2016 Annual Report

The University of Electro-Communications
Brain Science Inspired Life Support Research Center
http://blsc-uec.net/en/Preface
There are concerns that the decline of physical strength and sensory functions due to diseases
and ageing leads to the lowering of QOL (quality of life) of individuals in the mental as well as
physical aspects. These declined activities result in not only individual handicaps but also a lot of
disadvantages for societies surrounding them.

This indicates that one of the most important issues

is the efficient prevention and treatment of decline of physical abilities and sensory functions, andmoreover how we live together symbiotically with people of lowered QOL.
Since Brain Science Inspired Life Support Research Center (BLSC) was launched in 2013,
researchers from a wide spectrum of sciences such as neuroscience, information science, robotics,
ergonomics, bioengineering and optical science have cooperated and collaborated to carry out
investigation and development aiming at medical prevention and care, improvement of quality of
medicine, sophistication of medicine for post-treatment recovery. In 2016, we reorganized BLSC
that was originally composed of 3 research groups by adding a theoretical group. Now BLSC has 4
research groups: Basic technology development of optical measurements group; Measurement andmonitoring of in vivo brain functions group; Technology development for motor function recovery
for medical welfare group; and Theoretical and computational neuroscience group. Under thisreorganized group structure, we became to identify clearly the missions of respective groups andeasily recognize similarities and differences among studies conducted by individual BLSC members.
This in turn revitalizes individuals’ research by working together more closely within a group andcooperating with other groups to produce innovative technologies for life support. Also we devote
ourselves to fostering young scientists and engineers who will further promote such innovative
research and development.
The present annual report is to summarize all our activities in 2016 to restart our activities
towards the future. We reaffirm our determination to perform research more cooperatively and morecollaboratively making the best use of the current results reported here. If we could have yourunderstanding and support successively, we would be very happy.
August 25, 2017
Brain Science Inspired Life Support Research Center
Director

Takuji Koike

Index1. Mission

1

2. Group Structure2

3. Personnel Organization

3

4. Achievements in 2016

5

5. Research Funding in 2016

6

6. Seminars and Events

7

7. Activity Reports of Laboratories
Basic technology development of optical measurements Group
(1)
(2)
(3)

Yukio YAMADA Laboratory
Haruki NIWA Laboratory
Shojiro MAKI Laboratory

Measurement and monitoring of in vivo brain functions Group(4) Kazuto MASAMOTO Laboratory(5) Yoichi MIYAWAKI Laboratory(6) Hayaru SHOUNO Laboratory(7) Shinji MATSUDA Laboratory

12
18
22

28
33
40
43

Technology development for motor function recovery for medical welfare Group
(8)
(9)
(10)
(11)
(12)
(13)

Takuji KOIKE Laboratory
Yutaka KANO Laboratory
Hiroshi YOKOI／Yinlai JIANG Laboratory
Hidetaka OKADA Laboratory
Norihiro KOIZUMI Laboratory
Guanghao SUN Laboratory

46
50
54
65
70
74

Theoretical and Computational Neuroscience Group(14) Yoshiki KASHIMORI Laboratory(15) Shigeru TANAKA Laboratory(16) Tadashi YAMAZAKI Laboratory

78
82
88

Mission
BLSC aims to study science and engineering necessary for people to live
peacefully. In more detail, BLSC’s objective is to construct science and technology foralleviating inconvenience in the elderly and handicapped so as to live like a humanbeing, based on medicine engineering cooperation. Another objective is to foster
human resources to be able to pursue such research.
There are many people who feel decline in the ability of perception, cognition,communication and body action due to ageing, and hence have daily anxiety andinconvenience. Therefore BLSC is charged with a primary mission that it provides
such people with advanced technology for the fulfillment of their potentials by
assisting and strengthening their weakened functions. To complete the mission, UEC
researchers from different research fields got together to organize BLSC. This fact
made BLSC to have highly diversified and heterogeneous research areas.
In today’s medicine, people are judged to be either patients or healthy people
according to certain indices to identify the pathology, and the latter, if they do not feel
well, is difficult to receive medical treatment because of “not disease”. From thestandpoint of preventive medicine, however, health promotion technology is demanded
for those people. Similar cases are the elderly with weakened functions of perception,
cognition and movement. Thus, research and education on the development of assist
technology, rehabilitation and practical training programs for the elderly without disease
are the issues that BLSC needs to address.

1Group Structure
BLSC promotes project-based programs in research and education aiming at
fostering innovative human resources who are responsible for meeting technologicalneeds in the onsite medical welfare treatment. For this purpose, BLSC set the following
3 research groups that support the programs. Students develop expertise and practicalskills necessary for innovative research, solving problems under the project-based
programs.

Basic technology development of optical measurements group
This group focuses on research and education for the development of new optical probes,
optical imaging technology and multidimensional image analysis to evaluate the capabilities ofplasticity, self-recovery, and regeneration of organic functions. (Members: Yamada, Niwa & Maki)

Measurement and monitoring of in vivo brain functions group
This group focuses on research and education on the measurement of individual cells’
activities in response to external stimuli, the brain imaging of activities associated with motor
functions, and the monitoring and control of brain activities using BMI technology. (Members:
Masamoto, Miyawaki, Shouno & Matsuda)

Technology development for motor function recovery for medical welfare group
This group focuses on research and education on the technology development for motor
control and rehabilitation based on measurements of brain activities associated with motor functions.
(Members: Koike, Yokoi, Kano, Okada, Koizumi, Jiang & Sun)

Theoretical and computational neuroscience group
This group devotes itself to research and education on mathematical modeling of the nervous
system at the levels of cells and/or networks to understand the mechanisms of the brain structure,function and plasticity for the development of a next-generation artificial intelligence andengineering application to neurorehabilitation. (Members: Kashimori, Tanaka & Yamazaki)

2Personnel OrganizationName（as of 31 March, 2017 ）Web site

Position

KOIKE Takuji

http://www.bio.mce.uec.ac.jp/index.html

Director (2016- )KANO Yutaka

http://www.ecc.es.uec.ac.jp/

Vice Director (2016-)

YOKOI Hiroshi

http://www.hi.mce.uec.ac.jp/yklab/

Professor

OKADA Hidetaka

http://www.hb.mce.uec.ac.jp/

Professor

KASHIMORI Yoshiki

http://granule.pc.uec.ac.jp/wiki/wiki.cgi

Professor

SHOUNO Hayaru

http://daemon.inf.uec.ac.jp/ja/

Professor

MASAMOTO Kazuto

http://kjk.office.uec.ac.jp/Profiles/55/0005461/

Professor

profile.html

Professor

MIYAWAKI Yoichi

http://www.nvu.mi.uec.ac.jp

Professor

TANAKA Shigeru

http://tanaka-lab.net/jp/

SA Professor

NIWA Haruki

http://www.firefly.pc.uec.ac.jp/

SA Professor

YAMADA Yukio

http://www.nvu.mi.uec.ac.jp/old_html/index.html

SA Professor

MATSUDA Shinji

http://www.matsuda-lab.es.uec.ac.jp/

Associate Professor

KOIZUMI Norihiro

http://www.medigit.mi.uec.ac.jp/

Associate Professor

YAMAZAKI Tadashi

http://numericalbrain.org/

Associate Professor

JIANG Yinlai

http://www.hi.mce.uec.ac.jp/yklab/

Associate Professor

MAKI Shojiro

http://www.firefly.pc.uec.ac.jp/

Assistant Professor

SUN Guanghao

http://cargocollective.com/guanghao_sun

Assistant Professor*SA: Specially
Appointed

3

Visiting Scientists
Name

Affiliation

Position

ARAMAKI Yu

Chukyo University School of Health and Sport
Sciences, Professor

Visiting Professor

KATO Ryu

Faculty of Engineering Division of Systems
Research, Associate Professor

Visiting Associate
Professor

KANSAKU Kenji

Systems Neuroscience Section, ResearchInstitute of National Rehabilitation Center for
Persons with Disabilities・Chief

Visiting Professor

TAKAGI TakehikoDepartment of Orthopaedic Surgery, Tokai
University Assistant Professor

Visiting Professor

TAKAYAMA
Shinichiro

Department of Surgical Specialities, National
Center for Child Health and Development
Director

Visiting Professor

TAKITA Masatoshi

Brain Function Measurement Group, Human
Informatics Research Institute, National
Institute of Advanced Industrial Science andTechnology (AIST) Senior Researcher

Visiting Professor

NAKAMURA Tadashi

UEC Professor Emeritus
http://kaeru.pc.uec.ac.jp/

Visiting Professor

HOSHI Yoko

Department of Biomedical Optics, Institute for
Medical Photonics Research, Preeminent
Medical Photonics Education & ResearchCenter, Hamamatsu University School of
Medicine Professor

Visiting Professor

YAMAMURA Osamu

University of Fukui School of Medicine
Associate Professor

Visiting Professor

YU Wenwei

Department of Medical System Engineering,
Graduate School of Engineering, Chiba
University Professor

Visiting Professor

LU Baoliang

Department of Automation, School ofElectronic, Information and ElectricalEngineering, Shanghai Jiao Tong University,
China Professor

Visiting Professor

CAO Qixin

Director, Engineering Training Center,
Shanghai Jiao Tong University, China Professor

Visiting Professor

4

Achievements in 2016
１．Research
A. Refereed papers： 47（including 7 papers published in IF>4 journals）
B. Presentations at international conferences：22
C. Master patent applications：6
D. Productization：1

２．Education
A. Student guidance：64（Bachelor：43, Master：19, Doctor：2）
B. Awards：12（Faculty members：4, Students：8）

３．Public relations & Outreach activities
A. Media release：20
B. High school visit：95

Research Funding in 2016

Total budget：182,416,000 yen（Breakdown）○Project expense:“New human resource development program to support the super-aged society bybrain science inspired life support innovation”
FY 2016 Special expense: 4,488,000 yen; UEC burden: 4,488,000 yen○Grants‐in‐aid for Scientific Research (Kakenhi):（Scientific Research (A): 1, Scientific Research (B): 6, Scientific Research (C): 11,
Challenging Exploratory Research: 4, Innovative Areas: 4, Young Scientist: 1）
Total expense: 55,190,000 yen○Research funding from governmental resources other than Kakenhi:
Total expense: 109,621,000 yen (9 applications)○Private foundations:
Total expense: 3,997,000 yen (2 applications)○Expense for collaboration and donation from private companies:
Total expense: 4,632,000 yen (5 applications)6Seminars and Events
For general audience interested in neurosciences and technological research for life support in aged societies,
we have held “BLSC Seminar Series” continually about once a month since BLSC was established. We also held
“BLSC Spring School for High School Students” for FY2016. Summaries of these events and educational activities
are described below (in more detail, see the BLSC website: http://blsc-uec.net/). (Note: English translations fromJapanese are not authorized by the speakers, and technical terms may not be correct.)
1. BLSC Seminar Series
BLSC Seminars were held twelve times from 37th to 48th in FY2016. The member of BLSC who proposed a
subject and speaker was supposed to organize the seminar in turn.
37th seminar
Date and time: Apr. 15 (Fri.), 2016, 13：30 - 14：30
Place: Meeting Room #306, Building E-3, UEC
Speaker: Dr. Mamoru Fukuchi (Assistant Professor, Laboratory of Molecular Neurobiology, Graduate
School of Medicine and Pharmaceutical, University of Toyama)
Chair: Assis. Prof. Shojiro Maki
Title: Study of the expression control mechanism of brain-derived neurotrophic factor (BDNF) gene;
Toward understanding of the expressions of higher order functions of the brain-nerve system andcreations of new drugs
38th seminar
Date and time: May 18 (Wed.), 2016, 13：30 - 14：30
Place: Meeting Room #306, Building E-3, UEC
Speaker: Dr. Kazunori Hase (Professor, Mechanical Engineering, Graduate School of Science andEngineering, Tokyo Metropolitan University)
Chair: Prof. Hidetaka Okada
Title: Simulation of human walking with a nerve-musculoskeletal model and its applications
39th seminar
Date and time: Jun. 21 (Tue.), 2016, 16：15 - 17:45
Place: Room #802, Building E-4, UEC
Speaker: Dr. Yu Aramaki (Professor, School of Health and Sport Sciences, Chukyo University)
Chair: Assoc. Prof. Yoichi Miyawaki
Title: Sports and voxel-based morphometry (VBM)
40th seminar
Date and time: Jul. 27 (Wed.), 2016, 13：00 - 14:30
Place: Meeting Room #306, Building E-3, UEC
Speaker: Dr. Satoko Koganemaru (Researcher, Human Brain Research Center, Graduate School of
Medicine Kyoto University)
7

