研究者詳細 - 平野　仁一

論文 - 平野　仁一

分割表示 >> ／全件表示 45 件中 1 - 45 件目

Amyloid-β prediction machine learning model using source-based morphometry across neurocognitive disorders

Momota Y., Bun S., Hirano J., Kamiya K., Ueda R., Iwabuchi Y., Takahata K., Yamamoto Y., Tezuka T., Kubota M., Seki M., Shikimoto R., Mimura Y., Kishimoto T., Tabuchi H., Jinzaki M., Ito D., Mimura M.

Scientific Reports （Scientific Reports） 14 （ 1 ） 7633 2024年12月

ISSN 2045-2322

Previous studies have developed and explored magnetic resonance imaging (MRI)-based machine learning models for predicting Alzheimer’s disease (AD). However, limited research has focused on models incorporating diverse patient populations. This study aimed to build a clinically useful prediction model for amyloid-beta (Aβ) deposition using source-based morphometry, using a data-driven algorithm based on independent component analyses. Additionally, we assessed how the predictive accuracies varied with the feature combinations. Data from 118 participants clinically diagnosed with various conditions such as AD, mild cognitive impairment, frontotemporal lobar degeneration, corticobasal syndrome, progressive supranuclear palsy, and psychiatric disorders, as well as healthy controls were used for the development of the model. We used structural MR images, cognitive test results, and apolipoprotein E status for feature selection. Three-dimensional T1-weighted images were preprocessed into voxel-based gray matter images and then subjected to source-based morphometry. We used a support vector machine as a classifier. We applied SHapley Additive exPlanations, a game-theoretical approach, to ensure model accountability. The final model that was based on MR-images, cognitive test results, and apolipoprotein E status yielded 89.8% accuracy and a receiver operating characteristic curve of 0.888. The model based on MR-images alone showed 84.7% accuracy. Aβ-positivity was correctly detected in non-AD patients. One of the seven independent components derived from source-based morphometry was considered to represent an AD-related gray matter volume pattern and showed the strongest impact on the model output. Aβ-positivity across neurological and psychiatric disorders was predicted with moderate-to-high accuracy and was associated with a probable AD-related gray matter volume pattern. An MRI-based data-driven machine learning approach can be beneficial as a diagnostic aid.

Access to Document (DOI)

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

Kyuragi Y., Oishi N., Hatakoshi M., Hirano J., Noda T., Yoshihara Y., Ito Y., Igarashi H., Miyata J., Takahashi K., Kamiya K., Matsumoto J., Okada T., Fushimi Y., Nakagome K., Mimura M., Murai T., Suwa T.

Biological Psychiatry Global Open Science （Biological Psychiatry Global Open Science） 4 （ 4 ） 100314 2024年07月

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.

Access to Document (DOI)

Clinical characteristics and potential association to Parkinson’s disease and dementia with Lewy bodies in patients with major depressive disorder who received maintenance electroconvulsive therapy: a retrospective chart review study

Kudo S., Uchida T., Nishida H., Takamiya A., Kikuchi T., Yamagata B., Mimura M., Hirano J.

BMC Psychiatry （BMC Psychiatry） 23 （ 1 ） 243 2023年12月

Background: Maintaining remission after electroconvulsive therapy (ECT) is clinically relevant in patients with depression, and maintenance ECT has been introduced in patients who fail to maintain remission after ECT. However, the clinical characteristics and biological background of patients who receive maintenance ECT are poorly understood. Thus, this study aimed to examine the clinical background of patients who underwent maintenance ECT. Methods: Patients with major depressive disorder who underwent ECT followed by maintenance ECT (mECT group) and those who did not (acute ECT [aECT] group) were included. Clinical characteristics, including the results of neuroimaging examinations for Parkinson’s disease (PD) and dementia with Levy body (DLB) such as myocardial 123I-metaiodobenzylguanidine (MIBG) scintigraphy and dopamine transporter imaging single-photon emission computerized tomography (DaT-SPECT), were compared between the groups. Results: In total, 13 and 146 patients were included in the mECT and aECT groups, respectively. Compared to the aECT group, the mECT group showed a significantly higher prevalence of melancholic features (92.3% vs. 27.4%, p < 0.001) and catatonic features (46.2% vs. 9.6%, p = 0.002). Overall, 8 of the 13 patients in the mECT group and 22 of the 146 patients in the aECT group underwent neuroimaging examinations for PD/DLB. The rate of patients examined is significantly higher in the mECT group than in the aECT group (61.5% vs. 11.2%, p < 0.001). Among the groups examined, 7/8 patients in the mECT group and 16/22 patients in the aECT group showed relevant neuroimaging findings for PD/DLB; the positive rate was not significantly different between the two groups (87.5% vs. 72.7%, p = 0.638). Conclusions: Patients who receive acute and maintenance ECT may have underlying neurodegenerative diseases, including PD/DLB. Investigating the neurobiology of patients who receive maintenance ECT is important for developing appropriate treatments for depression.

Access to Document (DOI)

Development of medical device software for the screening and assessment of depression severity using data collected from a wristband-type wearable device: SWIFT study protocol

Kishimoto T., Kinoshita S., Kikuchi T., Bun S., Kitazawa M., Horigome T., Tazawa Y., Takamiya A., Hirano J., Mimura M., Liang K.C., Koga N., Ochiai Y., Ito H., Miyamae Y., Tsujimoto Y., Sakuma K., Kida H., Miura G., Kawade Y., Goto A., Yoshino F.

