Published papers

© 2018, The Author(s). Neural connectivity has recently been shown to be altered after spinal cord injury (SCI) not only in the spinal cord but also in the brain. However, to date, no studies have analyzed the functional alterations after SCI in various areas of the cerebral cortex over time. To examine the plasticity of the neural connectivity in the brain after SCI, we performed resting-state functional magnetic resonance imaging (rs-fMRI) in awake adult mice pre- and post-SCI. After a complete thoracic SCI, the functional connectivity between the primary motor (MOp) and primary sensory (SSp) areas was significantly decreased during the chronic phase. In contrast, the connectivity between the MOp and motivation area was increased. Thus, impairments in sensory and motor connections after SCI led to a time-dependent compensatory upregulation of “motor functional motivation”. Moreover, the functional connectivity between the SSp and pain-related areas, such as the caudoputamen (CP) and the anterior cingulate area (ACA), was strengthened during the chronic phase, thus suggesting that rs-fMRI can indicate the presence of neuropathic pain after SCI. Therefore, rs-fMRI is a useful tool for revealing the pathological changes that occur in the brain after SCI.

BACKGROUND/OBJECTIVE: To assess associations between improvements in neuropsychiatric symptoms (NPS) and neurocognitive change in patients with Alzheimer's disease (AD) during treatment using the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer Disease (CATIE-AD) dataset. METHODS: AD outpatients with NPS who needed pharmacological treatment (n = 421) were followed up with antipsychotics, citalopram, or placebo for up to 36 weeks (mean±SD = 252±52 days). The study aim was to investigate associations between improvement in each NPS evaluating scale (by Clinical Global Impression of Change [CGI-C], Neuropsychiatric Inventory [NPI], or Brief Psychiatric Scale [BPRS]) at endpoint (week 36 or early termination [ET], n = 340) and neurocognitive change (change score in the Mini-Mental State Examination [MMSE] between endpoint and baseline during the treatment). Multiple logistic regression analyses were performed on the associations between each NPS improvement and neurocognitive change as well as socio-clinico-demographic variables of interest. RESULTS: At endpoint, NPS improvement rates were 76.1%, 70.8%, and 58.1% in CGI-C, NPI, and BPRS, respectively, while MMSE score change was -2.3±3.8. NPS improvement was significantly related to more severe psychotic symptoms at baseline and preserved levels of neurocognition (smaller MMSE score change) among several variables. CONCLUSIONS: Our findings suggested that neurocognitive preservation may be associated with attaining optimal benefits from any treatment against NPSs in a longitudinal treatment course of patients with AD.

© 2018 The Author. Psychiatry and Clinical Neurosciences © 2018 Japanese Society of Psychiatry and Neurology Aim: Research on the adverse effects of Internet use has gained importance recently. However, there is currently insufficient data on Japanese young adults’ Internet use, so we conducted a survey targeting Japanese university students to research problematic Internet use (PIU). We also investigated the relationship between PIU and multiple psychiatric symptoms. Methods: A paper-based survey was conducted at five universities in Japan. Respondents were asked to fill out self-report scales regarding their Internet dependency using the Internet Addiction Test (IAT). Sleep quality, attention-deficit hyperactivity disorder (ADHD) tendency, depression, and anxiety symptom data were also collected based on respective self-reports. Results: There were 1336 responses and 1258 were included in the analysis. The mean IAT score (± SD) was 37.87 ± 12.59; and 38.2% of participants were classified as PIU, and 61.8% as non-PIU. The trend level for young women showed that they were more likely to be classified as PIU than young men (40.6% and 35.2% respectively, P = 0.05). Compared to the non-PIU group, the PIU group used the Internet longer (P < 0.001), had significantly lower sleep quality (P < 0.001), had stronger ADHD tendencies (P < 0.001), had higher Depression scores (P < 0.001), and had higher Trait-Anxiety scores (P < 0.001). Based on multiple logistic regression analyses, the factors that contributed to an increased risk of PIU were: being female (odds ratio [OR] = 1.52), being older (OR = 1.17), having poor sleep quality (OR = 1.52), having ADHD tendencies (OR = 2.70), having depression (OR = 2.24), and having anxiety tendencies (OR = 1.43). Conclusion: We found a high PIU prevalence among Japanese young adults. The factors that predicted PIU were: female sex, older age, poor sleep quality, ADHD tendencies, depression, and anxiety.