Chair: Assis. Prof. Tadashi Yamazaki
Title: Changes in brain activity and modification of human walking by transcranial oscillatory
stimulations of brain
41st seminar
Date and time: Sep. 9 (Fri.), 2016, 13：00 - 14:30
Place: Meeting Room #306, Building E-3, UEC
Speaker: Dr. Michisuke Yuzaki (Professor, Department of Physiology, School of Medicine, Keio
Univeristy)
Chair: Assoc. Prof. Shinya Matsuda
Title: Bridge over Troubled Synapses
42nd seminar
Date and time: Oct. 26 (Wed.), 2016, 13：00 - 14:30
Place: Meeting Room #301, Building E-3, UEC
Speaker: Dr. Hidenori Sakanashi (Senior Researcher, The Artificial Intelligence Research Center,
National Institute of Industrial Science and Engineering (AIST))
Chair: Prof. Hayaru Shouno
Title: Support for medical diagnostics with image recognition technology
43rd seminar
Date and time: Nov. 29 (Tue.), 2016, 13：00 - 14:30
Place: Meeting Room #306, Building E-3, UEC
Speaker: Dr. Kiyohiko Nakamura (Professor, Interdisciplinary Graduate School of Science andEngineering, Tokyo Institute of Technology)
Chair: Prof. Yoshiki Kashimori
Title: Neuro-mechanism which demands information
44th seminar
Date and time: Dec. 21 (Wed.), 2016, 13：00 - 14:30
Place: Meeting Room #306, Building E-3, UEC
Speaker: Dr. Norihiro Koizumi (Associate Professor, Department of Mechanical Engineering andIntelligent Systems, University of Electro-Communications)
Chair: Prof. Yukio Yamada
Title: Development of robots for ultrasonic diagnosis and therapy with ultra-high accuracy through
Me-Dic IT
45th seminar
Date and time: Jan. 27 (Fri.), 2016, 13：00 - 14:30
Place: Meeting Room #306, Building E-3, UEC
Speaker: Dr. Zhu Xiaoxiao (Specially Appointed Associate Professor, Global Alliance Laboratory,
University of Electro-Communications, and Researcher, Institute of Robotics, Shanghai Jiaotong
University, China)
8Chair: Prof. Hiroshi Yokoi
Title: ROS based Control of a 7-DoF Robot Arm for BMI
46th seminar
Date and time: Feb. 23 (Thu.), 2016, 13：00 - 14:30
Place: Meeting Room #306, Building E-3, UEC
Speaker: Dr. Sun Guanghao (Assistant Professor, Department of Mechanical Engineering and Intelligent
Systems, University of Electro-Communications)
Chair: Assoc. Prof. Norihiro Koizumi
Title: Development of practical medical devices for non-contact measurement of vital signs by
bio-sensors using microwave radar etc.
47th seminar
Date and time: Mar. 9 (Thu.), 2016, 13：00 - 14:30
Place: Meeting Room #306, Building E-3, UEC
Speaker: Dr. Gentaro Taga (Professor, Developmental Brain Science Laboratory, Department of Physicaland Health Education, Graduate School of Education, The University of Tokyo)
Chair: Prof. Yukio Yamada
Title: Study of brain development using hPod (hemoglobin Phase of oxygenation and deoxygenation) in
fNIRS (functional near-infrared spectroscopy)
48th seminar (In cooperation with Industry-UCB-UEC Workshop 2017 (IUUWS 2017))
Date and time: Apr. 27 (Mon.), 2017, 14:30 - 15:30
Place: Meeting Room #301, Building E-3, UEC
Speakers: Dr. Gerard Marriott (University of California, Berkeley, Professor)
Dr. Shojiro Maki (Department of Engineering Science, UEC, Assist. Prof.)
Titles: [Dr. Gerard Marriott] Engineering platelets and optical probes for applications in translational
medicine[Dr. Shojiro Maki] Chemistry of firefly bioluminescence
The statistics of the attendees to the seminar series in FY2016 are listed in the table below. In averages, thenumber of the total attendees per seminar was 27.7, and the numbers of the faculties of UEC, the students of UEC
and the others were 13.0, 13.0 and 1.7, respectively.
NumberFaculties of UEC

Students of UEC

Others

Total

37th

13

14

6

33

38th

15

13

3

31

39th

16

9

5

30

40th

13

23

1

37

41st

11

17

0

28

42nd

10

7

1

18

43rd

17

16

1

34

9

44th

10

21

0

31

45th

13

8

1

22

46th

12

2

1

15

47th

13

13

0

26

2. BLSC Spring School for High School Students
BLSC modified part of the hands-on training course for graduate students and designed contents of the spring
school easy for high school students to learn. In 2017, 2nd “Brain Science Life Support Research Center Spring
School” was held for 4 days Mon. Mar. 27 to Thu. Mar. 30, 2017. Seventeen high school students attended from
Tokyo, Ibaraki and Chiba prefectures. The time of the school per day was four and half hours, and one topic spent
two days for each of the first and second periods. Two topics were selected from the hands-on training course forgraduate students, and a manual for high school students was made by modifying the text of the hands-on training
course. The titles of the lectures and experiments, schedules, and numbers of participants are as follows. Details of
the Spring School are listed on the center's homepage(http://blsc-uec.net/wpblsc/wp-content/uploads/ReportBLSC-SpringSchool2017.pdf).
The participants learned the following two topics:

1st topic: See the hearing
Place: Labs. #730 and #507, Building E-4, UEC
Instructor: Prof. T. Koike

Teaching Assistants: N. Li, M. Sato, R. Kuroda, Y. Yoshimura
Contents:
1st day: Measurement of auditory brainstem response.
After normal hearing tests, weak electroencephalograms from brainstem induced by sound stimulus
were measured.
2nd day: Measurement of distortion components of otoacoustic emissions.
The distortion product otoacoustic emission generated in the ear by sound stimulus were measured
and the hearing ability was estimated.

2nd topic: Let’s make lightning of firefly
Place: Lab. #837, Building E-6, and lab. #408, SVBL Building, UEC
Instructor: Assis. Prof. S. Maki

Teaching Assistants: A. Kitada, R. Morimitsu, Y. Hachiro
Contents:
1st day: Organic synthesis of firefly D-luciferin was performed.
2nd day: Structure confirmation of the synthesized D-luciferin with instrument analyses (nuclear
magnetic resonance, mass, and infrared spectra).
Firefly bioluminescence was observed by using the synthesized D-luciferin.
10The participants were grouped into the following two.
1st group:
Date and time: Mon. Mar. 27, 2017, 13:00-17:30 and Tue. Mar. 28, 2017, 13:00-17:30
Number of participants: Five for the 1st topic, and four for the 2nd topic
2nd group:
Date and time: Wed. Mar. 29, 2017, 13:00-17:30 and Thu. Mar. 30, 2017, 13:00-17:30
Number of participants: Three for the 1st topic, and five for the 2nd topic

11

Yukio YAMADA Laboratory
1. Outline of Research and Education
1. 1 Basic Policy in Research and Education
The major research topics are medical and biological measurements using near infrared light, such as (1)diffuse optical tomography (DOT) for imaging blood oxygenation and blood volume based on near infrared
spectroscopy (NIRS), (2) optical mapping (or optical topography) for imaging brain function based on NIRS,(3) fluorescence tomography for imaging the distribution of fluorophore concentration inside bodies, (4)noninvasive and continuous measurement of blood glucose contents (BGC) using NIRS and (5) detection of
aspiration by the use of fluorescence in the near infrared wavelength range. In addition, as an industrial
application of NIRS (6) noncontact measurement of temperature and concentration distributions of aqueous
solutions in a microchannel is being examined. Summaries of the above research topics are described below.
(1) Diffuse Optical Tomography (DOT)The near infrared wavelength range from about 700 nm to 1200
nm is called as the biological optical window because light in the
wavelength range is weakly absorbed by biological tissue, and it ispossible to detect the light scattered and absorbed by tissue with the
thickness of about 10 cm. Utilizing this characteristics of weakabsorption of the near infrared light by tissue, DOT has beendeveloped to obtain tomographic images of tissue or organs of thesize larger than a few centimeters. DOT reconstructs the image of theabsorption properties of the tissue for the near infrared light, and thereconstructed absorption images are converted to tomographic
images of physiological information of the changes in blood statuses
such as the concentrations of oxy- and deoxy-hemoglobins and blood
volume. In contrast to X-ray computed tomography (X-ray CT)
where X-ray propagates straight in bodies, near infrared light does
not propagate straight but is strongly scattered by tissue. Therefore,
the algorithm of image reconstruction for X-ray CT cannot beapplied to DOT, and other algorithms are needed to be developed,
which are in the category of the inverse problem based on theFig. 1 (Top) Photo of DOT measurement
at a forearm, and (Bottom) DOT image

equation of light propagation in biological tissue. For solving theshowing

forward problem in the inverse problem, in this research, we study

deoxy-hemoglobin concentration due tothe methods to solve the radiative transfer equation and the photon

theincreaseinthethe muscle activity in the forearm.

diffusion equation describing light propagation in tissue as well as Monte Carlo methods statistically
reproducing light propagation. Figure 1 shows a photo of DOT measurement for investigation of the muscle
activity in the forearm during hand gripping (top), and the DOT image which reveals the increase in the
deoxy-hemoglobin concentration by 100 M due to the muscle activity (bottom). Prof. Yamada collaborated

