Published papers

Purpose : Neurological abnormality has been suggested to be involved in the pathogenesis of dry eye (DE) disease. We previously reported that autonomic nerve activity (ANA) may be a key for the symptom manifestation in short break up time of tear film (BUT) DE (sBUTDE), which exhibits severe symptoms even with little epithelial damage (Kaido et al. Invest Ophthalmol Vis Sci. 2023). In this study, we investigated whether the cause of ANA modulation is peripheral or central. Methods : This prospective, cross-sectional, comparative clinical study included 23 eyes of 23 patients with sBUTDE (mean age: 55.2 ±16.1 years), who were receiving conventional treatments, and 16 eyes of 16 non-DE controls (mean age: 55.4 ± 16.5 years). An ANA measurement and the Japanese version of the Ocular Surface Disease Index (J-OSDI) were administered. ANA was continuously measured for 10 min. under each of three conditions: eyes closed, eyes open, and eyes open under ocular surface anesthesia. The parameters were component of low-frequency (LF) reflecting cardiac sympathetic and parasympathetic nerve activity, high-frequency (HF) reflecting parasympathetic nerve activity alone, ration of LF over HF (LF/HF), component coefficient of variation (ccv) of LF (ccvLF), and ccvHF. Results : In sBUTDEs, HF and ccvHF were higher when the eyes are open than when the eyes are closed; LF/HF was higher when the eyes are closed than when the eyes are open, whereas non-DEs showed the opposite response. The difference values of HF, ccvHF, and LF/HF between the eyes closed and open were greater in sBUTDE than in non-DE. There were no significant changes in all parameters between the open eyes with and without anesthesia in both groups. In addition, the multiple regression analysis to determine the factors affecting J-OSDI scores with ANA parameters as independent variables showed that HF under eyes open was significantly associated with the J-OSDI scores. Conclusions : The symptom manifestation in sBUTDE may be explained by abnormalities in ANA, and the fact that blockade of peripheral stimulation does not change ANA may suggest central involvement of ANA.

Abstract Background Chronic occupational stress leads to physical and mental illnesses, highlighting the importance of effective stress management in modern societies. Recently, chronic stress-induced systemic low-grade inflammation has garnered increasing attention for its stress response and crucial pathological role in the development of both physical and mental illnesses. In this context, elevated salivary interleukin-6 (sIL-6) levels have been developed as measurable and non-invasive stress indicators. However, the factors associated with sIL-6 in stressed office workers, including the symptomatic manifestations of stress responses, have not been extensively investigated. Since direct measurement of inflammation is costly in routine stress management, identifying symptoms that reliably reflect inflammation could facilitate the development of more effective, inflammation-based stress management strategies. Methods In this cross-sectional study, stressed office workers were recruited through a screening process using a Brief Job Stress Questionnaire. Saliva samples were collected to measure sIL-6 levels, and participants completed questionnaires addressing their occupational environment, symptomatic manifestations, and lifestyle. After excluding one participant owing to a medical history that could potentially affect sIL-6 levels, 128 stressed office workers were included in the analysis. Results Our model-based analysis for symptomatic manifestation demonstrated that elevated sIL-6 was significantly associated with greater feelings of fatigue as well as relatively higher vigor. A separate model-based analysis for stressors revealed a significant association with higher qualitative job overload. Data-driven analyses further supported the finding that elevated sIL-6 was significantly associated with fatigue. Conclusions Our findings suggest that the feeling of fatigue may reflect chronic stress-induced systemic low-grade inflammation in the body, highlighting the importance of self-monitoring fatigue for early intervention. Inflammation based stress management holds promise in preventing both mental and physical illnesses in stressed office workers.

The evaluation of human emotions has been a multi-disciplinary area of research interest. Although there are several methods for such evaluation, such as subjective evaluation and behavioral taxonomy, direct evaluation from the human brain is more reliable. Electroencephalograph (EEG) signal analysis is particularly widely used because of its simplicity and convenience. In the present study, human emotional states were investigated using a newly developed EEG device with a single electrode. The developed device is lighter and cheaper than existing devices, although its feasibility is yet to be proven.

Cardiotocography records fetal heart rates and their temporal relationship to uterine contractions. To identify high risk fetuses, obstetricians inspect cardiotocograms (CTGs) by eye. Therefore, CTG traces are often interpreted differently among obstetricians, resulting in inappropriate interventions. However, few studies have focused on quantitative and nonbiased algorithms for CTG evaluation. In this study, we propose a newly constructed deep neural network model (CTG-net) to detect compromised fetal status. CTG-net consists of three convolutional layers that extract temporal patterns and interrelationships between fetal heart rate and uterine contraction signals. We aimed to classify the abnormal group (umbilical artery pH < 7.20 or Apgar score at 1 min < 7) and the normal group from CTG data. We evaluated the performance of the CTG-net with the F1 score and compared it with conventional algorithms, namely, support vector machine and k-means clustering, and another deep neural network model, long short-term memory. CTG-net showed the area under the receiver operating characteristic curve of 0.73 ± 0.04, which was significantly higher than that of long short-term memory. CTG-net, a quantitative and automated diagnostic aid system, enables early intervention for putatively abnormal fetuses, resulting in a reduction in the number of cases of hypoxic injury.

