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Recent studies focusing on neural activity captured by neuroimaging modalities have provided various metrics for elucidating the functional networks and dynamics of the entire brain. Functional magnetic resonance imaging (fMRI) can depict spatiotemporal functional neural networks and dynamic characteristics due to its excellent spatial resolution. However, its temporal resolution is limited. Neuroimaging modalities such as electroencephalography (EEG) and magnetoencephalography (MEG), which have higher temporal resolutions, are utilized for multi-temporal scale and multi-frequency-band analyzes. With this advantage, numerous EEG/MEG-bases studies have revealed the frequency-band specific functional networks involving dynamic functional connectivity and multiple temporal-scale time-series patterns of neural activity. In addition to analyzing neural data, the examination of behavioral data can unveil additional aspects of brain activity through unimodal and multimodal data analyzes performed using appropriate integration techniques. Among the behavioral data assessments, pupillometry can provide comprehensive spatial-temporal-specific features of neural activity. In this perspective, we summarize the recent progress in the development of metrics for analyzing neural data obtained from neuroimaging modalities such as fMRI, EEG, and MEG, as well as behavioral data, with a special focus on pupillometry data. First, we review the typical metrics of neural activity, emphasizing functional connectivity, complexity, dynamic functional connectivity, and dynamic state transitions of whole-brain activity. Second, we examine the metrics related to the time-series data of pupillary diameters and discuss the possibility of multimodal metrics that combine neural and pupillometry data. Finally, we discuss future perspectives on these multiple and multimodal metrics.

Abstract Background Studies in many populations have reported associations between circulating cytokine levels and various physiological or pathological conditions. However, the reliability of cytokine measurements in population studies, which measure cytokines in multiple assays over a prolonged period, has not been adequately examined; nor has stability during sample storage or intra-individual variation been assessed. Methods We assessed (1) analytical reliability in short- and long-term repeated measurements; (2) stability and analytical reliability during long-term sample storage, and (3) variability within individuals over seasons, of four cytokines—osteopontin (OPN), osteoprotegerin (OPG), vascular endothelial growth factor-A (VEGF-A), and interleukin-17A (IL-17A). Measurements in plasma or serum samples were made with commercial kits according to standard procedures. Estimation was performed by fitting a random or mixed effects linear model on the log scale. Results In repeated assays over a short period, OPN, OPG, and VEGF-A had acceptable reliability, with intra- and inter-assay coefficients of variation (CV) less than 0.11. Reliability of IL-17A was poor, with inter- and intra-assay CV 0.85 and 0.43, respectively. During long-term storage, OPG significantly decayed (− 33% per year; 95% confidence interval [− 54, − 3.7]), but not OPN or VEGF-A (− 0.3% or − 6.3% per year, respectively). Intra- and inter-assay CV over a long period were comparable to that in a short period except for a slight increase in inter-assay CV of VEGF-A. Within-individual variation was small for OPN and VEGF-A, with intra-class correlations (ICC) 0.68 and 0.83, respectively, but large for OPG (ICC 0.11). Conclusions We conclude that OPN and VEGF-A can be reliably measured in a large population, that IL-17A is suitable only for small experiments, and that OPG should be assessed with caution due to degradation during storage and intra-individual variation. The overall results of our study illustrate the need for validation under relevant conditions when measuring circulating cytokines in population studies.

Abstract Heated tobacco products (HTPs) have emerged as novel alternatives to conventional cigarettes (CCs), marketed by the tobacco industry as having a reduced potential for harm. Nevertheless, a significant dearth of information remains regarding the long-term effects of HTPs on the central nervous system (CNS). Here, we sought to shed light on the repercussions of prolonged exposure to HTPs on the CNS, employing a mouse model mimicking prodromal Alzheimer's disease (AD). Our study entailed subjecting App knock-in mice to 16 weeks of HTP exposure, administered 5 days per week, with serum cotinine concentration serving as confirmation of HTP exposure within this model. Histological analysis, aimed at assessing amyloid pathology, unveiled a minimal impact attributable to HTPs. However, exploration of differentially expressed genes in the cerebral cortex, using unadjusted p values, indicated an association between HTP exposure and non-inflammatory pathways, specifically linked to neurohypophyseal and neuropeptide hormone activity within the CNS. Of note, similar results have already been observed after exposure to CCs in vivo. Our study not only contributes insights into the potential non-inflammatory effects of HTPs within the context of AD pathogenesis but also underscores the significance of continued research to comprehend the full scope of their impact on the CNS.

Abstract Cognitive functions produced by large-scale neural integrations are the most representative ‘emergence phenomena’ in complex systems. A novel approach focusing on the instantaneous phase difference of brain oscillations across brain regions has succeeded in detecting moment-to-moment dynamic functional connectivity. However, it is restricted to pairwise observations of two brain regions, contrary to large-scale spatial neural integration in the whole-brain. In this study, we introduce a microstate analysis to capture whole-brain instantaneous phase distributions instead of pairwise differences. Upon applying this method to electroencephalography signals of Alzheimer’s disease (AD), which is characterised by progressive cognitive decline, the AD-specific state transition among the four states defined as the leading phase location due to the loss of brain regional interactions could be promptly characterised. In conclusion, our synthetic analysis approach, focusing on the microstate and instantaneous phase, enables the capture of the instantaneous spatiotemporal neural dynamics of brain activity and characterises its pathological conditions.

Abstract Background Corticobasal syndrome (CBS) is a neurodegenerative disease diagnosed based on clinical manifestations such as asymmetrical parkinsonism, limb apraxia, and speech and language impairment. The background pathology of CBS is commonly a variety of proteinopathies, but association with cerebrovascular disease has also been reported. Foix-Chavany-Marie syndrome (FCMS) is a rare neurological disorder characterized by facio-pharyngo-glossal diplegia with automatic-voluntary movement dissociation presenting with bilateral paresis of the facial, lingual, pharyngeal and masticatory muscles. FCMS is commonly attributable to stroke. Transactive response DNA binding protein of 43 kD (TDP-43) proteinopathy is also known as the pathological background of FCMS, while the pathological background of the majority of CBS cases consists of diverse tauopathies instead of TDP-43 proteinopathy. In this report, we describe a case mimicking FCMS that was finally diagnosed as CBS with suggested 4-repeat tauopathy. Case presentation A 68-year-old female started experiencing difficulty speaking followed by difficulty writing, and especially texting, several years before her visit. Her impairment had been gradually worsening, and she came to our hospital. On neurological examination, she demonstrated the facial apraxia, frontal lobe dysfunction, and upper motor neuron signs. She presented some characteristics suggestive of FCMS. Her symptoms exhibited rapid progression and myoclonus, parkinsonism, and left-side dominant cortical sensory deficit occurred, resulting in the fulfillment of diagnostic criteria for CBS after 9 months. Tau PET imaging displayed notable ligand uptake in the brainstem, subthalamic nuclei, basal ganglia, and bilateral subcortical frontal lobe, suggesting that her pathological background was 4-repeat tauopathy. As a result of her progressive dysphagia, she became unable to eat and passed away after 12 months. Conclusion We hereby present an atypical case of CBS showing clinical features mimicking FCMS at first presentation. TDP-43 proteinopathy was suspected based on the clinical symptoms in the early stages of the disease; however, the clinical course and imaging findings including tau PET suggested that her pathological background was 4-repeat tauopathy.