12

with Prof. Y. Hoshi, University of Hamamatsu School of Medicine, who was the leader of a project for DOT
sponsored by Japan Agency for Medical Research and Development (AMED), and with Prof. Y. Iso, Kyoto
University, who is the leader of a project of “Mathematical analyses of light propagation in biological tissue
toward medical applications” sponsored by Japan Society for Promotion of Science (JSPS).
(2) Optical mapping (Optical topography)
Optical mapping images the changes in the blood status in the brain using NIRS as DOT does, but cannot
obtain tomographic images. Optical mapping simply maps the 2D distribution of the light intensities which
are detected at multiple positions on the head surface after the source light is irradiated on the head surface,
propagates through the brain surface, and is reemitted from the head surface. Although the mapping images
reflect the changes in the blood status caused by the brain activity, interpretation of the images needs careful
understanding of the phenomena occurring inside the head because the images are affected by various factors
such as the spatial variation of the skull thickness, and the change in the blood volume (or blood flow) in theskin. Prof. Y. Yamada worked in cooperation with Japan Optical Brain Functional Imaging Society in thisresearch topic.
(3) Fluorescence tomography
As an application of DOT, fluorescence tomography is developed to image the distribution offluorophore concentration inside a body. When a body contains fluorophore which emits fluorescence in thenear infrared wavelength range, it is possible to obtain a tomographic images of the fluorophore
concentration by measuring the fluorescence light emitted from the body surface. This technology is
expected to be used mainly for small animals in the development of new drugs for early diagnosis of breast
cancers, and so on. Prof. Y. Yamada collaborated with Prof. G. Nishimura, Hokkaido University, who was theleader of a project for fluorescence tomography sponsored by AMED,(4) Noninvasive measurement of blood glucose contents (BGC) by NIRS
If the conventional method of BGC measurement using blood sampling with painful finger pricking is
replaced by a noninvasive measurement method, pains experienced by diabetes patients will be greatly
alleviated. However, the development of noninvasive measurement of BGC is very difficult and still
unsuccessful even after a few tens of years so far. The purpose of this research is to develop a noninvasive
measurement method of BGC using NIRS. The most frequently used method in the past utilized multivariate
analyses to build calibration functions from simultaneously measured BGC and spectra of light reflectedfrom the skin by pre-experiments. However, the performance of this method using multivariate analyses wasfound to be limited. So we have been developing two new approaches: one approach builds calibration
functions in multivariate analyses from numerically simulated measurement data without the necessity ofpre-experiments, and the other approach modifies the classical least squares (CLS) method to introduce
imaginary components for canceling out the change in the scattering properties of the skin during themeasurement.

13

(5) Aspiration detection using fluorescenceAt the occasion of the symposium co-sponsored by the University of Electro-Communications UEC) andJapan Commons for Collaborating Medicine and Engineering, which was held on Nov. 15, 2015, Dr. Y.
Michiwaki of Musashino Red Cross Hospital (MRCH) gave a presentation titled as “Development of
medical devises assisting the reduction of suffocation accidents and serious pneumonia caused by dysphagiaof elderly patients.” After his presentation, UEC started a research project in collaboration with MRCH todevelop a new method for aspiration detection by the use of fluorescence, which is useful to examine
whether food is trapped at the branch between the trachea and esophagus. Hokkaido University joined thecollaboration by providing a high performance fluorescence measurement instrument.
(6) Noninvasive measurement of temperature of aqueous solution and solute concentration
The optical absorption spectrum of water in the near infrared wavelength range slightly changes withtemperature. Using the characteristics of the spectrum, a new method to noninvasively measure and image
the change in the temperature of aqueous solutions has been developed in this research. Additionally using
the dependency of the absorption strength on the solute concentration in the aqueous solution, it is possible
to simultaneously measure and image the changes in the temperature and solute concentration in the aqueous
solution. This method will be applied to measure and image the temperature, solute concentration, reaction
rate, etc. in microscale channels in biochips and chemical chips.

1.2 Achievements and State of Progress (April, 2016 - March, 2017)(1) Diffuse optical tomography
As for the results and present status of the research topic of DOT, we have developed a new method forsolving the radiative transfer equation which is considered as the most accurate equation describing thephenomena of light propagation in biological tissue, and have found the effect of void regions like thetrachea on the light propagation. Also we wrote a review article about DOT. These results were published ininternational journals (Refs. 1 to 4 of Item 2.1).
(2) Optical mapping
Japan Optical Functional Brain Imaging Society (JOFBIS) started a committee for publishing a
guidebook for beginners working with optical mapping. This guidebook gives notes and advices inmeasurements of optical mapping and functional brain imaging using NIRS in general. Yukio Yamada was
assigned for the chair of the committee and the first edition was published and expected to contribute tosound development of this technology (Ref. 1 of Item 2.2)
(3) Fluorescence tomography
As for the fluorescence tomography, Yukio Yamada worked as a collaborating researcher to a project ofJapan Agency for Medical research and Development (AMED) for developing a new algorithm of image
reconstruction and for improving the image quality.

14(4) Noninvasive measurement of blood glucose contents (BGC) by NIRS
By cooperating with a company which has been collaborating with our group for a few years in the past,
a new method of noninvasive NIRS measurement of BGC has been developed and the second paper is inpreparation to be submitted to an academic journal. Also Yukio Yamada was invited by Samsung, Korea, togive a talk and to discuss about this topic. Our research of this topic is progressing steadily despite itsdifficulty.
(5) Aspiration detection using fluorescenceThis research started in December 2015, and we made preliminary experiments after some discussions
about the fluorophores, phantom experiments, etc. But, we failed to detect fluorescence in the preliminary
experiments using an existing measuring instrument in UEC. Then, another measuring instrument developedby Hokkaido University in the project of the item (3) above was used for detecting fluorescence with ahigher sensitivity. We succeeded in detecting fluorescence emitted from the fluorophore embedded in beef.
We prepared documents for application to the approval of human experiments. Also we prepared documentsfor patent application.
(6) Noninvasive measurement of temperature of aqueous solution and solute concentration
This topic has been developed to simultaneous measurement and imaging of both temperature and soluteconcentration, and a paper describing the results was published in an international journal (Ref. 5 of Item2.1). The paper was highly evaluated and selected one of the highlights in 2016 of the journal indicating that
our research activities are progressing soundly and steadily.

1. 3 Future Plan
For the research topics of (1) diffuse optical tomography and (3) fluorescence tomography, the projects
sponsored by Japan Agency for Medical Research and Development (AMED) were terminated at the end of
the fiscal year of 2016. But the principal investigator will continue to collaborate with the researchers
involved in the projects. For the topic of (2) optical mapping, the principal investigator will take part intranslation of the pamphlet in Japanese into English under the collaboration with Japan Optical Functional
Brain Imaging Society (JOFBIS). Also he will cooperate with researchers who are preparing for aninternational conference to be held at the University of Tokyo in September 2018.
For the topic of (4) noninvasive measurement of blood glucose contents (BGC) by NIRS, the principal
investigator will continue collaboration with the related company, and will submit a paper to an international
journal. For the topic of (5) aspiration detection using fluorescence, the group including the principal
investigator will continue to accumulate data by preliminary experiments and proceed to in vivo experiments
using human in 2017. For the topic of (6) noncontact measurement of temperature and solute concentration
in aqueous solution, the principal investigator will continue to work in collaboration with the associate
professor of Tokyo Metropolitan University.

15

2. Research Achievements
2. 1 Reviewed papers [〇: Impact factor greater than 4]
For the topic of (1) Diffuse optical tomography(1) Hiroyuki Fujii, Shinpei Okawa, Ken Nadamoto, Eiji Okada, Yukio Yamada, Yoko Hoshi, and Masao
Watanabe Numerical Modeling of Photon Migration in Human Neck Based on the Radiative Transport
Equation. Journal of Applied Nonlinear Dynamics 5, 117–125 (2016).
(2) Yoko Hoshi and Yukio Yamada Overview of diffuse optical tomography and its clinical applications.
Journal of Biomedical Optics 21 (9) 091312 (2016). doi: 10.1117/1. JBO.21.9.091312. (Invited Review
Paper)(3) Hiroyuki Fujii, Shinpei Okawa, Yukio Yamada, Yoko Hoshi, Masao Watanabe Renormalization of thehighly forward-peaked phase function using the double exponential formula for radiative transfer.
Journal of Mathematical Chemistry published on line: 21 July 2016. DOI: 10.1007/s10910-016-0670-3.
(4) H. Fujii, Y. Yamada, K. Kobayashi, M. Watanabe and Y. Hoshi Modeling of light propagation in thehuman neck for diagnoses of thyroid cancers by diffuse optical tomography. International Journal for
Numerical Methods in Biomedical Engineering Version of Record online : 27 Oct. 2016, DOI:
10.1002/cnm.2826.
For the topic of (6) Noninvasive measurement of temperature of aqueous solution and solute concentration(5) Naoto Kakuta, Hiroki Yamashita, Daisuke Kawashima, Katsuya Kondo, Hidenobu Arimoto and Yukio
Yamada Simultaneous imaging of temperature and concentration of ethanol–water mixtures in
microchannel using near-infrared dual-wavelength absorption technique. Measurement Science andTechnology 27 (2016) 115401 (12 pages). doi:10.1088/0957-0233/27/11/115401. (Selected as one of the2016 Highlights of Measurement Science and Technology)

2.2 Book, non-refereed articles and translation
For the topic of (2) Optical mapping(1) Y. Yamada et al. Ed., For better measurement of fNIRS (functional near-infrared spectroscopy). 1st. Ed.,
Japan Optical Functional Brain Imaging Society (JOFBIS). Mar. 2017.

2.3 Invited lectures(1) (Invited Talk) Yukio Yamada, “Non-invasive near-infrared blood glucose measurement: two new
approaches,” Current Challenges on Noninvasive Glucose Sensing and Its Future Directions, Samsung
Future Tech Forum, Suwan, Korea, Oct. 25, 2016.

2.4 Award(1) For the topic of (6) Noninvasive measurement of temperature of aqueous solution and soluteconcentration, The paper published in the journal of Measurement Science and Technology titled as
Simultaneous imaging of temperature and concentration of ethanol–water mixtures in microchannel
using near-infrared dual-wavelength absorption technique. 27 (2016) 115401, was selected as one of16

the Highlights in 2016.

3. Research funding
None

4. Collaboration
4.1 Inside BLSC
(1) For the topic of (5) Aspiration detection using fluorescence, collaboration with Profs. Shojiro Maki,
Haruki Niwa, and Takuji Koike.

4.2 Outside UEC(1) For the topic of (1) Diffuse optical tomography, collaboration with Prof. S. Hoshi, Department of
Biomedical Optics, Institute for Medical Photonics Research, Preeminent Medical Photonics
Education & Research Center, Hamamatsu University School of Medicine, and with Assoc. Prof. H.
Fujii, Faculty of Engineering, Hokkaido University.
(2) For the topic of (3) Fluorescence tomography, collaboration with Assis. Prof. G. Nishimura, ResearchInstitute for Electronic Science, Hokkaido University.
(3) For the topic of (4) Noninvasive measurement of blood glucose contents (BGC) by NIRS,
collaboration with Dr. K. Maruo, Panasonic Healthcare co. Ltd.
(4) For the topic of (5) Aspiration detection using fluorescence, collaboration with Dr. Y. Michiwaki ofMusashino Red Cross Hospital (MRCH) and Assis. Prof. G. Nishimura, Research Institute forElectronic Science, Hokkaido University.
(5) For the topic of (6) noncontact measurement of temperature and concentration distributions ofaqueous solution, collaboration with Prof. N. Kakuta of Tokyo Metropolitan University.