Frontiers in Psychiatry （Frontiers in Psychiatry） 13 1025517 2022年12月

ISSN 1664-0640

Introduction: Few biomarkers can be used clinically to diagnose and assess the severity of depression. However, a decrease in activity and sleep efficiency can be observed in depressed patients, and recent technological developments have made it possible to measure these changes. In addition, physiological changes, such as heart rate variability, can be used to distinguish depressed patients from normal persons; these parameters can be used to improve diagnostic accuracy. The proposed research will explore and construct machine learning models capable of detecting depressive episodes and assessing their severity using data collected from wristband-type wearable devices. Methods and analysis: Patients with depressive symptoms and healthy subjects will wear a wristband-type wearable device for 7 days; data on triaxial acceleration, pulse rate, skin temperature, and ultraviolet light will be collected. On the seventh day of wearing, the severity of depressive episodes will be assessed using Structured Clinical Interview for DSM-5 (SCID-5), Hamilton Depression Rating Scale (HAMD), and other scales. Data for up to five 7-day periods of device wearing will be collected from each subject. Using wearable device data associated with clinical symptoms as supervisory data, we will explore and build a machine learning model capable of identifying the presence or absence of depressive episodes and predicting the HAMD scores for an unknown data set. Discussion: Our machine learning model could improve the clinical diagnosis and management of depression through the use of a wearable medical device. Clinical trial registration: [https://jrct.niph.go.jp/latest-detail/jRCT1031210478], identifier [jRCT1031210478].

Access to Document (DOI)

Intergenerational concordance of brain structure between depressed mothers and their never-depressed daughters

Minami F., Hirano J., Ueda R., Takamiya A., Yamagishi M., Kamiya K., Mimura M., Yamagata B.

Psychiatry and Clinical Neurosciences （Psychiatry and Clinical Neurosciences） 76 （ 11 ） 579 - 586 2022年11月

ISSN 13231316

Aim: Parents have significant genetic and environmental influences, which are known as intergenerational effects, on the cognition, behavior, and brain of their offspring. These intergenerational effects are observed in patients with mood disorders, with a particularly strong association of depression between mothers and daughters. The main purpose of our study was to investigate female-specific intergenerational transmission patterns in the human brain among patients with depression and their never-depressed offspring. Methods: We recruited 78 participants from 34 families, which included remitted parents with a history of depression and their never-depressed biological offspring. We used source-based and surface-based morphometry analyses of magnetic resonance imaging data to examine the degree of associations in brain structure between four types of parent-offspring dyads (i.e. mother-daughter, mother-son, father-daughter, and father-son). Results: Using independent component analysis, we found a significant positive correlation of gray matter structure between exclusively the mother-daughter dyads within brain regions located in the default mode and central executive networks, such as the bilateral anterior cingulate cortex, posterior cingulate cortex, precuneus, middle frontal gyrus, middle temporal gyrus, superior parietal lobule, and left angular gyrus. These similar observations were not identified in other three parent-offspring dyads. Conclusions: The current study provides biological evidence for greater vulnerability of daughters, but not sons, in developing depression whose mothers have a history of depression. Our findings extend our knowledge on the pathophysiology of major psychiatric conditions that show sex biases and may contribute to the development of novel interventions targeting high-risk individuals.

Access to Document (DOI)

White matter alterations in the dorsal attention network contribute to a high risk of unsafe driving in healthy older people

Yamamoto Y., Hirano J., Ueda R., Yoshitake H., Yamagishi M., Kimura M., Kamiya K., Shino M., Mimura M., Yamagata B.

Psychiatry and Clinical Neurosciences Reports （Psychiatry and Clinical Neurosciences Reports） 1 （ 3 ） 2022年09月

Aim: Healthy older drivers may be at high risk of fatal traffic accidents. Our recent study showed that volumetric alterations in gray matter in the brain regions within the dorsal attention network (DAN) were strongly related to the risk of unsafe driving in healthy older people. However, the relationship between white matter (WM) structural connectivity and driving ability in healthy older people is still unclear. Methods: We used diffusion tensor imaging to examine the association between microstructural alterations in the DAN and the risk of unsafe driving among healthy older people. We enrolled 32 healthy older individuals aged over 65 years and screened unsafe drivers using an on-road driving test. We then determined the pattern of WM aberrations in unsafe drivers using tract-based spatial statistics. Results: The analysis demonstrated that unsafe drivers had significantly higher axial diffusivity values in nine WM clusters compared with safe drivers. These results were primarily observed bilaterally in the dorsal superior longitudinal fasciculus, which is involved in the DAN. Furthermore, correlation analyses showed that higher axial diffusivity values in the superior longitudinal fasciculus were associated with lower Trail Making Test A scores within unsafe drivers. This result suggests that functionally, WM microstructural alterations in the DAN are associated with attention problems, which may contribute to the risk of unsafe driving among healthy older people. Conclusion: Our findings may elucidate the neurobiological mechanisms underlying the increased risk of unsafe driving in healthy older people, potentially facilitating the development of new interventions to prevent fatal accidents.

Access to Document (DOI)

Individual Prediction of Remission Based on Clinical Features Following Electroconvulsive Therapy: A Machine Learning Approach.

Nakajima K, Takamiya A, Uchida T, Kudo S, Nishida H, Minami F, Yamamoto Y, Yamagata B, Mimura M, Hirano J

The Journal of clinical psychiatry （Journal of Clinical Psychiatry） 83 （ 5 ） 2022年08月

ISSN 0160-6689

Objective: Previous prediction models for electroconvulsive therapy (ECT) responses have predominantly been based on neuroimaging data, which has precluded widespread application for severe cases in real-world clinical settings. The aims of this study were (1) to build a clinically useful prediction model for ECT remission based solely on clinical information and (2) to identify influential features in the prediction model. Methods: We conducted a retrospective chart review to collect data (registered between April 2012 and March 2019) from individuals with depression (unipolar major depressive disorder or bipolar disorder) diagnosed via DSM-IV-TR criteria who received ECT at Keio University Hospital. Clinical characteristics were used as candidate features. A light gradient boosting machine was used for prediction, and 5-fold cross-validation was performed to validate our prediction model. Results: In total, 177 patients with depression underwent ECT during the study period. The remission rate was 63%. Our model predicted individual patient outcomes with 71% accuracy (sensitivity, 86%; specificity, 46%). A shorter duration of the current episodes, lower baseline severity, higher dose of antidepressant medications before ECT, and lower body mass index were identified as important features for predicting remission following ECT. Conclusions: We developed a prediction model for ECT remission based solely on clinical information. Our prediction model demonstrated accuracy comparable to that in previous reports. Our model suggests that introducing ECT earlier in the treatment course may contribute to improvements in clinical outcomes.