Abstract Providing standardized, high-quality rehabilitation for critically ill patients is a crucial issue. In 2017, the Japanese Society of Intensive Care Medicine (JSICM) promulgated the “Evidence-Based Expert Consensus for Early Rehabilitation in the Intensive Care Unit” to advocate for the early initiation of rehabilitations in Japanese intensive care settings. Building upon this seminal work, JSICM has recently conducted a rigorous systematic review utilizing the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. This endeavor resulted in the formulation of Clinical Practice Guidelines (CPGs), designed to elucidate best practices in early ICU rehabilitation. The primary objective of this guideline is to augment clinical understanding and thereby facilitate evidence-based decision-making, ultimately contributing to the enhancement of patient outcomes in critical care settings. No previous CPGs in the world has focused specifically on rehabilitation of critically ill patients, using the GRADE approach. Multidisciplinary collaboration is extremely important in rehabilitation. Thus, the CPGs were developed by 73 members of a Guideline Development Group consisting of a working group, a systematic review group, and an academic guideline promotion group, with the Committee for the Clinical Practice Guidelines of Early Mobilization and Rehabilitation in Intensive Care of the JSICM at its core. Many members contributed to the development of the guideline, including physicians and healthcare professionals with multiple and diverse specialties, as well as a person who had been patients in ICU. Based on discussions among the group members, eight important clinical areas of focus for this CPG were identified. Fourteen important clinical questions (CQs) were then developed for each area. The public was invited to comment twice, and the answers to the CQs were presented in the form of 10 GRADE recommendations and commentary on the four background questions. In addition, information for each CQ has been created as a visual clinical flow to ensure that the positioning of each CQ can be easily understood. We hope that the CPGs will be a useful tool in the rehabilitation of critically ill patients for multiple professions. Graphical Abstract

Abstract Aim This study aimed to identify atypical hubs in the whole‐brain networks of patients with schizophrenia (SZ) and examine the effects of antipsychotic medications, using electroencephalography (EEG) data. Methods We estimated the functional connectivity across all electrodes by applying the phase lag index to the EEG signals of 21 drug‐naïve patients with SZ and 31 age‐matched healthy controls. Betweenness centrality (BC), a measure of hub status, was calculated for each electrode and frequency band. Data from 14 patients were re‐evaluated after initiating treatment with antipsychotic medications. Results BC values decreased significantly at the Fz site in the beta band, decreased significantly at Pz in the gamma band, and increased significantly at O1 in the gamma band among patients with SZ. These changes persisted after antipsychotic treatment and were unrelated to clinical symptoms. Conclusion The abnormal hub topology we observed, especially in the high‐frequency band, may reflect the pathophysiology of SZ, and this study highlights the utility of BC analysis of EEG data for detecting alterations in the whole‐brain networks of patients with SZ.

Studies have reported that health care professionals experienced a lack of sleep during the coronavirus disease 2019 (COVID-19) pandemic and that such lack of sleep and working environment affect their performance. However, to the authors' knowledge, no study has yet investigated the relationship between sleep duration and working environment among Japanese physiotherapists during the COVID-19 pandemic. This study retrospectively investigated the sleep duration of physiotherapists directly providing physiotherapy to patients with COVID-19 within the red zone and analyzed the association between sleep duration and working environment using logistic regression analysis. Among the 565 physiotherapists studied, the average sleep duration was 6 (6-7) h, and 381 (67.4%) had an average sleep duration of ≤6 h. Less experienced physiotherapists were 1.03 times more likely to sleep ≤6 h, and those in charge of patients with COVID-19 as the supervisor ordered were 0.64 times more likely to sleep ≤6 h. Moreover, physiotherapists with a significant increase in the frequency of internal online meetings and those who had been providing physiotherapy to patients with COVID-19 for >6 months were 2.34 and 2.05 times more likely to sleep ≤6 h, respectively. During the COVID-19 pandemic in Japan, two-thirds of the physiotherapists directly providing physiotherapy to patients with COVID-19 slept less than the recommended duration. This study highlights the need for appropriate workload and work hour management for physiotherapists according to their experience and workload, as well as establishing a medical care system that includes work rotation to ensure that the recommended sleep duration is satisfied.

Two-dimensional (2D) clinical gait analysis systems are more affordable and portable than contemporary three-dimensional (3D) clinical models. Using the Vicon 3D motion capture system as the standard, we evaluated the internal statistics of the Imasen and open-source OpenPose gait measurement systems, both designed for 2D input, to validate their output based on the similarity of results and the legitimacy of their inner statistical processes. We measured time factors, distance factors, and joint angles of the hip and knee joints in the sagittal plane while varying speeds and gaits during level walking in three in-person walking experiments under normal, maximum-speed, and tandem scenarios. The intraclass correlation coefficients of the 2D models were greater than 0.769 for all gait parameters compared with those of Vicon, except for some knee joint angles. The relative agreement was excellent for the time–distance gait parameter and moderate-to-excellent for each gait motion contraction range, except for hip joint angles. The time–distance gait parameter was high for Cronbach’s alpha coefficients of 0.899–0.993 but low for 0.298–0.971. Correlation coefficients were greater than 0.571 for time–distance gait parameters but lower for joint angle parameters, particularly hip joint angles. Our study elucidates areas in which to improve 2D models for their widespread clinical application.

Accumulation of TMEM106B fibrils composed of cleaved C-terminal fragments (CTF) of transmembrane protein 106B (TMEM106B) has recently been observed in the brains of elderly subjects and individuals with neurodegenerative diseases. To date, one antibody recognizing the residues 239-250 has been found to display immunoreactivity to the TMEM106B CTF, thereby defining TMEM106B C-terminal immunoreactive (TMEM-ir) material. Immunohistochemical characterization of the CTF using antibodies targeting different immunogens could further shed light on the attributes of TMEM-ir material and the biological relevance of TMEM106B fibril accumulation in vivo. Therefore, we generated and validated five polyclonal antibodies against distinct CTF immunogens, namely the residues 140-163, 164-187, 188-211, 239-250, and 253-274. The antibody recognizing the residues 239-250 (antibody no. 5: 239-250) was employed to identify cases positive for TMEM-ir material. Among the remaining four antibodies, antibody no. 3: 188-211 exhibited significant immunoreactivity in TMEM-ir material-positive cases. Comparative analyzes indicated that antibody no. 3: 188-211 and antibody no. 5: 239-250 likely recognized the same TMEM-ir material. The TMEM-ir material detected by antibody no. 3: 188-211 was observed across multiple brain cell types without co-localization with other pathogenic proteins. In conclusion, our findings suggest that the antibody recognizing the residues 188-211 displays immunohistochemical reactivity to TMEM-ir material. Therefore, in addition to the established antibody recognizing the residues 239-250, the antibody recognizing the residues 188-211 can potentially be used in immunohistochemical studies to further elucidate the significance of CTF accumulation in the brain.

IntroductionMeasuring whole-brain networks of the 40 Hz auditory steady state response (ASSR) is a promising approach to describe the after-effects of transcranial direct current stimulation (tDCS). The main objective of this study was to evaluate the effect of tDCS on the brain network of 40 Hz ASSR in healthy adult males using graph theory. The second objective was to identify a population in which tDCS effectively modulates the brain network of 40 Hz ASSR.MethodsThis study used a randomized, sham-controlled, double-blinded crossover approach. Twenty-five adult males (20–24 years old) completed two sessions at least 1 month apart. The participants underwent cathodal or sham tDCS of the dorsolateral prefrontal cortex, after which 40 Hz ASSR was measured using magnetoencephalography. After the signal sources were mapped onto the Desikan–Killiany brain atlas, the statistical relationships between localized activities were evaluated in terms of the debiased weighted phase lag index (dbWPLI). Weighted and undirected graphs were constructed for the tDCS and sham conditions based on the dbWPLI. Weighted characteristic path lengths and clustering coefficients were then measured and compared between the tDCS and sham conditions using mixed linear models.ResultsThe characteristic path length was significantly lower post-tDCS simulation (p = 0.04) than after sham stimulation. This indicates that after tDCS simulation, the whole-brain networks of 40 Hz ASSR show a significant functional integration. Simple linear regression showed a higher characteristic path length at baseline, which was associated with a larger reduction in characteristic path length after tDCS. Hence, a pronounced effect of tDCS is expected for those who have a less functionally integrated network of 40 Hz ASSR.DiscussionGiven that the healthy brain is functionally integrated, we conclude that tDCS could effectively normalize less functionally integrated brain networks rather than enhance functional integration.

IntroductionMaintaining high cognitive functions is desirable for “wellbeing” in old age and is particularly relevant to a super-aging society. According to their individual cognitive functions, optimal intervention for older individuals facilitates the maintenance of cognitive functions. Cognitive function is a result of whole-brain interactions. These interactions are reflected in several measures in graph theory analysis for the topological characteristics of functional connectivity. Betweenness centrality (BC), which can identify the “hub” node, i.e., the most important node affecting whole-brain network activity, may be appropriate for capturing whole-brain interactions. During the past decade, BC has been applied to capture changes in brain networks related to cognitive deficits arising from pathological conditions. In this study, we hypothesized that the hub structure of functional networks would reflect cognitive function, even in healthy elderly individuals.MethodTo test this hypothesis, based on the BC value of the functional connectivity obtained using the phase lag index from the electroencephalogram under the eyes closed resting state, we examined the relationship between the BC value and cognitive function measured using the Five Cognitive Functions test total score.ResultsWe found a significant positive correlation of BC with cognitive functioning and a significant enhancement in the BC value of individuals with high cognitive functioning, particularly in the frontal theta network.DiscussionThe hub structure may reflect the sophisticated integration and transmission of information in whole-brain networks to support high-level cognitive function. Our findings may contribute to the development of biomarkers for assessing cognitive function, enabling optimal interventions for maintaining cognitive function in older individuals.