5. Outreach activities
5.1 Paper review of academic journals(1) Optical Review(2) Biomedical Optics Express(3) Journal of Biomedical Optics(4) Physics in Medicine and Biology

5.2 Other outreach activities(1) Visiting Professor, Faculty of Engineering, Nihon University(2) Visiting Researcher, Health Research Institute, National Institute of Advanced Industrial andScientific Technology (AIST)17

Haruki NIWA Laboratory
1. Outline of Research and Education
1.1 Basic Policy in Research and Education(1) Development of bioluminescent substrates emitting near-infrared "biological optical window" light.
Bioimaging that utilizes the firefly bioluminescence system (Fig. 1) is widely applied as the standard
imaging technology in bioscience for visualizing various phenomena. Light in the near-infrared (NIR) region
from about 650 nm to 1200 nm is known as the "biological optical window”; light in this region is highly
tissue-permeable and thus optimal for visualizing deep site phenomena. However, the bioluminescencewavelength (max) using natural D-luciferin (1) and synthetic D-luciferin analogs such as CycLuc1 (3) isshorter than 610 nm, and there are no practical substrates emitting in the NIR biological optical window thatis suitable for visualizing deep site phenomena. Efforts to elongate the bioluminescence emission
wavelength are being actively pursued all over the world. There are two approaches for controlling theemission wavelength, one approach targets the luciferase enzyme and the other targets the substrate luciferin.
We aim to develop a practical firefly bioluminescent material that emits light in the NIR biological optical
window region by changing the chemical structure of the substrate.

Figure 1. Bioluminescence reaction of firefly.
(2) Development of a non-invasive pulmonary aspiration risk detection system that utilizes NIR biological
optical window light.
One of the main causes of death among elderly people is pneumonia. More than 90% of pneumonia inelderly people is caused by pulmonary aspiration (mis-swallowing). As a cause of pulmonary aspiration, it
is reported that ingested food unconsciously remains in the junction of the esophagus and the trachea(piriform sinus located in the laryngeal cavity) and flows into the trachea. Therefore, if the remnant foodresidue in the piriform sinus can be detected at an early stage, the risk of pulmonary aspiration can bedetected, leading to the prevention of pulmonary aspiration. However, there is no simple practical device

18and method for non-invasive detection of the remnant food residue in the piriform sinus leading toaspiration from outside the body. Therefore, we aim to develop a noninvasive and simple system fordetecting food remains in the piriform sinus using fluorescence in the NIR biological optical window withhigh tissue permeability.
(3) Brain Science Inspired Life Support Research Center (BLSC) Spring School for high school students.
As part of the outreach activities of BLSC, we operate the Spring School every year, so that high school
students can gain experience at the forefront of brain science research.

1.2 Achievements and State of Progress (April 2016–March 2017)(1) Development of bioluminescent substrates emitting near-infrared "biological optical window" light.
The previously developed firefly bioluminescent substrate "AkaLumine" that emits light in the NIR"biological optical window" has an emission wavelength (max 677 nm) applicable for deep site bioimaging(Ref. 1). However, AkaLumine was found to possess poor water solubility (<2 mM), which is inconvenient
for practical use in vivo. We, therefore, developed AkaLumine hydrochloride [AkaLumine-HCl (2);solubility: <40 mM] and evaluated its bioluminescence performance using cancer-cell bearing miceinoculated with firefly luciferase-expressing lung cancer cells. When AkaLumine-HCl (2) was used as thebioluminescent substrate, more light was detected on the mouse body surfaces in comparison with
D-luciferin (1) (max 577 nm) or a synthetic luciferin analog CycLuc1 (3) (max 603), indicating that
AkaLumine-HCl (2) is more effective for deep site bioimaging than D-luciferin (1) and CycLuc1 (3) (Ref.2).

1(D-luciferin)

2(AkaLumine hydrochloride)3(CycLuc1)(2) Development of a non-invasive pulmonary aspiration risk detection system that utilizes NIR biological
optical window light.
Simulation experiments for the detection of remnant food residue in the piriform sinus by utilizing hightissue-permeable NIR region (biological window) light were carried out in a joint study. NIR fluorescencefrom samples containing a fluorescent dye could be detected through a biological tissue model of more than
2 cm thickness.
(3) BLSC Spring School for high school students.
In March 2017, the second “Brain Science Life Support Research Center Spring School” was held over 4
days. The lecture and experiment for each subject took 4.5 h (3 school h) per day for 2 days. In the Spring
School, the students tackled two subjects at the forefront of brain science research, supported by the19instructors and teaching assistants. The titles of the lectures and experiments, schedules, and participants areasfollows.

DetailsoftheSpringSchoolarelistedonthecenter's

homepage(http://blsc-uec.net/wpblsc/wp-content/uploads/ReportBLSC-SpringSchool2017.pdf).

1.3 Future Plans(1) Development of bioluminescent substrates emitting NIR "biological optical window" light.
We will continue the development of new bioluminescent substrates with the enhanced brightness andimproved water solubility when compared with AkaLumine-HCl (2).
Furthermore, we eager to develop new bioluminescent substrates emitting NIR light in "the second
biological optical window (>1000 nm)"; the light in this region is more tissue-permeable than the first
biological optical window (650–700 nm) light and should be optimal for visualizing deep site phenomena.
(2) Development of a non-invasive pulmonary aspiration risk detection system that utilizes NIR biological
optical window light.
We will continue the collaborative study on the construction of a noninvasive aspiration risk detection
system.
(3) BLSC Spring School for high school students.
We will continue to implement the Spring School with new titles.

2. Research Achievements
2. 1 Reviewed papers [〇: Impact factor greater than 4](1) Masahiro Kiyama, Ryohei Saito, Satoshi Iwano, Rika Obata, Haruki Niwa, Shojiro A. Maki Multicolor
Bioluminescence Obtained Using Firefly Luciferin. Current Topics in Medicinal Chemistry 16 (24)2648-2655, 2016.
(2) Takahiro Kuchimaru, Satoshi Iwano, Masahiro Kiyama, Shun Mitsumata, Tetsuya Kadonosono, Haruki
Niwa, Shojiro Maki, and Shinae Kizaka-Kondoh A luciferin analog achieves highly sensitive
deep-tissue imaging using near-infrared bioluminescence. Nature Communications 7, 11856-, 2016.

3. Research funding
None

4. Collaboration
4.1 Inside BLSC
(1) Shojiro Maki: Development of a non-invasive pulmonary aspiration risk detection system that utilizes
NIR biological optical window light (2015~).

20

4.2 Outside UEC(1) Dr. Yukihiro Michiwaki (Japanese Red Cross Musashino Hospital):
Development of a non-invasive pulmonary aspiration risk detection system that utilizes NIR bi
ological optical window light (2015~).
(2) Assistant Professor Goro Nishimura (Hokkaido University):
Development of a non-invasive pulmonary aspiration risk detection system that utilizes NIR bi
ological optical window light (2016~).

5. Outreach activities
5.1 Other outreach activities(1) Part-time lecturer of Department of chemistry, Graduate school of Science, Toho University.

21

Shojiro MAKI Laboratory
1. Outline of Research and Education
1. 1 Basic Policy in Research and Education
Our principle is “innovation of optical in vivo imaging by artificial luciferins” for future life science
technology. Our principles also include “Orphan Drug” development which is high risk and may be avoided
by researchers.
“Cancer Eradication (anti-cancer)” and “Practical Applications of Regenerative Medicine” are the mostimportant goals in life science research. It’s no exaggeration to say that these are universal targets.

Deep

tissues are challenging for optical imaging technology. MRI, CT, and X-ray are good for in vivo imaging,
however they do not have as high a resolution as optical imaging. Many top scientists think that R&D ishindered by today’s resolution limits. Whereas optical imaging has high resolution, it is hardly suitable fordeep tissues because the wave number (ca. 560-630 nm) is too short for deep tissue imaging using traditional
methods.
So, our challenge
is to innovate an NIR(near infrared) probe
andpractical

applications. It is moresuitableforbioluminescent probes
than fluorescent probes
becausebioluminescencedoes

not require irradiation.
Researchers need NIR
bioluminescent probes
for imaging cancer cells and/or graft cells in regenerative medicine research. In traditional technology, thenatural firefly (ca. 560 nm) and the sea firefly (ca. 480 nm) are employed as bio-luminescent probes and are
ill-suited for imaging deep tissues. Top scientists long for a modified NIR emission using a man-made probe
based on the firefly bioluminescence system.
Recently, top scientists wish to observe medium or large animals for practical application ofregenerative medicine. To promote research, a bio-optical (650-900 nm) light with high permeability of bodytissue is needed. The technology race is very hot in the world for optical in vivo imaging. In our lab, we havemarketed two NIR luciferins (“AkaLumine”: Wako Pure Chemical Industries, Ltd. and “Tokeoni”:
Sigma-Aldrich Co. LLC.). These are the only two luciferins sold as NIR luciferins in the world.

22

1.2 Achievements and State of Progress (April, 2016 - March, 2017)
We have innovated a new luciferin analogue “SeMpai” and solved the low solubility of “AkaLumine” (Wako Pure Chemical Industries, Ltd.) and the low pH problems of “TokeOni” (Sigma-Aldrich Co.
LLC.). Industrial production of “SeMpai” is in progress by KUROGANE KASEI Co., Ltd. We havesuccessfully performed in vivo optical imaging of a miniature swine using “TokeOni” as a probe.

1. 3 Future Plan
We will develop technology for in vivo optical imaging of miniature swine by optimization of probe,
animal, and instrument. We strive to innovate a system for high-performance in vivo optical imaging.

2. Research Achievements
2. 1 Reviewed papers [〇: Impact factor greater than 4](1) Shuji Ioka, Tsuyoshi Saitoh, Satoshi Iwano, Koji Suzuki, Shojiro Maki, Haruki Niwa, Atsushi Miyawaki,
Masaya Imoto, Shigeru Nishiyama Synthesis and evaluation of the luminescent properties of firefly
luciferin analogues. Chemistry, A European Journal 22, 1-9 (2016).
(2) Takahiro Kuchimaru, Satoshi Iwano, Masahiro Kiyama, Shun Mitsumata, Tetsuya Kadonosono, Haruki
Niwa, Shojiro Maki, and Shinae Kizaka-Kondoh, A luciferin analog generating near-infraredbioluminescence achieves highly sensitive deep-tissue imaging. Nature Communications 7, 11856 (2016).

23

(3) Yoshihisa Suzuki, Minoru Yamaji, Shojiro Maki, Takashi Hirano Enhanced brightness of
2,6-diphenylthiazolo[4,5-b]pyrazines by introducing double electron donating groups. Journal of
Photochemistry and Photobiology A: Chemistry 314, 93-95 (2016).
(4) Masahiro Kiyama, Ryohei Saito, Satoshi Iwano, Rika Obata, Haruki Niwa, Shojiro Maki Multicolor
bioluminescence obtained using firefly luciferin. Current Topics in Medicinal Chemistry 16 (24),2648-2655 (2016).
(5) Sojiro Hachiya, Daisuke Hashizume, Hiroshi Ikeda, Minoru Yamaji, Shojiro Maki, Haruki Niwa,
Takashi Hirano, Spectroscopic properties of BF2 complexes of N-(5-phenyl-2-pyrazinyl) pivalamides
exhibiting fluorescence in solution and solid state. Photochemistry and Photobiology A: Chemistry 311,
206-214 (2016)(6) Shuji Ioka, Tsuyoshi Saitoh, Satoshi Iwano, Koji Suzuki, Shojiro A. Maki, Atsushi Miyawaki, Masaya
Imoto and Shigeru Nishiyama Synthesis of firefly luciferin analogues and evaluation of the luminescent
properties. Chemistry A European Journal 22 (27), 9330–9337 (2016).

