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Abstract Quantum information processors benefit from high clock frequencies to fully harness quantum advantages before they are lost to decoherence. All-optical systems offer unique benefits due to their inherent 100-THz carrier frequency, enabling the development of THz-clock frequency processors. However, the bandwidth of quantum light sources and measurement devices has been limited to the MHz range, with nonclassical state generation rates in the kHz range. In this study, we demonstrated broadband generation and quantum tomography of non-Gaussian states using an optical parametric amplifier (OPA) as a squeezed light source and an optical phase-sensitive amplifier (PSA). Our system includes a 6-THz squeezed-light source, a 6-THz PSA, and a 66-GHz homodyne detector. We successfully generated non-Gaussian states at a 0.9 MHz rate with sub-nanosecond wave packets using a continuous-wave laser. The performance is currently limited by the jitter of superconducting detectors, restricting the usable bandwidth to 1 GHz. Our technique extends the bandwidth to GHz, potentially increasing non-Gaussian state generation rates for practical optical quantum processors using OPAs.

Risa Hirata,1 Naoko E Katsuki,1 Hitomi Shimada,2 Eiji Nakatani,3 Kiyoshi Shikino,4,5 Chihiro Saito,6 Kaori Amari,7 Yoshimasa Oda,8 Midori Tokushima,1 Masaki Tago1 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Shimada Hospital of Medical Corporation Chouseikai, Saga, Japan; 3Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan; 4Department of General Medicine, Chiba University Hospital, Chiba, Japan; 5Department of Community-Oriented Medical Education, Chiba University Graduate School of Medicine, Chiba, Japan; 6Shizuoka General Hospital, Shizuoka, Japan; 7Department of Emergency Medicine, Saga-Ken Medical Centre Koseikan, Saga, Japan; 8Department of General Medicine, Yuai-Kai Foundation and Oda Hospital, Saga, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpPurpose: There has been no large-scale investigation into the association between the use of lemborexant, suvorexant, and ramelteon and falls in a large population. This study, serving as a pilot investigation, was aimed at examining the relationship between inpatient falls and various prescribed hypnotic medications at admission.Patients and Methods: This study was a sub-analysis of a multicenter retrospective observational study conducted over a period of 3 years. The target population comprised patients aged 20 years or above admitted to eight hospitals, including chronic care, acute care, and tertiary hospitals. We extracted data on the types of hypnotic medications prescribed at admission, including lemborexant, suvorexant, ramelteon, benzodiazepines, Z-drugs, and other hypnotics; the occurrence of inpatient falls during the hospital stay; and patients’ background information. To determine the outcome of inpatient falls, items with low collinearity were selected and included as covariates in a forced-entry binary logistic regression analysis.Results: Overall, 150,278 patients were included in the analysis, among whom 3,458 experienced falls. The median age of the entire cohort was 70 years, with men constituting 53.1%. Binary logistic regression analysis revealed that the prescription of lemborexant, suvorexant, and ramelteon at admission was not significantly associated with inpatient falls.Conclusion: The administration of lemborexant, suvorexant, and ramelteon at admission may not be associated with inpatient falls.Keywords: lemborexant, hypnotics, in-hospital falls, risk factor

Abstract Children’s secure attachment with their primary caregivers is crucial for physical, cognitive, and emotional maturation. Yet, the causal links between specific parenting behaviors and infant attachment patterns are not fully understood. Here we report infant attachment in New World monkeys common marmosets, characterized by shared infant care among parents and older siblings and complex vocal communications. By integrating natural variations in parenting styles and subsecond-scale microanalyses of dyadic vocal and physical interactions, we demonstrate that marmoset infants signal their needs through context-dependent call use and selective approaches toward familiar caregivers. The infant attachment behaviors are tuned to each caregiver’s parenting style; infants use negative calls when carried by rejecting caregivers and selectively avoid neglectful and rejecting caregivers. Family-deprived infants fail to develop such adaptive uses of attachment behaviors. With these similarities with humans, marmosets offer a promising model for investigating the biological mechanisms of attachment security.

Masaki Tago,1 Risa Hirata,1 Naoko E Katsuki,1 Eiji Nakatani,2 Midori Tokushima,1 Tomoyo Nishi,1 Hitomi Shimada,3 Shizuka Yaita,1 Chihiro Saito,4 Kaori Amari,5 Kazuya Kurogi,6 Yoshimasa Oda,7 Kiyoshi Shikino,8,9 Maiko Ono,10 Mariko Yoshimura,11 Shun Yamashita,1 Yoshinori Tokushima,1 Hidetoshi Aihara,1 Motoshi Fujiwara,1 Shu-ichi Yamashita1 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan; 3Shimada Hospital of Medical Corporation Chouseikai, Saga, Japan; 4Shizuoka General Hospital, Shizuoka, Japan; 5Department of Emergency Medicine, Saga-Ken Medical Centre Koseikan, Saga, Japan; 6Department of General Medicine, National Hospital Organization Ureshino Medical Center, Saga, Japan; 7Department of General Medicine, Yuai-Kai Foundation and Oda Hospital, Saga, Japan; 8Department of General Medicine, Chiba University Hospital, Chiba, Japan; 9Department of Community-Oriented Medical Education, Chiba University Graduate School of Medicine, Chiba, Japan; 10Department of General Medicine, Karatsu Municipal Hospital, Saga, Japan; 11Safety Management Section, Saga University Hospital, Saga, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpPurpose: We conducted a pilot study in an acute care hospital and developed the Saga Fall Risk Model 2 (SFRM2), a fall prediction model comprising eight items: Bedriddenness rank, age, sex, emergency admission, admission to the neurosurgery department, history of falls, independence of eating, and use of hypnotics. The external validation results from the two hospitals showed that the area under the curve (AUC) of SFRM2 may be lower in other facilities. This study aimed to validate the accuracy of SFRM2 using data from eight hospitals, including chronic care hospitals, and adjust the coefficients to improve the accuracy of SFRM2 and validate it.Patients and Methods: This study included all patients aged ≥ 20 years admitted to eight hospitals, including chronic care, acute care, and tertiary hospitals, from April 1, 2018, to March 31, 2021. In-hospital falls were used as the outcome, and the AUC and shrinkage coefficient of SFRM2 were calculated. Additionally, SFRM2.1, which was modified from the coefficients of SFRM2 using logistic regression with the eight items comprising SFRM2, was developed using two-thirds of the data randomly selected from the entire population, and its accuracy was validated using the remaining one-third portion of the data.Results: Of the 124,521 inpatients analyzed, 2,986 (2.4%) experienced falls during hospitalization. The median age of all inpatients was 71 years, and 53.2% were men. The AUC of SFRM2 was 0.687 (95% confidence interval [CI]:0.678– 0.697), and the shrinkage coefficient was 0.996. SFRM2.1 was created using 81,790 patients, and its accuracy was validated using the remaining 42,731 patients. The AUC of SFRM2.1 was 0.745 (95% CI: 0.731– 0.758).Conclusion: SFRM2 showed good accuracy in predicting falls even on validating in diverse populations with significantly different backgrounds. Furthermore, the accuracy can be improved by adjusting the coefficients while keeping the model’s parameters fixed.Keywords: accidental falls, inpatients, validation study, accident prevention