Abstract Aim This study aimed to investigate gamma oscillations related to face processing of children with autism spectrum disorders and typically developed children using magnetoencephalography. Methods We developed stimuli that included naturalistic real‐time eye‐gaze situations between participants and their mothers. Eighteen young children with autism spectrum disorders (62−97 months) and 24 typically developed children (61−79 months) were included. The magnetoencephalography data were analyzed in the bilateral banks of the superior temporal sulcus, fusiform gyrus, and pericalcarine cortex for frequency ranges 30–59 and 61–90 Hz. The gamma oscillation normalized values were calculated to compare the face condition (children gazing at mother's face) and control measurements (baseline) using the following formula: (face − control)/(face + control). Results The results revealed significant differences in gamma oscillation normalized values in the low gamma band (30–59 Hz) in the right banks of the superior temporal sulcus, right fusiform gyrus, and right pericalcarine cortex between children with autism spectrum disorders and typically developed children. Furthermore, there were significant differences in gamma oscillation normalized values in the high gamma band (61–90 Hz) in the right banks of the superior temporal sulcus, bilateral fusiform gyrus, and bilateral pericalcarine cortex between the groups. Conclusion This report is the first magnetoencephalography study revealing atypical face processing in young children with autism spectrum disorders using relevant stimuli between participants and their mothers. Our naturalistic paradigm provides a useful assessment of social communication traits and a valuable insight into the underlying neural mechanisms in children with autism spectrum disorders.

BackgroundPhysical therapy (PT) is beneficial for critically ill patients, but the extent of its application in the intensive care unit (ICU) differs between countries. Here, we compared the extent of PT intervention in the ICU in Japan, the Philippines, and Taiwan by evaluating the sociodemographic and ICU-related profiles of ICU physical therapists.Materials and methodsIn this cross-sectional study, a semistructured nationwide online survey was distributed to ICU physical therapists in the three countries.ResultsWe analyzed the responses of 164 physical therapists from Japan, Philippines, and Taiwan. Significant differences were observed between the countries in all sociodemographic variables and the following ICU-related profiles of physical therapists: ICU work experience, duration of the ICU posting, number of hours per day spent in the ICU, on-call ICU PT service engagement, source of ICU patient referral, therapist-patient ratio, and ICU-related PT training participation (p < 0.05). Medical, surgical, and neurologic ICUs were the most common ICU workplaces of the ICU physical therapists, but only surgical and neurologic ICUs exhibited significant differences between the countries (p < 0.05). Standard PT techniques in the ICU were passive and active-assisted range of motion, positioning, and breathing exercises but were implemented with significantly different frequencies between the countries (p < 0.05). The most common challenge faced in ICU PT service delivery by respondents from all three countries was lack of training prior to ICU duty, and lack of training was even bigger challenge in Japan than in other two countries after adjustment of age, highest educational attainment, and work experience.ConclusionThe differences in the health-care system between Japan, the Philippines, and Taiwan were related to differences in the compliance with internationally recommended PT practice standards in the ICU, differences in the type of PT intervention prioritized, and the challenges encountered in ICU PT service delivery.

In recent years, there have been increasing knowledge gaps and biases in public health information. This has become especially evident during the COVID-19 pandemic and has contributed to the spread of misinformation. With constant exposure to disinformation and misinformation through television, the internet, and social media, even university students studying healthcare-related subjects lack accurate public health knowledge. This study aimed to assess university students' knowledge levels of basic public health topics before they started their specialized education. Participants in this cross-sectional study were first-year students from medical schools, health-related colleges, and liberal arts colleges. A self-administered electronic survey was conducted from April to May 2021 at a private university in Japan, comprising six colleges with seven programs. Data analysis, conducted from June to December 2022, included students' self-reported public health knowledge, sources of information, and self-assessment of knowledge levels. Among the 1,562 students who received the questionnaire, 549 (192 male [35%], 353 female [64.3%], and 4 undisclosed [0.7%]) responded to one question (participants' response rate for each question; 59.6%-100%). The results showed that students had limited public health knowledge, especially in sexual health topics, and 10% of students reported not learning in class before university admission the following 11 topics: two on Alcohol, Tobacco, and Other Drugs; eight on Growth, Development, and Sexual Health; and one on Personal and Community Health. These results indicate significant knowledge gaps and biases, as well as gender gaps, in public health education, especially in the area of sexual health, which may help educators and educational institutions to better understand and prepare for further specialized education. The findings also suggest a need to supplement and reinforce the foundation of public health knowledge for healthcare majors at the time of university admission.

IMPORTANCE:. Early risk assessment of functional decline in patients with sepsis is clinically challenging. Recently, there is increasing interest in the nonvolitional evaluation of skeletal muscle quality. OBJECTIVES:. The aim of this study was to assess the relationship between skeletal muscle quality and functional decline after intensive care. DESIGN, SETTING, AND PARTICIPANTS:. This pilot study was a single-center prospective observational study conducted from March 2021 to February 2022. We included consecutive patients with sepsis who were admitted to our ICU. MAIN OUTCOMES AND MEASURES:. The primary outcome was hospital-acquired disability (HAD), which is defined as a decrease in the Barthel index score of at least 5 points from pre-hospital to hospital discharge. Muscle quality was assessed by: 1) muscle echogenicity with ultrasound and 2) phase angle (PhA) with bioelectrical impedance analysis, both of which were measured on ICU days less than 3, 3–5, 5–7, 7–10, and 10–14. We compared longitudinal changes in muscle echogenicity and PhA between the HAD and non-HAD groups using two-way repeated measures analysis of variance with mixed models. RESULTS:. Among the 22 patients, 7 (31.8%) had HAD. Muscle echogenicity was higher in the HAD group than in the non-HAD group (p < 0.001); however, no interaction effects were found between the two groups (p = 0.189). PhA showed a main effect on each evaluation day in patients (p = 0.040) and a significant interaction effect between the groups, including an early decreased pattern in the HAD group (p = 0.036). CONCLUSIONS AND RELEVANCE:. Higher muscle echogenicity and a decreased PhA pattern are related to HAD. Noninvasive assessment of muscle quality using ultrasound and bioelectrical impedance analysis may be useful in predicting the functional prognosis of patients with sepsis.

Abstract Background Advanced glycation end-products, indicated by skin autofluorescence (SAF) levels, could be prognostic predictors of all-cause and cardiovascular mortality in patients with diabetes mellitus (DM) and renal disease. However, the clinical usefulness of SAF levels in patients with heart failure (HF) who underwent cardiac rehabilitation (CR) remains unclear. This study aimed to investigate the associations between SAF and MACE risk in patients with HF who underwent CR. Methods This study enrolled 204 consecutive patients with HF who had undergone CR at our university hospital between November 2015 and October 2017. Clinical characteristics and anthropometric data were collected at the beginning of CR. SAF levels were noninvasively measured with an autofluorescence reader. Major adverse cardiovascular event (MACE) was a composite of all-cause mortality and unplanned hospitalization for HF. Follow-up data concerning primary endpoints were collected until November 2017. Results Patients’ mean age was 68.1 years, and 61% were male. Patients were divided into two groups according to the median SAF levels (High and Low SAF groups). Patients in the High SAF group were significantly older, had a higher prevalence of chronic kidney disease, and more frequently had history of coronary artery bypass surgery; however, there were no significant between-group differences in sex, prevalence of DM, left ventricular ejection fraction, and physical function. During a mean follow-up period of 590 days, 18 patients had all-cause mortality and 36 were hospitalized for HF. Kaplan–Meier analysis showed that patients in the high SAF group had a higher incidence of MACE (log-rank P

BackgroundNutritional epidemiology has shown that inadequate dietary protein intake is associated with poor brain function in the elderly population. The plasma free amino acid (PFAA) profile reflects nutritional status and may have the potential to predict future changes in cognitive function. Here, we report the results of a 2-year interim analysis of a 3-year longitudinal study following mild cognitive impairment (MCI) participants.MethodIn a multicenter prospective cohort design, MCI participants were recruited, and fasting plasma samples were collected. Based on clinical assessment of cognitive function up to 2 years after blood collection, MCI participants were divided into two groups: remained with MCI or reverted to cognitively normal (“MCI-stable,” N = 87) and converted to Alzheimer’s disease (AD) (“AD-convert,” N = 68). The baseline PFAA profile was compared between the two groups. Stratified analysis based on apolipoprotein E ε4 (APOE ε4) allele possession was also conducted.ResultsPlasma concentrations of all nine essential amino acids (EAAs) were lower in the AD-convert group. Among EAAs, three branched-chain amino acids (BCAAs), valine, leucine and isoleucine, and histidine (His) exhibited significant differences even in the logistic regression model adjusted for potential confounding factors such as age, sex, body mass index (BMI), and APOE ε4 possession (p < 0.05). In the stratified analysis, differences in plasma concentrations of these four EAAs were more pronounced in the APOE ε4-negative group.ConclusionThe PFAA profile, especially decreases in BCAAs and His, is associated with development of AD in MCI participants, and the difference was larger in the APOE ε4-negative population, suggesting that the PFAA profile is an independent risk indicator for AD development. Measuring the PFAA profile may have importance in assessing the risk of AD conversion in the MCI population, possibly reflecting nutritional status.Clinical trial registration[https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000025322], identifier [UMIN000021965].

