Published papers

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Background: The neural basis of treatment-resistant schizophrenia (TRS) remains unclear. Previous neuroimaging studies suggest that aberrant connectivity between the anterior cingulate cortex (ACC) and default mode network (DMN) may play a key role in the pathophysiology of TRS. Thus, we aimed to examine the connectivity between the ACC and posterior cingulate cortex (PCC), a hub of the DMN, computing isolated effective coherence (iCoh), which represents causal effective connectivity. Methods: Resting-state electroencephalogram with 19 channels was acquired from seventeen patients with TRS and thirty patients with non-TRS (nTRS). The iCoh values between the PCC and ACC were calculated using sLORETA software. We conducted four-way analyses of variance (ANOVAs) for iCoh values with group as a between-subject factor and frequency, directionality, and laterality as within-subject factors and post-hoc independent t-tests. Results: The ANOVA and post-hoc t-tests for the iCoh ratio of directionality from PCC to ACC showed significant findings in delta (t45 = 7.659, p = 0.008) and theta (t45 = 8.066, p = 0.007) bands in the left side (TRS < nTRS). Conclusion: Left delta and theta PCC and ACC iCoh ratio may represent a neurophysiological basis of TRS. Given the preliminary nature of this study, these results warrant further study to confirm the importance of iCoh as a clinical indicator for treatment-resistance.

© 2019 Kumazaki, Muramatsu, Yoshikawa, Matsumoto, Ishiguro, Mimura and Kikuchi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Interventions for job interviews targeting the impaired theory of mind observed in individuals with autism spectrum disorders (ASD) are limited. We developed a role-play-based guidance system for job interviews using an android robot resembling a real person. Individuals with ASD worked in pairs and played dual roles in mock job interviews. Specifically, one participant acted as the interviewee, while the other participant operated the android robot and acted as the interviewer. Eight individuals with high-functioning ASD participated in this study. After the training sessions, participants learned to understand the point of view of the interviewer, which may contribute to increased recognition of the importance of gestures and the motivation to learn how to behave in a job interview. In addition, participants reported improved self-confidence. These results provide preliminary support for the efficacy of playing dual roles using android robots.

© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc. The ability to sustain goal-directed action is essential for success in many domains, but little is known about the corresponding neural substrates. Using fiber photometry to monitor population neural activity, we demonstrate that engagement in sustained food- or punishment-motivated behavior is associated with suppression of ventral but not dorsal hippocampal activity. Using optogenetic stimulation, we demonstrate that this suppression is required for goal-directed behavior, whereas optogenetic suppression of the ventral hippocampus (vHP) enhances the ability to sustain goal-directed behavior. Suppression of vHP during sustained goal-directed behavior was accompanied by increased activity in median but not dorsal raphe, implicating serotonergic signaling through Htr3a as a mechanism of vHP suppression during successful goal-directed behavior. Sustainment of goal-directed action may require suppression of vHP because of the structure’s well-documented role in behavioral inhibition.

© 2019 Yuki Hidaka et al. The functional visual acuity test which is the average of the visual acuities measured during a specific time frame (standard, 60 seconds) has been used recently to assess the visual function in various conditions. The availability of a shorter version of the functional visual acuity test promises to be patient friendly in that it is a simple screening test performed in a shorter period of time than the standard test. The results of measurements of the FVA test between the 30-second measurement time (short-version FVA test) and the standard 60-second measurement are compared, and the feasibility of the short-version FVA test instead of the standard FVA test is investigated. Twenty-eight healthy volunteers (25 men and 3 women) were enrolled in this prospective observational study. All subjects underwent measurement of the binocular distance-corrected visual acuity and the binocular distance-corrected FVA with the 60-second and 30-second measurement times. The interchangeability of the corrected-distance FVA, maximal VA, visual maintenance ratio, and average response time in the short-version and the standard FVA tests was evaluated using the Bland-Altman method, and the results showed agreements of the two tests except for the minimal VA. The short-version FVA test is equivalent to the standard method except for evaluating the visual acuity fluctuations and promises to be a simple visual screening test that can be performed in a shorter time.