2.2 Book, non-refereed articles and translation(1) Hidenori Kato and Shojiro Maki Development of NIR luciferin. Bio industry, 33 (10), 22-27 (2016).
(2) Shojiro Maki Firefly Bioluminescence toward to in vivo imaging. The Journal of Japan Society for
LASER surgery and medicine 37 (4), 448-453 (2017).

2.3 Invited lectures(1) Shojiro Maki, “Innovation of firefly bioluminescence for NIR in vivo imaging probe” The 12th
International Symposium on Organic Reactions and the 6th German-Japanese Symposium on
Electro-synthesis, Kyoto, Japan, April 22-24 (2016).
(2) Shojiro Maki, “Chemistry of firefly bioluminescence”, Industry-UCB-UEC-Workshop 2017
(IUUWS2017), Tokyo, Japan, March 27-28 (2017).
(3) Shojiro Maki, “Realities of the research of practical application for top of the word technology”, 40th
Symposium on Electro-Organic Chemistry, Meeting for Young Scientists, Nigata, June 24 (2016).
(4) Shojiro Maki, “Discovery of imaging technology by firefly bioluminescence”, 50th Symposium of
kougaku5-kansai.org, Osaka, December 11 (2016).
(5) Shojiro Maki, “Discovery of imaging technology by firefly bioluminescence”, 3rd IPU Minato Mirai
Symposium, Yokohama, February 20 (2017).

2.4 Media release(1) Press Release ”First Development of NIR Luciferin for in vivo imaging” June 14 (2016).
(2) “Development of NIR Luciferin”, The Chemical Daily, June 15 (2016).
(3) “Development of Luciferin having 40 folds up brightness”, The NIKKAN KOGYO SHIMBUN, LTD.,
June 24 (2016).
(4) ”First Development of NIR Luciferin for in vivo imaging”, UEC Social media, July 25 (2016).
(5) “Luciferase gets deep and sensitive”, Nature Methods, 13, 615 (2016).

24

(6) “Cancer cell is emitted. Live Swine Imaging succeeded”, The NIKKAN KOGYO SHIMBUN, LTD.,
February 20 (2017).

2.5 Patent(1) P2017-063253 “A new coelenterazine analogue”
Inventor：Masahiro Kiyama, Shojiro MAKI，Takashi Hirano, Satoshi Iwano, Atsushi Miyawaki．
Applicant: RIKEN, Institute of Physical and Chemical Research, The University ofElectro-Communications
Date of application: March 28, 2017

2.6 Productization(1) “TokeOni” Kurogane Kasei Co. Ltd., Sigma-Aldrich Co. LLC. (2016~)

2.7 Award(1) Nobuo Kitada, JSPS Fellowships for Japanese Junior Scientist April 2016.
(2) Nobuo Kitada, poster award (Society of Bioluminescence & Chemiluminescence) February 2017.
(3) Nobuo Kitada, Best Student Award (The University of Electro-Communications)

2.8

March 2017

Student guidance(1) Yoshifumi Hachiro, 2016, Bachelor (engineering)(2) Narumi, Higashi, 2016, Bachelor (engineering)

2.9 Study abroad programs for students(1) Ryohei Saito, University of California Berkeley (Cell engineering, G. Marriott lab.) 2016. 10- 2017.3

3. Research funding
3.1 Grant-in-aid for scientific research(1) Shojiro Maki (allot) ”resonance Bio-imaging”, 3704, 2015-2019, total 20,000: yen (Grant-in-Aid for
Scientific Research on Innovative Areas)

3.2. Competitive external research funding(1) Shojiro Maki (allot) “Practical application of in vivo imaging material for deep inside body (AS2614119N)” A-step (Ministry of Education, Culture, Sports, Science and Technology, Japan) 2014-2016,
total: 34,460,000 yen(2) Shojiro Maki (representative) “Practical application of imaging material”, Kurogane Kasei Co., Ltd.
2012-current, 500,000 yen annually.

25

4. Collaboration
4.1 Inside BLSC
(1) Prof. Atsushi Nakamura “Innovation of in vivo optical imaging technology without transgenic”

4.2 Outside UEC(1) Prof. Tsuyoshi Saito, Prof. Masaya Imoto, Prof. Koji Suzuki, Prof. Rika Obata, Prof. Shigeru
Nishiyama, Tsukuba University and Keio University “Study of imaging material” 2014 July – current(2) Mr. Hidenori Kato, Kurogane Kasei Co., Ltd., “Innovtion & Practical Application of NIR firefly
luciferin” 2012 April – current(3) Prof. Shotaro Yamano, The Cancer Institute Of JFCR, “Development of in vivo imaging material”,
2014 October - current(4) Prof. Yoshihiro Miwa, Tsukuba University,”Study of imaging technology by new firefly luciferin”,
2014 April – current(5) Prof. Shinae Kondo and Prof. Takahiro Kuchimaru, Tokyo Institute of Technology “Development ofin vivo imaging technology”, 2014 April – current(6) Prof. Kazuhiro Chiba, “Study of bio-imaging material”, 2015 Augst – current(7) Prof. Kenji Hirayama, Nagasaki University, “Dynamics study of in vivo imaging material in livebody”, 2015 November – current(8) Prof. Rika Numano, Toyohashi University of Technology, “Study of firefly imaging material”, 2015
November – 2017 November(9) Dr. Yoshiyuki Ito, JEOL Ltd. “New aspect for instrumental analysis”, 2016 December – current
NDA (Non-disclosure agreement)(1) Prof. Ken Annoura, National Institute of Infectious Diseases, Japan, “About NIR imaging material”,
2014 January – current(2) Dr. Hiroyuki Sato, Perkin Elmer Japan, Co., Ltd. “Study of imaging material”,
2017 March – current
MTA (Material transfer agreement)(1) Prof. Rika Numano, Toyohashi University of Technology, “Study of firefly imaging material” 2012
December - unlimited

5. Outreach activities
5.1 Extension lectures(1) Extension lecture for children (experimental class, Shibuya-ku, Tokyo), 11 June 2016
(2) Extension lecture for children (experimental class, The University of Electro-Communications), 25
July, and 2 August 2016(3) School visit. Kakegawa Nishi Shizuoka Prefectural High School, Shizuoka, 7, September 2016(4) School visit. Tachikawa International High School, Tokyo, 6, October 201626

(5) Extension lecture for children (experimental class, Shibuya-ku, Tokyo), January 2017(6) Spring School for High School Students, (The University of Electro-Communications), 27-30 March,
2017

5.2 Other outreach activities(1) Research and education at other universities Expert Network Investigator Science and Technology
Foresight Center of National Institute of Science & Technology Policy (NISTEP)(2) Scientific Support Programs for Cancer Research, Grant-in-Aid for Scientific Research on Innovative
Areas, Ministry of Education, Culture, Sports, Science and Technology(3) Executive Board Member (Society of Electro Transfer Chemistry)（2008- current）

27

Kazuto MASAMOTO Laboratory
1. Outline of Research and Education
1. 1 Basic Policy in Research and Education
The goal of our research is to elucidate the cellular mechanism of neurovascular communications inmaintaining appropriate balances of energy supply-demand in the brain. To achieve this goal, we areworking to develop new imaging and analytical methods to capture and quantify the long-term changes incellular networks in the neurovascular unit. By using live imaging techniques with two-photon laser
scanning fluorescence microscopy, we are trying to understand the structural and functional plasticity of theneurovascular unit in both healthy and disease condition. This is critically important to prevent and manage
neurodegenerative disorders, such as Alzheimer’s disease and age-dependent cognitive declines.
In our laboratory, an experimental animal model with chronic hypoxia exposure has been used todevelop new imaging and analysis techniques and to test their feasibility for understanding a large volumeof the cellular structures and functions in in vivo mouse brains. Chronic hypoxia is the condition underwhich the animals were exposed to low oxygen environment, such as 8-9% oxygen in nitrogen balanced, up
to 2-3 weeks continuously. This is the minimum condition of oxygen availability that the animal can survive
by adjusting their physiological states. It was well-characterized that the hypoxia-induced adaptation ofbrain vasculature completes within 3 weeks of hypoxia induction. Hypoxia is one of the strongest stimulant
to provoke morphological and metabolic changes in the brain and is involved in pathogenesis of many brain
diseases, such as cerebral ischemia and hypoperfusion.
The experiments have been carried out by using several transgenic mice that express fluorescentproteins in neurons, glia, and vascular cells, while the imaging was performed using two-photon microscopy
through a closed cranial window (3-4 mm in diameter) according to a Tomita-Seylaz method, made on thecortex. The animals were housed in a hypoxic chamber to expose hypoxia (8-9% oxygen), and follow-up
imaging was repeatedly performed at the same cortical location. The image was typically captured over 0.5
mm by 0.5 mm areas and depths up to 0.8 mm from the cortical surface. The blood plasma andastrocyte/oligodendrocyte were labeled with intraperitoneal injection of sulforhodamine 101 (10 mM insaline, 8 mL/kg body weight). The images captured were three-dimensionally reconstructed andquantitatively analyzed using custom-written Matlab software.

1.2 Achievements and State of Progress (April, 2016 - March, 2017)
First of all, we showed that microglia, one of glia in the brain, participate in growth and connection of
new capillaries formed under chronic hypoxia. This finding is novel, while microglia in the rodent cortex iswell-defined as an active player to monitor and modulate neural synaptic connections. Our results first time
showed that the microglia is also an active player that reconstruct the cortical vascular networks in the adultbrains.
Secondly, we successfully characterized that the cerebral blood flow (CBF) response to neural andastrocyte stimulation has different signaling pathways, depending on the neural circuits evoked. This work
was a collaborative work with Professors Norihiro Suzuki and Kenji F Tanaka in Keio university school of28

medicine, Japan. We used transgenic mice that express photosensitive cation channel (i.e.,channelrhodopsin-2; ChR2) in either cortical neurons under muscarinic acetylcholine receptor (mAChR) M4
and astrocytes, and compared the CBF responses to photostimulation to them using laser speckle flowgraphy.
Also, we topically applied several drugs over the stimulated cortex to identify signaling pathways involvedin this process of the CBF responses. The response of CBF to the ChR2-neuron stimulation was shown to belocalized over the irradiated spot, whereas the CBF response to the ChR2-astrocyte stimulation showed arather widespread increase. This observation is partly supported by the result of pharmacologicalmanipulation on the CBF response to photostimulation.
Thirdly, we newly established hemodynamic measurement tools for human brain microcirculation
under neurosurgery and the capillary-level hematocrit changes using green fluorescence protein(GFP)-labeled red blood cells (RBCs) in the transgenic rats. These results were presented at Japanese
microcirculation conference held in Toyama at the end of March, 2017.