Abstract Background Peak oxygen uptake (peak VO2) is known not only as an index of aerobic fitness but also one of an index of life expectancy. Frailty, sarcopenia, and cachexia are associated with a poor prognosis and high mortality. The purpose of this study was to determine the relationships of peak VO2 with the features of sarcopenia, frailty, and cachexia, to provide insight into which might mediate the poor prognosis. Methods The first group of participants was 175 community‐dwelling older Japanese outpatients (58 men and 117 women; mean age 77.6 ± 6.4 years), in whom we assessed the features of sarcopenia, frailty, and cachexia, and measured peak VO2 during cardiopulmonary exercise. To confirm the relationships, we analysed another group of 162 participants (77.3 ± 5.5 years). Results There were significant correlations between peak VO2 and the features of sarcopenia, frailty, and cachexia, with the exception of high sensitivity C‐reactive protein. Multiple linear regression analysis for the prediction of peak VO2 (mL/min) identified following formula: predicted peak VO2 = −11.6 × age (years) + 25.5 × haemoglobin concentration (g/dL) + 114.2 × skeletal muscle mass index (kg/m2) + 8.9 × hand grip strength (kg) + 226.4 × usual walking speed (m/s) − 65.8 × fatiguability (absence 0, presence 1) − 177.4 × chronic heart failure (absence 0, presence 1) + 437.1 (R2 = 0.627, P

Recent studies suggest that the maintenance of cognitive function in the later life of older people is an essential factor contributing to mental wellbeing and physical health. Particularly, the risk of depression, sleep disorders, and Alzheimer's disease significantly increases in patients with mild cognitive impairment. To develop early treatment and prevention strategies for cognitive decline, it is necessary to individually identify the current state of cognitive function since the progression of cognitive decline varies among individuals. Therefore, the development of biomarkers that allow easier measurement of cognitive function in older individuals is relevant for hyperaged societies. One of the methods used to estimate cognitive function focuses on the temporal complexity of electroencephalography (EEG) signals. The characteristics of temporal complexity depend on the time scale, which reflects the range of neuron functional interactions. To capture the dynamics, composed of multiple time scales, multiscale entropy (MSE) analysis is effective for comprehensively assessing the neural activity underlying cognitive function in the brain. Thus, we hypothesized that EEG complexity analysis could serve to assess a wide range of cognitive functions in older adults. To validate our hypothesis, we divided older participants into two groups based on their cognitive function test scores: a high cognitive function group and a low cognitive function group, and applied MSE analysis to the measured EEG data of all participants. The results of the repeated-measures analysis of covariance using age and sex as a covariate in the MSE profile showed a significant difference between the high and low cognitive function groups (F = 10.18, p = 0.003) and the interaction of the group × electrodes (F = 3.93, p = 0.002). Subsequently, the results of the post-hoct-test showed high complexity on a slower time scale in the frontal, parietal, and temporal lobes in the high cognitive function group. This high complexity on a slow time scale reflects the activation of long-distance neural interactions among various brain regions to achieve high cognitive functions. This finding could facilitate the development of a tool for diagnosis of cognitive decline in older individuals.

Abstract1: Non-astringent persimmon (Diospyros kaki Thunb.) paste is typically produced by treating astringent persimmon fruit with alcohol or dry ice (to remove tannins) followed by abrasion. However, considering the large yield of astringent persimmons harvested in a short time, this long, laborious method has hindered the use of persimmon paste in food processing. Herein, the addition of polysaccharides was used to produce a non-astringent persimmon paste while maintaining its quality. Among the nine evaluated polysaccharides, high- (HM) and low-methoxyl (LM) pectins, carrageenan, xanthan gum, and sodium alginate exhibited high astringency removal efficiencies. No astringency recurrence was observed after freezing when HM or LM pectin, guar gum, carrageenan, or sodium alginate were added. Moreover, the addition of HM pectin, or LM pectin, or sodium alginate prevented astringency upon heating. Additionally, guar, xanthan, tara gum, or carrageenan effectively inhibited syneresis. Thus, high-quality pastes could be easily and efficiently produced using a combination of polysaccharides.

Background: Low-intensity resistance training (RT) combined with neuromuscular electrical stimulation (NMES) is one method of exercise to improve the deterioration of physical function. However, it is unclear whether low-intensity RT combined with NMES (RT + NMES) can be safely implemented. Objective: This study aimed to examine the influence of low-intensity RT + NMES on autonomic activity and cardiovascular responses in healthy adults. Methods: This study was an open-label, randomized controlled cross-over trial. The exercise intensity of isometric knee extension RT was set to 40% of the maximum voluntary contraction (peak torque). NMES was adjusted to a biphasic asymmetrical waveform with the frequency maintained at 50 Hz and a phase duration of 300 μs. The difference in the change in autonomic activity and cardiovascular responses was compared by assessing heart rate variability, blood pressure, and heart rate during RT and RT+NMES. Results: Twenty healthy male college students (mean age 21.0±0.6 years) participated in this study. The ratio of low- and high-frequency components of heart rate variability, systolic blood pressure, and heart rate increased during exercise in the RT and RT+NMES sessions (P

Abstract Aims Functional decline is associated with worse outcomes in patients with elderly heart failure (HF), but little is known about the prognostic impact of hospital‐acquired disability (HAD) during hospital stay after acute HF. The present study examines the prognostic significance of HAD in the prediction of all‐cause mortality in elderly patients who admitted for acute HF. Methods and results This retrospective study was performed in 1941 elderly patients aged ≥65 years or older from the cardiovascular physiotherapy for acute HF patients in the Tokyo metropolitan area registry and excluded those who died in hospital. HAD was defined as any decline in the Barthel index (BI) before discharge compared with the BI within 1 month before hospital admission. The primary outcome of this study was all‐cause death and HF readmission. A total of 565 (29%) deaths and 789 (41%) HF readmission occurred over a median follow‐up period of 1.7 years. A total of 476 patients (25%) had HAD during hospital stay after acute HF. In multivariable analysis, HAD predicted all‐cause death [hazard ratio (HR): 1.772; 95% confidence interval (CI): 1.450–2.167; P

Abstract Adult attention-deficit/hyperactivity disorder (ADHD) frequently leads to psychological/social dysfunction if unaddressed. Identifying a reliable biomarker would assist the diagnosis of adult ADHD and ensure that adults with ADHD receive treatment. Pupil diameter can reflect inherent neural activity and deficits of attention or arousal characteristic of ADHD. Furthermore, distinct profiles of the complexity and symmetricity of neural activity are associated with some psychiatric disorders. We hypothesized that analysing the relationship between the size, complexity of temporal patterns, and asymmetricity of pupil diameters will help characterize the nervous systems of adults with ADHD and that an identification method combining these features would ease the diagnosis of adult ADHD. To validate this hypothesis, we evaluated the resting state hippus in adult participants with or without ADHD by examining the pupil diameter and its temporal complexity using sample entropy and the asymmetricity of the left and right pupils using transfer entropy. We found that large pupil diameters and low temporal complexity and symmetry were associated with ADHD. Moreover, the combination of these factors by the classifier enhanced the accuracy of ADHD identification. These findings may contribute to the development of tools to diagnose adult ADHD.