© 2018 The Authors. PURPOSE. Sleep is an essential life habit and closely associated with lifespan, diabetes, hypertension, and mental health. Sleep disorders are a prominent, but overlooked problem in patients with dry eye disease (DED), characterized by a poor sleep index, short sleep duration, long sleep latency, and poor subjective sleep. DED and sleep disorders are more prevalent in women than men. Moreover, sleep quality in DED is worse than in other eye diseases, including glaucoma, retinal diseases, cataract, and allergic and chronic conjunctivitis. METHODS. We reviewed the literature for studies investigating sleep and health, eyes and sleep, and DED and sleep, in terms of systemic and eye health, especially in women. RESULTS. Two studies reported that approximately half of patients with DED suffer from poor sleep. The severity of mood disorders, including anxiety and depression, is correlated strongly with sleep disorders in DED, and the symptoms and signs of DED, especially pain, also are correlated with sleep quality. Sleep disorders are documented in primary Sjögren’s syndrome and an association with sleep apnea and depression is suggested. Primary Sjögren’s syndrome includes arthritis and other rheumatic disease causing pain and fatigue; however, how sicca contributes to sleep disorders is not known. CONCLUSIONS. Possible explanations for sleep disorders in DED may be depression, pain, and eye exposure at night. Reciprocal effects may be expected and consultation-liaison psychiatry is recommended for the management of sleep disorders in DED. Topical medication and lid heating also may be advantageous for sleep quality in DED.

© The Author(s) 2019. Getting enough quality sleep plays a vital role in protecting our mental health, physical health, and quality of life. Sleep deprivation can make it difficult to concentrate on daily activities, and lower sleep quality is associated with hypertension, hyperglycemia, and hyperlipidemia. The amount of sleep we get is important, but in recent years, quality sleep has also been deemed significant. Polysomnography, which has been the gold standard in assessing sleep quality based on stages, requires that the subject be attached to electrodes, which can disrupt sleep. An easier method to objectively measure sleep is therefore needed. The aim of this study was to construct an easy and objective sleep stage monitoring method. A cross-sectional study for healthy subjects has been done in our research. A new easy model for monitoring the sleep stages is built on only heart rate calculated by the electrocardiogram. This enabled us to easily assess the sleep quality based on five stages. This experiment included a total of 50 subjects. The overall accuracy in determining the five sleep stages was 66.0 percent. Four stages for sleep are identified accurately compared with other conventional methods. Despite there are no five sleep stage separation method using only heart rate, our method achieved the five separation for sleep with a relatively good accuracy. This study represents a great contribution to the field of sleep science. Because sleep stages can be recognized by the heart rate alone, sleep can be noninvasively assessed with any heart rate meter. This method will make it easier to determine sleep stages and diagnose sleep disorders.

© 2019 Japanese Psychogeriatric Society Aim: The aim of this study was to examine sociopsychological characteristics of the oldest old in Japan. We conducted a baseline survey of a community-based cohort of persons aged 95 or older. Methods: Participants were aged 95+ years and resided in Arakawa Ward in Tokyo on 1 January 2016. We mailed a questionnaire to these individuals to assess their physical, mental, and social status. Subsequently, if respondents agreed, we conducted in-home interviews and examined their physical and cognitive function. Also, we mailed non-respondents a simplified version of full questionnaire. Additionally, we examined the basic registered data of the study population and the status of their Long-term Care Insurance. Data at baseline and 1-year follow-up were compared. Results: With regard to Long-term Care Insurance, 423 residents aged 95+ years (78.0%) were on long-term care level, 35 (6.5%) were on support level, and 84 (15.5%) did not require support. At the 1-year follow-up, 275 (50.7%) had the same care level, 107 (19.7%) required a greater level of care, and 131 had died (annual death rate: 24.2%). Compared to the simplified questionnaire group (n = 128) and the full questionnaire-only group (n = 14), a higher proportion of respondents who had completed the full questionnaire and had in-home interviews (n = 26) were men, lived only with a spouse, had higher activities of daily living, and reported more positive feelings and well-being. Conclusions: In the late nonagenarian population, the annual death rate was high, and care needs increased rapidly. However, some persons maintained the same care level or even showed improvement and successful ageing.

