatment-resistant cases. After ECT, regional gray matter volume (GMV) increases have been repeatedly reported both in depression and schizophrenia. However, the interpretation of these findings remains entangled because GMV changes do not necessarily correlate with treatment effects and may be influenced by the intervention itself. We hypothesized that the comparison of longitudinal magnetic resonance imaging data between the two diagnostic groups will provide clues to distinguish diagnosis-specific and transdiagnostic changes. METHOD: Twenty-nine Japanese participants, including 18 inpatients with major depressive disorder and 11 with schizophrenia, underwent longitudinal voxel-based morphometry before and after ECT. We investigated GMV changes common to both diagnostic groups and those specific to each group. Moreover, we also evaluated potential associations between GMV changes and clinical improvement for each group. RESULTS: In both diagnostic groups, GMV increased in widespread areas after ECT, sharing common regions including: anterior temporal cortex; medial frontal and anterior cingulate cortex; insula; and caudate nucleus. In addition, we found a schizophrenia-specific GMV increase in a region including the left pregenual anterior cingulate cortex, with volume increase significantly correlating with clinical improvement. CONCLUSIONS: Transdiagnostic volume changes may represent the effects of the intervention itself and pathophysiological changes common to both groups. Conversely, diagnosis-specific volume changes are associated with treatment effects and may represent pathophysiology-specific impacts of ECT.

Neuronal Loss in the Bilateral Medial Frontal Lobe Revealed by 123I-iomazenil Single-photon Emission Computed Tomography in Patients with Moyamoya Disease: The First Report from Cognitive Dysfunction Survey of Japanese Patients with Moyamoya Disease (COSMO-Japan Study).

Cognitive impairment in adult patients with moyamoya disease (MMD) is sometimes overlooked and can occur in patients with no ischemic or hemorrhagic lesions. Better profiling and reliable diagnostic methods that characterize the group and associate the impairments and pathology of MMD are required in order to deliver appropriate treatments and support. The potential of 123I-iomazenil single-photon emission computed tomography (SPECT) for this issue has been reported in some studies, but the universality of this method remains unclear. A multicenter study of adult patients (aged 18-60 years) with MMD who experienced difficulties in social lives despite normal activities of daily living was implemented to delineate the common characteristics of this group of patients. In this study, iomazenil SPECT, besides patient characteristics, cognitive functions, and conventional imaging, was acquired to examine whether this method is suitable as a universal diagnostic tool. A total of 36 patients from 12 institutes in Japan were included in this study. Domain scores of world health organization quality of life 26 indicated low self-rating in physical health and psychological domains. The percentages of patients who had <85 in each index were 27.8%-33.3% in the WAIS-III and 16.7%-47.2% in the Wechsler Memory Scale-Revised. The group analysis of iomazenil SPECT demonstrated a decreased accumulation in the bilateral medial frontal areas in comparison with the normal control, whereas there were no specific characteristics on conventional imaging in the cohort. Iomazenil SPECT is a possible universal diagnostic method for the extraction of patients with cognitive impairment in MMD.

GPCR-mediated calcium and cAMP signaling determines psychosocial stress susceptibility and resiliency.

Chronic stress increases the risk of developing psychiatric disorders, including mood and anxiety disorders. Although behavioral responses to repeated stress vary across individuals, the underlying mechanisms remain unclear. Here, we perform a genome-wide transcriptome analysis of an animal model of depression and patients with clinical depression and report that dysfunction of the Fos-mediated transcription network in the anterior cingulate cortex (ACC) confers a stress-induced social interaction deficit. Critically, CRISPR-Cas9-mediated ACC Fos knockdown causes social interaction deficits under stressful situation. Moreover, two classical second messenger pathways, calcium and cyclic AMP, in the ACC during stress differentially modulate Fos expression and regulate stress-induced changes in social behaviors. Our findings highlight a behaviorally relevant mechanism for the regulation of calcium- and cAMP-mediated Fos expression that has potential as a therapeutic target for psychiatric disorders related to stressful environments.