Access to Document (DOI)

Impact of Sevoflurane and Thiopental Used Over the Course of Electroconvulsive Therapy: Propensity Score Matching Analysis

Yatomi T., Uchida T., Takamiya A., Wada M., Kudo S., Nakajima K., Nishida H., Yamagata B., Mimura M., Hirano J.

Frontiers in Human Neuroscience （Frontiers in Human Neuroscience） 16 933622 2022年07月

ISSN 1662-5161

Objective: Although anesthetics play an important role in electroconvulsive therapy (ECT), the clinical efficacy and seizure adequacy of sevoflurane in the course of ECT remain unclear. The purpose of this study was to examine the clinical efficacy and seizure adequacy of sevoflurane, compared with those of thiopental, in the course of ECT in patients with mood disorders. Methods: We conducted a retrospective chart review. Patients who underwent a course of ECT and received sevoflurane (n = 26) or thiopental (n = 26) were included. Factors associated with ECT and treatment outcomes were compared between the two groups using propensity score (PS) matching. Between-group differences were examined using an independent t-test for continuous variables and a χ2-test for categorical variables. Results: Patients who received sevoflurane needed more stimulations (sevoflurane: 13.2 ± 4 times, thiopental: 10.0 ± 2.5 times, df = 51, p = 0.001) and sessions (sevoflurane: 10.0 ± 2.1 times, thiopental: 8.4 ± 2.1 times, df = 51, p = 0.01) and had more inadequate seizures (sevoflurane: 5 ± 3.9 times, thiopental: 2.7 ± 2.7 times, df = 51, p = 0.015). Remission and response rates were similar in both groups. Conclusion: The present findings indicate that sevoflurane should be used with caution in ECT and only when the clinical rationale is clear.

Access to Document (DOI)

Hirano J., Takamiya A., Yamamoto Y., Minami F., Mimura M., Yamagata B.

Frontiers in Psychiatry （Frontiers in Psychiatry） 12 772339 2021年12月

ISSN 1664-0640

Multichannel near-infrared spectroscopy (NIRS), including 52-channel NIRS (52ch-NIRS), has been used increasingly to capture hemodynamic changes in the brain because of its safety, low cost, portability, and high temporal resolution. However, optode caps might cause pain and motion artifacts if worn for extended periods of time because of the weight of the cables and the pressure of the optodes on the scalp. Recently, a small NIRS apparatus called compact NIRS (cNIRS) has been developed, and uses only a few flexible sensors. Because this device is expected to be more suitable than 52ch-NIRS in the clinical practice for patients with children or psychiatric conditions, we tested whether the two systems were clinically comparable. Specifically, we evaluated the correlation between patterns of hemodynamic changes generated by 52ch-NIRS and cNIRS in the frontopolar region. We scanned 14 healthy adults with 52ch-NIRS and cNIRS, and measured activation patterns of oxygenated-hemoglobin [oxy-Hb] and deoxygenated-hemoglobin [deoxy-Hb] in the frontal pole while they performed a verbal fluency task. We performed detailed temporal domain comparisons of time-course patterns between the two NIRS-based signals. We found that 52ch-NIRS and cNIRS showed significant correlations in [oxy-Hb] and [deoxy-Hb] time-course changes in numerous channels. Our findings indicate that cNIRS and 52ch-NIRS capture similar task-dependent hemodynamic changes due to metabolic demand, which supports the validity of cNIRS measurement techniques. Therefore, this small device has a strong potential for clinical application with infants and children, as well as for use in the rehabilitation or treatment of patients with psychiatric disorders using biofeedback.

Access to Document (DOI)

Neuronal network mechanisms associated with depressive symptom improvement following electroconvulsive therapy

Takamiya A., Kishimoto T., Hirano J., Nishikata S., Sawada K., Kurokawa S., Yamagata B., Kikuchi T., Mimura M.

Psychological Medicine （Psychological Medicine） 51 （ 16 ） 2856 - 2863 2021年12月

ISSN 00332917

Background Electroconvulsive therapy (ECT) is the most effective antidepressant treatment for severe depression. Although recent structural magnetic resonance imaging (MRI) studies have consistently reported ECT-induced hippocampal volume increases, most studies did not find the association of the hippocampal volume changes with clinical improvement. To understand the underlying mechanisms of ECT action, we aimed to identify the longitudinal effects of ECT on hippocampal functional connectivity (FC) and their associations with clinical improvement. Methods Resting-state functional MRI was acquired before and after bilateral ECT in 27 depressed individuals. A priori hippocampal seed-based FC analysis and a data-driven multivoxel pattern analysis (MVPA) were conducted to investigate FC changes associated with clinical improvement. The statistical threshold was set at cluster-level false discovery rate-corrected p < 0.05. Results Depressive symptom improvement after ECT was positively associated with the change in the right hippocampus-ventromedial prefrontal cortex FC, and negatively associated with the right hippocampus-superior frontal gyrus FC. MVPA confirmed the results of hippocampal seed-based analyses and identified the following additional clusters associated with clinical improvement following ECT: the thalamus, the sensorimotor cortex, and the precuneus. Conclusions ECT-induced change in the right frontotemporal connectivity and thalamocortical connectivity, and changes in the nodes of the default mode network were associated with clinical improvement. Modulation of these networks may explain the underlying mechanisms by which ECT exert its potent and rapid antidepressant effect.