Masaki Tago,1 Risa Hirata,1 Naoko E Katsuki,1 Yuki Otsuka,2 Taro Shimizu,3 Yosuke Sasaki,4 Kiyoshi Shikino,5 Takashi Watari,6 Hiromizu Takahashi,7 Kazunobu Une,8 Toshio Naito,7 Fumio Otsuka,2 Rachel Thompson,9 Susumu Tazuma8,10 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan; 3Department of Diagnostic and Generalist Medicine, Dokkyo Medical University, Tochigi, Japan; 4Department of General Medicine and Emergency Care, Toho University School of Medicine, Tokyo, Japan; 5Department of General Medicine, Chiba University Hospital, Chiba, Japan; 6General Medicine Center, Shimane University Hospital, Izumo, Japan; 7Department of General Medicine, Juntendo University Faculty of Medicine, Tokyo, Japan; 8Department of Critical Care and General Medicine, Onomichi General Hospital, Hiroshima, Japan; 9Executive Team, Snoqualmie Valley Hospital, Snoqualmie, WA, USA; 10JR Hiroshima Hospital, Hiroshima, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpIntroduction: Hospitalists in Japan have been at the forefront of the COVID-19 pandemic. However, contributions of Japanese hospitalists during the COVID-19 pandemic and hospitalists’ awareness of crisis management education remain unclear.Material and Methods: We conducted a questionnaire survey to investigate the role of Japanese hospitalists during the COVID-19 pandemic. The questionnaire was conducted using email and Google Forms targeting the chairpersons of facilities certified by the Japanese Society of Hospital General Medicine (JSHGM). Members of the academic committee of the JSHGM and several hospitals conducted a narrative review and determined the questions for the survey in a discussion.Results: We conducted descriptive statistics based on the responses of 97 hospitals that agreed to participate in this survey. In total, 91.8% of general medicine departments in the included hospitals were involved in the medical care of COVID-19 patients. Furthermore, in 73.2% of hospitals, hospitalists were involved in infection control for COVID-19 inside or outside the hospital. Our survey revealed that Japanese hospitalists were responsible for COVID-19 treatment in over 60% of hospitals and contributed to hospital management, infection control, and vaccination. In total, 79.4% of hospitals answered that “training of personnel who can provide practical care for emerging infectious diseases is necessary”, 78.4% indicated that “the establishment of an infection control system in advance to prepare emerging infectious diseases in the hospital is necessary”, and 74.2% stated that “the establishment of an educational system for responding to emerging infectious diseases is necessary.”.Conclusion: In conclusion, during the pandemic, in addition to inpatient care, Japanese hospitalists provided outpatient care for COVID-19, which is the role of primary care physicians in other countries. Furthermore, Japanese hospitalists who experienced the COVID-19 pandemic expressed the need for personnel development and education to prepare for future emerging infectious disease pandemics.Keywords: COVID-19 pandemic, hospitalist, hospital management

Cav3.2, a T-type calcium channel (T-channel) family member, is expressed in the nociceptors and spinal cord, and its activity is largely suppressed by zinc under physiological conditions. In rats, intrathecal and intraplantar administration of a zinc chelator, TPEN, caused T-channel-dependent mechanical hyperalgesia, and the intraplantar, but not intrathecal, TPEN induced Cav3.2 upregulation in the dorsal root ganglion. In mice, intraplantar TPEN also caused mechanical allodynia, which was abolished by T-channel inhibitors or Cav3.2 gene deletion. Together, spinal and peripheral zinc deficiency appears to enhance Cav3.2 activity in the spinal postsynaptic neurons and nociceptors, respectively, thereby promoting pain.

Yoshinori Tokushima,1,2 Masaki Tago,1,2 Midori Tokushima,1,3 Shun Yamashita,1 Yuka Hirakawa,1 Hidetoshi Aihara,1 Naoko E Katsuki,1 Motoshi Fujiwara,1 Shu-ichi Yamashita1 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Community Medical Support Institute, Faculty of Medicine, Saga University, Saga, Japan; 3Saga Medical Career Support Center, Saga University Hospital, Saga, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81 952 34 3238, Fax +81 952 34 2029, Email tagomas@cc.saga-u.ac.jpIntroduction: The educational effects of a hands-on clinical clerkship on medical students at the Department of General medicine of Japanese university hospitals remain to be clarified. This study aimed to determine how such education affects medical students’ self-evaluation of their clinical skills.Methods: We enrolled 5th-year-grade students at the Department of General Medicine, Saga University Hospital, Japan in 2017. The students were divided into those who were going to have Japanese traditional-style observation-based training mainly in the outpatient clinic (Group O) and those in the 2018, new-style, hands-on clinical clerkship as one of the group practice members in outpatient and inpatient clinics (Group H). A questionnaire survey using the 4-point Likert scale for self-evaluation of the students’ clinical skills at the beginning and the end of their training was conducted in both groups. The pre- and post-training scores of each item in both groups were compared and analyzed using the Mann–Whitney test.Results: All 99 students in Group O and 121 of 123 students in Group H answered the questionnaires. The response rate was 99%. Two items regarding the abilities of “can perform a systemic physical examination quickly and efficiently” and “can clearly explain the current medical condition, therapeutic options, or risks associated with treatment, and discuss the process for obtaining informed consent” showed higher scores in the post-training survey in Group H than in Group O. There were no differences in these scores in the pre-training survey between the two groups.Conclusion: A hands-on clinical clerkship at the Department of General medicine in a university hospital in Japan provided medical students with higher self-confidence in their skills of performing a physical examination and better understanding of patients’ treatment options and the process of informed consent than observation-based training.Keywords: general medicine, hands-on clinical clerkship, medical education, observation-based training