© 2020 Cambridge Philosophical Society The cognitive map has been taken as the standard model for how agents infer the most efficient route to a goal location. Alternatively, path integration – maintaining a homing vector during navigation – constitutes a primitive and presumably less-flexible strategy than cognitive mapping because path integration relies primarily on vestibular stimuli and pace counting. The historical debate as to whether complex spatial navigation is ruled by associative learning or cognitive map mechanisms has been challenged by experimental difficulties in successfully neutralizing path integration. To our knowledge, there are only three studies that have succeeded in resolving this issue, all showing clear evidence of novel route taking, a behaviour outside the scope of traditional associative learning accounts. Nevertheless, there is no mechanistic explanation as to how animals perform novel route taking. We propose here a new model of spatial learning that combines path integration with higher-order associative learning, and demonstrate how it can account for novel route taking without a cognitive map, thus resolving this long-standing debate. We show how our higher-order path integration (HOPI) model can explain spatial inferences, such as novel detours and shortcuts. Our analysis suggests that a phylogenetically ancient, vector-based navigational strategy utilizing associative processes is powerful enough to support complex spatial inferences.

© MDPI AG. All rights reserved. Loss of cognitive ability is commonly associated with dementia, a broad category of progressive brain diseases. However, major depressive disorder may also cause temporary deterioration of one’s cognition known as pseudodementia. Differentiating a true dementia and pseudodementia is still difficult even for an experienced clinician and extensive and careful examinations must be performed. Although mental disorders such as depression and dementia have been studied, there is still no solution for shorter and undemanding pseudodementia screening. This study inspects the distribution and statistical characteristics from both dementia patient and depression patient, and compared them. It is found that some acoustic features were shared in both dementia and depression, albeit their correlation was reversed. Statistical significance was also found when comparing the features. Additionally, the possibility of utilizing machine learning for automatic pseudodementia screening was explored. The machine learning part includes feature selection using LASSO algorithm and support vector machine (SVM) with linear kernel as the predictive model with age-matched symptomatic depression patient and dementia patient as the database. High accuracy, sensitivity, and specificity was obtained in both training session and testing session. The resulting model was also tested against other datasets that were not included and still performs considerably well. These results imply that dementia and depression might be both detected and differentiated based on acoustic features alone. Automated screening is also possible based on the high accuracy of machine learning results.

© 2018 Matsuguma et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. It is well recognized that visual impairments (VI) worsen individuals’ mental condition. However, little is known about the positive aspects including subjective happiness, positive emotions, and strengths. Therefore, the purpose of this study was to investigate the positive aspects of persons with VI including their subjective happiness, positive emotions, and strengths use. Positive aspects of persons with VI were measured using the Subjective Happiness Scale (SHS), the Scale of Positive and Negative Experience-Balance (SPANE-B), and the Strengths Use Scale (SUS). A cross-sectional analysis was utilized to examine personal information in a Tokyo sample (N = 44). We used a simple regression analysis and found significant relationships between the SHS or SPANE-B and SUS; on the contrary, VI-related variables were not correlated with them. A multiple regression analysis confirmed that SUS was a significant factor associated with both the SHS and SPANE-B. Strengths use might be a possible protective factor from the negative effects of VI.

© 2017 Pharmacological intervention in the substantia nigra is known to induce repetitive behaviors in rodents, but a direct causal relationship between a specific neural circuit and repetitive behavior has not yet been established. Here we demonstrate that optogenetic activation of dopamine D1 receptor-expressing MSNs terminals in the substantia nigra pars reticulata resulted in sustained and chronic repetitive behaviors. These data show for the first time that activation of the striatonigral direct pathway is sufficient to generate motor stereotypies.