Access to Document (DOI)

Electroconvulsive Therapy for Patients with Depression Who Lack Capacity for Consent: Doing Good and Doing No Harm

Takamiya A., Bouckaert F., Sienaert P., Uchida T., Kudo S., Yamagata B., Kishimoto T., Mimura M., Hirano J.

Journal of ECT （Journal of ECT） 37 （ 3 ） 171 - 175 2021年09月

ISSN 10950680

Objective Electroconvulsive therapy (ECT) is provided in real-world clinical settings for patients lacking capacity for consent. The aim of this study was to investigate the clinical characteristics and clinical effectiveness of ECT in this population. Methods A retrospective chart review was conducted to collect data from patients who received ECT to treat their depressive episodes between April 2012 and March 2019. Differences in clinical characteristics and short-/long-term clinical outcomes between patients who received ECT with their relatives' consent and patients who received ECT by their own consent were examined. The short-/long-term clinical outcomes were determined by clinical global impression scores and readmission rate, respectively. Results Of 168 patients with depressive episodes, 34 (20.2%) received ECT with their relatives' consent. Those patients were older, had lower body mass index, and had shorter episode duration. They also exhibited more frequent psychotic, melancholic, and catatonic features. The main indication for ECT in this population was the need for rapid recovery. Patients lacking capacity for consent showed similar remission (61.8%) and response (82.4%) rates to those with capacity for consent. Readmission rate was not significantly different between groups. Conclusions There were no significant differences in short-/long-term ECT effectiveness between patients with/without capacity for consent. Electroconvulsive therapy is the only established and effective treatment in clinical settings for the most severe cases, wherein patients are incapable of giving consent but need rapid recovery. A general rejection of this practice due to concerns surrounding consent may be unethical under the ethical principles of medical care.

Access to Document (DOI)

Association of electroconvulsive therapy-induced structural plasticity with clinical remission

Takamiya A., Kishimoto T., Hirano J., Kikuchi T., Yamagata B., Mimura M.

Progress in Neuro-Psychopharmacology and Biological Psychiatry （Progress in Neuro-Psychopharmacology and Biological Psychiatry） 110 110286 2021年08月

ISSN 02785846

Background: Electroconvulsive therapy (ECT) is the most effective treatment for severe depression. Recent neuroimaging studies have consistently reported that ECT induces volume increases in widely distributed brain regions. However, it still remains unclear about ECT-induced volume changes associated with clinical improvement. Methods: Longitudinal assessments of structural magnetic resonance imaging were conducted in 48 participants. Twenty-seven elderly melancholic depressed individuals (mean 67.5 ± 8.1 years old; 19 female) were scanned before (TP1) and after (TP2) ECT. Twenty-one healthy controls were also scanned twice. Whole-brain gray matter volume (GMV) was analyzed via group (remitters, nonremitters, and controls) by time (TP1 and TP2) analysis of covariance to identify ECT-related GMV changes and GMV changes specific to remitters. Within-subject and between-subjects correlation analyses were conducted to investigate the associations between clinical improvement and GMV changes. Depressive symptoms were evaluated using the 17-item Hamilton Depression Rating Scale (HAM-D), and remission was defined as HAM-D total score ≤ 7. Results: Bilateral ECT increased GMV in multiple brain regions bilaterally regardless of clinical improvement. Remitters showed a larger GMV increase in the right-lateralized frontolimbic brain regions compared to nonremitters and healthy controls. GMV changes in the right hippocampus/amygdala and right middle frontal gyrus showed correlations with clinical improvement in within−/between-subjects correlation analyses. Conclusions: ECT-induced GMV increase in the right frontolimbic regions was associated with clinical remission.

Access to Document (DOI)

Regional Gray Matter Volume Identifies High Risk of Unsafe Driving in Healthy Older People

Yamamoto Y., Yamagata B., Hirano J., Ueda R., Yoshitake H., Negishi K., Yamagishi M., Kimura M., Kamiya K., Shino M., Mimura M.

Frontiers in Aging Neuroscience （Frontiers in Aging Neuroscience） 12 592979 2020年12月

ISSN 1663-4365

In developed countries, the number of traffic accidents caused by older drivers is increasing. Approximately half of the older drivers who cause fatal accidents are cognitively normal. Thus, it is important to identify older drivers who are cognitively normal but at high risk of causing fatal traffic accidents. However, no standardized method for assessing the driving ability of older drivers has been established. We aimed to establish an objective assessment of driving ability and to clarify the neural basis of unsafe driving in healthy older people. We enrolled 32 healthy older individuals aged over 65 years and classified unsafe drivers using an on-road driving test. We then utilized a machine learning approach to distinguish unsafe drivers from safe drivers based on clinical features and gray matter volume data. Twenty-one participants were classified as safe drivers and 11 participants as unsafe drivers. A linear support vector machine classifier successfully distinguished unsafe drivers from safe drivers with 87.5% accuracy (sensitivity of 63.6% and specificity of 100%). Five parameters (age and gray matter volume in four cortical regions, including the left superior part of the precentral sulcus, the left sulcus intermedius primus [of Jensen], the right orbital part of the inferior frontal gyrus, and the right superior frontal sulcus), were consistently selected as features for the final classification model. Our findings indicate that the cortical regions implicated in voluntary orienting of attention, decision making, and working memory may constitute the essential neural basis of driving behavior.

Access to Document (DOI)

AIによる脳波を用いた電気けいれん療法の効果予測

平野仁一

上原記念生命科学財団研究報告集（(公財)上原記念生命科学財団） 34 1 - 4 2020年12月

Machine-learning approach to predict on-road driving ability in healthy older people

Yamamoto Y., Hirano J., Yoshitake H., Negishi K., Mimura M., Shino M., Yamagata B.