1. 3 Future Plan
For in vivo microscopic imaging, we will introduce a series of new transgenic animals that allow forreal time in vivo imaging of cellular activities with a high sensitivity. For acquired images of the brain cells
and microvessels, we will work to develop an image-based quantitative method for 3d reconstruction imagesof the cellular and vascular morphology. In addition to these technical improvements, new animal models toassess behavior and cognitive functions of the animals as well as to explore these plastic changes inneurovascular unit during physical or optogenetic activation of cerebral blood flow.

2. Research Achievements
2. 1 Reviewed papers [〇: Impact factor greater than 4](1) Kanno I, Seki C, Takuwa H, Jin ZH, Boturyn D, Dumy P, Furukawa T, Saga T, Ito H, Masamoto K.
Positron emission tomography of cerebral angiogenesis and TSPO expression in a mouse model ofchronic hypoxia. Journal of Cerebral Blood Flow and Metabolism. 2017 Jan 1 (in press)(2) Ito H, Takuwa H, Tajima Y, Kawaguchi H, Urushihata T, Taniguchi J, Ikoma Y, Seki C, Ibaraki M,
Masamoto K, Kanno I. Changes in effective diffusivity for oxygen during neural activation anddeactivation estimated from capillary diameter measured by two-photon laser microscope. The Journal of
Physiological Sciences 67(2):325-330. (2017)(3) Hoshikawa R, Kawaguchi H, Takuwa H, Ikoma Y, Tomita Y, Unekawa M, Suzuki N, Kanno I,
Masamoto K. Dynamic Flow Velocity Mapping from Fluorescent Dye Transit Times in the Brain Surface
Microcirculation of Anesthetized Rats and Mice. Microcirculation. 23(6):416-425. (2016)(4) Masamoto K, Hoshikawa R, Kawaguchi H. Fluorescence Imaging of Blood Flow Velocity in the Rodent
Brain. Current Topics in Medicinal Chemistry 16(24):2677-2684. (2016) Review(5) Unekawa M, Tomita Y, Masamoto K, Toriumi H, Osada T, Kanno I, Suzuki N. Dynamic diameter29

response of intraparenchymal penetrating arteries during cortical spreading depression and elimination ofvasoreactivity to hypercapnia in anesthetized mice. Journal of Cerebral Blood Flow and Metabolism
37(2):657-670. (2017)(6) Nishino A, Tajima Y, Takuwa H, Masamoto K, Taniguchi J, Wakizaka H, Kokuryo D, Urushihata T,
Aoki I, Kanno I, Tomita Y, Suzuki N, Ikoma Y, Ito H. Long-term effects of cerebral hypoperfusion onneural density and function using animal model of misery perfusion. Scientific Reports 6, 25072 (2016)(7) Sudo H, Tsuji AB, Sugyo A, Takuwa H, Masamoto K, Tomita Y, Suzuki N, Imamura T, Koizumi M,
Saga T. Establishment and evaluation of a new highly metastatic tumor cell line 5a-D-Luc-ZsGreen
expressing both luciferase and green fluorescent protein. International Journal of Oncology
48(2):525-532 (2016)

2.2 Book, non-refereed articles and translation(1) Nishijima Y, Akamatsu Y, Masamoto K, Liu J. Chapter 19 - Vascular remodeling after cerebral ischemia.
(Caplan LR, Biller J, Leary MC, Lo EH, Thomas AJ, Yenari M, and Zhang JH, eds. Primer on
Cerebrovascular Diseases, Second Edition. San Diego: Academic Press). (2017/03/18).
(2) Masamoto K, Hirase H, Yamada K. Preface. Progress in Brain Research 225:xv. (2016)(3) Kanno I, Masamoto K. Bridging macroscopic and microscopic methods for the measurements of cerebral
blood flow: Toward finding the determinants in maintaining the CBF homeostasis. Progress in Brain
Research 225:77-97 (2016)(4) Masamoto K, Hirase H, Yamada K, Kanno I. Neurovascular coupling-What next? Progress in Brain
Research 225:269-272 (2016)

2.3 Invited lectures(1) Masamoto K: Optogenetic investigation of blood flow regulation in the brain: toward understanding therole of neurogenic and gliogenic control of cerebral microcirculation. The 10th Asia-Pacific Laser
Symposium (APLS 2016) May 11-14, Jesu island, Korea(2) Masamoto K, Kanno I, Tomita Y, Suzuki N: Cerebral microvascular restructuring and microglial
adaptation to chronic hypoxia in the animal models. The 41th Annual Meeting of Japanese Society for
Microcirculation (2016.09.23) Kokuyo hall, Tokyo(3) Masamoto K: Astrocytic regulation of cerebral blood flow. Optogenetics 2016 (2016.09.29) Keio
University, Tokyo(4) Masamoto K: Four-dimensional imaging of neurovascular unit by in vivo two-photon microscopy.
Oxygen Dynamics seminar (2016.1014) Nihon University, Fukushima(5) Masamoto K: Chronic microscopic imaging of neurovascular units. The 23th Tohoku Cerebral Blood
Flow conferences (2016.11.19) Koyo Grand hotel, Miyagi(6) Masamoto K: Optogenetic perturbation of glio-vascular coupling in the mouse cerebral cortex. The 39th30

Annual Meeting of the Molecular Biology Society of Japan (2016.12.2) Pacific Yokohama, Kanagawa

2.4 Award(1) The Best Presentation Award: Sugashi T, Yoshihara K, Hachiya R, Takuwa H, Kanno I, Tomita Y,
Suzuki N, Masamoto K: Morphological analysis of 3D in vivo images by correcting inhomogeneity of
optical resolutions. Symposium on Fuzzy, Artificial Intelligence, Neural Networks and Computational
Intelligence in Osaka (FAN 2016), (2016.10.27), Osaka University, Osaka

2.5

Student guidance(1) Masahiro Nitta, M.Eng 2016(2) Hiroya Yuki, M.Eng 2016(3) Satoshi Sasaki, B.Eng 2016(4) Nao Hatakeyama, B.Eng 2016
(5) Ryota Hachiya, B.Eng. 2016

3. Research funding
3.1 Grant-in-aid for scientific research(1) Kiban C (H28-30) Understanding the role of cerebral angiogenesis and blood flow enhancer against thecognitive decline. (PI: Masamoto K)

4. Collaboration
4.1 Inside BLSC
(1) Miyawaki’s laboratory(2) Kano’s laboratory

4.2 Outside UEC(1) National Institute of Radiological Sciences, Department of Functional Brain Imaging Research(2) Keio University, School of Medicine(3) Hirosaki University, Graduate School of Medicine and School of Medicine(4) Osaka University, Graduate School of Engineering Science(5) Tokyo Metropolitan Geriatric Hospital(6) Edogawa Hospital(7) Korean Brain Research Institute

5. Outreach activities
5.1 Editor of academic journals(1) Editorial Board: Journal of Cerebral Blood Flow and Metabolism(2) Editorial Board: Japanese Society of Cerebral Blood Flow and Metabolism

315.2 Paper review of academic journals(1) Journal of Cerebral Blood Flow and Metabolism(2) Cerebral Blood Flow and Metabolism(3) NeuroImage(4) Brain Research(5) Medial Physics(6) International Journal of Numerical Methods in Biomedical Engineering(7) Journals of the Japan Society of Mechanical Engineers

32

Yoichi MIYAWAKI Laboratory
1. Outline of Research and Education
1. 1 Basic Policy in Research and Education
Representation of sensory and perceptual information in the human brain
We receive sensory information by seeing,
hearing, and touching the physical world. Sensory
information propagates to the brain and yields ourperception.

Althoughsensory/perceptual

weperform

informationthese

processing

naturally and smoothly in the daily life, such tasks
are very hard for machines to perform even withthe state-of-art technologies.
Our laboratory aims to elucidate how thehuman brain processes and represents sensory andperceptual information so naturally and smoothly
Figure 1: Experiments using fMRI system

by performing psychophysical experiments and(ATR-Promotions BAIC).

human brain imaging.
Our

psychophysicalexperiments

uses

systematically-controlled sensory stimuli (mainly in visual,auditory, and tactile domains) and quantifies perceptual
contents of human observes of the stimuli. Stimuli andbehavioral responses are analyzed with techniques such as
statistics, information theory, and system identification.
Human brain imaging is also a major part ofresearch

activity

psychophysical

in

our

laboratory

as

well

as

experiments.

Particularsensory

andperceptual experience corresponds to particular activity
pattern of the human brain. Thus, objective measurement
and analysis of brain activity patterns is promising
approach to unveil subjective sensory and perceptual

Figure 2: Experiments using MEG system

experience. We mainly use functional magnetic imaging(ATR-Promotions BAIC).

(fMRI) and magnetoencephalography (MEG) to measure
human brain activity noninvasively. fMRI measures signals related to blood flow changes associated withneural activity in the brain with high-spatial resolution, whereas MEG measures magnetic field signals
generated by neural current in the brain with high-temporal resolution. We choose either of these methods or
combine both depending on the purpose of experiments.

33

Computational analysis of brain activity patterns
Human brain activity is a large-scale high-dimensional data. Standard measurement of fMRI and MEG
signals consists of 104-5 –dimension data points per every second. Conventional analysis focused on only
limited aspects of such data set and information contained in the rest were simply discarded or ignored. For
example, a typical method of fMRI data is toperform statistical tests on intensity changes infMRI signals for each single brain location
independently. The method does not consider
correlational information between multiple
brain locations, although fMRI signals at 105
different

brain

locationsareobtained

simultaneously.
Our laboratory uses novel methods that
exploit as much as information contained in thelarge-scale high-dimensional brain activity data.
Machine learning is one of such examples.
One example is analysis of brain activity
patterns using machine learning techniques. In
this method, brain activity are converted into
multidimensional

patterns

andFigure 3: Classification analysis using multivariatecomputersignal patterns.

programs are trained to learn statistical
relationship between the brain activity patterns and thecorresponding

experimental

conditions.

Close

investigations on learning processes and acquired
parameters of the computer programs provide
important clues for understanding of information
representation in the brain activity patterns while
taking correlational information between multiple
brain locations into account.
Application to medical engineering
The trained computer programs can be also used
to predict experimental conditions corresponding to

Figure 4: Retinotopy map identified in lower

given brain activity patterns. This feature is alsovisual cortex.

useful in designing brain-machine interface thattranslates human thoughts into machine commands.

By developing computer programs with highperformance in prediction, we will realize prosthetic limbs that can be controlled by human motor intention
and monitor systems that visualize what we are imagining in mind.