Risa Hirata,1 Masaki Tago,1 Naoko E Katsuki,1 Yoshimasa Oda,2 Midori Tokushima,1 Yoshinori Tokushima,1 Yuka Hirakawa,1 Shun Yamashita,1 Hidetoshi Aihara,1 Motoshi Fujiwara,1 Shu-ichi Yamashita1 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Department of General Medicine, Yuai-Kai Foundation and Oda Hospital, Saga, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Tel +81-952-34-3238, Fax +81-952-34-2029, Email tagomas@cc.saga-u.ac.jpIntroduction: In our former study, we had validated the previously developed predictive model for in-hospital falls (Saga fall risk model) using eight simple factors (age, sex, emergency admission, department of admission, use of hypnotic medications, history of falls, independence of eating, and Bedriddenness ranks [BRs]), proving its high reliability. We found that only admission to the neurosurgery department, history of falls, and BRs had significant relationships with falls. In the present study, we aimed to clarify whether each of these three items had a significant relationship with falls in a different group of patients.Methods: This was a single-center based, retrospective study in an acute care hospital in a rural city of Japan. We enrolled all inpatients aged 20 years or older admitted from April 2015 to March 2018. We randomly selected patients to fulfill the required sample size. We performed multivariable logistic regression analysis using forced entry on the association between falls and each of the eight items in the Saga fall risk model 2.Results: A total of 2932 patients were randomly selected, of whom 95 (3.2%) fell. The median age was 79 years, and 49.9% were men. Multivariable analysis showed that female sex (odds ratio [OR] 0.6, 95% confidence interval [CI] 0.39– 0.93, p = 0.022), having a history of falls (OR 1.9, 95% CI 1.16– 2.99, p = 0.010), requiring help with eating (OR 1.9, 95% CI 1.12– 3.35, p = 0.019), BR of A (OR 6.6, 95% CI 2.82– 15.30, p < 0.001), BR of B (OR 7.5, 95% CI 2.95– 19.06, p < 0.001), and BR of C (OR 4.1, 95% CI 1.53– 11.04, p = 0.005) were significantly associated with falls.Conclusion: History of falls and BRs were independently associated with in-hospital falls.Keywords: bedridden, Bedriddenness ranks, fall, predictive model, validation, Saga fall risk model 2

Masaki Tago,1 Kiyoshi Shikino,2 Risa Hirata,1 Takashi Watari,3 Shun Yamashita,1 Yoshinori Tokushima,1 Midori Tokushima,1 Hidetoshi Aihara,1 Naoko E Katsuki,1 Motoshi Fujiwara,1 Shu-ichi Yamashita1 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Department of General Medicine, Chiba University Hospital, Chiba, Japan; 3General Medicine Center, Shimane University Hospital, Shimane, JapanCorrespondence: Masaki Tago, Department of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, Japan, Email tagomas@cc.saga-u.ac.jpBackground: It is unclear how much effort Japanese university general medicine (GM) departments, which teach basic medical skills and have a high affinity for clinical practice, devote to medical education, particularly undergraduate education. This study aimed to clarify the contribution of GM departments of Japanese universities to medical education.Patients and Methods: This was a questionnaire-based descriptive study of GM departments of Japanese universities. We sent the questionnaire created using Google Forms by email, and the universities responded by Internet. The department chairperson of the universities’ main hospital was responsible for completing the questionnaire. It covered the number of staff, inpatients over the previous 3 years, affiliated hospitals, classroom lectures, and practical training sessions per year for each academic year in medical faculty and students accepted for clinical clerkship. Items also included the effort for clinical training, research, and education and the effort for undergraduate, initial clinical residency, and specialty program training.Results: In all, 46 of 71 universities responded, and we included 43 in our analysis. The median number of medical staff was 7; the median number of inpatients over the previous 3 years was 76. The median number of classroom lectures of the GM department was 1 for 1st-year, 5 for 3rd-year, 9 for 4th-year, and 0 for 2nd-, 5th-, and 6th-year students. The median total number of accepted students for clinical clerkship was 120. The median educational effort of the GM department was 30. With total educational effort set at 100, the median effort for undergraduate education was 45, for postgraduate residency 30, and for specialty program training 20.Conclusion: The undergraduate medical education by GM departments of Japanese universities was provided mainly in clinical settings for almost all medical students. A focus on exposing students to GM in early academic years would improve the educational environment.Keywords: clinical clerkship, general medicine, medical education, specialty program, university

Abstract Auditory steady-state responses (ASSRs) are basic neural responses used to probe the ability of auditory circuits to produce synchronous activity to repetitive external stimulation. Reduced ASSR has been observed in patients with schizophrenia, especially at 40 Hz. Although ASSR is a translatable biomarker with a potential both in animal models and patients with schizophrenia, little is known about the features of ASSR in monkeys. Herein, we recorded the ASSR from humans, rhesus monkeys, and marmosets using the same method to directly compare the characteristics of ASSRs among the species. We used auditory trains on a wide range of frequencies to investigate the suitable frequency for ASSRs induction, because monkeys usually use stimulus frequency ranges different from humans for vocalization. We found that monkeys and marmosets also show auditory event-related potentials and phase-locking activity in gamma-frequency trains, although the optimal frequency with the best synchronization differed among these species. These results suggest that the ASSR could be a useful translational, cross-species biomarker to examine the generation of gamma-band synchronization in nonhuman primate models of schizophrenia.

The teleoperation feature of a leader–follower robot is used to operate the robot in a working environment that is dangerous to the operator. This paper proposes a method for estimating the intended operation of the operator of the leader–follower robot and generating behaviors for the follower robot. By generating partially autonomous robot behavior, our proposed method decreases the burden on the operator and realizes a safe controller that is robust against misoperation or disturbances. Owing to the impact of misoperation on estimation and the potential for unintended movement of the follower robot, our proposed estimation method relies on historical values of intended operation. The proposed method was verified through simulation using real operation inputs to the leader system based on practical scenarios, including misoperation.

Abstract An increase in number of neurons is presumed to underlie the enhancement of cognitive abilities in brain evolution. The evolution of human cognition is then expected to have accompanied a prolongation of net neural-processing time due to the accumulation of processing time of individual neurons over an expanded number of neurons. Here, we confirmed this prediction and quantified the amount of prolongation in vivo, using noninvasive measurements of brain responses to sounds in unanesthetized human and nonhuman primates. Latencies of the N1 component of auditory-evoked potentials recorded from the scalp were approximately 40, 50, 60, and 100 ms for the common marmoset, rhesus monkey, chimpanzee, and human, respectively. Importantly, the prominent increase in human N1 latency could not be explained by the physical lengthening of the auditory pathway, and therefore reflected an extended dwell time for auditory cortical processing. A longer time window for auditory cortical processing is advantageous for analyzing time-varying acoustic stimuli, such as those important for speech perception. A novel hypothesis concerning human brain evolution then emerges: the increase in cortical neuronal number widened the timescale of sensory cortical processing, the benefits of which outweighed the disadvantage of slow cognition and reaction.