© Wolters Kluwer Health, Inc. All rights reserved. Objective We aimed to examine attitudes toward electroconvulsive therapy (ECT) among involuntary patients, voluntary patients, and their relatives. Methods Patients experiencing a major depressive episode and receiving ECT and their relatives were recruited for the survey. Patients and their relatives answered the self-rating questionnaires with a 7-point Likert scale. We explored differences in the survey results between involuntary and voluntary patients, as well as differences in the survey results between patients and their relatives. Results We recruited 97 participants (53 patients and 44 relatives) for the survey. Approximately 80% of the patients showed positive attitudes toward ECT. There were no statistically significant differences between involuntary (n = 23) and voluntary (n = 30) patients across multiple aspects of the ECT experience, including treatment satisfaction, positive or adverse effects of ECT, and treatment preference in the future. Relatives were more satisfied with the positive effects of ECT and with the information offered before ECT treatment than the patients themselves. Conclusions Approximately 80% of the patients showed overall satisfaction with ECT irrespective of consent status. Relatives were more satisfied with ECT than patients. Electroconvulsive therapy can be a lifesaving treatment for severely depressed patients, and the subjective experience of involuntary patients should be taken into consideration when discussing involuntary ECT treatment.

© 2020 The Author(s). Aquaporin-4 (AQP4) has been suggested to be involved in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD), which may be due to the modulation of neuroinflammation or the impairment of interstitial fluid bulk flow system in the central nervous system. Here, we show an age-dependent impairment of several behavioral outcomes in 5xFAD AQP4 null mice. Twenty-four-hour video recordings and computational analyses of their movement revealed that the nighttime motion of AQP4-deficient 5xFAD mice was progressively reduced between 20 and 36 weeks of age, with a sharp deterioration occurring between 30 and 32 weeks. This reduction in nighttime motion was accompanied by motor dysfunction and epileptiform neuronal activities, demonstrated by increased abnormal spikes by electroencephalography. In addition, all AQP4-deficient 5xFAD mice exhibited convulsions at least once during the period of the analysis. Interestingly, despite such obvious phenotypes, parenchymal amyloid β (Aβ) deposition, reactive astrocytosis, and activated microgliosis surrounding amyloid plaques were unchanged in the AQP4-deficient 5xFAD mice relative to 5xFAD mice. Taken together, our data indicate that AQP4 deficiency greatly accelerates an age-dependent deterioration of neuronal function in 5xFAD mice associated with epileptiform neuronal activity without significantly altering Aβ deposition or neuroinflammation in this mouse model. We therefore propose that there exists another pathophysiological phase in AD which follows amyloid plaque deposition and neuroinflammation and is sensitive to AQP4 deficiency.

