Keio University

[Recipients Selected] FY2023 KGRI Pre-startup Research Grant

Publish: June 28, 2023
KGRI

2023.06.28

Since fiscal year 2020, KGRI has been providing Pre-startup Research Grants for embryonic research in the pre-startup phase to strongly promote globalization and interdisciplinary research at Keio University. This fiscal year, as a result of revising the method for publicizing the application guidelines, while the number of applications remained level, there was a slight increase in applications from a broader range of research fields than before.

This fiscal year's recipients are as follows. We hope that this grant will be used appropriately and effectively by the recipients and will serve as a support for the development of their respective research. Furthermore, we anticipate that from the next fiscal year onward, cross-disciplinary research teams will be formed within the university, leading to the acquisition of larger research funds and more global and interdisciplinary developments.

[Recipients]

"Elucidating the Time-Meaning Dynamics in the Language of Patients with Dementia and Aphasia"

Norihiro Itaguchi (Associate Professor, Faculty of Letters)

Research Results Report

■Research Outline

This study aims to innovate quantitative evaluation methods for language symptoms caused by aging, brain dysfunction, and other factors by integrating two types of analysis: multi-scale temporal information analysis and semantic network analysis based on natural language processing. The behavioral data to be analyzed are responses to the Verbal Fluency Task (VFT). In the VFT, participants are asked to name as many words as possible belonging to a certain semantic category (e.g., animals) within a fixed time. This task is widely used in psychological research and clinical settings because it can easily and sensitively assess conditions such as aging and dementia. This study as a whole consists of five sub-studies: (1) establishing a VFT analysis method using multi-scale temporal information, (2) developing a speech recognition system to quantify temporal information, (3) establishing a VFT analysis method based on LDA semantic networks, (4) elucidating the "time-meaning" linguistic characteristics caused by aging and brain dysfunction and identifying their neural basis, and (5) releasing an integrated package for research acceleration and clinical application.

<Research Results Report>

■Purpose

In fiscal year 2023, the objective was to establish (a) a VFT analysis method based on LDA semantic networks and (b) a VFT analysis method using multi-scale temporal information from among the sub-studies. LDA (Latent Dirichlet Allocation, Blei, 2003) is a natural language processing technique. In this study, the goal was to apply LDA to Wikipedia articles to construct a standard semantic network (animal subcategories) that would serve as a benchmark for semantic analysis. Multi-scale temporal information is an analytical approach that examines VFT responses from multiple time scales. In this study, we investigated how VFT performance changes not only on the time scale within the task but also on a long-term scale at the rehabilitation level.

■Methods

(a) First, we created a list of 670 animal names from the Japanese version of Wikipedia (1,125,721 articles) and performed LDA analysis on 30,459 articles containing two or more of these words, totaling 102,467 words. The parameters used were a topic number of 10 and α=0.4. Based on the constructed animal subcategory semantic network, we calculated the number of correct responses and the MCS (Mean Cluster Size) for VFT response data from university students and determined the correlation coefficient between them.

(b) Four patients showing a decline in language function or frontal lobe function due to stroke performed the VFT continuously for 20 to 31 days. The duration varied according to each patient's condition. In addition to the commonly used number of correct words and errors, we calculated MCS, mean word frequency, and the frequency regression coefficient as performance evaluation indices. The frequency regression coefficient is an index that shows the frequency effect within the task. We examined how these indices changed on the rehabilitation scale.

■Results

(a) We developed a method to visualize multiple pieces of information from responses within a one-minute task, including response timing, word frequency, and clusters. The correlation coefficient r between the number of correct responses and MCS in healthy young adults was -.19 (p=.20).

(b) We developed a method to visualize how the semantic clusters within each patient's task change over the long-term scale of rehabilitation, measured in days. The number of correct responses improved in all patients. Mis-categorization errors decreased in all patients, but only one patient showed a decrease in repetition errors. MCS increased in two patients, mean word frequency decreased in two patients, and the frequency regression coefficient decreased in three patients.