Neuroscience research has been expanding, providing new insights into brain and nervous system function and potentially transformative technological applications. In recent years, there has been a flurry of prominent international scientific academies and intergovernmental organizations calling for engagement with different publics on social, ethical, and regulatory issues related to neuroscience and neurotechnology advances. Neuroscientific activities and outputs are value-laden; they reflect the cultural, ethical, and political values that are prioritized in different societies at a given time and impact a variety of publics beyond the laboratory. The focus on engagement in neuroscience recognizes the breadth and significance of current neuroscience research whilst acknowledging the need for a neuroethical approach that explores the epistemic and moral values influencing the neuroscientific agenda. The field of neuroethics is characterized by its focus on the social, legal, and philosophical implications of neuroscience including its impact on cultural assumptions about the cognitive experience, identity, consciousness, and decision-making. Here, we outline a proposal for neuroethics engagement that reflects an enhanced and evolving understanding of public engagement with neuroethical issues to create opportunities to share ideation, decision-making, and collaboration in neuroscience endeavors for the benefit of society. We demonstrate the synergies between public engagement and neuroethics scholarship and activities that can guide neuroethics engagement.

Noninvasive electroencephalogram (EEG) in unanesthetized nonhuman primates is useful for basic science and biomedical applications but presents several technical challenges. In particular, multiple EEG electrode application to the scalp of small-sized monkeys, such as common marmosets, has been difficult, if not impossible. Here, we describe a novel approach, using the “dip-in electrode” method, which enables multichannel noninvasive EEG recording in a marmoset through short and small silicone tubes, with an internal diameter of 4 mm. First, the cut face of the tube was glued to the shaved scalp. Then, the tube was filled with the electrode gel, and a small electrode (4 mm in diameter) was dipped into the gel to contact the skin electrically while being electrically isolated from the neighboring channels. The minimum inter-electrode distance was 6 mm, which was limited by the outer diameter of the tubes. A proof of concept was provided through successful 32-channel recording of scalp EEG and topographic mapping of the cortical auditory evoked potentials in an unanesthetized marmoset. This had not been possible with the existing methods using gauze or tape for electrode fixation. Our method provides a feasible means for noninvasive scalp recording of EEG and evoked potentials in marmoset monkeys and possibly other nonhuman primates and non-primate mammals.

Magnetization measurements of the triangular lattice antiferromagnet CsFeCl$_{3}$ at 1.4 K for $H \parallel c$ were performed in pulsed high magnetic fields of up to 51 T under high pressures of up to 0.80 GPa. At ambient pressure, the magnetization below $H_{\rm c1}$ = 4 T is small, and then it changes steeply between $H_{\rm c1}$ and $H_{\rm c2}$ = 12 T, followed by a gradual increase in magnetization up to $H_{\rm m}$ = 33 T where a two-step metamagnetic transition occurs. With increasing pressure, the $H_{\rm c1}$ and $H_{\rm m}$ shifted to the low-field side, while the $H_{\rm c2}$ shifted to the opposite side. The change in $H_{\rm m}$ may depend on the difference in the single-ion anisotropies on pressure in the lowest $J$ = 1 and the excited $J$ = 2 states.

Shun Yamashita, Masaki Tago, So Motomura, Satsuki Oie, Hidetoshi Aihara, Naoko E Katsuki, Shu-ichi Yamashita Department of General Medicine, Saga University Hospital, Saga, JapanCorrespondence: Shun YamashitaDepartment of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, JapanTel +81952343238Fax +81952342029Email sy.hospitalist.japan@gmail.comPurpose: Infective endocarditis (IE) may be diagnosed as fever of unknown origin due to its delusively non-descriptive clinical features, especially in outpatient clinics. Our objective is to develop a prediction model to discriminate patients to be diagnosed as “definite” IE from “non-definite” by modified Duke criteria among patients with undiagnosed fever, using only history and results of physical examinations and common laboratory examinations.Patients and Methods: The study was a single-center case–control study. Inpatients at Saga University Hospital diagnosed with IE from 2007 to 2017 and patients with undiagnosed fever from 2015 to 2017 were enrolled. Patients diagnosed with definite IE according to the modified Duke criteria, except those definitely diagnosed with other disorders responsible for fever, were allocated to the IE group. Patients without IE among those defined as non-definite according to the modified Duke criteria were allocated to the undiagnosed fever group. We developed a prediction model to pick up patients who would be “definite” by modified Duke criteria, which was subsequently assessed by area under the curve (AUC).Results: A total of 144 adult patients were included. Of these, 59 patients comprised the IE group. We developed the prediction model using five indicators, including transfer by ambulance, cardiac murmur, pleural effusion, neutrophil count, and platelet count, with a sensitivity 84.7%, a specificity 84.7%, an AUC 0.893 (95% confidence interval 0.828– 0.959), a shrinkage coefficient 0.635, and a stratum-specific likelihood ratio 0.2– 50.4.Conclusion: Our prediction model, which uses only indicators easy to gain, facilitates prediction of patients with IE. These indicators can be acquired even at common hospitals and clinics, without requiring advanced medical equipment or invasive examinations.Trial Registration Number: UMIN000041344.Keywords: infective endocarditis, undiagnosed fever, case–control study, prediction model, area under the curve

Takashi Watari,1,2,* Masaki Tago,3,* Kiyoshi Shikino,4 Shun Yamashita,3 Naoko E Katsuki,3 Motoshi Fujiwara,3 Shu-ichi Yamashita3 1General Medicine Center, Shimane University Hospital, Shimane, Japan; 2Master of Healthcare Quality and Patient Safety, Harvard Medical School, Boston, MA, USA; 3Department of General Medicine, Saga University Hospital, Saga, Japan; 4Department of General Medicine, Chiba University Hospital, Chiba, Japan*These authors contributed equally to this workCorrespondence: Masaki TagoDepartment of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga, 849-8501, JapanTel +81 952 34 3238Fax +81 952 34 2029Email tagomas@cc.saga-u.ac.jpPurpose: The training of generalist physicians in university hospitals needs to emphasize development of their research role in order to continue improving their research capacity and their standing in academic hospitals in Japan. This cross-sectional descriptive study aimed to survey departments of general medicine (GM) in university hospitals in Japan to identify the research areas and themes pursued by academic generalist physicians.Patients and Methods: The heads of the departments of GM from 71 university hospitals in Japan were enrolled. The main outcomes studied were the identification of the main research areas and themes in academic departments of GM, based on the classification of the National Grants-in-Aid for Scientific Research (KAKENHI): clinical research, public health, preventive medicine, medical education, basic science, health services and safety and quality.Results: We received 47 of 71 replies (66.2% response rate). Clinical research was the most common area of research (62%), followed by public health and preventive medicine (14%), medical education (11%), and basic sciences (9%). Only one department identified health services and safety and quality as a research area (2%). There was marked variability in research areas across the different departments, with 23% of the research targeting the highest specialties, particularly organ-specific research in the fields of gastroenterology, cardiology, immunology, neurology, metabolic endocrinology, and hematology-oncology.Conclusion: The training of generalist physicians in university hospitals needs to emphasize development of their research role in order to continue improving the research capacity and the standing generalist physicians in academic hospitals in Japan.Keywords: general medicine, research, academic activity