Psychiatry and Clinical Neurosciences （Psychiatry and Clinical Neurosciences） 74 （ 9 ） 488 - 495 2020年09月

ISSN 13231316

Aim: In Japan, fatal traffic accidents due to older drivers are on the rise. Considering that approximately half the older drivers who have caused fatal accidents are cognitively normal healthy people, it has been required to detect older drivers who are cognitively normal but at high risk of having fatal traffic accidents. However, a standardized method for assessing the driving ability of older drivers has not yet been established. We thus aimed to identify a new sensing method for the evaluation of the on-road driving ability of healthy older people on the basis of vehicle behaviors. Methods: We enrolled 33 healthy older individuals aged over 65 years and utilized a machine-learning approach to dissociate unsafe drivers from safe drivers based on cognitive assessments and a functional visual acuity test. Results: The linear support vector machine classifier successfully dissociated unsafe drivers from safe drivers with accuracy of 84.8% (sensitivity of 66.7% and specificity of 95.2%). Five clinical parameters, namely age, the first trial of the Rey Auditory Verbal Learning Test immediate recall, the delayed recall of the Rey–Osterrieth Complex Figure Test, the result of the free-drawn Clock Drawing Test, and maximal visual acuity, were consistently selected as essential features for the best classification model. Conclusion: Our findings improve our understanding of clinical risk factors leading to unsafe driving and may provide insight into a new intervention that prevents fatal traffic accidents caused by healthy older people.

Access to Document (DOI)

Predicting Individual Remission after Electroconvulsive Therapy Based on Structural Magnetic Resonance Imaging: A Machine Learning Approach

Takamiya A., Liang K.C., Nishikata S., Tarumi R., Sawada K., Kurokawa S., Hirano J., Yamagata B., Mimura M., Kishimoto T.

Journal of ECT （Journal of ECT） 36 （ 3 ） 205 - 210 2020年09月

ISSN 10950680

Objective To identify important clinical or imaging features predictive of an individual's response to electroconvulsive therapy (ECT) by utilizing a machine learning approach. Methods Twenty-seven depressed patients who received ECT were recruited. Clinical demographics and pretreatment structural magnetic resonance imaging (MRI) data were used as candidate features to build models to predict remission and post-ECT Hamilton Depression Rating Scale scores. Support vector machine and support vector regression with elastic-net regularization were used to build models using (i) only clinical features, (ii) only MRI features, and (iii) both clinical and MRI features. Consistently selected features across all individuals were identified through leave-one-out cross-validation. Results Compared with models that include only clinical variables, the models including MRI data improved the prediction of ECT remission: the prediction accuracy improved from 70% to 93%. Features selected consistently across all individuals included volumes in the gyrus rectus, the right anterior lateral temporal lobe, the cuneus, and the third ventricle, as well as 2 clinical features: psychotic features and family history of mood disorder. Conclusions Pretreatment structural MRI data improved the individual predictive accuracy of ECT remission, and only a small subset of features was important for prediction.

Access to Document (DOI)

Modulation of hippocampal functional connectivity and depressive symptom improvement following ECT

Takamiya A., Kishimoto T., Hirano J., Nakajima K., Katayama N., Kikuchi T., Yamagata B., Nakagawa A., Mimura M.

EUROPEAN PSYCHIATRY 63 S373 - S373 2020年07月

ISSN 0924-9338

Widespread White Matter Aberrations Are Associated with Phonemic Verbal Fluency Impairment in Chronic Traumatic Brain Injury

Yamagata B., Ueda R., Tasato K., Aoki Y., Hotta S., Hirano J., Takamiya A., Nakaaki S., Tabuchi H., Mimura M.

Journal of Neurotrauma （Journal of Neurotrauma） 37 （ 7 ） 975 - 981 2020年04月

ISSN 08977151

Microstructural white matter (WM) disruption and resulting abnormal structural connectivity form a potential underlying pathology in traumatic brain injury (TBI). Herein, to determine the potential mechanism of cognitive deterioration in TBI, we examined the association of damage to specific WM tracts with cognitive function in TBI patients. We recruited 18 individuals with mild-to-moderate/severe TBI in the chronic phase and 17 age-matched controls. We determined the pattern of WM aberrations in TBI using tract-based spatial statistics (TBSS) and then examined the relationship between cognitive impairment and WM damage using the threshold-free cluster enhancement correction in TBSS. TBSS analysis showed that TBI patients exhibited WM aberrations in a wide range of brain regions. In the majority of these regions, lower fractional anisotropy (FA) largely overlapped with increased radial diffusivity, but not with axial diffusivity. Further, voxel-wise correction in TBSS demonstrated that higher FA values were associated with better performance in the phonemic verbal fluency task (VFT) in widespread WM regions, but not with the semantic VFT. Despite variation in the magnitude and location of brain injury between individual cases, chronic TBI patients exhibited widespread WM aberrations. We confirmed the findings of previous studies that WM integrity is lower across the spectrum of TBI severity in chronic subjects compared to controls. Further, phonemic VFT may be a more sensitive cognitive measure of executive dysfunction associated with WM aberrations in TBI compared with semantic VFT.

Access to Document (DOI)

Factors Associated with Delirium following Electroconvulsive Therapy: A Systematic Review

Tsujii T., Uchida T., Suzuki T., Mimura M., Hirano J., Uchida H.