■Discussion

The objectives for fiscal year 2023, which were to establish (a) a VFT analysis method based on LDA semantic networks and (b) a VFT analysis method using multi-scale temporal information, were largely achieved (some indices and analyses are not included in this report as they are yet to be published in a paper). The result of the correlation analysis in study (a) supports the idea that MCS evaluates aspects that cannot be assessed by the conventional number of correct responses, thus demonstrating its usefulness. As for study (b), we were able to highlight the rehabilitation progress that depended on the patients' symptoms. Within the scope of this report, the rehabilitation progress of the frequency regression coefficient represents a highly novel analysis that simultaneously evaluates multiple time scales, and quantitatively demonstrating its transformation process is a major achievement.

"The Significance of Diagnosing and Treating Latent Tuberculosis in Dialysis Patients Using IGRA Tests, Considered from the Perspective of Tuberculosis Prevalence"

Ayumu Yoshifuji (Senior Assistant Professor, School of Medicine)

Research Results Report

■Research Outline

In 2022, an estimated 10.6 million people worldwide were infected with tuberculosis, and 1.3 million died from it. In Japan, the incidence rate of tuberculosis is 8.2 per 100,000 people, but it remains highly prevalent in countries like Thailand (176.0) and Vietnam (155.0). Furthermore, it is known that after the initiation of dialysis, the incidence of tuberculosis in dialysis patients is 10 to 25 times higher than in the general population. When a dialysis patient develops tuberculosis, there is a high risk of airborne transmission to other dialysis patients sharing the same time and space, as well as a high risk of severe illness.

Therefore, this study aims to clarify the significance, from both medical and health economics perspectives, of early diagnosis and treatment of latent tuberculosis infection—a state of being infected with tuberculosis but not yet having developed the disease—by using a blood test called the Interferon-Gamma Release Assay (IGRA) on patients starting dialysis in Thailand, Vietnam, Belgium, and Japan, countries with varying degrees of tuberculosis prevalence.

<Research Results Report>

■Purpose

To examine the significance, from medical and health economics perspectives, of screening for and treating latent tuberculosis using IGRA tests to prevent the onset of tuberculosis in dialysis patients in low-prevalence countries (Japan, Belgium) and high-prevalence countries (Thailand, Vietnam).

■Methods

At dialysis medical institutions in Japan, Belgium, Thailand, and Vietnam:

① Cross-sectional study: IGRA tests will be conducted at two time points, the start and end of the study, on patients receiving dialysis at the target medical institutions.

② Prospective cohort study: IGRA tests will be conducted on patients at the time of dialysis initiation and 6 months later at the target medical institutions, and the presence or absence of tuberculosis onset within 12 months of initiation will be examined.

The primary endpoint is the prevalence of latent tuberculosis infection. Secondary endpoints include the incidence of tuberculosis, costs of IGRA testing and tuberculosis treatment, costs of infection control measures at the time of tuberculosis onset, and the QOL (EQ-5D) of patients with latent tuberculosis and those who develop tuberculosis.

■Results

In this pre-startup study, we held web meetings with participating facilities to discuss the protocol.

Subsequently, we visited Thailand, Vietnam, and Belgium to discuss the operational methods for implementing the research (patient recruitment methods, in-hospital research support systems, specimen transport, test measurement methods, and data entry systems), and the operational methods were decided. The research is now at a stage where it can begin as soon as funding is secured.

■Discussion

We were able to make preparations to launch this PROJECT. We would like to secure research funding and actually begin operations.

Based on the research results, we will make proposals regarding tuberculosis policies in each country and aim to achieve the WHO's goal of "ending TB by 2030."

"Development of a POCT-type Immune Prediction System to Contribute to Optimal Self-Determination for Vaccination"

Yoshinori Kamimino (Senior Assistant Professor, School of Medicine)

Research Results Report

■Research Outline

We will develop and evaluate a Point of Care Testing (POCT) tool using immunochromatography and a smartphone to assess antibodies acquired through vaccination. At the same time, we will develop an antibody decay prediction formula to create a system that allows anyone to easily know their current and future antibody levels after vaccination, enabling them to make their own decisions regarding booster shots and other matters.