Female sex in patients with atrial fibrillation (AF) is a controversial and paradoxical risk factor for stroke—controversial because it increases the risk of stroke only among older women of some ethnicities and paradoxical because it appears to contradict male predominance in cardiovascular diseases. However, the underlying mechanism remains unclear. We conducted simulations to examine the hypothesis that this sex difference is generated non-causally through left truncation due to competing risks (CR) such as coronary artery diseases, which occur more frequently among men than among women and share common unobserved causes with stroke. We modeled the hazards of stroke and CR with correlated heterogeneous risk. We assumed that some people died of CR before AF diagnosis and calculated the hazard ratio of female sex in the left-truncated AF population. In this situation, female sex became a risk factor for stroke in the absence of causal roles. The hazard ratio was attenuated in young populations without left truncation and in populations with low CR and high stroke incidence, which is consistent with real-world observations. This study demonstrated that spurious risk factors can be identified through left truncation due to correlated CR. Female sex in patients with AF may be a paradoxical risk factor for stroke.

Abstract Background Phase angle (PA), measured by bioelectrical impedance analysis (BIA) has been studied as indicator of nutritional status or muscle function in hemodialysis (HD) patients. It remains unclear if the phase angle is associated protein-energy wasting (PEW) or frailty, which are common complication in hemodialysis patients. The aim of this study is to determine whether BIA-derived PA is a marker of PEW or frailty in HD patients. Methods This retrospective observational study included 116 adult HD patients (35% female, 64 ± 12 years of age) in a single dialysis center. Patients were classified according to the PA quartiles into four groups; 1) first quartile: PA

Abstract Aims The kinetics of recovery‐period oxygen uptake (VO2) are affected by the O2 deficit generated during exercise. However, studies using ramp tests (RTs) and constant work rate tests (CT) have differently characterized VO2 responses to increased exercise intensity differently. We used these two types of loading patterns to investigate the effects of low‐intensity, medium‐intensity, and high‐intensity exercises on the half time (T1/2) of recovery‐period VO2 and the mechanism. Methods and results Ten healthy men aged 21.2 ± 0.9 years underwent symptom‐limited cardiopulmonary exercise tests with the ramp protocol to determine their anaerobic threshold. All subjects subsequently underwent three submaximal RT and CT at low, moderate, and high intensities. In all RTs, subjects began exercise by warming up (20 W). In CT, T1/2 was significantly lengthened as exercise intensity increased (CT‐low: 34.0 ± 3.9 s, CT‐moderate: 39.5 ± 3.5 s, CT‐high:44.6 ± 4.2 s; P

BackgroundCommercially available active video games (AVGs) have recently been used for rehabilitation in some specific patient populations but rarely in those with cardiovascular disease (CVD). Commercially available AVGs are designed to increase motivation for continuous play, which could be applicable to the long-term cardiac rehabilitation process. ObjectiveThe objective of this scoping review was to assess the effectiveness of AVG-induced physical exercise, safety management, and patient adherence by applying commercially available AVGs to cardiac rehabilitation. MethodsFour databases (CINAHL, MEDLINE, PubMed, and SPORTDiscus) were searched for all years up to August 12, 2020. Articles were retained if they were written in English, included patients with CVD who were aged 18 years or older, and used AVGs as part of a physical exercise program. The included studies were then evaluated from the viewpoints of effectiveness as physical exercise, safety, and adherence management. ResultsAmong 120 nonduplicate articles reviewed, 5 (4.2%) were eligible for inclusion, of which 3 (2.5%) were reported by the same research group. The AVG consoles used were Xbox Kinect and Nintendo Wii, and sports-related programs were adopted for the intervention. No adverse cardiac events occurred in the identified studies, and dropout rates tended to be low. ConclusionsAVGs appear to be safe and feasible for promoting an active lifestyle in patients with CVD. However, the effectiveness of AVGs alone as a therapeutic exercise to improve physical function may be limited.

With the aging process, brain functions, such as attention, memory, and cognitive functions, degrade over time. In a super-aging society, the alteration of neural activity owing to aging is considered crucial for interventions for the prevention of brain dysfunction. The complexity of temporal neural fluctuations with temporal scale dependency plays an important role in optimal brain information processing, such as perception and thinking. Complexity analysis is a useful approach for detecting cortical alteration in healthy individuals, as well as in pathological conditions, such as senile psychiatric disorders, resulting in changes in neural activity interactions among a wide range of brain regions. Multi-fractal (MF) and multi-scale entropy (MSE) analyses are known methods for capturing the complexity of temporal scale dependency of neural activity in the brain. MF and MSE analyses exhibit high accuracy in detecting changes in neural activity and are superior with regard to complexity detection when compared with other methods. In addition to complex temporal fluctuations, functional connectivity reflects the integration of information of brain processes in each region, described as mutual interactions of neural activity among brain regions. Thus, we hypothesized that the complementary relationship between functional connectivity and complexity could improve the ability to detect the alteration of spatiotemporal patterns observed on electroencephalography (EEG) with respect to aging. To prove this hypothesis, this study investigated the relationship between the complexity of neural activity and functional connectivity in aging based on EEG findings. Concretely, MF and MSE analyses were performed to evaluate the temporal complexity profiles, and phase lag index analyses assessing the unique profile of functional connectivity were performed based on the EEGs conducted for young and older participants. Subsequently, these profiles were combined through machine learning. We found that the complementary relationship between complexity and functional connectivity improves the classification accuracy among aging participants. Thus, the outcome of this study could be beneficial in formulating interventions for the prevention of age-related brain dysfunction.

Intracellular amyloid β peptide (Aβ) accumulation has drawn attention in relation to the pathophysiology of Alzheimer’s disease in addition to its extracellular deposition as senile plaque. Cellular uptake of extracellular Aβ is one of the possible mechanisms by which intracellular Aβ deposits form. Given the relevance of Aβ inside cells, it is important to understand the mechanism by which it is taken up by them. In this study, we elucidated that Neuro2A and SH-SY5Y cells internalize specifically oligomerized Aβ in a time- and dose-dependent manner. The depletion of plasma membrane cholesterol with methyl-β-cyclodextrin or treatment with trypsin diminished the internalization of oAβ, suggesting that the oAβ uptake might be both a lipid raft-dependent and heparan sulfate proteoglycan-mediated process. Treatment with a macropinocytosis inhibitor (ethylisopropyl amiloride and wortmannin) also drastically reduced the uptake of oligomer-Aβ (oAβ). oAβ-treated cells exhibited an increase in Rac1 activity, indicating that macropinocytosis induced by oAβ is regulated by these small GTPases. These findings suggest that macropinocytosis is a major endocytic route through which oAβ42 enters cells.

BackgroundThe COVID-19 pandemic has required an increased need for rehabilitation activities applicable to patients with chronic diseases. Telerehabilitation has several advantages, including reducing clinic visits by patients vulnerable to infectious diseases. Digital platforms are often used to assist rehabilitation services for patients in remote settings. Although web portals for medical use have existed for years, the technology in telerehabilitation remains a novel method. ObjectiveThis scoping review investigated the functional features and theoretical approaches of web portals developed for telerehabilitation in patients with chronic diseases. MethodsPubMed and Web of Science were reviewed to identify articles associated with telerehabilitation. Of the 477 nonduplicate articles reviewed, 35 involving 14 portals were retrieved for the scoping review. The functional features, targeted diseases, and theoretical approaches of these portals were studied. ResultsThe 14 portals targeted patients with chronic obstructive pulmonary disease, cardiovascular, osteoarthritis, multiple sclerosis, cystic fibrosis diseases, and stroke and breast cancer survivors. Monitoring/data tracking and communication functions were the most common, followed by exercise instructions and diary/self-report features. Several theoretical approaches, behavior change techniques, and motivational techniques were found to be utilized. ConclusionsThe web portals could unify and display multiple types of data and effectively provide various types of information. Asynchronous correspondence was more favorable than synchronous, real-time interactions. Data acquisition often required assistance from other digital tools. Various functions with patient-centered principles, behavior change strategies, and motivational techniques were observed for better support shifting to a healthier lifestyle. These findings suggested that web portals for telerehabilitation not only provided entrance into rehabilitation programs but also reinforced participant-centered treatment, adherence to rehabilitation, and lifestyle changes over time.