Yoshinori Tokushima,1,* Masaki Tago,1,* Midori Tokushima,1 Naoko E Katsuki,1 Shinji Iwane,2 Yuichiro Eguchi,3 Shu-ichi Yamashita1 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Fujioka Hospital, Saga, Japan; 3Eguchi Hospital, Saga, Japan*These authors contributed equally to this workCorrespondence: Masaki TagoDepartment of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga 849-8501, JapanTel +81 952 34 3238Fax +81 952 34 2029Email tagomas@cc.saga-u.ac.jpObjective: To investigate effects of an altered medical environment between 2010 and 2015 on viral hepatitis treatment behaviors of doctors who were not hepatology specialists.Methods: Charts of patients who were identified as hepatitis B surface antigen (HBs-Ag)-positive or hepatitis C virus antibody (HCV-Ab)-positive by university hospital departments not specializing in hepatology from January to December 2015 were retrospectively reviewed. Patients were assigned to a “referred” group or a “non-referred” group based on whether they were subsequently referred to the Hepatology Department. Age, sex, type of department visited (one of various internal medicine departments, or a different department), and blood test results were compared in the two groups.Results: Among 7,824 patients screened for HBs-Ag, 82 were positive. Twenty-nine (35.4%) had subsequently been referred to the Hepatology Department, which was higher than the 2010 referral rate (20.6%). In multivariate analysis, patients in the referred group were significantly more likely to have visited one of various internal medicine departments, and they had higher levels of platelet count and γ-glutamyl transpeptidase. Among 7,778 patients screened for HCV-Ab, 279 were positive. Only 33 (11.8%) had subsequently been referred to the Hepatology Department, which was lower than the 2010 referral rate (18.7%). In multivariate analysis, patients in the referred group were significantly more likely to have visited an internal medicine department.Conclusion: HCV-antibody-positive patients screened by departments not specializing in hepatology were not managed adequately in 2015. This suggests a need for education of doctors not specializing in hepatology, particularly those not working in internal medicine departments.Keywords: hepatitis B virus, hepatitis C virus, hepatitis B, hepatitis C, referral, department

Shun Yamashita,1 Masaki Tago,1 Midori Tokushima,1 Tomotaro Nakashima,1 Naoko E Katsuki,1 Keizo Anzai,2 Shu-ichi Yamashita1 1Department of General Medicine, Saga University Hospital, Saga, Japan; 2Division of Metabolism and Endocrinology, Faculty of Medicine, Saga University, Saga, JapanCorrespondence: Masaki TagoDepartment of General Medicine, Saga University Hospital, 5-1-1 Nabeshima, Saga 849-8501, JapanTel +81952343238Fax +81952342029Email tagomas@cc.saga-u.ac.jpBackground: Our hospital’s department of general medicine is often involved in the diagnosis and treatment of diseases that are considered by other hospitals or other departments in our hospital to be difficult to diagnose correctly.Objective: The aim of this study was to clarify how patients with infective endocarditis (IE) being admitted to our hospital’s department of general medicine were examined and treated and to elucidate their prognosis compared with patients admitted to other departments.Materials and Methods: Inpatients of Saga University Hospital with definite IE from September 2007 to August 2017 were divided into 2 groups: those admitted to the general medicine department (the GM group) and those admitted to other departments (the non-GM group).Results: Seventy-four patients were included; 17 (23%) were admitted to the general medicine department. In the GM group, the percentage of patients diagnosed with definite or suspected IE was lower (0% vs 32%, p=0.008), as was the rate of patients with echocardiographic findings that fulfilled the major modified Duke’s criteria (71% vs 98%, p≤ 0.001), preadmission. The GM group had higher percentages of patients with back or joint pain (41% vs 9%, p=0.001) and complications, including pyogenic spondylitis (35% vs 2%, p≤ 0.001), deep-seated abscesses (24% vs 5%, p=0.024), pyogenic arthritis (18% vs 0%, p=0.001), and glomerulonephritis (77% vs 37%, p=0.004) than did the non-GM group. Mortality within 30 days of admission to our hospital (12% vs 14%, p=0.753) and overall in-hospital mortality (12% vs 18%, p=0.570) did not significantly differ.Conclusion: The general medicine department could have accurately diagnosed IE, given appropriate treatments, and obtained similar prognoses to those of IE patients treated by other departments, including cardiology and cardiovascular surgery, even in patients for whom diagnosing IE was more difficult or who had less typical echocardiographic findings preadmission.Keywords: infective endocarditis, echocardiographic findings of infective endocarditis, general medicine, cardiology, cardiovascular surgery

Abstract Environmental DNA (eDNA) analysis has seen rapid development in the last decade, as a novel biodiversity monitoring method. Previous studies have evaluated optimal strategies, at several experimental steps of eDNA metabarcoding, for the simultaneous detection of fish species. However, optimal sampling strategies, especially the season and the location of water sampling, have not been evaluated thoroughly. To identify optimal sampling seasons and locations, we performed sampling monthly or at two‐monthly intervals throughout the year in three dam reservoirs. Water samples were collected from 15 and nine locations in the Miharu and Okawa dam reservoirs in Fukushima Prefecture, respectively, and five locations in the Sugo dam reservoir in Hyogo Prefecture, Japan. One liter of water was filtered with glass‐fiber filters, and eDNA was extracted. By performing MiFish metabarcoding, we successfully detected a total of 21, 24, and 22 fish species in Miharu, Okawa, and Sugo reservoirs, respectively. From these results, the eDNA metabarcoding method had a similar level of performance compared to conventional long‐term data. Furthermore, it was found to be effective in evaluating entire fish communities. The number of species detected by eDNA survey peaked in May in Miharu and Okawa reservoirs, and in March and June in Sugo reservoir, which corresponds with the breeding seasons of many of fish species inhabiting the reservoirs. In addition, the number of detected species was significantly higher in shore, compared to offshore samples in the Miharu reservoir, and a similar tendency was found in the other two reservoirs. Based on these results, we can conclude that the efficiency of species detection by eDNA metabarcoding could be maximized by collecting water from shore locations during the breeding seasons of the inhabiting fish. These results will contribute in the determination of sampling seasons and locations for fish fauna survey via eDNA metabarcoding, in the future.