<Research Results Report>

■Purpose

Although there are large individual differences in immune acquisition from vaccines, vaccinations, such as for the COVID-19 vaccine, are currently administered based on government recommendations, regardless of an individual's immune status. To make this more personalized, we aim to develop a device that contributes to self-determination. By using a POCT-type antibody measurement tool that allows anyone to easily know their immune status, and by enabling them to predict its decay using a prediction formula, individuals can know their current and future immunity and decide on the necessity and timing of booster shots based on their own judgment.

■Methods

Using antibody titer data and samples obtained from a long-term cohort study on the immune evaluation of the COVID-19 vaccine conducted at Keio University Hospital, we will determine the optimal mathematical model to predict antibody titer decay. At the same time, we will evaluate the accuracy of a POCT system for quantitative antibody measurement using immunochromatography and a smartphone, and determine the correlation between the obtained optical measurement values and the values from the international standard method.

■Results

We determined a mathematical model to predict the decay of antibody titers for six months after two doses of the COVID-19 vaccine. The prediction accuracy was very high. Furthermore, when we evaluated the accuracy of the POCT system for quantitative antibody measurement using immunochromatography and a smartphone with 800 serum samples, we found that although appropriate dilution is necessary in the high-titer range, the correlation coefficient with the existing method exceeded 0.8, indicating a good correlation.

■Discussion

It has become clear that it is possible to predict immune decay and easily assess immunity after COVID-19 vaccination. In the future, by integrating the mathematical model with the POCT system for quantitative antibody measurement and developing an application with an improved user interface, it is expected to become possible to easily measure antibody titers and predict their decay. Furthermore, it is considered necessary to develop a similar system for other vaccine-preventable diseases (VPDs) besides COVID-19.

"Subtypes and Longitudinal Changes of Frailty and Sarcopenia in Community-Dwelling Older Adults: An International Comparison between Japan, the US, and Italy"

Yusuke Osawa (Associate Professor, Graduate School of Health Management)

Research Results Report

■Research Outline

With aging, the musculoskeletal system, including muscles and bones which are organs for moving the body, and body shape change. Many previous studies have shown that these age-related changes increase the risk of motor dysfunction, falls, and fractures. However, it is not fully clear whether these aging phenomena differ by country or race. Therefore, this study aimed to examine age-related changes in physique, body composition, and motor function after the age of 40, using data from prospective cohort studies of community residents in Japan, the US, and Italy. It is also believed that aging phenomena do not progress independently in each organ but rather that organs influence each other as they age. From this perspective, this study, using data from the aforementioned cohort studies, aimed to:

① Compare aging phenomena in physique, body composition, and motor function between cohorts and by gender.

② Examine the longitudinal association between the decline in muscle mass and bone mineral density.

<Research Results Report>

■Purpose

Muscles and various organs influence each other through humoral factors. Also, a decline in muscle quality and quantity leads to a decrease in physical activity and a decline in the function of other organs, which in turn causes a further decline in muscle quality and quantity. The prevalence of sarcopenia, diagnosed by a decline in muscle mass, strength, and physical function, varies from 18-35% by country, but the underlying factors are not clear. Furthermore, the condition where sarcopenia coexists with other organ phenotypes and functional declines, such as osteoporosis and obesity, has a higher risk of various health-related outcomes like death and functional disability than a single condition. In this study, we examined aging phenomena in physique, body composition, and motor function using data from three prospective cohort studies in Japan, the US, and Italy. We also examined the longitudinal association in the changes of muscle mass and bone mineral density.

■Methods

Data on morphology (height, weight, BMI), body composition (muscle mass, fat mass, bone mineral density), and motor function (grip strength and walking speed) from three prospective cohort studies in three countries were used for analysis: the Baltimore Longitudinal Study of Aging (BLSA; USA; n=1563; 65.9±13.1 years), the National Institute for Longevity Sciences - Longitudinal Study of Aging (NILS-LSA; Aichi Prefecture; n=3983; 56.9±13.0 years), and the Invecchiare in Chianti, aging in the Chianti area (InCHIANTI; Italy; n=1325; 70.7±12.4 years). We used a generalized additive mixed-effect model to estimate age-related changes for each variable by cohort and gender. We also used a bi-variate linear mixed-effect model to examine the association of longitudinal changes in muscle mass and bone mineral density.