34

1.2 Achievements and State of Progress (April, 2016 - March, 2017)
Dynamics of neural representation of visual object categories
We can visually recognize objects quickly and accurately. Object recognition of human vision issuperior in its speed and accuracy to machine vision. It has been considered as one of the most difficult
function to realize by artificial systems. To elucidate how the human brain performs object recognition soquickly and accurately, we have conducted experiments that combine MEG and fMRI to achieve highresolution in temporal and spatial domains.
In this year, we proceeded with experiment based on the results obtained in the last year and succeededwith analyses of information of object category represented in the brain activity patterns of the specified
brain areas at the specified time. In particular, we found the temporal relationship between the level ofcategory abstraction and the representation time of the object category. In addition, we started to measureeye movement while a subject observes images and reveled its temporal characteristics.
Neural representation of tactile information
We can obtain spatial information of the external environment by touch as well as vision. We perform
fMRI experiments to measure brain activity patterns evoked by simple tactile stimuli given to the fingertips
to explore where and how tactile information is represented in the human brain.
In this year, we applied the searchlight method that enables us to examine information representation
over the whole brain as well as analyses based on the region of interests, to achieve hypothesis-free analysis
and evaluation.
Development of analysis tools and simulation methods
To analyze brain activity patterns effectively, it is also important to develop analysis tools andsimulation methods. In the previous year, we developed a method based on deep convolutional neuralnetwork to extract higher-order features contained in object images. In this year, we proceeded with thismethod to apply other data sets than object images used in our experiments.
In addition, we developed a statistical model that learns relationship between brain activity patterns andexperimental conditions while selecting only important brain areas as input features to the model. The modelis based on L0-norm optimization and succeeded in outperforming the previous models.
It is also important to identify source location corresponding to the measured MEG signals for the
analysis of MEG data. We developed a novel method to evaluate accuracy of MEG source localization andfound a new problematic phenomenon when MEG source localization and pattern classification analysis are
combined.

1. 3 Future Plan

Dynamics of neural representation of visual object categories
In addition to the analysis of relationship between the level of category abstraction and therepresentation time of object categories, we proceed with analysis of specificity of therepresentation time of each object category. We also proceed with experiments and analyses to35

examine relationship between eye movement and object recognition.
Neural representation of tactile information
We proceed with analyses to reveal where and how tactile information is represented in thebrain activity patterns. We are planning to use various types of tactile stimuli in addition to
those used previously.
Development of analysis tools and simulation methods
We proceed with image feature extraction using DCNN and other methods to analyze
relationship between extracted image features and brain activity patterns. In addition, we apply
L0-norm-optimized classification model and the evaluation method of MEG source
localization to real data and examine their methodological validity.

2. Research Achievements
2. 1 Reviewed papers [〇: Impact factor greater than 4](1)

Yoichi Miyawaki,“Analysis of human brain activity using sparse modeling,”
system/control/information, vol.61, no.4, pp.138 - 145 (2017).

(2)

Yoichi Miyawaki, “Multivariate analysis of magnetic resonance imaging signals of the human brain,”
Current Topics in Medicinal Chemistry, vol.16, pp.2685 - 2693 (2016).

2.2 Book, non-refereed articles and translation(1) Yoichi Miyawaki,“What are you seeing? Inside of your brain can be seen – neural information decoding:techniques to visualize mind from brain activity,”in Science of mind and brain from perspectives ofusual and unusual situations，eds. Makoto Miyazaki, Masaki Abe, Yuki Yamada, Corona publishing (inpress).

2.3 Invited lectures(1) Yoichi Miyawaki, “Study of visual image representation in human brain using neural decoding,” The
fifth MEET Young Cardiologists, Niigata University (Chuo-ku, Niigata) (October 10, 2017, scheduled).
(2) Yoichi Miyawaki, Noriki Ito, Masashi Sato, Yoshiyuki Kabashima, “Inferring informative brain areas
by sparse feature selection,” The 40th Japan Neurosceience Society，Makuhari Messe（Mihama-ku,
Chiba）(July 20 – 23, 2017, scheduled).
(3) Yoichi Miyawaki, “Analysis of brain activity using machine learning and mechanisms of humansensation and perception,” Plenary of engineers’ meeting of the University of Electro-Communications,
The University of Electro-Communications（Chofu, Tokyo）(July 16, 2017, scheduled).
(4) Yoichi Miyawaki, Masashi Sato, “Neural representation of perceptual experience revealed bymultivariate pattern analysis of human brain activity,” Industry-UCB-UEC Workshop 2017, The
University of Electro-Communications (Chofu, Tokyo), March 27 – 28, 2017.

36

(5) Yoichi Miyawaki, “Analyzing mechanism of brain and mid using information science,” Public lecturesof the University of Electro-Communications and the Yomiuri Shimbun, “Expanding future by advanced
technology of the 21st century: message from comprehensive communications sciences，The University
of Electro-Communications（Chofu, Tokyo），October 8, 2016.
(6) Yoichi Miyawaki, “Deciphering visual information represented by human brain activity patterns,”
Invited visit and talk at LIRMM/CNRS, Montpellier, France, June 27, 2016.

2.4 Media release(1) “電気通信大学・読売講座 詳報 - 脳活動から視覚解く” ，読売新聞 2016 年 10 月 15 日多摩
版 27 面(2) “電気通信大学・読売講座 – 人の夢 脳活動で判別” ，読売新聞 2016 年 10 月 9 日多摩版 22
面(3) “電気通信大学・読売講座 - 脳とこころ情報科学で解明” ，読売新聞 2016 年 10 月 7 日多摩版

2.5

Student guidance(1) Shota Eto，2016，Bachelor（Engineering）(2) Kazuaki Akamatsu，2016，Master（Engineering）(3) Noriki Ito，2016，Master（Engineering）(4) Megumi Nozaki，2016，Master（Engineering）

2.6 Visit of oversea researchers and students(1) Yu Aramaki ， Brain Science Inspired Life Support Research Center, Visiting Professor/Chukyo
University, Professor, Research theme: Analysis of neural information of athletes，2016/4－2017/3.
(2) Masashi Sato，Research fellowship for young scientists (DC2), Japan Society for the Promotion of
Science/Ph.D. students, Department of Mechanical Engineering and Intelligent Systems, Graduate
School of Informatics and Engineering，Research theme: Study of temporal structure of object category
representation in the human visual cortex，2016/4－2019/3.

2.7 Study abroad programs for students(1) Shotaro Fuchibe，LIRMM/CNRS, Montpellier University（André Crosnier’s lab.），2016/8－2016/10（International internship）.

3. Research funding
3.1 Grant-in-aid for scientific research(1) Yoichi Miyawaki（P.I.）, Analysis of human brain activity at high spatio-temporal resolution andidentification of informative brain areas using sparse modeling, KAKENHI Innovative Areas “sparsemodeling”, FY2016- FY2017.

37

(2)

Yoichi Miyawaki（Co-P.I.）, Controlling artificial limbs as own limb: natural learning of artificial limbs
using human brain activity, KAKENHI challenging Exploratory Research, FY2015- FY2016.

(3) Yoichi Miyawaki（P.I.）, Study of tactile information representation in the visual cortex using neural
decoding technique, KAKENHI (C), FY2014-FY2016.

3.2. Competitive external research funding(1) Yoichi Miyawaki（P.I.）, Research and development of fast object recognition algorithm based on neural
information representation, SCOPE, FY2014 – FY2016.
(2) Yoichi Miyawaki（P.I.）, Study of fast extraction of object recognition information from human brain
activity, Yazaki Memorial Foundation for Science and Technology, Specific Research Grant, FY2015 –FY2017.
(3) Yoichi Miyawaki（P.I.）, Development and application of high spatio-temporal resolution analysis ofhuman neural activity, The Naito Foundation, Research Grant, FY2015 – FY2016.

4. Collaboration
4.1 Inside BLSC
(1) Kazuto Masamoto, Image analysis of structural features of astrocytes, FY2015(2) Hiroshi Yokoi, Soichiro Morishita, Substitution of motor and communication functions using BMI（development of intelligent electric assistance devices for BMI control）, FY2013-

4.2 Outside UEC(1) Gowrishankar Ganesh, CNRS-AIST Joint Robotics Laboratory, CNRS - Institut des sciences del'ingénierie et des systèmes (INSIS)（university/national institute）, Controlling artificial limbs as own

limb: natural learning of artificial limbs using human brain activity, FY2015(2) Norihiro Sadato, Ryo Kitada, NIPS／SOKENDAI（national institute/university）, Study of tactile
information representation in the visual cortex using neural decoding technique, FY2014(3) Yukiyasu

Kamitani ， Kyoto

University ／ ATR

computational

neurosciencelaboratories（university/private company）, Study of tactile information representation in the visual cortex usingneural decoding technique, FY2014(4) Yoshiyuki Kabashima, Tokyo Institute of Technology（university），Development of L0-norm
optimization algorithm，FY2015-(5) Okito Yamashita, Masa-aki Sato, ATR computational neuroscience laboratories（private company）,
Study of MEG source localization, FY2015-

5. Outreach activities
5.1 Paper review of academic journals(1) Reviewer of Scientific reports(2) The 31st International Congress of Psychology (ICP2016) Program Committee(3) Review committee of the best presentation award of Vision Society of Japan 2016 winter meeting38

(4) Recommendation and selection committee of Japanese Neural Network Society

5.2 Other outreach activities(1) Board member of Japanese Neural Network Society(2) Board member of SIGTX of Virtual Reality Society of Japan(3) Lecture in Tochigi high school(4) Public lecture of the University of Electro-Communications and the Yomiuri Shimbun

39

Hayaru SHOUNO Laboratory
1. Outline of Research and Education
1.1 Basic Policy in Research and Education
Our main research field is in medical application using the technique in the artificial intelligence, such
like deep learning, sparse modeling, Bayesian inference and so on. In these years, our main research field isin a lot of ways of medical image application, lung thesis detection, classification, noise reducing in medical
image, PET or CT image reconstruction and so on. We solve these problems in one simple principle forward
and inverse model. The following figure shows a concept schematic diagram of the model. In the model, we
assume the observation data y comes from some hidden components x through the model described by theconditional probability p(y | x). So when we infer the hidden components x from the observed data y, we
should consider the inverse model p(x | y). In each forward and inverse model, we apply some machinelearning techniques. For example, considering the classification task of lung disease, we should extract
several effective components from the image data and evaluate the efficacy of each component.

1.2. Achievements and State of Progress (April, 2013 - March, 2016)(1) Classification of Diffuse Lung Disease with Deep Convolution Neural Network
Deep convolutional neural networks (DCNNs) are inspired from the vision system. The DCNN shows
good performance for the classification task in the field of computer vision and machine learning. In our40study, we train the DCNN using the transfer-style learning, which introduce some other domain’s
knowledge into the learning machine. In 2015, we propose reusing method of the feature extractor part in
the DCNN that is trained with massive natural images. The feature extractor for the natural image shows
improving the classification performances. In 2016, we extend the transfer style method in multiple stage.
At the first we train the DCNN with massive natural image. After that, we also train the DCNN with texture
dataset. And at last, we train the DCNN with the target CT image of diffuse lung disease. Now we obtain the
97.2% accuracy for the small dataset of the CT image.
(2) The relationship analysis for the DCNN with Network-in-Network (NIN).
In the DCNN architecture, the basic operations, which are called convolution and pooling operations,
repeat for obtaining a good feature representations. This mechanism was identical to the Fukushima's
Neocognitron. On the other hand, the importance on the interaction of feature extraction was ignored in the
network architecture. In these years, in order to embed the feature relationship, the Network-In-Network(NIN) structure has been proposed. We can consider the NIN as a embedding of translational symmetric
Perceptron into the feature extraction layer. The NIN is only proposed for improving classification
performance. We focused on the weight coupling of the Perceptron and interpreted what NIN means when
we define the neighborhood relation of cells to be extracted by this weight. As a result, in the lower level offeature extraction layer, NIN plays a role of emphasizing the similar orientation feature and depress theorthogonal feature. In the higher order layer, the NIN also emphasize similar curvature and suppress the
opposite side curvature. Moreover, the face like features are suppressed.
In the early visual area, such like V1 area in the monkey, the orientation continuity of the column isobserved. The cells which are responding to the similar orientations are assigned in the near position, andthe cell prefers opposite orientation are assigned in the further. This structure coincides to the NIN structure.
So that, the orientation continuity might have a meaning from the viewpoint of the classification.
(3) Feature selection using Monte Carlo method
In the field of machine learning such like classification and regression task, the feature selection is a
useful method not only improving the performance but also the estimating the statistical structure.
Especially, in the texture classification problem, estimating the efficient feature combinations is an
important problem. In order to estimate the statistical structure, we apply a Monte Carlo based method. The
Monte Carlo based method is an enumerated method, so it requires a lot of computational cost, however, we
can obtain the better feature combination rather than that of the other optimization method such like sparsemodeling based method.