Background Previous studies have attempted to characterize depression using electroencephalography (EEG), but results have been inconsistent. New noise reduction technology allows EEG acquisition during conversation. Methods We recorded EEG from 40 patients with depression as they engaged in conversation using a single-channel EEG device while conducting real-time noise reduction and compared them to those of 40 healthy subjects. Differences in EEG between patients and controls, as well as differences in patients’ depression severity, were examined using the ratio of the power spectrum at each frequency. In addition, the effects of medications were examined in a similar way. Results In comparing healthy controls and depression patients, significant power spectrum differences were observed at 3 Hz, 4 Hz, and 10 Hz and higher frequencies. In the patient group, differences in the power spectrum were observed between asymptomatic patients and healthy individuals, and between patients of each respective severity level and healthy individuals. In addition, significant differences were observed at multiple frequencies when comparing patients who did and did not take antidepressants, antipsychotics, and/or benzodiazepines. However, the power spectra still remained significantly different between non-medicated patients and healthy individuals. Limitations The small sample size may have caused Type II error. Patients’ demographic characteristics varied. Moreover, most patients were taking various medications, and cannot be compared to the non-medicated control group. Conclusion A study with a larger sample size should be conducted to gauge reproducibility, but the methods used in this study could be useful in clinical practice as a biomarker of depression.

Cardiovascular disease is the number one cause of death in the world and is a serious problem. In the case of cardiopulmonary arrest due to myocardial infarction, the survival rate is as low as 13.3% one month after resuscitation, which birthed the need for continuous heart monitoring. In this study, we develop a Ballistocardiogram (BCG) measurement system using a load cell installed on a chair and a heart rate estimation algorithm that is robust to waveform changes, with the aim of constructing a non-contact heart rate acquisition system. The proposed system was evaluated by utilizing data obtained from 13 healthy subjects and 1 subject with abnormal ECG who were simultaneously measured with ECG. The output of the BCG system was confirmed to change with the same period as the ECG data obtained as the correct answer, and the synchronization of the R-peak positions was confirmed for all cases. As a result of comparing the heart rate intervals estimated from BCG and those obtained from ECG, it was confirmed that the same heart rate variability (HRV) features could be obtained even for abnormal ECG subject.

Synthetic corticosteroids, the most well-known anti-inflammatory drugs globally, are effective against inflammatory diseases despite their adverse effects that decrease a patient’s quality of life (QOL). One of these effects is sleep disturbance, which causes other health issues and further diminishes the QOL. However, the acute effects of steroid drugs on sleep-wake issues are not fully understood and must be clarified in detail using experimental animals. Therefore, this study examines the dose-dependent effect of dexamethasone (DXM), one of the strongest steroid drugs, on the sleep-wake architecture of mice. We conducted acute DXM administration at multiple doses and 24-hour EEG/EMG recordings. Our results revealed that DXM increased the time spent in arousal and decreased that of NREM sleep, even at very low doses. These results imply that steroid-induced sleep disturbance must be addressed at any dosage.

n recent years, urban air mobility (UAM) technologies have been studied worldwide. However, social acceptance of UAMs and drones remains underexplored. Without adequate research, the anticipated “aerial industrial revolution” from drone use and flying vehicles may face social issues. To address this, the authors’ group proposed a social acceptance evaluation method combining subjective questionnaires with objective stress evaluations using a Kansei Analyzer based on a simple electroencephalograph and confirmed the effectiveness of this method. Related studies have assessed subjective stress from drone noise, but stress varies by the applications of the UAMs and stakeholders. It is critical to assess the stress people perceive from noise for each application and each stakeholder. This study evaluates sensitivity indices, including stress, for UAM uses, focusing on people uninvolved with UAMs, who face the greatest disadvantages. We conduct statistical tests for changes in cognitive sensitivities and physiological stress that is affected by the instruction in benefits of the UAM applications, focusing on residents uninvolved with UAMs, who face the greatest disadvantages. The study concludes with a summary of the benefit-effect assessment results.