■Results

Compared to the results of the two Western cohort studies, the NILS-LSA showed lower values for both men and women in physique as measured by weight and BMI, and in body composition as measured by muscle mass, fat mass, and bone mineral density. Also, looking at the secular changes after age 40, Japanese individuals showed a downward trend, whereas Westerners, especially in the US, showed a non-linear change for both men and women, with weight and fat mass tending to increase from around age 40 to 65, and then tending to decrease. Regarding muscle mass, a downward trend was observed in all cohorts and genders, but the amount of age-related decline was larger in US men, who have larger muscle mass. The age-related changes in bone mineral density showed a more pronounced gender difference than cohort difference; women showed a significant decrease in their 50s around menopause, followed by a gentle downward trend. On the other hand, men showed a gentle downward trend. The longitudinal association of the decline in muscle mass and bone mineral density showed a positive correlation between the two, but the strength of the correlation was stronger in NILS-LSA than in BLSA.

■Discussion

We conducted a comparative study of age-related changes in muscle, fat, and bone by gender and cohort (country) using data from three cohort studies in Japan, the US, and Italy. The results showed that Westerners, who originally have a larger physique, had a greater degree of age-related decline, as seen in the magnitude of the slope, compared to Japanese individuals. Similarly, when compared by gender, men in all cohort studies had a greater degree of age-related decline than women. Furthermore, the longitudinal association between muscle and bone showed a difference between cohorts, suggesting that there are differences by country and race in the age-related changes of the musculoskeletal system centered on muscle. Regarding these cohort or gender differences, genetic predispositions, lifestyle differences, or both interacting with each other may be involved, and in the future, it will be necessary to consider bioinformatics and lifestyle habits when examining these age-related changes.

"Designing Social Welfare Services that Incorporate Culture and Arts into Daily Life"

Chihiro Sato (Senior Assistant Professor, Graduate School of Media Design)

Research Results Report

■Research Outline

This research is engaged in designing social welfare services that enable individuals forced into isolation due to aging or disability to remain connected to their local community and maintain both physical and mental health. Japan, a super-aging country, boasts the world's longest life expectancy. However, in response to the Ministry of Health, Labour and Welfare's challenge of extending healthy life expectancy—the period of life one can live without limitations on daily activities—the training of personnel to meet the diversifying welfare needs has not kept pace. As a result of activities funded by a past KGRI Pre-startup Research Grant, the principal investigator has built strong relationships of trust with the Yachiyo City Council of Social Welfare, community comprehensive support centers, the second-tier living support council, and residents such as branch association members, neighborhood association members, welfare commissioners, and community welfare volunteers. A particularly strong cooperative relationship has been established with the Yachiyo City Yonemoto Branch Association. Leveraging this strength, the research aims to demonstrate that daily cultural and artistic physical activities improve the psychological well-being of individuals in need of social welfare, and to propose this as a case for how an inclusive community should be.

<Research Results Report>

■Purpose

This research conducts Participatory Design activities with various local organizations, led by the Yachiyo City Council of Social Welfare in Chiba Prefecture, while fostering international collaboration between Japan and the UK. It investigates how these activities contribute to improving the psychological well-being of participants. The study treats this as a case study for enabling diverse residents with aging and disabilities to live physically and mentally healthy lives for as long as possible. It explores how to provide the freedom to choose one's own methods of self-realization and ways of connecting with others, and how to build a social environment ecosystem to extend healthy life expectancy.

■Methods

With British disabled artist Jason Wilsher-Mills as a co-researcher, we conducted workshops for employees of Yakuju Will, a special subsidiary company in Yachiyo City, Chiba. The workshops involved creating self-portraits with a single finger on a tablet as a form of self-expression for people with disabilities. Other workshops for disabled individuals in Yachiyo City included a craft workshop for making Christmas tree ornaments and a DIY workshop with iron beads. With the support of researcher Giulia Barbareschi, who specializes in physical disabilities and accessibility, we held a men-only stretch workshop for the elderly, as well as a photo collage workshop and a gardening workshop.