Journal of ECT （Journal of ECT） 35 （ 4 ） 279 - 287 2019年12月

ISSN 10950680

Objectives Delirium following electroconvulsive therapy (ECT) has been a clinical challenge, which, however, has not been investigated through a systematic literature review. The objective of this study was to systematically synthesize available evidence regarding factors associated with post-ECT delirium. Methods We conducted a systematic literature search for any type of original investigations that reported risk factors of post-ECT delirium, using PubMed. Results The literature search identified 43 relevant articles. One study found an association between catatonic feature and increased risk of postictal delirium. Five studies reported that the presence of cerebrovascular disease, Parkinson disease, or dementia was related to higher incidence of post-ECT delirium. Incidence of post-ECT course delirium was increased with bitemporal stimulation (3 studies). One study showed that ultrabrief pulse ECT reduced reorientation time following seizure compared with brief pulse ECT. High stimulus intensity resulted in more prolonged reorientation time after ECT than lower stimulus intensity (2 studies). Longer seizure length was significantly associated with post-ECT delirium in 1 study. Eight studies that examined postictal delirium in association with medications used, including lithium, did not show any consistent finding in their relationships. Four studies showed decreased incidence of postictal delirium in those receiving dexmedetomidine. Conclusions Limited evidence suggests that catatonic feature, cerebrovascular disease, Parkinson disease, dementia, bitemporal electrode placement, high stimulus intensity, or longer seizure length are associated with an increased risk of post-ECT delirium. Moreover, dexmedetomidine and ultrabrief pulse ECT seem to have preventive effects of post-ECT delirium.

Access to Document (DOI)

Concomitant use of alcohol and benzodiazepine hypnotics in psychiatric outpatients: A cross-sectional survey

Uchida T., Hirano J., Sakurai H., Suzuki T., Mimura M., Uchida H.

International Clinical Psychopharmacology （International Clinical Psychopharmacology） 34 （ 6 ） 291 - 297 2019年11月

ISSN 02681315

Concomitant use of benzodiazepines and alcohol appears prevalent in a clinical setting. The objectives of this study were as follows: (1) to investigate the prevalence of concomitant use of benzodiazepine hypnotics and alcohol in psychiatric outpatients, (2) to examine the clinical characteristics and factors associated with the concomitant use, and (3) to investigate the awareness of the psychiatrists-in-charge about the concomitant use. Outpatients with schizophrenia, depression, and insomnia who were receiving benzodiazepine hypnotics were asked to fill in a sleeping diary for seven consecutive days in which use of hypnotics and alcohol was also recorded. Clinical characteristics were assessed, and logistic analysis was performed to examine factors associated with the concomitant use. In addition, psychiatrists-in-charge were asked as to whether they thought their patients were concomitantly using them. The prevalence rate of the concomitant use was 39.8% (37/93). The CAGE score showed significant positive association with the concomitant use (odds ratio = 2.40, 95% confidence interval = 1.39-4.16, P = 0.002). Only in 32.4% of the concomitant users were suspected by their psychiatrists. The results suggest that concomitantly used benzodiazepine hypnotics and alcohol appears prevalent, and has been frequently overlooked by treating psychiatrists. The CAGE questionnaire may be helpful to screen such potentially hazardous users.

Access to Document (DOI)

Thalamic volume, resting-state activity, and their association with the efficacy of electroconvulsive therapy

Takamiya A., Kishimoto T., Liang K.c., Terasawa Y., Nishikata S., Tarumi R., Sawada K., Kurokawa S., Hirano J., Yamagata B., Mimura M.

Journal of Psychiatric Research （Journal of Psychiatric Research） 117 135 - 141 2019年10月

ISSN 00223956

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.

Access to Document (DOI)

Prolonged Post-Electroconvulsive Therapy Delirium Controlled With Donepezil.

Takamiya A, Sawada K, Hirano J, Mimura M, Kishimoto T

The journal of ECT 35 （ 3 ） e29 - e30 2019年09月

ISSN 1095-0680

Access to Document (DOI)

Brain functional alterations observed 4-weekly in major depressive disorder following antidepressant treatment

Yamagata B., Yamanaka K., Takei Y., Hotta S., Hirano J., Tabuchi H., Mimura M.

Journal of Affective Disorders （Journal of Affective Disorders） 252 25 - 31 2019年06月

ISSN 01650327

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.

Access to Document (DOI)

Structural Magnetic Resonance Imaging for Individual Predictions for Electroconvulsive Therapy Remission Utilizing Machine Learning

Takamiya Akihiro, Liang Kuo-ching, Nishikata Shiro, Kurokawa Shunya, Sawada Kyosuke, Hirano Jinichi, Yamagata Bun, Mimura Masaru, Kishimoto Taishiro

BIOLOGICAL PSYCHIATRY 85 （ 10 ） S263 - S263 2019年05月

ISSN 0006-3223

Electroconvulsive therapy modulates resting-state EEG oscillatory pattern and phase synchronization in nodes of the default mode network in patients with depressive disorder

Takamiya A., Hirano J., Yamagata B., Takei S., Kishimoto T., Mimura M.

Frontiers in Human Neuroscience （Frontiers in Human Neuroscience） 13 1 2019年02月

ISSN 1662-5161

Introduction: Electroconvulsive therapy (ECT) has antidepressant effects, but it also has possible cognitive side effects. The effects of ECT on neuronal oscillatory pattern and phase synchronization, and the relationship between clinical response or cognitive change and electroencephalogram (EEG) measurements remain elusive. Methods: Individuals with unipolar depressive disorder receiving bilateral ECT were recruited. Five minutes of resting, eyes-closed, 19-lead EEG recordings were obtained before and after a course of ECT. Non-overlapping 60 artifact-free epocs of 2-s duration were used for the analyses. We used exact low resolution electromagnetic tomography (eLORETA) to compute the whole-brain three-dimensional intracortical distribution of current source density (CSD) and phase synchronization among 28 regions-of-interest (ROIs). Paired t-tests were used to identify cortical voxels and connectivities showing changes after ECT. Montgomery Asberg Depression Rating Scale (MADRS) and Mini-Mental State Examination (MMSE) were used to evaluate the severity of depression and the global cognitive function. Correlation analyses were conducted to identify the relationship between changes in the EEG measurements and changes in MADRS or MMSE. Results: Thirteen depressed patients (five females, mean age: 58.4 years old) were included. ECT increased theta CSD in the anterior cingulate cortex (ACC), and decreased beta CSD in the frontal pole (FP), and gamma CSD in the inferior parietal lobule (IPL). ECT increased theta phase synchronization between the posterior cingulate cortex (PCC) and the anterior frontal cortex, and decreased beta phase synchronization between the PCC and temporal regions. A decline in beta synchronization in the left hemisphere was associated with cognitive changes after ECT. Conclusion: ECT modulated resting-state EEG oscillatory patterns and phase synchronization in central nodes of the default mode network (DMN). Changes in beta synchronization in the left hemisphere might explain the ECT-related cognitive side effects.