© 2020, The Author(s). Background: 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. Methods: The Japan Prospective Studies Collaboration for Aging and Dementia (JPSC-AD) is a multisite, population-based prospective cohort study of dementia, which was designed to enroll approximately 10,000 community-dwelling residents aged 65 years or older from 8 sites in Japan and to follow them up prospectively for at least 5 years. Baseline exposure data, including lifestyles, medical information, diets, physical activities, blood pressure, cognitive function, blood test, brain magnetic resonance imaging (MRI), and DNA samples, were collected with a pre-specified protocol and standardized measurement methods. The primary outcome was the development of dementia and its subtypes. The diagnosis of dementia was adjudicated by an endpoint adjudication committee using standard criteria and clinical information according to the Diagnostic and Statistical Manual of Mental Disorders, 3rd Revised Edition. For brain MRI, three-dimensional acquisition of T1-weighted images was performed. Individual participant data were pooled for data analyses. Results: The baseline survey was conducted from 2016 to 2018. The follow-up surveys are ongoing. A total of 11,410 individuals aged 65 years or older participated in the study. The mean age was 74.4 years, and 41.9% were male. The prevalence of dementia at baseline was 8.5% in overall participants. However, it was 16.4% among three sites where additional home visit and/or nursing home visit surveys were performed. Approximately two-thirds of dementia cases at baseline were Alzheimer’s disease. Conclusions: The prospective cohort data from the JPSC-AD will provide valuable insights regarding the risk factors and etiology of dementia as well as for the development of predictive models and diagnostic markers for the future onset of dementia. The findings of this study will improve our understanding of dementia and provide helpful information to establish effective preventive strategies for dementia in Japan.

© 2019 Japan Geriatrics Society Aim: Few cohort studies targeting the oldest-old individuals have been carried out. The subiculum in the hippocampus is thought to be related to memory function, and atrophy of this structure might result in the conversion from amnestic mild cognitive impairment to Alzheimer's disease. Thus, we sought to examine the relationship between subiculum volumes and memory function in individuals aged ≥95 years, using a novel cognitive examination called the Addenbrooke's Cognitive Examination III (ACE-III) and an advanced magnetic resonance imaging analytical method, Multiple Automatically Generated Templates Brain Segmentation Algorithm (MAGeTbrain), to measure hippocampal subfield volumes. Methods: A part of the cohort data of the Arakawa 95+ study for the oldest-old aged ≥95 years was used. A total of 10 individuals completed all of the examinations. The MAGeT brain was applied to estimate the subfield volumes of the hippocampus. Correlation analyses and multiple regression analyses were carried out to examine a relationship among ACE-III memory scores and the subfield volumes in the hippocampus, including the subiculum. Results: There was a significant relationship between ACE-III memory scores and subdivision volumes. Regression analyses showed that subiculum volumes were associated with ACE-III memory scores in the oldest-old individuals (β = 0.721, P = 0.019; F 1, 8 = 8.67, adjusted R 2 = 0.46). Conclusions: The subiculum might play a pivotal role in memory function in the oldest-old individuals aged ≥95 years. The present finding warrants further research including larger sample sizes. Geriatr Gerontol Int 2019; 19: 347–351.

© 2019 Suzuki, Ohgidani, Kuwano, Chrétien, Lorin de la Grandmaison, Onaya, Tominaga, Setoyama, Kang, Mimura, Kanba and Kato. Suicide is one of the most disastrous outcomes for psychiatric disorders. Recent advances in biological psychiatry have suggested a positive relationship between some specific brain abnormalities and specific symptoms in psychiatric disorders whose organic bases were previously completely unknown. Microglia, immune cells in the brain, are regarded to play crucial roles in brain inflammation by releasing inflammatory mediators and are suggested to contribute to various psychiatric disorders such as depression and schizophrenia. Recently, activated microglia have been suggested to be one of the possible contributing cells to suicide and suicidal behaviors via various mechanisms especially including the tryptophan-kynurenine pathway. Animal model research focusing on psychiatric disorders has a long history, however, there are only limited animal models that can properly express psychiatric symptoms. In particular, to our knowledge, animal models of human suicidal behaviors have not been established. Suicide is believed to be limited to humans, therefore human subjects should be the targets of research despite various ethical and technical limitations. From this perspective, we introduce human biological studies focusing on suicide and microglia. We first present neuropathological studies using the human postmortem brain of suicide victims. Second, we show recent findings based on positron emission tomography (PET) imaging and peripheral blood biomarker analysis on living subjects with suicidal ideation and/or suicide-related behaviors especially focusing on the tryptophan-kynurenine pathway. Finally, we propose future perspectives and tasks to clarify the role of microglia in suicide using multi-dimensional analytical methods focusing on human subjects with suicidal ideation, suicide-related behaviors and suicide victims.