We conducted interviews and surveys with the participants of each workshop to verify the value that these cultural and artistic physical activities provided to them.

■Results

The works created in the above workshops were integrated and exhibited at the "Totteoki no Sakuhinten" (Exhibition of Special Works) at a citizen's gallery in Yachiyo City, Chiba, to coincide with Disability Week in December. Although the exhibition was hosted by the Yachiyo City Association for the Welfare of Persons with Physical Disabilities, it was held in cooperation with the Yachiyo City Council of Social Welfare, the Owens Yachiyo Citizen's Gallery, and the special subsidiary company Yakuju Will, and was viewed by a wide range of people. Social recognition was broadened, partly due to coverage by local newspapers and a television feature by J:COM. This also contributed to securing a Grant-in-Aid for Scientific Research (B) from FY2023 to FY2025.

The published papers are as follows:

- Sifan Chen, Danyang Peng, Giulia Barbareschi, Chihiro Sato, and Dunya Chen, 2023. "BeadMuse AI: Enhancing Inclusive and Independent Crafting Through Adaptive Pixel Art Templates". In IoT '23: The International Conference on the Internet of Things (IoT2023). ACM, New York, NY, USA. 211-218. DOI: 10.1145/3627050.3631580

- Adwitiyo Pramudito, Giulia Barbareschi, and Chihiro Sato, 2023. "Enhancing Self-Reflection in Older Adults through Collage Making". In IoT '23: The International Conference on the Internet of Things (IoT2023). ACM, New York, NY, USA. 236-239. DOI: 10.1145/3627050.3631568

- Sifan Chen, Yasuhiro Yoshizawa, Giulia Barbareschi, Dunya Chen, Chihiro Sato, 2024. "Service Design Aiming to Improve Workplace Inclusivity through DIY Craft Activities." The 12th Annual Conference of the Serviceology Society of Japan, 2024.

- Momoha Nakano, Chihiro Sato, 2024. "Turning Food Banks into New Community Spaces: The After-School Art Workshop 'M+Project' to Promote Learning and Play for Local Children." The 12th Annual Conference of the Serviceology Society of Japan, 2024.

- Sungjoo Park, Christopher Changmok Kim, Giulia Barbareschi, Kai Kunze, Chihiro Sato. "'Men-Only Stretch Sharing Session': Implementing an Exercise Program in an Aging Housing Complex." The 12th Annual Conference of the Serviceology Society of Japan, 2024.

- Adwitiyo Pramudito, Chihiro Sato, 2024. "Reflection as a Community Born from Personal Stories." The 12th Annual Conference of the Serviceology Society of Japan, 2024.

- Minako Matsui, Chihiro Sato, 2024. "The Role of the Engawa (Veranda) in Promoting Service Exchange: A Case Study of a Welfare Facility in Yachiyo City, Chiba." The 12th Annual Conference of the Serviceology Society of Japan, 2024.

- Qianrong Fu, Yifan Xu, Dunya Chen, Giulia Barbareschi, Chihiro Sato, 2024. "Empowering People with Intellectual Disabilities Connection to the Community through Adaptive Fabric Art." The 12th Annual Conference of the Serviceology Society of Japan, 2024.

- Yifan Xu, Qianrong Fu, Dunya Chen, Giulia Barbareschi, Chihiro Sato, 2024. "Making Personalized Souvenirs and Memories through Creative Craft Activities." The 12th Annual Conference of the Serviceology Society of Japan, 2024.

- Jianrui Zhao, Donna Dunya Chen, Chihiro Sato, 2024. "Collaboratively Cocreate a Gardening Program within a Local Ecosystem to Strengthen the Relationship in an Aging Community." The 12th Annual Conference of the Serviceology Society of Japan, 2024.

■Discussion

We aim for further expansion centered on the local stakeholders who participated in this research activity. We will work closely with the Council of Social Welfare to explore the potential for application, designing it as a social welfare service through the flow of workshop implementation → artwork exhibition → recognition by diverse residents. Also, while this time we focused on creating art using tablets, in the future we will design social welfare services by interpreting "culture and arts" more broadly. Specifically, we have already begun considering photography, gardening, electronics, fitness, and games, and welfare commissioners and various support centers are also preparing a cooperative framework. We will continue to diligently conduct research to address the question of "how to provide the freedom to choose one's own methods of self-realization and ways of connecting with others."