Burnout among physiotherapists has been reported worldwide during the coronavirus disease 2019 (COVID-19) pandemic. However, no information was found on the prevalence of burnout among physiotherapists in Japan during the COVID-19 pandemic. Physiotherapists directly providing physiotherapy to patients with COVID-19 in the red zone of 487 medical facilities were evaluated for the prevalence of burnout using the Japanese version of the Maslach Burnout Inventory-General Survey (MBI-GS). The association between the presence or absence of burnout and the working environment was analyzed using logistic regression analysis. Among the 566 physiotherapists analyzed, 99 (17.5%) satisfied the MBI-GS criteria for burnout. Multivariate analysis showed that burnout was associated with the year of physiotherapy experiences [odds ratio (OR) 0.96, 95% confidence interval (CI) 0.93-0.99], feeling slight burden with infection control (OR 0.53, 95% CI 0.32-0.87), not feeling too burdened with infection control (OR 0.27, 95% CI 0.06-0.83), establishment of staffing standards for physiotherapy according to the number of beds (OR 1.80, 95% CI 1.09-2.96), and relaxation time (OR 0.49, 95% CI 0.30-0.82). Moreover, the OR increased as the self-improvement time decreased (OR 38.3, 95% CI 6.64-731). In Japan, the prevalence of burnout among physiotherapists during the COVID-19 pandemic was an intermediate value between the prevalence of burnout among physicians and nurses reported in previous studies. This study found the need to establish appropriate staffing standards for physiotherapy and support systems including secure self-improvement time and appropriate training according to physiotherapy experiences and each medical facility.

Introduction Cardiac surgery for older patients, postoperative functional decline and the need for long-term care have received increasing attention as essential outcomes in recent years. Therefore, prevention of functional decline and long-term care dependency after cardiac surgery are important; however, our current understanding of postoperative functional trajectory and effects of postoperative regular exercise on long-term functional decline and long-term care dependency is limited. Therefore, we will conduct a multicentre, prospective cohort study to (1) examine the effect of hospital-acquired disability on long-term functional decline and long-term care dependency and (2) investigate the favourable effect of postoperative regular exercise on long-term functional decline and long-term care dependency in older patients after cardiac surgery.Methods and analysis We designed a prospective, multicentre cohort study to enrol older patients aged≥65 years undergoing elective coronary artery bypass graft or valve surgery. We will conduct medical record reviews to collect data on patient demographics, comorbidities, operative details, progression of in-hospital postoperative cardiac rehabilitation and functional trajectory from a few days before cardiac surgery to the day before hospital discharge. They will be followed up for 2 years to obtain information on their health status including functional status, regular exercise and clinical events by mail. Primary endpoints of this study are long-term functional decline and long-term care dependency after cardiac surgery. Secondary endpoints are readmission due to cardiac events or all-cause mortality.Ethics and dissemination The study protocol was approved by the Ethics Committee of the Department of Physical Therapy, Faculty of Health Science, Juntendo University, and of each collaborating hospital. We obtained written informed consent from all study participants after the description of the study procedures. Publication of the study results is anticipated in 2025.

BackgroundHeart failure is one of the world’s most frequently diagnosed cardiovascular diseases. An important element of heart failure management is cardiac rehabilitation, the goal of which is to improve patients’ recovery, functional capacity, psychosocial well-being, and health-related quality of life. Patients in cardiac rehabilitation may lack sufficient motivation or may feel that the rehabilitation process does not meet their individual needs. One solution to these challenges is the use of telerehabilitation. Although telerehabilitation has been available for several years, it has only recently begun to be utilized in heart failure studies. Especially within the past 5 years, we now have several studies focusing on the effectiveness of telerehabilitation for heart failure management, all with varying results. Based on a review of these studies, this paper offers an assessment of the effectiveness of telerehabilitation as applied to heart failure management. ObjectiveThe aim of this scoping review was to assess the effects of telerehabilitation in the management of heart failure by systematically reviewing the available scientific literature within the period from January 1, 2015, to December 31, 2020. MethodsThe literature search was carried out using PubMed and EMBASE. After duplicates were removed, 77 articles were screened and 12 articles were subsequently reviewed. The review followed the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses for scoping reviews) guidelines. As measures of the effectiveness of telerehabilitation, the following outcomes were used: patients’ quality of life, physical capacity, depression or anxiety, and adherence to the intervention. ResultsA total of 12 articles were included in this review. In reviewing the effects of telerehabilitation for patients with heart failure, it was found that 4 out of 6 randomized controlled trials (RCTs), a single prospective study, and 4 out of 5 reviews reported increased quality of life for patients. For physical capacity, 4 RCTs and 3 systematic reviews revealed increased physical capacity. Depression or depressive symptoms were reported as being reduced in 1 of the 6 RCTs and in 2 of the 5 reviews. Anxiety or anxiety-related symptoms were reported as reduced in only 1 review. High adherence to the telerehabilitation program was reported in 4 RCTs and 4 reviews. It should be mentioned that some of the reviewed articles described the same studies although they employed different outcome measures. ConclusionsIt was found that there is a tendency toward improvement in patients’ quality of life and physical capacity when telerehabilitation was used in heart failure management. The outcome measures of depression, anxiety, and adherence to the intervention were found to be positive. Additional research is needed to determine more precise and robust effects of telerehabilitation.

Parent-child book reading is important for fostering the development of various lifelong cognitive and social abilities in young children. Despite numerous reports describing the effects of familiarity on shared reading for children, the exact neural basis of the functional network architecture remains unclear. We conducted Magnet-Encephalographic (MEG) experiments using graph theory to elucidate the role of familiarity in shared reading in a child's brain network and to measure the connectivity dynamics of a child while Listening to Storybook Reading (LSBR), which represents the daily activity of shared book reading between the child and caregiver. The LSBR task was performed with normally developing preschool- and school-age children (N = 15) under two conditions: reading by their own mother (familiar condition) vs. an experimenter (unfamiliar condition). We used the phase lag index (PLI), which captures synchronization of MEG signals, to estimate functional connectivity. For the whole brain network topology, an undirected weighted graph was produced using 68 brain regions as nodes and interregional PLI values as edges for five frequency bands. Behavioral data (i.e., the degree of attention and facial expressions) were evaluated from video images of the child's face during the two conditions. Our results showed enhanced widespread functional connectivity in the alpha band during the mother condition. In the mother condition, the whole brain network in the alpha band exhibited topographically high local segregation with high global integration, indicating an increased small-world property. Results of the behavioral analysis revealed that children were more attentive and showed more positive facial expressions in the mother condition than in the experimenter condition. Behavioral data were significantly correlated with graph metrics in the mother condition but not in the experimenter condition. In this study, we identified the neural correlates of a familiarity effect in children's brain connectivity dynamics during LSBR. Furthermore, these familiarity-related brain dynamics were closely linked to the child's behavior. Graph theory applied to MEG data may provide useful insight into the familiarity-related child brain response in a naturalistic setting and its relevance to child attitudes.

Stochastic resonance is a phenomenon in which the effects of additive noise strengthen the signal response against weak input signals in non-linear systems with a specific barrier or threshold. Recently, several studies on stochastic resonance have been conducted considering various engineering applications. In addition to additive stochastic noise, deterministic chaos causes a phenomenon similar to the stochastic resonance, which is known as chaotic resonance. The signal response of the chaotic resonance is maximized around the attractor-merging bifurcation for the emergence of chaos-chaos intermittency. Previous studies have shown that the sensitivity of chaotic resonance is higher than that of stochastic resonance. However, the engineering applications of chaotic resonance are limited. There are two possible reasons for this. First, the stochastic noise required to induce stochastic resonance can be easily controlled from outside of the stochastic resonance system. Conversely, in chaotic resonance, the attractor-merging bifurcation must be induced via the adjustment of internal system parameters. In many cases, achieving this adjustment from outside the system is difficult, particularly in biological systems. Second, chaotic resonance degrades owing to the influence of noise, which is generally inevitable in real-world systems. Herein, we introduce the findings of previous studies concerning chaotic resonance over the past decade and summarize the recent findings and conceivable approaches for the reduced region of orbit feedback method to address the aforementioned difficulties.

Reduced integrity of neural pathways from frontal to sensory cortices has been suggested as a potential neurobiological basis of attention-deficit hyperactivity disorder. Neurofeedback has been widely applied to enhance reduced neural pathways in attention-deficit hyperactivity disorder by repeated training on a daily temporal scale. Clinical and model-based studies have demonstrated that fluctuations in neural activity underpin sustained attention deficits in attention-deficit hyperactivity disorder. These aberrant neural fluctuations may be caused by the chaos–chaos intermittency state in frontal-sensory neural systems. Therefore, shifting the neural state from an aberrant chaos–chaos intermittency state to a normal stable state with an optimal external sensory stimulus, termed chaotic resonance, may be applied in neurofeedback for attention-deficit hyperactivity disorder. In this study, we applied a neurofeedback method based on chaotic resonance induced by “reduced region of orbit” feedback signals in the Baghdadi model for attention-deficit hyperactivity disorder. We evaluated the stabilizing effect of reduced region of orbit feedback and its robustness against noise from errors in estimation of neural activity. The effect of chaotic resonance successfully shifted the abnormal chaos-chaos intermittency of neural activity to the intended stable activity. Additionally, evaluation of the influence of noise due to measurement errors revealed that the efficiency of chaotic resonance induced by reduced region of orbit feedback signals was maintained over a range of certain noise strengths. In conclusion, applying chaotic resonance induced by reduced region of orbit feedback signals to neurofeedback methods may provide a promising treatment option for attention-deficit hyperactivity disorder.