© 2019 The Author(s). Background: Besides research on psychiatric diseases related to problematic Internet use (PIU), a growing number of studies focus on the impact of Internet on subjective well-being (SWB). However, in previous studies on the relationship between PIU and SWB, there is little data for Japanese people specifically, and there is a lack of consideration for differences in perception of happiness due to cultural differences. Therefore, we aimed to clarify how happiness is interdependent on PIU measures, with a focus on how the concept of happiness is interpreted among Japanese people, and specifically among Japanese university students. Methods: A paper-based survey was conducted with 1258 Japanese university students. Respondents were asked to fill out self-report scales regarding their happiness using the Interdependent Happiness Scale (IHS). The relationship between IHS and Internet use (Japanese version of the Internet addiction test, JIAT), use of social networking services, as well as social function and sleep quality (Pittsburgh Sleep Quality Index, PSQI) were sought using multiple regression analyses. Results: Based on multiple regression analyses, the following factors related positively to IHS: female gender and the number of Twitter followers. Conversely, the following factors related negatively to IHS: poor sleep, high- PIU, and the number of times the subject skipped a whole day of school. Conclusions: It was shown that there was a significant negative correlation between Japanese youths' happiness and PIU. Since epidemiological research on happiness that reflects the cultural background is still scarce, we believe future studies shall accumulate similar evidence in this regard.

© 2020 Elsevier B.V. Despite previous neuroimaging studies demonstrating morphological abnormalities of the thalamus and other subcortical structures in patients with schizophrenia, the potential role of the thalamus and its subdivisions in the pathophysiology of this illness remains elusive. It is also unclear whether similar changes of these structures occur in individuals at high risk for psychosis. In this study, magnetic resonance imaging was employed with the Multiple Automatically Generated Templates (MAGeT) brain segmentation algorithm to determine volumes of the thalamic subdivisions, the striatum (caudate, putamen, and nucleus accumbens), and the globus pallidus in 62 patients with schizophrenia, 38 individuals with an at-risk mental state (ARMS) [4 of whom (10.5%) subsequently developed schizophrenia], and 61 healthy subjects. Cognitive function of the patients was assessed by using the Brief Assessment of Cognition in Schizophrenia (BACS) and the Schizophrenia Cognition Rating Scale (SCoRS). Thalamic volume (particularly the medial dorsal and ventral lateral nuclei) was smaller in the schizophrenia group than the ARMS and control groups, while there were no differences for the striatum and globus pallidus. In the schizophrenia group, the reduction of thalamic ventral lateral nucleus volume was significantly associated with lower BACS score. The pallidal volume was positively correlated with the dose of antipsychotic treatment in the schizophrenia group. These results suggest that patients with schizophrenia, but not those with ARMS, exhibit volume reduction in specific thalamic subdivisions, which may underlie core clinical features of this illness.