(Total of 5 recipients, 800,000 yen each)

"Elucidating the Psychological Processes in Problem-Solving Scenarios through Dialogue with AI"

Sayaka Kan (Associate Professor, Faculty of Letters)

Research Results Report

■Research Outline

We conducted a study to determine whether people can share understanding with conversational AI, build good relationships, and trust it as a clue to perceive reality. A survey of users of ChatGPT, a type of conversational AI, revealed that people feel a moderate level of subjective shared reality with ChatGPT. The higher the subjective shared reality, the greater the feeling of rapport with ChatGPT and the higher the perceived trustworthiness of ChatGPT as an information source. It was also shown that the direct influence of feeling that ChatGPT responded well on the sense of rapport and trust in ChatGPT is partially mediated by the degree of subjective shared reality with ChatGPT. From these results, it can be said that people can establish subjective shared reality even with conversational AI, and as a result, they can build good relationships with it and trust it as a clue to perceive reality.

<Research Results Report>

■Purpose

It is believed that people can build good relationships and solidify their perception of reality by sharing understanding with others (Rogginac-Milon, et al., 2021). Therefore, this study aimed to clarify whether people can also share understanding with conversational AI, build good relationships, and trust it as a clue to perceive reality.

■Methods

An online survey was conducted with users of a conversational AI (ChatGPT).

[Respondents] 492 individuals (average age 49.94, standard deviation 11.27)

[Main question items] ① Overall satisfaction with answers obtained from ChatGPT, (all of the following refer to "the last time you used ChatGPT") ② Satisfaction with the answers obtained from ChatGPT, ③ Relationship between the user and ChatGPT, ④ Subjective shared reality, ⑤ Sense of rapport, ⑥ Epistemological trust, ⑦ Responsiveness

■Results

・Users are moderately satisfied with the answers obtained from ChatGPT in general, with younger people being more satisfied and women being more satisfied than men.

・There is a positive correlation between satisfaction with the answers obtained from ChatGPT in the last usage scenario and the relationship between the user and ChatGPT.

・The higher the subjective shared reality, the higher the sense of rapport and epistemological trust.

・The direct effect of responsiveness on the sense of rapport and epistemological trust is partially mediated by subjective shared reality.

■Discussion

・The higher satisfaction among younger people is likely due to their higher skill in using ChatGPT compared to older people, and the higher satisfaction among women compared to men is likely because the tasks women use ChatGPT for are simpler.

・This study cannot clarify whether high satisfaction leads to feeling a closer relationship, or if feeling a closer relationship leads to high satisfaction.

・People can establish subjective shared reality with ChatGPT, and as a result, they can build good relationships with it and trust it as a clue to perceive reality.

"Elucidating the Mechanism of Neurodegeneration through the Autonomous Diffusion of Single Molecules"

Yorihiro Maeda (Senior Assistant Professor, School of Medicine)

Research Results Report

■Research Outline

Alzheimer's disease (AD) is a representative form of dementia that occurs in the elderly, but the development of its therapeutic drugs has either ended in failure or has only achieved limited effects in patients in the early stages of the disease. Therefore, this study focused on the tau protein, which is thought to play a major role from the mid-stage of the disease onward. The tau protein was thought to be involved in the regulation of neuronal excitability because its expression shows an anti-epileptic effect and its overexpression causes epilepsy-like symptoms, but its control mechanism was unknown. Furthermore, it is also thought that Alzheimer's disease can be caused or exacerbated by epilepsy. Therefore, we used a culture system that induces mainly inhibitory neurons from human iPS cells to investigate its control mechanism. Neuronal excitability is controlled by the balance of excitatory and inhibitory signals. Particularly in AD, there are reports that the degeneration of inhibitory neurons is involved in the onset of the disease, so we examined the change in the lateral diffusion of the GABA receptor, which is the receptor for inhibitory signals, on the neuronal cell membrane due to the expression of the tau protein. First, we succeeded in the world's first single-molecule live imaging in human iPS-derived neurons. As a result, we discovered that the suppression of tau protein expression promotes the lateral diffusion of the GABA receptor, which is thought to reduce inhibitory signals. We also discovered that Gephyrin, the scaffolding structure under the cell membrane of the GABA receptor, is reduced. From these findings, it was thought that the tau protein controls the overactivity of the neural network by increasing its excitability through the reduction of inhibitory signals in inhibitory neurons.