Abstract It is agreed upon that adult hippocampal neurogenesis (AHN) occurs in the dentate gyrus (DG) in rodents. However, the existence of AHN in humans, particularly in elderly individuals, remains to be determined. Recently, several studies reported that neural progenitor cells, neuroblasts, and immature neurons were detected in the hippocampus of elderly humans, based on the expressions of putative markers for these cells, claiming that this provides evidence of the persistence of AHN in humans. Herein, we briefly overview the phenomenon that we call “dematuration,” in which mature neurons dedifferentiate to a pseudo-immature status and re-express the molecular markers of neural progenitor cells and immature neurons. Various conditions can easily induce dematuration, such as inflammation and hyper-excitation of neurons, and therefore, the markers for neural progenitor cells and immature neurons may not necessarily serve as markers for AHN. Thus, the aforementioned studies have not presented definitive evidence for the persistence of hippocampal neurogenesis throughout adult life in humans, and we would like to emphasize that those markers should be used cautiously when presented as evidence for AHN. Increasing AHN has been considered as a therapeutic target for Alzheimer’s disease (AD); however, given that immature neuronal markers can be re-expressed in mature adult neurons, independent of AHN, in various disease conditions including AD, strategies to increase the expression of these markers in the DG may be ineffective or may worsen the symptoms of such diseases.

Abstract Dam‐mediated biological invasions are a serious problem all over the world. Once established in reservoirs, the invasive species have catastrophic impacts on the river ecosystems downstream, and thus, rapid monitoring of invasive species is an urgent issue for the effective removal of them and the conservation management of native ecosystems. Here, we verified the utility of environmental DNA (eDNA) analysis as a tool to effectively monitor three invasive fish species (bluegill, largemouth bass, and smallmouth bass) in reservoirs using multiplex real‐time PCR. First, to determine the optimal sampling location and season to detect eDNA from these species, we analyzed the eDNA in water samples from shore and offshore sites in three reservoirs all year around. We found that eDNA detection rates either did not differ between sampling locations or were higher for shore than offshore sites. In addition, eDNA detection rates were higher in spring (breeding season of target species) and/or summer than winter. Second, we extensively surveyed the distribution of the three species in 30 reservoirs in Japan using eDNA analysis. Consequently, a single eDNA‐based surveillance in summer allowed to match approximately 90% of the presence/absence of the invasive fish species known from 27 yr of administrative capture‐based surveillances. Given these results, we recommend collecting the replicated water samples from shore sites in summer or the breeding season for the effective detection of invasive fish eDNA in reservoirs. Our eDNA assays with multiplex real‐time PCR enable the rapid and sensitive monitoring of invasive fish distribution in reservoirs.

Abstract The selective serotonin reuptake inhibitor fluoxetine (FLX) is widely used to treat depression and anxiety disorders. Chronic FLX treatment reportedly induces cellular responses in the brain, including increased adult hippocampal and cortical neurogenesis and reversal of neuron maturation in the hippocampus, amygdala, and cortex. However, because most previous studies have used rodent models, it remains unclear whether these FLX-induced changes occur in the primate brain. To evaluate the effects of FLX in the primate brain, we used immunohistological methods to assess neurogenesis and the expression of neuronal maturity markers following chronic FLX treatment (3 mg/kg/day for 4 weeks) in adult marmosets (n = 3 per group). We found increased expression of doublecortin and calretinin, markers of immature neurons, in the hippocampal dentate gyrus of FLX-treated marmosets. Further, FLX treatment reduced parvalbumin expression and the number of neurons with perineuronal nets, which indicate mature fast-spiking interneurons, in the hippocampus, but not in the amygdala or cerebral cortex. We also found that FLX treatment increased the generation of cortical interneurons; however, significant up-regulation of adult hippocampal neurogenesis was not observed in FLX-treated marmosets. These results suggest that dematuration of hippocampal neurons and increased cortical neurogenesis may play roles in FLX-induced effects and/or side effects. Our results are consistent with those of previous studies showing hippocampal dematuration and increased cortical neurogenesis in FLX-treated rodents. In contrast, FLX did not affect hippocampal neurogenesis or dematuration of interneurons in the amygdala and cerebral cortex.

Although an enormous number of animal studies on blast-induced traumatic brain injury (bTBI) have been conducted, there still remain many uncertain issues in its neuropathology and mechanisms. This is partially due to the complex and hence difficult experimental environment settings, e.g., to minimize the effects of blast winds (tertiary mechanism) and to separate the effects of brain exposure and torso exposure. Since a laser-induced shock wave (LISW) is free from dynamic pressure and its energy is spatially well confined, the effects of pure shock wave exposure (primary mechanism) solely on the brain can be examined by using an LISW. In this study, we applied a set of four LISWs in the impulse range of 15–71 Pa·s to the rat brain through the intact scalp and skull; the interval between each exposure was ~5 s. For the rats, we conducted locomotor activity, elevated plus maze and forced swimming tests. Axonal injury in the brain was also examined by histological analysis using Bodian silver staining. Only the rats with exposure at higher impulses of 54 and 71 Pa·s showed significantly lower spontaneous movements at 1 and 2 days post-exposure by the locomotor activity test, but after 3 days post-exposure, they had recovered. At 7 days post-exposure, however, these rats (54 and 71 Pa·s) showed significantly higher levels of anxiety-related and depression-like behaviors by the elevated plus maze test and forced swimming test, respectively. To the best of the authors' knowledge, there have been few studies in which a rat model showed both anxiety-related and depression-like behaviors caused by blast or shock wave exposure. At that time point (7 days post-exposure), histological analysis showed significant decreases in axonal density in the cingulum bundle and corpus callosum in impulse-dependent manners; axons in the cingulum bundle were found to be more affected by a shock wave. Correlation analysis showed a statistically significant correlation between the depression like-behavior and axonal density reduction in the cingulum bundle. The results demonstrated the dependence of behavior deficits and axonal injury on the shock wave impulse loaded on the brain.