© 2019 Electroconvulsive therapy (ECT) is the most effective antidepressant treatment. Biological predictors of clinical outcome to ECT are valuable. We aimed to examine multimodal magnetic resonance imaging (MRI) data that correlates to the efficacy of ECT. Structural and resting-state functional MRI data were acquired from 46 individuals (25 depressed individuals who received ECT, and 21 healthy controls). Whole-brain grey matter volume (GMV) and fractional amplitude of low frequency fluctuations (fALFF) were investigated to identify brain regions associated with post-ECT Hamilton Depression Rating Scale (HAM-D) total scores. GMV and fALFF values were compared with those in healthy controls using analysis of covariance (ANCOVA). Remission was defined by HAM-D ≤7. A multiple regression analysis revealed that pretreatment smaller GMV in the left thalamus was associated with worse response to ECT (i.e. higher post-ECT HAM-D). Pretreatment higher fALFF in the right anterior insula, and lower fALFF in the left thalamus and the cerebellum were associated with worse outcomes. The left thalamus was identified in both GMV and fALFF analyses. Nonremitters showed significantly smaller thalamic GMV compared to remitters and controls. We found that pretreatment thalamic volume and resting-state activity were associated with the efficacy of ECT. Our results highlight the importance of the thalamus as a possible biological predictor and its role in the underlying mechanisms of ECT action.

© 2019, The Author(s). A third of dementia cases could be attributable to modifiable risk-factors. Midlife high-density lipoprotein cholesterol (HDL-C) is a measure which could help identify individuals at reduced risk of developing age-related cognitive decline. The Japan Public Health Centre-based prospective (JPHC) Study is a large population-based cohort which started in 1990. This study included 1299 participants from Saku area in Nagano prefecture. Participants had HDL-C measured in 1995–1996, and underwent a mental health screening in 2014–2015. Of these, 1114 participants were included in MCI analyses, and 781 participants were included in dementia analyses. Logistic regression models were used to determine odds ratios (OR) and 95% confidence intervals (CI) for the association between HDL-C quartiles and MCI and dementia, respectively. For dementia analysis, quartiles 2–4 were collapsed due to low number of cases. Missing data was addressed through multiple imputations. There were 386 cases of MCI and 53 cases of dementia. Compared to the lowest HDL-C quartile, the highest HDL-C quartile was significantly inversely associated with MCI (OR = 0.47, 95% CI, 0.28–0.79) in the multivariable analysis. High HDL-C (quartiles 2–4) was inversely associated with dementia compared to low HDL-C (quartile 1) (OR = 0.37, 95% CI, 0.16–0.88). This study has found that high midlife HDL-C levels are inversely associated with both late-life MCI and dementia in a Japanese population.

© 2018 Elsevier B.V. Backgrounds: The intestinal microbiota is considered as a potential common underpinning pathophysiology of Functional Gastrointestinal Disorders (FGIDs) and psychiatric disorders such as depression and anxiety. Fecal Microbiota Transplantation (FMT) has been reported to have therapeutic effects on diseases related to dysbiosis, but few studies have evaluated its effect on psychiatric symptoms. Methods: We followed 17 patients with either Irritable Bowel Syndrome (IBS), Functional Diarrhea (FDr) or Functional Constipation (FC) who underwent FMT for the treatment of gastrointestinal symptoms and observation of psychiatric symptoms. Changes in Hamilton Rating Scale for Depression (HAM-D) and subscale of sleep-related items, Hamilton Rating Scale for Anxiety (HAM-A) and Quick Inventory for Depressive Symptoms (QIDS) between baseline and 4 weeks after FMT, and relationship with the intestinal microbiota were measured. Results: At baseline, 12 out of 17 patients were rated with HAM-D ≥ 8. Significant improvement in HAM-D total and sleep subscale score, HAM-A and QIDS were observed (p = 0.007, p = 0.007, p = 0.01, p = 0.007, respectively). Baseline Shannon index indicated that microbiota showed lower diversity in patients with HAM-D ≥ 8 compared to those of healthy donors and patients with HAM-D < 8. There was a significant correlation between baseline Shannon index and HAM-D score, and a correlation between Shannon index change and HAM-D improvement after FMT. Limitations: The small sample size with no control group. Conclusions: Our results suggest that depression and anxiety symptoms may be improved by FMT regardless of gastrointestinal symptom change in patients with IBS, FDr and FC, and the increase of microbiota diversity may help to improve patient's mood.