<Research Results Report>

■Purpose

In this proposal, we aimed to elucidate the mechanism by which the tau protein, a key molecule in Alzheimer's disease, controls the excessive excitability of neurons by measuring the diffusion of receptors or structural proteins inside and outside neurons using single-molecule live imaging, a representative example of interdisciplinary technology that combines life sciences and physical chemistry.

■Methods

We generated neurons enriched with inhibitory neurons from human iPS cells and examined the transmission efficiency of inhibitory signals from the lateral diffusion of GABA receptors on the cell surface.

■Results

It was found that the lateral diffusion of GABA receptors was reduced by suppressing the expression of the tau protein. It was also observed that the cluster amount of Gephyrin, the scaffolding structure of the GABA receptor, was reduced.

■Discussion

Inhibitory neurons output inhibitory signals. Since a state where inhibitory signals to the inhibitory neurons themselves are reduced due to the decrease in tau protein was considered, it was thought that the tau protein may control neuronal excitability by activating inhibitory neurons. In particular, it was thought that it controls its activity by controlling the cluster formation of the GABA receptor, Gephyrin.

"Shape Optimization Study to Improve the Acoustic Stability of an Epithesis with a Built-in Cartilage Conduction Hearing Aid"

Takanori Nishiyama (Senior Assistant Professor, School of Medicine)

Research Results Report

■Research Outline

Microtia is a congenital disease with a prevalence of about 1 in 10,000 people, and many cases are complicated by auricular deformity and external auditory canal atresia, making both aesthetic and functional aspects of hearing the targets of treatment. The treatment for auricular deformity has traditionally been mainly surgical treatment by auricular reconstruction, but its completeness is often not high. In addition, the results of hearing improvement surgery for external auditory canal atresia are not good, and a non-invasive treatment method that simultaneously improves both aesthetic and hearing aspects for microtia has not been established worldwide. Therefore, we devised an innovative treatment method that simultaneously improves both aesthetic and hearing aspects by fusing a high-definition epithesis using 3D printing technology and a new hearing aid called a cartilage conduction hearing aid, which was invented in Japan in 2017. In September 2021, we started the world's first prospective clinical study using an Epithesis with a built-in Cartilage Conduction Hearing Aid (APiCHA). However, since there is a possibility that the howling sound, a type of noise, may become louder when APiCHA is used in combination than when the cartilage conduction hearing aid is used alone, we created a microtia model and verified the occurrence of the howling sound.

<Research Results Report>

■Purpose

To verify the changes in howling sound caused by the combined use of APiCHA compared to when the cartilage conduction hearing aid is used alone, and to search for an APiCHA shape that is less likely to produce howling sound.

■Methods

For the microtia model, we will measure the noise level at a distance of 5 cm from the vibrator under each condition: without a cartilage conduction hearing aid, with a cartilage conduction hearing aid alone, with APiCHA, and with a modified APiCHA. We will then consider the effect on the howling sound under each condition.

■Results

The noise level ± standard deviation (SD) for each condition was 53.9±1.8 dB without a cartilage conduction hearing aid, 53.4±2.4 dB with a cartilage conduction hearing aid alone, and 56.2±1.1 dB with APiCHA. It was found that the howling sound significantly (P = 0.011) increased with the combined use of APiCHA compared to the cartilage conduction hearing aid alone. When a slit was made at the cable intersection of the APiCHA to improve fixation, the howling sound tended to increase further to 58.1±1.8 dB (P = 0.059). By filling the internal space of the APiCHA with silicone, it improved significantly to 53.2±1.1 dB (P = 0.0047), and it was found that the howling sound did not increase compared to the cartilage conduction hearing aid alone (P = 0.85).