Appropriate processing of others’ facial emotions is a fundamental ability of primates in social situations. Several moods and anxiety disorders such as depression cause a negative bias in the perception of facial emotions. Depressive patients show abnormalities of activity and gray matter volume in the perigenual portion of the anterior cingulate cortex (ACC) and an increase of activation in the amygdala. However, it is not known whether neurons in the ACC have a function in the processing of facial emotions. Furthermore, detecting predators quickly and taking avoidance behavior are important functions in a matter of life and death for wild monkeys. the existence of predators in their vicinity is life-and-death information for monkeys. In the present study, we recorded the activity of single neurons from the monkey ACC and examined the responsiveness of the ACC neurons to various visual stimuli including monkey faces, snakes, foods, and artificial objects. About one-fourth of the recorded neurons showed a significant change in activity in response to the stimuli. The ACC neurons exhibited high selectivity to certain stimuli, and more neurons exhibited the maximal response to monkey faces and snakes than to foods and objects. The responses to monkey faces and snakes were faster and stronger compared to those to foods and objects. Almost all of the neurons that responded to video stimuli responded strongly to negative facial stimuli, threats, and scream. Most of the responsive neurons were located in the cingulate gyrus or the ventral bank of the cingulate sulcus just above or anterior to the genu of the corpus callosum, that is, the perigenual portion of the ACC, which has a strong mutual connection with the amygdala. These results suggest that the perigenual portion of the ACC in addition to the amygdala processes emotional information, especially negative life-and-death information such as conspecifics’ faces and snakes.

Abstract Purpose To evaluate the efficacy and safety of self‐injections of the prefilled recombinant human chorionic gonadotropin (r‐hCG) in a syringe in assisted reproductive technology (ART) treatment for the maturation trigger (MT), as compared to self‐injections of conventional hCG and intranasal administration of gonadotropin‐releasing hormone agonist (GnRH‐a). Methods Between January and April, 2017, 396 patients who underwent oocyte retrieval were recruited. Of these, 396 patients were classified into three groups, according to the types of MT: (1) the urinary human chorionic gonadotropin (u‐hCG) group that consisted of patients who had a self‐injection of u‐hCG (n = 127); (2) the GnRH‐a group that received nasal administration of GnRH‐a (n = 159); and (3) the r‐hCG group that had a self‐injection of r‐hCG (n = 110). Several ART outcomes were evaluated. Results The mature oocyte retrieval rate was not different between the u‐hCG, r‐hCG, and GnRH‐a groups and the fertilization and cleavage rates were similar between the three groups. The clinical pregnancy rates did not significantly differ between the GnRH‐a group and the u‐hCG group; however, it was significantly lower in the GnRH‐a group, compared to the r‐hCG group. No difference was observed in the incidence of moderate or more severe ovarian hyperstimulation syndrome among the three groups. Conclusion The self‐injection of the prefilled r‐hCG is a favorable MT for ART patients.

Tokushima Y, Tago M, Tokushima M, et al. Int J Gen Med. 2020;13:743—750. The authors have advised there are errors in Table 1 on page 746 in the Hbs-Ag positive patients’ data. The errors were introduced during the creation of the Table. The correct Table 1 is shown below: The errors were only in the patients’ background and do not affect the main results (consultation rate, comparison of RF and non-RF groups), discussion, or conclusion of the paper. The authors apologize for these errors. Read the original article

For achieving retrograde gene transfer, we have so far developed two types of lentiviral vectors pseudotyped with fusion envelope glycoprotein, termed HiRet vector and NeuRet vector, consisting of distinct combinations of rabies virus and vesicular stomatitis virus glycoproteins. In the present study, we compared the patterns of retrograde transgene expression for the HiRet vs. NeuRet vectors by testing the cortical input system. These vectors were injected into the motor cortex in rats, marmosets, and macaques, and the distributions of retrograde labels were investigated in the cortex and thalamus. Our histological analysis revealed that the NeuRet vector generally exhibits a higher efficiency of retrograde gene transfer than the HiRet vector, though its capacity of retrograde transgene expression in the macaque brain is unexpectedly low, especially in terms of the intracortical connections, as compared to the rat and marmoset brains. It was also demonstrated that the NeuRet but not the HiRet vector displays sufficiently high neuron specificity and causes no marked inflammatory/immune responses at the vector injection sites in the primate (marmoset and macaque) brains. The present results indicate that the retrograde transgene efficiency of the NeuRet vector varies depending not only on the species but also on the input projections.

Invasive alien species are a serious threat to freshwater ecosystems and overall biodiversity. Although invasive alien species management in the form of environmental governance has often been practiced under an adaptive governance scheme, prevailing theoretical and practical difficulties must be solved to enhance policy effectiveness and outcomes. Our objective was to clarify how it is possible to make adaptive governance work in biodiversity conservation, especially invasive alien species management in freshwater ecosystems. To fulfill this objective, we investigated two analytical concepts - invasion management and adaptive governance - and studied a case of invasive alien aquatic plant management in Lake Biwa, Japan. The conclusion of our analysis and the lessons learned can be summarized as the following three points: First, whether learning processes are properly equipped by local environmental governance is critical for adaptive governance. We provide insights into three aspects of learning: the system where scientific knowledge is produced and shared for policy preparation, implementation, and evaluation; where social learning and processes that support social learning occur; and where a process of organizational learning occurs. Second, we discuss the role and function of government in adaptive governance, which indicates that interactive governance is possible even when a government initiates a governing process, and that an interactive governing structure would be fundamental for addressing social-ecological complexities and uncertainties. Third, the transition from symptomatic treatments toward precautionary actions for invasive alien species, which is essential for policy effectiveness and outcomes, can be fostered by an interactive governing structure. In addition, organizational learning can induce the transition, through which the competency trap caused by conformity bias in invasive alien species management could be avoided.

Recent studies have revealed that hardness perception is determined by visual information along with the haptic input. This study investigated the cortical regions involved in hardness perception modulated by visual information using functional magnetic resonance imaging (fMRI) and multivoxel pattern analysis (MVPA). Twenty-two healthy participants were enrolled. They were required to place their left and right hands at the front and back, respectively, of a mirror attached to a platform placed above them while lying in a magnetic resonance scanner. In conditions SFT, MED, and HRD, one of three polyurethane foam pads of varying hardness (soft, medium, and hard, respectively) was presented to the left hand in a given trial, while only the medium pad was presented to the right hand in all trials. MED was defined as the control condition, because the visual and haptic information was congruent. During the scan, the participants were required to push the pad with the both hands while observing the reflection of the left hand and estimate the hardness of the pad perceived by the right (hidden) hand based on magnitude estimation. Behavioral results showed that the perceived hardness was significantly biased toward softer or harder in >73% of the trials in conditions SFT and HRD; we designated these trials as visually modulated (SFTvm and HRDvm, respectively). The accuracy map was calculated individually for each of the pair-wise comparisons of (SFTvm vs. MED), (HRDvm vs. MED), and (SFTvm vs. HRDvm) by a searchlight MVPA, and the cortical regions encoding the perceived hardness with visual modulation were identified by conjunction of the three accuracy maps in group analysis. The cluster was observed in the right sensory motor cortex, left anterior intraparietal sulcus (aIPS), bilateral parietal operculum (PO), and occipito-temporal cortex (OTC). Together with previous findings on such cortical regions, we conclude that the visual information of finger movements processed in the OTC may be integrated with haptic input in the left aIPS, and the subjective hardness perceived by the right hand with visual modulation may be processed in the cortical network between the left PO and aIPS.