Access to Document (DOI)

Electroconvulsive Therapy Induces Age-Dependent Volume Increase in the Human Dentate Gyrus

Takamiya Akihiro, Chung Jun Ku, Plitman Eric, Chakravarty Mallar, Sawada Kyosuke, Hirano Jinichi, Yamagata Bun, Graff-Guerrero Ariel, Kishimoto Taishiro, Mimura Masaru

BIOLOGICAL PSYCHIATRY 83 （ 9 ） S188 - S188 2018年05月

ISSN 0006-3223

Frontal and temporal cortical functional recovery after electroconvulsive therapy for depression: A longitudinal functional near-infrared spectroscopy study.

Hirano J, Takamiya A, Yamagata B, Hotta S, Miyasaka Y, Pu S, Iwanami A, Uchida H, Mimura M

Journal of psychiatric research 91 26 - 35 2017年08月

ISSN 0022-3956

Access to Document (DOI)

Resilience and spirituality in patients with depression and their family members: A cross-sectional study.

Ozawa C, Suzuki T, Mizuno Y, Tarumi R, Yoshida K, Fujii K, Hirano J, Tani H, Rubinstein EB, Mimura M, Uchida H

Comprehensive psychiatry 77 53 - 59 2017年08月

ISSN 0010-440X

Access to Document (DOI)

Aberrant Spatial and Temporal Prefrontal Activation Patterns in Medication-Naïve Adults with ADHD.

Yamagata B, Takei Y, Itahashi T, Pu S, Hirano J, Mimura M, Iwanami A

Frontiers in psychiatry 8 274 2017年

ISSN 1664-0640

Access to Document (DOI)

Self-rated cognitive functions following chemotherapy in patients with breast cancer: a 6-month prospective study.

Kitahata R, Nakajima S, Uchida H, Hayashida T, Takahashi M, Nio S, Hirano J, Nagaoka M, Suzuki T, Jinno H, Kitagawa Y, Mimura M

Neuropsychiatric disease and treatment 13 2489 - 2496 2017年

ISSN 1176-6328

Access to Document (DOI)

High-dose antidepressants affect near-infrared spectroscopy signals: A retrospective study.

Takamiya A, Hirano J, Ebuchi Y, Ogino S, Shimegi K, Emura H, Yonemori K, Shimazawa A, Miura G, Hyodo A, Hyodo S, Nagai T, Funaki M, Sugihara M, Kita M, Yamagata B, Mimura M

NeuroImage. Clinical 14 648 - 655 2017年

Access to Document (DOI)

A longitudinal functional neuroimaging study in medication-naïve depression after antidepressant treatment.

Tomioka H, Yamagata B, Kawasaki S, Pu S, Iwanami A, Hirano J, Nakagome K, Mimura M

PloS one 10 （ 3 ） e0120828 2015年

Access to Document (DOI)

A review on schizophrenia and relapse--a quest for user-friendly psychopharmacotherapy.

Suzuki T, Uchida H, Takeuchi H, Tsuboi T, Hirano J, Mimura M

Human psychopharmacology 29 （ 5 ） 414 - 26 2014年09月

ISSN 0885-6222

Access to Document (DOI)

The impact of prolactin-raising antipsychotics on bone mineral density in patients with schizophrenia: findings from a longitudinal observational cohort.

Takahashi T, Uchida H, John M, Hirano J, Watanabe K, Mimura M, Correll CU, Kishimoto T

Schizophrenia research 147 （ 2-3 ） 383 - 6 2013年07月

ISSN 0920-9964

Access to Document (DOI)

An open-label study of algorithm-based treatment versus treatment-as-usual for patients with schizophrenia.

Hirano J, Watanabe K, Suzuki T, Uchida H, Den R, Kishimoto T, Nagasawa T, Tomita Y, Hara K, Ochi H, Kobayashi Y, Ishii M, Fujita A, Kanai Y, Goto M, Hayashi H, Inamura K, Ooshima F, Sumida M, Ozawa T, Sekigawa K, Nagaoka M, Yoshimura K, Konishi M, Inagaki A, Saito T, Motohashi N, Mimura M, Okubo Y, Kato M

Neuropsychiatric disease and treatment 9 1553 - 64 2013年

ISSN 1176-6328

Access to Document (DOI)

Dental conditions in inpatients with schizophrenia: a large-scale multi-site survey.

Tani H, Uchida H, Suzuki T, Shibuya Y, Shimanuki H, Watanabe K, Den R, Nishimoto M, Hirano J, Takeuchi H, Nio S, Nakajima S, Kitahata R, Tsuboi T, Tsunoda K, Kikuchi T, Mimura M

BMC oral health 12 32 2012年08月

Access to Document (DOI)

A cross-sectional study of plasma risperidone levels with risperidone long-acting injectable: implications for dopamine D2 receptor occupancy during maintenance treatment in schizophrenia.

Ikai S, Remington G, Suzuki T, Takeuchi H, Tsuboi T, Den R, Hirano J, Tsunoda K, Nishimoto M, Watanabe K, Mimura M, Mamo D, Uchida H

The Journal of clinical psychiatry 73 （ 8 ） 1147 - 52 2012年08月

ISSN 0160-6689

Access to Document (DOI)

Electroconvulsive therapy and meningioma: a brief review.

Teraishi T, Nakatake M, Hirano J, Ide M, Kuwahara T, Nomura S

Nihon shinkei seishin yakurigaku zasshi = Japanese journal of psychopharmacology 32 （ 2 ） 57 - 61 2012年04月

ISSN 1340-2544

Is switching antidepressants following early nonresponse more beneficial in acute-phase treatment of depression?: a randomized open-label trial.