■Discussion

Although there was a tendency for the howling sound to increase with the combined use of APiCHA compared to the cartilage conduction hearing aid alone, it was found that by filling the internal space of the APiCHA with silicone, the howling sound could be prevented from increasing. It was found that to optimize the fixation and howling sound of the APiCHA, it is useful to create a slit at the cable intersection and fill the internal space.

"Preliminary Research for Femtech Development: Understanding the Industry's Current Status and Issues to Identify Blind Spots"

Ai Hasegawa (Associate Professor, Faculty of Science and Technology)

Research Results Report

In preparation for publication

"Elucidating the Brain Mechanisms of Drummer's Dystonia"

Shinya Fujii (Associate Professor, Faculty of Environment and Information Studies)

Research Results Report

■Research Outline

To elucidate a part of the brain mechanism of drummer's dystonia, we investigated the actual state of physical disorders in drummers, the characteristics of performance and muscle activity when dystonia symptoms occur, and the excitatory-inhibitory function of the motor cortex in drummers with dystonia. The investigation revealed that professional drummers often experience dystonia symptoms in the right foot, which plays the bass drum, and the left hand, which plays the snare drum. It was also found that dystonia symptoms frequently occur on the first beat of a drum pattern, and specific performance timing, sound amplitude, and muscle activity patterns during symptomatic episodes were identified. In addition, preliminary results were obtained regarding the excitatory-inhibitory function of the motor cortex in drummers with dystonia.

<Research Results Report>

■Purpose

The purpose of this study was to investigate the actual state of physical disorders in drummers, the characteristics of performance and muscle activity when dystonia symptoms occur, and the excitatory-inhibitory function of the motor cortex in drummers with dystonia, in order to elucidate a part of the brain mechanism of drummer's dystonia.

■Methods

Using a questionnaire survey method, we investigated the actual state of physical disorders in about a thousand drummers in Japan. For one drummer with dystonia affecting the right lower limb, we conducted a case study by recording the bass drum sound during drum pattern performance and analyzing the surface electromyography activity data of the right lower limb. We investigated the frequency of symptom occurrence and compared the performance timing, sound amplitude, and lower limb muscle activity patterns between symptomatic and asymptomatic periods. For the same drummer, we conducted a preliminary experiment to evaluate the excitatory-inhibitory function of the motor cortex by measuring intracortical facilitation and short-interval intracortical inhibition using the transcranial magnetic stimulation method.

■Results

The questionnaire survey revealed that professional drummers experience dystonia symptoms more often in the right foot, which plays the bass drum, and the left hand, which plays the snare drum, compared to the right hand or left foot, which mainly play the hi-hat (Yamaguchi et al., ICMPC, 2023). The case study showed that when a drummer with dystonia symptoms in the right lower limb plays a drum pattern, the symptoms frequently occur on the first beat, and the performance timing is earlier and the sound amplitude is smaller during symptomatic periods compared to asymptomatic periods (Honda et al., bioRxiv, 2024). Analysis of the muscle activity patterns revealed that there are specific muscle activity patterns when symptoms occur (Honda et al., bioRxiv, 2024; Sata et al., ICMPC, 2023). In the experiment using the transcranial magnetic stimulation method, we confirmed that an increase and decrease in motor evoked potentials were observed in the intracortical facilitation and short-interval intracortical inhibition paradigms.

■Discussion

It is suggested that dystonia symptoms in professional drummers may frequently occur in the bass drum and snare drum, which form the backbone of the rhythm pattern. In drumming, the first beat is the downbeat that is the cornerstone of the rhythm pattern, and it is suggested that increased timing prediction and attention may be related to the occurrence of dystonia symptoms. The characteristics of performance timing, sound amplitude, and muscle activity patterns associated with the occurrence of dystonia symptoms may be applicable as quantitative evaluation indicators for symptom occurrence. Previous studies have reported a decrease in inhibition and an increase in excitation in the primary motor cortex of pianists with dystonia symptoms (Furuya et al., J Physiol, 2018), and it is expected that further studies on the excitatory-inhibitory function of the motor cortex will be conducted on multiple drummers in the future.

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