Abstract Background This study investigated the prevalence of sarcopenia or sarcopenic obesity and their association with frailty and protein-energy wasting (PEW) in hemodialysis patients. Methods The present study enrolled 117 adult hemodialysis patients (35% female, 64 ± 12 years old) from single units of a hemodialysis center. The patients were divided into four groups: normal, obese, sarcopenia, and sarcopenic obesity. Sarcopenia was diagnosed by Asian Working Group for Sarcopenia (AWGS) criteria, and obesity was defined as an extensive percent body fat mass greater than 40% in females and 30% in males. Skeletal muscle mass and percent fat mass were evaluated by multifrequency whole-body bioimpedance electrical analysis after a midweek dialysis session. Handgrip strength and a short physical performance battery (SPPB) were assessed before a dialysis session as indicators of muscle strength and physical performance. Moreover, participants completed the Kihon Checklist and the criteria proposed by the International Society of Renal Nutrition and Metabolism expert panel to classify frailty and PEW. We performed multivariate logistic regression analysis to identify the clinical risk of frailty and PEW in patients with sarcopenia or sarcopenic obesity. Results Forty-six (39.3%) patients were classified as normal; 18 (15.4%), as obese; 35 (29.9%), as having sarcopenia; and 18 (15.4%), as having sarcopenic obesity. The sarcopenia or sarcopenic obesity group had significantly lower handgrip strength than the normal or obesity group (all p < 0.05). In addition, the sarcopenia and sarcopenic obesity groups had significantly lower SPPB scores than the normal group (p < 0.05, respectively). In the multivariate analysis, the sarcopenic obesity group had a significantly higher risk of frailty than the normal group in the multivariate analysis after adjusting for age and gender (OR 4.518, 95%CI 1.218–16.752, p = 0.024). However, sarcopenic obesity was not associated with a higher likelihood of PEW, and sarcopenia imposed a significantly higher risk of PEW (OR 4.272, 95%CI 1.157–15.778, p = 0.029) than that in the normal group after adjusting for confounding factors. Conclusion Sarcopenic obesity was closely associated with frailty compared with the normal condition in HD patients. However, sarcopenic obesity was not associated with a higher likelihood of PEW.

Alzheimer's disease (AD) is the most common form of dementia and is a progressive neurodegenerative disease that primarily develops in old age. In recent years, it has been reported that early diagnosis of AD and early intervention significantly delays disease progression. Hence, early diagnosis and intervention are emphasized. As a diagnostic index for AD patients, evaluating the complexity of the dependence of the electroencephalography (EEG) signal on the temporal scale of Alzheimer's disease (AD) patients is effective. Multiscale entropy analysis and multifractal analysis have been performed individually, and their usefulness as diagnostic indicators has been confirmed, but the complemental relationship between these analyses, which may enhance diagnostic accuracy, has not been investigated. We hypothesize that combining multiscale entropy and fractal analyses may add another dimension to understanding the alteration of EEG dynamics in AD. In this study, we performed both multiscale entropy and multifractal analyses on EEGs from AD patients and healthy subjects. We found that the classification accuracy was improved using both techniques. These findings suggest that the use of multiscale entropy analysis and multifractal analysis may lead to the development of AD diagnostic tools.

Many neuroimaging studies on morality focus on functional brain areas that relate to moral judgment specifically in morally negative situations. To date, there have been few studies on differences in brain activity under conditions of being morally good and bad along a continuum. To explore not only the brain regions involved but also their functional connections during moral judgments, we used magnetoencephalography (MEG), which is superior to other imaging modalities for analyzing time-dependent brain activities; only men were recruited because sex differences might be a confounding factor. While analyses showed that general patterns of brain activation and connectivity were similar between morally good judgments (MGJs) and morally bad judgments (MBJs), activation in brain areas that subserve emotion and “theory of mind” on the right hemisphere was larger in MGJ than MBJ conditions. In the left local temporal region, the connectivity between brain areas related to emotion and reward/punishment was stronger in MBJ than MGJ conditions. The time-frequency analysis showed distinct laterality (left hemisphere dominant) occurring during early moral information processing in MBJ conditions compared to MGJ conditions and phase-dependent differences in the appearance of theta waves between MBJ and MGJ conditions. During MBJs, connections within the hemispheric regions were more robust than those between hemispheric regions. These results suggested that the local temporal region on the left hemisphere is more important in the execution of MBJs during early moral valence processing than in that with MGJs. Shorter neuronal connections within the hemisphere may allow to make MBJs punctual.

In addition to photic reflex function, the temporal behavior of the pupil diameter reflects levels of arousal and attention and thus internal cognitive neural activity. Recent studies have reported that these behaviors are characterized by baseline activity, temporal complexity, and symmetricity (i.e., degree of symmetry) between the right and left pupil diameters. We hypothesized that experimental analysis to reveal relationships among these characteristics and model-based analysis focusing on the newly discovered contralateral projection from the locus coeruleus (LC) to the Edinger-Westphal nucleus (EWN) within the neural system for controlling pupil diameter could contribute to another dimension of understanding of complex pupil dynamics. In this study, we aimed to validate our hypothesis by analyzing the pupillary hippus in the healthy resting state in terms of sample entropy (SampEn), to capture complexity, and transfer entropy (TranEn), to capture symmetricity. We also constructed a neural model embedded with the new findings on neural pathways. The following results were observed: first, according to surrogate data analysis, the complexity and symmetricity of pupil diameter changes reflect a non-linear deterministic process. Second, both the complexity and the symmetricity are unimodal, peaking at intermediate pupil diameters. Third, according to simulation results, the neural network that controls pupil diameter has an inverted U-shaped profile of complexity and symmetricity vs. baseline LC activity; this tendency is enhanced by the contralateral synaptic projections from the LCs to the EWNs. Thus, we characterized the typical relationships between the baseline activity and the complexity and symmetricity of the pupillometric data in terms of SampEn and TranEn. Our evaluation method and findings may facilitate the development of estimation and diagnostic tools for exploring states of the healthy brain and psychiatric disorders based on measurements of pupil diameter.

Bipolar disorder (BD), which involves mood swings between mania and depression, is associated with multiple relapses during long-term treatment and high suicide and morbidity rates. In BD, the circadian rhythms, which are measured by daily mood scores and actigraphic records, are disturbed. Chronotherapy has emerged as a potential treatment for BD because it stabilizes the disturbed circadian rhythms and improves BD symptoms. Concrete treatments include light therapy and combination therapy (light therapy and drugs). However, some patients have difficulty adjusting to light therapy; inappropriate light and duration of treatment increase risks for inducing mixed states and the emergence of conditions, such as hypomania and autonomic hyperactivation. Therefore, it is important to devise methods for optimizing chronotherapy for BD. We aimed to develop feedback signals for the frontal cortex, which were based on the delayed feedback method as one of the chaos control methods, to stabilize the disturbed circadian rhythms of BD. Concrete procedures of this study are indicated as follows: first, circadian rhythms of BD are reproduced using the frontal cortex and hypothalamus neural system, which has been previously proposed. Second, the delayed feedback signal is developed by using bifurcation analysis. Third, the effect of delayed feedback signal is evaluated by index for complexity, and power spectrum under the condition with/without stochastic noise in feedback term. We found that application of the delayed feedback signal to the frontal cortical neural activity induces the periodic state of circadian rhythms from the disturbed complex and is feasible for treating BD. However, when increasing the influence of noise in feedback term, the stabilizing effect is diminished. In conclusion, we developed a stabilizing method for disturbed circadian rhythms of BD using the circadian neural systems. The present study highlights the potential usefulness of the chaos control method for treating BD.