Nakajima S, Uchida H, Suzuki T, Watanabe K, Hirano J, Yagihashi T, Takeuchi H, Abe T, Kashima H, Mimura M

Progress in neuro-psychopharmacology & biological psychiatry 35 （ 8 ） 1983 - 9 2011年12月

ISSN 0278-5846

Access to Document (DOI)

Clinical and demographic characteristics associated with postural instability in patients with schizophrenia.

Koreki A, Tsunoda K, Suzuki T, Hirano J, Watanabe K, Kashima H, Uchida H

Journal of clinical psychopharmacology 31 （ 1 ） 16 - 21 2011年02月

ISSN 0271-0749

Access to Document (DOI)

頻回の嘔吐により食道破裂をきたした摂食障害の1例

平野仁一, 重村淳, 吉野相英, 野村総一郎

精神科治療学（(株)星和書店） 24 （ 3 ） 371 - 374 2009年03月

ISSN 0912-1862

我々は、嘔吐により発症した突発性食道破裂および縦隔気腫を合併した摂食障害の症例(神経性無食欲症、むちゃ食い/排出型)を経験したので、その詳細を報告する。症例は30歳女性、以前より過食嘔吐を頻回に繰り返していた。感冒症状と腹痛を主訴に当院受診し入院となった。胸部X線検査にて皮下気腫と縦隔気腫を認め、上部消化管内視鏡検査にて食道に裂傷を認め食道破裂と診断された。低栄養のため創傷治癒が遅延する可能性が高く、中心静脈栄養を考慮した。しかし肥満恐怖から中心静脈栄養施行への同意が得られず、中心静脈栄養への不安から過呼吸発作が頻回となったため絶飲食を主体とした保存的治療を継続した。胸部CT、内視鏡検査で裂傷の治癒を確認しながら食事を徐々に再開し、32病日に退院となった。摂食障害合併症としての食道破裂の報告は多くないが、致死的経過を辿りうる性質上、嘔吐を伴う症例では、本合併症を念頭に置きながら経過を見る必要があると考えられた。(著者抄録)

ペースメーカー装着患者の修正型電気けいれん療法

平野仁一, 宮崎誠樹, 吉野相英, 野村総一郎

脳と精神の医学（日本生物学的精神医学会） 19 （ 3 ） 181 - 184 2008年09月

ISSN 0915-7328

61歳女。58歳、大動脈弁閉鎖不全症・三尖弁閉鎖不全症、洞不全症候群のために弁置換術・ペースメーカー植え込み術を施行した。心労が募り、不眠、食思不振、全身倦怠感、意欲低下をきたした。milnacipranによって症状は改善し、症状改善に伴い、治療を自己中断した。治療中断直後から意欲低下、抑うつ気分が再燃し、病状は一進一退を繰り返した。fulvoxamineで焦燥感、希死念慮の改善を認めたが、左心室瘤が発見され、手術目的にて転院となった。心室瘤切除術は無事終了したが、亜昏迷状態となった。経口摂取困難な状態が続くため、術後管理終了後に再転院となった。難治性のうつ病に加え、高齢で身体消耗が激しいため、ペースメーカー装着中であったが修正型電気けいれん療法を施行した。早期より亜昏迷状態は改善した。心収縮能は良好で、心不全徴候も認めなかった。

最小用量のparoxetineを投与することによりセロトニン症候群発症へ至った1症例　5-hydroxytryptamine 1A受容体と腎不全の関与を中心として

梅田寿美代, 平野仁一, 重村淳, 丹生谷正史, 野村総一郎

精神科治療学（(株)星和書店） 23 （ 2 ） 239 - 243 2008年02月

ISSN 0912-1862

少量の抗うつ薬を2回投与することによって、セロトニン症候群を惹起した症例を経験した。合併症として腎不全を有することが一因と考えられたが、これ以外に、併用されていた抗精神病薬perospironeの有する5-hydroxytryptamine 1A(5-HT1A)受容体へのアゴニスト作用の関与も推察された。近年、強迫神経症や難治性うつ病の治療場面で抗うつ薬と非定型抗精神病薬が併用される機会も多いことから、注意を要する薬物相互作用と考えここに報告する。(著者抄録)

Stress vulnerabilities in an animal model of post-traumatic stress disorder.

Wakizono T, Sawamura T, Shimizu K, Nibuya M, Suzuki G, Toda H, Hirano J, Kikuchi A, Takahashi Y, Nomura S

Physiology & behavior 90 （ 4 ） 687 - 95 2007年03月

ISSN 0031-9384

Access to Document (DOI)

私のカルテから　脳炎による緊張病症候群に修正型電気けいれん療法が奏功した1例

平野仁一, 小林伸久, 澤村岳人, 宮崎誠樹, 長峰正典, 吉野相英, 野村総一郎

精神医学（(株)医学書院） 47 （ 5 ） 573 - 574 2005年05月

ISSN 0488-1281

原因と特定されない脳炎から緊張病症候群を呈し,修正型電気けいれん療法(mECT)が奏効した1例(31歳女性)を報告した.本症例は脳炎から重度の緊張病症状を呈しており,救命上も早急に治療効果の得られる治療法を選択する必要性があった.mECT導入後,筋緊張亢進といった緊張病症状は軽減しており,脳炎より発症した緊張病症候群に対する選択肢としてmECTが有用である可能性が示唆された.緊張病症候群に対するECTの作用機序は不明であるが,パーキンソン病においてECTによるドーパミン系の亢進が示唆されていることから,緊張病症候群においてもドーパミン系の変化が関与しているのではないかと考えられた

　前のページ - 次のページ　

平野 仁一

論文 - 平野 仁一

平野　仁一

論文 - 平野　仁一