© 2019 Background: Major depressive disorder (MDD) is a heterogeneous condition. Identifying the brain responses to antidepressant treatment is of particular interest as these may represent potential neural networks related to treatment response, forming one aspect of the biological markers of MDD. Near-infrared spectroscopy (NIRS) is suitable for repeated measurements with short intervals because of its noninvasiveness, and can provide detailed time courses of functional alterations in prefrontal regions. Methods: We conducted a 12-week longitudinal study to explore prefrontal hemodynamic changes at 4-week intervals following sertraline treatment in 11 medication-naïve participants with MDD using 52-channel NIRS. Results: While all participants achieved remission after treatment, intra-class correlation coefficient of oxygenated hemoglobin [oxy-Hb] values throughout the 12-week observation was moderate at the spatially and temporally contiguous cluster located in the left inferior frontal and temporal gyri. There was a significant negative correlation between mean [oxy-Hb] values in the significant cluster at 4 weeks and changes in Hamilton Rating Scale for Depression total score from 4 to 8 weeks (r = −0.73, P = 0.011) and from 4 to 12 weeks (r = −0.63, P = 0.039). Limitations: Without healthy controls for comparison, we were unable to fully evaluate whether improvement of [oxy-Hb] activations after treatment in MDD reached normal levels or not. Conclusion: Our NIRS findings of detailed prefrontal hemodynamic alterations over short interval observations such as 4 weeks may have revealed potential trait marker for MDD and biological maker for predicting clinical response to sertraline treatment in MDD.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. We investigated the feasibility of our novel evaluation system for use with children with autism spectrum disorders (ASD). We prepared the experimental setting with two humanoid robots in reference to the birthday party scene in the Autism Diagnostic Observational Schedule (ADOS). We assessed the relationship between social communication ability measured in the ADOS condition (i.e., with a human clinician) and in a robotic condition for children with ASD. There were significant correlations between the social communication scores in the gold-standard ADOS condition and the robotic condition for children with ASD. The current work provides support for a unique application of a robotic system (i.e., two robot-mediated interaction) to evaluate the severity of autistic traits for children with ASD.

© 2018, The Author(s). Technological agents could be effective tools to be used in interventions for enhancing social orienting for some young children with ASD. We examined response to social bids in preschool children with ASD and typical development (TD) at a very early age (i.e., around 3 years) using social prompts presented by technological agents of various forms and human comparisons. Children with ASD demonstrated less response overall to social bids compared to TD controls, across agents or human. They responded more often to a simple humanoid robot and the simple avatar compared to the human. These results support the potential utilization of specific robotic and technological agents for harnessing and potentially increasing motivation to socially-relevant behaviors in some young children with ASD.

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Olfactory adaptation is an important process that allows the individual to adjust to changes in the environment. This process has been proposed to be aberrant in individuals with autism spectrum disorders (ASD). However, few studies have examined olfactory adaptation in children with ASD. We examined olfactory adaptation in children with ASD and typically developing (TD) children using a pulse ejection system, which resolved problems associated with previous laboratory-based olfactory psychophysical studies. Nine children with ASD and nine TD children participated in this study and all participants completed the entire experiment. Using this system, we found that the TD group showed greater adaptation than the ASD group. Our results provide a better understanding of olfactory adaptation in children with ASD.

© 2018 Kumazaki, Warren, Swanson, Yoshikawa, Matsumoto, Takahashi, Sarkar, Ishiguro, Mimura, Minabe and Kikuchi. Research suggests that many individuals with autism spectrum disorder (ASD) often demonstrate challenges providing appropriate levels of information during conversational interchanges. Considering the preference of individuals with ASD, and recent rapid technological advances, robotic systems may yield promise in promoting certain aspects of conversation and interaction such as self-disclosure of appropriate personal information. In the current work, we evaluated personal disclosures of events with specific emotional content across two differing robotic systems (android and simplistic humanoid) and human interactions. Nineteen participants were enrolled in this study: 11 (2 women and 9 men) adolescents with ASD and 8 (4 women and 4 men) adolescents with TD. Each participant completed a sequence of three interactions in a random order. Results indicated differences regarding comfort level and length of disclosures between adolescents with ASD and typically developing (TD) controls in relation to system interactions. Specifically, adolescents with ASD showed a preference for interacting with the robotic systems compared to TD controls and demonstrated lengthier disclosures when interacting with the visually simple humanoid robot compared to interacting with human interviewer. The findings suggest that robotic systems may be useful in eliciting and promoting aspects of social communication such as self-disclosure for some individuals with ASD.