Despite growing evidence that high creativity leads to mental well-being in older individuals, the neurophysiological bases of creativity remain elusive. Creativity reportedly involves multiple brain areas and their functional interconnections. In particular, functional magnetic resonance imaging (fMRI) is used to investigate the role of patterns of functional connectivity between the default network and other networks in creative activity. These interactions among networks play the role of integrating various neural processes to support creative activity and involve attention, cognitive control, and memory. The electroencephalogram (EEG) enables researchers to capture a pattern of band-specific functional connectivity, as well as moment-to-moment dynamics of brain activity; this can be accomplished even in the resting-state by exploiting the excellent temporal resolution of the EEG. Furthermore, the recent advent of functional connectivity analysis in EEG studies has focused on the phase-difference variable because of its fine spatio-temporal resolution. Therefore, we hypothesized that the combining method of EEG signals having high-temporal resolution and the phase synchronization analysis having high-spatio-temporal resolutions brings a new insight of functional connectivity regarding high creative activity of older participants. In this study, we examined the resting-state EEG signal in 20 healthy older participants and estimated functional connectivities using the phase lag index (PLI), which evaluates the phase synchronization of EEG signals. Individual creativity was assessed using the S-A creativity test in a separate session before the EEG recording. In the analysis of associations of EEG measures with the S-A test scores, the covariate effect of the intelligence quotient was evaluated. As a result, higher individual S-A scores were significantly associated with higher node degrees, defined as the average PLI of a node (electrode) across all links with the remaining nodes, across all nodes at the alpha band. A conventional power spectrum analysis revealed no significant association with S-A scores in any frequency band. Older participants with high creativity exhibited high functional connectivity even in the resting-state, irrespective of intelligence quotient, which supports the theory that creativity entails widespread brain connectivity. Thus, PLIs derived from EEG data may provide new insights into the relationship between functional connectivity and creativity in healthy older people.

Despite growing evidence of aberrant neuronal complexity in Alzheimer’s disease (AD), it remains unclear how this variation arises. Neural oscillations reportedly comprise different functions depending on their own properties. Therefore, in this study, we investigated details of the complexity of neural oscillations by decomposing the oscillations into frequency, amplitude, and phase for AD patients. We applied resting-state magnetoencephalography (MEG) to 17 AD patients and 21 healthy control subjects. We first decomposed the source time series of the MEG signal into five intrinsic mode functions using ensemble empirical mode decomposition. We then analyzed the temporal complexities of these time series using multiscale entropy. Results demonstrated that AD patients had lower complexity on short time scales and higher complexity on long time scales in the alpha band in temporal regions of the brain. We evaluated the alpha band complexity further by decomposing it into amplitude and phase using Hilbert spectral analysis. Consequently, we found lower amplitude complexity and higher phase complexity in AD patients. Correlation analyses between spectral complexity and decomposed complexities revealed scale-dependency. Specifically, amplitude complexity was positively correlated with spectral complexity on short time scales, whereas phase complexity was positively correlated with spectral complexity on long time scales. Regarding the relevance of cognitive function to the complexity measures, the phase complexity on the long time scale was found to be correlated significantly with the Mini-Mental State Examination score. Additionally, we examined the diagnostic utility of the complexity characteristics using machine learning (ML) methods. We prepared a feature pool using multiple sparse autoencoders (SAEs), chose some discriminating features, and applied them to a support vector machine (SVM). Compared to the simple SVM and the SVM after feature selection (FS + SVM), the SVM with multiple SAEs (SAE + FS + SVM) had improved diagnostic accuracy. Through this study, we 1) advanced the understanding of neuronal complexity in AD patients using decomposed temporal complexity analysis and 2) demonstrated the effectiveness of combining ML methods with information about signal complexity for the diagnosis of AD.

Chronotherapy is a treatment for mood disorders, including major depressive disorder, mania, and bipolar disorder (BD). Neurotransmitters associated with the pathology of mood disorders exhibit circadian rhythms. A functional deficit in the neural circuits related to mood disorders disturbs the circadian rhythm; chronotherapy is an intervention that helps resynchronize the patient's biological clock with the periodic daily cycle, leading to amelioration of symptoms. In previous reports, Hadaeghi et al. proposed a non-linear dynamic model composed of the frontal and sensory cortical neural networks and the hypothalamus to explain the relationship between deficits in neural function in the frontal cortex and the disturbed circadian rhythm/mood transitions in BD (hereinafter referred to as the Hadaeghi model). In this model, neural activity in the frontal and sensory lobes exhibits periodic behavior in the healthy state; while in BD, this neural activity is in a state of chaos-chaos intermittency; this temporal departure from the healthy periodic state disturbs the circadian pacemaker in the hypothalamus. In this study, we propose an intervention based on a feedback method called the “reduced region of orbit” (RRO) method to facilitate the transition of the disturbed frontal cortical neural activity underlying BD to healthy periodic activity. Our simulation was based on the Hadaeghi model. We used an RRO feedback signal based on the return-map structure of the simulated frontal and sensory lobes to induce synchronization with a relatively weak periodic signal corresponding to the healthy condition by applying feedback of appropriate strength. The RRO feedback signal induces chaotic resonance, which facilitates the transition to healthy, periodic frontal neural activity, although this synchronization is restricted to a relatively low frequency of the periodic input signal. Additionally, applying an appropriate strength of the RRO feedback signal lowered the amplitude of the periodic input signal required to induce a synchronous state compared with the periodic signal applied alone. In conclusion, through a chaotic-resonance effect induced by the RRO feedback method, the state of the disturbed frontal neural activity characteristic of BD was transformed into a state close to healthy periodic activity by relatively weak periodic perturbations. Thus, RRO feedback-modulated chronotherapy might be an innovative new type of minimally invasive chronotherapy.

Abstract Introduction In the early development of human infants and toddlers, remarkable changes in brain cortical function for auditory processing have been reported. Knowing the maturational trajectory of auditory cortex responses to human voice in typically developing young children is crucial for identifying voice processing abnormalities in children at risk for neurodevelopmental disorders and language impairment. An early prominent positive component in the cerebral auditory response in newborns has been reported in previous electroencephalography and magnetoencephalography (MEG) studies. However, it is not clear whether this prominent component in infants less than 1 year of age corresponds to the auditory P1m component that has been reported in young children over 2 years of age. Methods To test the hypothesis that the early prominent positive component in infants aged 0 years is an immature manifestation of P1m that we previously reported in children over 2 years of age, we performed a longitudinal MEG study that focused on this early component and examined the maturational changes over three years starting from age 0. Five infants participated in this 3‐year longitudinal study. Results This research revealed that the early prominent component in infants aged 3 month corresponded to the auditory P1m component in young children over 2 years old, which we had previously reported to be related to language development and/or autism spectrum disorders. Conclusion Our data revealed the development of the auditory‐evoked field in the left and right hemispheres from 0‐ to 3‐year‐old children. These results contribute to the elucidation of the development of brain functions in infants.

Mental imagery behaviors of various modalities include visual, auditory, and motor behaviors. Their alterations are pathologically involved in various psychiatric disorders. Results of earlier studies suggest that imagery behaviors are correlated with the modulated activities of the respective modality-specific regions and the additional activities of supramodal imagery-related regions. Additionally, despite the availability of complexity analysis in the neuroimaging field, it has not been used for neural decoding approaches. Therefore, we sought to characterize neural oscillation related to multimodal imagery through complexity-based neural decoding. For this study, we modified existing complexity measures to characterize the time evolution of temporal complexity. We took magnetoencephalography (MEG) data of eight healthy subjects as they performed multimodal imagery and non-imagery tasks. The MEG data were decomposed into amplitude and phase of sub-band frequencies by Hilbert–Huang transform. Subsequently, we calculated the complexity values of each reconstructed time series, along with raw data and band power for comparison, and applied these results as inputs to decode visual perception (VP), visual imagery (VI), motor execution (ME), and motor imagery (MI) functions. Consequently, intra-subject decoding with the complexity yielded a characteristic sensitivity map for each task with high decoding accuracy. The map is inverted in the occipital regions between VP and VI and in the central regions between ME and MI. Additionally, replacement of the labels into two classes as imagery and non-imagery also yielded better classification performance and characteristic sensitivity with the complexity. It is particularly interesting that some subjects showed characteristic sensitivities not only in modality-specific regions, but also in supramodal regions. These analyses indicate that two-class and four-class classifications each provided better performance when using complexity than when using raw data or band power as input. When inter-subject decoding was used with the same model, characteristic sensitivity maps were also obtained, although their decoding performance was lower. Results of this study underscore the availability of complexity measures in neural decoding approaches and suggest the possibility of a modality-independent imagery-related mechanism. The use of time evolution of temporal complexity in neural decoding might extend our knowledge of the neural bases of hierarchical functions in the human brain.