The anterior cingulate cortex (ACC), surrounding the genu of the corpus callosum, plays important roles in emotional processing and is functionally divided into the dorsal, perigenual, and subgenual subregions (dACC, pgACC, and sgACC, respectively). Previous studies have suggested that the pgACC and sgACC have distinctive roles in the regulation of emotion. In order to elicit appropriate emotional responses, these ACC regions require sensory information from the environment. Anatomically, the ACC has rich connections with the temporal lobe, where the higher-order processing of sensory information takes place. To clarify the organization of sensory inputs into the ACC subregions, we injected neuronal tracers into the pgACC, sgACC, and dACC and compared the afferent connections. Previously, we analyzed the afferent projections from the amygdala and found a distinct pattern for the sgACC. In the present study, the patterns of the afferent projections were analyzed in the temporal cortex, especially the temporal pole (TP) and medial temporal areas. After tracers were injected into the sgACC, we observed labeled neurons in the TP and the subiculum of the hippocampal formation. The majority of the labeled cell bodies were found in the superficial layers of the TP (“feedforward” type projections). The pgACC received afferent projections from the TP, the entorhinal cortex (EC), and the parahippocampal cortex (PHC), but not from the hippocampus. In each area, the labeled cells were mainly found in the deep layers (“feedback” type projection). The pattern for the dACC was similar to that for the pgACC. Previous studies suggested that the pgACC, but not the sgACC receive projections from the dorsolateral prefrontal cortex (DLPFC). These data suggest that the sgACC plays crucial roles for emotional responses based on sensory and mnemonic inputs from the anterior temporal lobe, whereas the pgACC is more related to the cognitive control of emotion.

The auditory cortex integrates auditory information over time to obtain neural representations of sound events, the time scale of which critically affects perception. This work investigated the species differences in the time scale of integration by comparing humans and monkeys regarding how their scalp-recorded cortical auditory evoked potentials (CAEPs) decrease in amplitude as stimulus duration is shortened from 100 ms (or longer) to 2 ms. Cortical circuits tuned to processing sounds at short time scales would continue to produce large CAEPs to brief sounds whereas those tuned to longer time scales would produce diminished responses. Four peaks were identified in the CAEPs and labeled P1, N1, P2, and N2 in humans and mP1, mN1, mP2, and mN2 in monkeys. In humans, the N1 diminished in amplitude as sound duration was decreased, consistent with the previously described temporal integration window of N1 (>50 ms). In macaques, by contrast, the mN1 was unaffected by sound duration, and it was clearly elicited by even the briefest sounds. Brief sounds also elicited significant mN2 in the macaque, but not the human N2. Regarding earlier latencies, both P1 (humans) and mP1 (macaques) were elicited at their full amplitudes even by the briefest sounds. These findings suggest an elongation of the time scale of late stages of human auditory cortical processing, as reflected by N1/mN1 and later CAEP components. Longer time scales of integration would allow neural representations of complex auditory features that characterize speech and music.

Our daily lives are filled with rhythmic movements, such as walking, sports, and dancing, but the mechanisms by which the brain controls rhythmic movements are poorly understood. In this review, we examine the literature on neuropsychological studies of patients with focal brain lesions, and functional brain imaging studies primarily using finger-tapping tasks. These studies suggest a close connection between sensory and motor processing of rhythm, with no apparent distinction between the two functions. Thus, we conducted two functional brain imaging studies to survey the rhythm representations relatively independent of sensory and motor functions. First, we determined brain activations related to rhythm processing in a sensory modality-independent manner. Second, we examined body part-independent brain activation related to rhythm reproduction. Based on previous literature, we discuss how brain areas contribute rhythmic motor control. Furthermore, we also discuss the mechanisms by which the brain controls rhythmic movements.

Learning and memory processes are similarly organized in humans and monkeys; therefore, monkeys can be ideal models for analyzing human aging processes and neurodegenerative diseases such as Alzheimer’s disease. With the development of novel gene modification methods, common marmosets (Callithrix jacchus) have been suggested as an animal model for neurodegenerative diseases. Furthermore, the common marmoset’s lifespan is relatively short, which makes it a practical animal model for aging. Working memory deficits are a prominent symptom of both dementia and aging, but no data are currently available for visual working memory in common marmosets. The delayed matching-to-sample task is a powerful tool for evaluating visual working memory in humans and monkeys; therefore, we developed a novel procedure for training common marmosets in such a task. Using visual discrimination and reversal tasks to direct the marmosets’ attention to the physical properties of visual stimuli, we successfully trained 11 out of 13 marmosets in the initial stage of the delayed matching-to-sample task and provided the first available data on visual working memory in common marmosets. We found that the marmosets required many trials to initially learn the task (median: 1316 trials), but once the task was learned, the animals needed fewer trials to learn the task with novel stimuli (476 trials or fewer, with the exception of one marmoset). The marmosets could retain visual information for up to 16 s. Our novel training procedure could enable us to use the common marmoset as a useful non-human primate model for studying visual working memory deficits in neurodegenerative diseases and aging.

When sounds occur with temporally structured patterns, we can feel a rhythm. To memorize a rhythm, perception of its temporal patterns and organization of them into a hierarchically structured sequence are necessary. On the other hand, rhythm perception can often cause unintentional body movements. Thus, we hypothesized that rhythm information can be manifested in two different ways; temporal and motor representations. The motor representation depends on effectors, such as the finger or foot, whereas the temporal representation is effector-independent. We tested our hypothesis with a working memory paradigm to elucidate neuronal correlates of temporal or motor representation of rhythm and to reveal the neural networks associated with these representations. We measured brain activity by fMRI while participants memorized rhythms and reproduced them by tapping with the right finger, left finger, or foot, or by articulation. The right inferior frontal gyrus and the inferior parietal lobule exhibited significant effector-independent activations during encoding and retrieval of rhythm information, whereas the left inferior parietal lobule and supplementary motor area (SMA) showed effector-dependent activations during retrieval. These results suggest that temporal sequences of rhythm are probably represented in the right fronto-parietal network, whereas motor sequences of rhythm can be represented in the SMA-parietal network.