Purpose: To measure autonomic nerve activity (ANA) in several eye conditions and verify whether ANA modulation is regulated by peripheral or central control in short tear film break-up time dry eye (sBUTDE). Methods: This study included 23 eyes of 23 patients with sBUTDE (mean age 55.2 ± 16.1 years; range 21–88 years) and 24 eyes of 24 age-matched non-dry eye (DE) controls. An ANA measurement, personality questionnaire, and Ocular Surface Disease Index were administered. ANA was continuously measured for 10 minutes under three conditions: eyes closed, eyes open, and eyes open under ocular surface anesthesia. Results: The low-frequency (LF)/high-frequency (HF) ratio (LF/HF) with eyes closed was significantly higher in the sBUTDE group than in the control group (P < 0.05). In the sBUTDE group, HF increased and LF/HF decreased with eye opening compared with those in the control group; HF with eyes open decreased with ocular surface anesthesia and reached the same level as that in the control group. Among patients where HF decreased or LF/HF increased with eye opening, 57.1% or 64.3% showed a tendency to return to the ANA state with eyes closed by ocular surface anesthesia, respectively. Factors associated with DE symptoms included break-up time, HF with eyes open, and “openness” (P < 0.05). Conclusions: ANA modulation can be caused by peripheral, central, or mixed abnormalities in sBUTDE. Furthermore, personality traits may play a role in symptom induction. Understanding the pathogenesis of sBUTDE may aid in the treatment of cases that are refractory to conventional treatments.

Introduction: Carbonated water (CarbW) affects the swallowing function associated with the action of the brainstem. In addition, CarbW ingestion promotes mean blood flow in the middle cerebral artery, which is associated with blood flow to the frontal and temporal lobes. In this milieu, studies regarding the effect of drinking CarbW on brain activity are of significance. In the present study, we compared the changes in cerebral blood flow in the frontal region before and after the ingestion of CarbW or uncarbonated water (SW).Methods: Near-infrared spectroscopy was used to continuously measure the cerebral blood flow at 22 channels in the frontal region of 13 healthy young adults for 10 min before and after the ingestion of CarbW or SW. We statistically compared the changes in oxyhemoglobin concentration before and after the ingestion of CarbW or SW.Results: Compared with that before CarbW ingestion, the oxyhemoglobin concentration in the left frontal region increased after CarbW ingestion. In particular, a significant increase (p < 0.05) was observed in the ch21 region. On the contrary, no marked increase or decrease in cerebral blood flow was observed after SW ingestion compared with that before ingestion.Discussion: The activated part of the frontal region (ch21) corresponds to the vicinity of the orbitofrontal cortex, which is reportedly activated by rewarding stimuli. In addition, as the orbitofrontal cortex is located at the terminal end of the reward pathway of the mesocortical system, CarbW ingestion might have acted on the dopaminergic reward pathway of the mesocortical system.

Group housing is a highly important factor in animal welfare for social animals, including non-human primates (NHPs) such as cynomolgus monkeys. In research facilities, NHPs are conventionally identified by an identification number (ID) tattooed on their bodies. However, since NHPs constantly move around the cage and their IDs are often difficult to see, experimenters must use time-consuming procedures to restrain and visually identify each animal. Such restraint is not only stressful but also potentially causes injuries to animals, and this can affect the quality and accuracy of the research and the well-being of animals. We therefore developed an automated real-time face recognition system for use with cynomolgus monkeys to achieve safe and accurate animal identification. Face and facial feature detection were performed using a Mask Region-based Convolutional Neural Network with a ResNet50-Feature Pyramid Network backbone. For feature extraction, Eigenface method and Local Binary Pattern Histogram were compared, while three types of classifiers: multi-class Support Vector Machine (SVM), k-Nearest Neighbor, and Linear Discriminant Analysis were compared. The best result was obtained using the combination of Eigenface/SVM-quadratic kernel, with a training accuracy of 100% and a 10-fold cross validation accuracy of 95.48%. This novel system could potentially be a powerful tool for accurate animal identification, reducing stress in NHPs and time-consuming work for the experimenters. As such, it can contribute to a digital transformation of preclinical research on NHPs.

Although noninvasive brain-computer interfaces (BCI) based on electroencephalographic (EEG) signals have been studied increasingly over the recent decades, their performance is still limited in two important aspects. First, the difficulty of performing a reliable detection of BCI commands increases when EEG epoch length decreases, which makes high information transfer rates difficult to achieve. Second, the BCI system often misclassifies the EEG signals as commands, although the subject is not performing any task. In order to circumvent these limitations, the hemodynamic fluctuations in the brain during stimulation with steady-state visual evoked potentials (SSVEP) were measured using near-infrared spectroscopy (NIRS) simultaneously with EEG. BCI commands were estimated based on responses to a flickering checkerboard (ON-period). Furthermore, an "idle" command was generated from the signal recorded by the NIRS system when the checkerboard was not flickering (OFF-period). The joint use of EEG and NIRS was shown to improve the SSVEP classification. For 13 subjects, the relative improvement in error rates obtained by using the NIRS signal, for nine classes including the "idle" mode, ranged from 85% to 53%, when the epoch length increase from 3 to 12 s. These results were obtained from only one EEG and one NIRS channel. The proposed bimodal NIRS-EEG approach, including detection of the idle mode, may make current BCI systems faster and more reliable.