1. 3. Future Plan
In our future plan, we integrate the component techniques into a system. In the next step we analyze thefeature in the DCNN, and design the effective feature. Currently, it is hard understanding what is happenedin the DCNN, so that interpretation of the representation in the DCNN is important task for understand thehidden components.

41

Moreover, our application for small database system might be applicable for another field application.
Thus, we are going to try to analyze some other field.
We also apply image restoration task for real application. Now we are going to apply the noise
reduction method into a positron emission tomography (PET) image reconstruction. The PET image is noisy
and clear image is desired for diagnosis.

2. Research Achievements
2.1 Non-refereed articles or translation(1) (invited) H. Shouno, A. Suzuki, S. Suzuki, and S. Kido，Deep Convolution Neural Network with
2-stage transfer learning for medical image classification. The Brain & Neural Networks, Vol.24(2017)
No.1 pp 3-12, (in Japanese), http://doi.org/10.3902/jnns.24.3(2) (invited) H. Shouno, S. Suzuki，An application of deep learing for medical image analysis,
Vol.33(2016), pp75-80, (in Japanese)(3) (invited) H. Shouno, Basic Technology for Sparse Modeling with Some Historical View, Vol.99(5),pp.376-380, (in Japanese)

2.2 Student guidance

4 undergraduate and 3 master course students

3. Research funding
3.1. Grant-in-aid for scientific research(1) Grant-in-aid for scientific research on Innovative Areas, MEXT, Japan, 16H01542 “Establishment ofsparse texture image analysis using deep learning”(2) Grant-in-aid for scientific research on Innovative Areas, MEXT, Japan, 26108002, "MultidisciplinaryComputational Anatomy and Its Application to Highly Intelligent Diagnosis and Therapy”(3) Grant-in-aid for scientific research (C), MEXT, Japan, 16K00328, “Development of algorithm forreconstruction of tomographic image using sparse basis”

4. Collaborators
None

5. Outreach activities
None

42

Shinji MATSUDA Laboratory
1. Outline of Research and Education
1. 1 Basic Policy in Research and Education
Research
Brains are composed from numerous number of neurons and Glial cells. The function of brains,
including higher brain functions, are mediated by the signal transduction between neurons. The signaltransduction between neurons are called synaptic transmission, and the efficiency of synaptic transmission
can be regulated by neural activities. This phenomena is called synaptic plasticity, which is thought to be thecellular basis for memory and learning. The molecular mechanisms for synaptic plasticity have been actively
studied all over the world.
I have been studied the molecular basis for the long-term depression (LTD) which is the one form of
the synaptic plasticity: the efficiency of synaptic transmission is reduced for a long term. Recently, I also
tried to develop the new technique to control LTD by light stimulation, and to directly examine therelationship between LTD and learning by using this technique. When the cerebellar LTD was blocked bylight by using this technique, motor learning was impaired. These results indicated that the cerebellar LTD
directly control the motor learning. Moreover, I also study the molecular mechanism of long term
potentiation (LTP) another form of synaptic plasticity, in which the efficiency of synaptic transmission isenhanced for a long term. I would like to also develop the controlling method for LTP.

Educations
I would like to bring up the students who can contribute to the progress of the science. For the
students in “Bioscience and Technology Program”, I am going to give lectures not only on neuroscience but
also on the basic biology.

Moreover, I will discuss with the students about how the basic knowledge of

biology can be obtained and how life should be studied in the future.
For the students out of the “Bioscience and Technology Program”, I am going to start with befundamentals on biology and move to the current knowledge. Recently, the fusion research between biology
and other fields are actively carried out. Therefore, students need to prepare for these studies even though
they will not be specialists for the biology.
For the students in my own laboratory, I would like to carry out the forefront research in theneuroscience field together with them. I also would like to bring up the top scientists who can contribute the43neuroscience. For this purpose, I will let them think research plan by themselves and let them carry out theirplans by themselves.

1.2 Achievements and State of Progress (April, 2016 - March, 2017)
Although it is well established that the LTD is induced by the clathrin mediated endocytosis of AMPA
receptors, it was unknown how clathrin can be recruited to the postsynaptica site by neuronal activities.
Until 2017, we have develop the new technique to control the induction of LTD by light stimulation in order
to directly examine the relationship between synaptic plasticity and learning. We have also generated knockin mouse, whose cerebellar LTD can be blocked by light stimulation. By using this mouse, we haveexamined whether the motor learning such as OKR could be affected by the light stimulation to the
cerebellum. The results indicated that the light stimulation significantly reduced the motor learning
efficiency of the knock in mouse, although these mice can normally learn the OKR in the absence of lightstimulations. These results indicated that the cerebellar LTD plays critical roles for certain kinds of motor
learning. I also contributed to generate the chemical labeling method for AMPA receptors.

1. 3 Future Plan
For the future direction, we are going to express Light-driven proton pump in various brain regions
and try to examine the relationship between LTD and learning process. We are going to express our proton
pump in cerebellum and block the cerebellar LTD at various timing, and we would like to examine therelationship between the timing of LTD induction and motor learning (Figure 2).

We would like to directly examine the relationship between cellular level phenomena, such as
synaptic plasticity and behavior of living animals such as memory and learning. By these approach, wewould like to contribute to the progress of neuroscience.

44

2. Research Achievements
2. 1 Reviewed papers [〇: Impact factor greater than 4](1) Wakayama S, Kiyonaka S, Arai I, Kakegawa W, Matsuda S, Ibata K, Nemoto YL, Kusumi A, Yuzaki M,
Hamachi I. Chemical labelling for visualizing native AMPA receptors in live neurons. Nature
Commun. 2017 Apr 7; 8: 14850. doi: 10.1038/ncomms14850.
2.2 Book, non-refereed articles and translation(1) Matsuda S, Yuzaki M. AP-4. Encyclopedia of Signaling Molecules 2nd Edition, Springer (2016).

2.3

Student guidance(1) Hiroki Yamazaki: M1(2) Rikako Ito, Shunichi Koga, Ryusuke Suzuki: B4

3. Research funding
3.1 Grant-in-aid for scientific research(1) JSPS KAKENHI Grant Number 17K07048

4. Collaboration
4.1 Outside UEC
Michisuke Yuzaki, Keio University、Molecular mechanisms and controlling of synaptic plasticity,2013~

5. Outreach activities
5.1 Paper review of academic journals(1) PLOS ONE reviewer

45

Takuji KOIKE Laboratory
1. Outline of Research and Education
1. 1 Basic Policy in Research and Education
In modern society, the importance of various information has increased each day, and the reduced
ability related to information exchange through hearing has impaired not only physical wellness but alsomental-health status. The impairment of ability brings disadvantage to both of individuals and the society
surrounding them. Thus, prevention of hearing loss, effective treatments, and construction of an inclusive
society are the most important issues in the modern society.
The auditory system consists of the external ear, the middle ear, and the inner ear (cochlea). The
cochlea is filled with lymph fluid, and the sensory cells exist on the basilar membrane which divides thecochlear duct.

Sounds travelling through the atmosphere are converted into the vibration of the lymph

fluid and perceived by the sensory cells. The middle ear serves as an impedance matching device between
the air and the lymph fluid and effectively transmits the sound energy to the cochlea. The ossicles aresupported in the tympanic cavity by ligaments and tendons to make it easier to vibrate. However, if these
ligaments and tendons are pathologically ossified, the ossicular vibration is restricted, and conductive
hearing loss occurs. If the cochlear functions and the auditory nerve functions are impaired, thesensorineural hearing loss occurs. In addition, mixed hearing loss in which both kinds of hearing loss are
mixed may occur.

Figure 1

Researches in audiology

46

The relationships between the changes in the vibrations in the auditory system and healing loss have notbeen fully clarified, because the auditory system exists intracranially and its vibration is in nanometer order.
Hence, we have investigated the mechanisms of auditory disorders and the methods for treatments
collaborating with the neighboring medical departments and hospitals. The topics are as follows:Modelling of the auditory systems; Clarification of the vibration of the auditory periphery and its
pathological changes, and development of the effective methods for treatment.



Measurement of auditory evoked response in fetus; Development of new hearing screening methods for
fetuses by measuring hart rate changes induced by the stimulus vibrations which are applied on thesurface of the abdomen of a mother.



Development of implantable bone conduction hearing aid; Hi-Fi and minimally invasive devices forbetter QOL.

Development of surgery assisting apparatus; Measurements of ossicular mobility during surgery.

1.2 Achievements and State of Progress (April, 2016 - March, 2017)(1) Modelling of the auditory systems
This research intends to clarify the mechanisms of hearing disorders and to develop better methods oftreatments, which are difficult to identify through clinical researches and specimens. Numerical cochlear
models in which the active motilities of the outer hair cells are considered have been constructed.
Simulations were performed using the models, and the vibrations of the lymph liquid and basilar membranein the cochlea were analyzed. Through the simulations, the transmission mechanisms in the peripheral
auditory systems have been clarified. As clinical applications, the mechanisms of hearing losses caused byotosclerosis and endolymphatic hydrops were investigated. The Outstanding Presentation Award was given
to the research from the Society for Bioacoustics.
(2) Measurement of auditory evoked response in fetus
Measurements of heart rate variability and brain waves induced by vibratory stimulation applied tomaternal abdominal wall were performed. Positive reactions were obtained from approximately 90% of the
fetuses with normal hearing which is confirmed after the birth.
(3) Development of implantable bone conduction hearing aid
A prototype of the bone-conduction hearing aid in which Giant Magnetostrictive Material is used as thevibrator was created. By improving the design of the vibrator and the method of transdermal signaltransmission, the device showed higher efficiency comparing to the existing bone-conduction hearing aid.
We got a European Patent for the basic specifications and operating function of the hearing aid and areworking with a company toward practical use of the new hearing aid.
(3) Development of surgery assisting apparatus
An apparatus for measuring ossicular mobility has been developed, and the ossicular mobility inpatients has been measured during tympanoplasty. This work was supported by Saitama Leading Edge

47

Project (Medical Innovation) in this year, and some prototypes were constructed and tested with the help of
medical equipment makers and medical institutions.

1. 3 Future Plan
With regard to the modeling of the auditory system, we have tried to construct more detailed models inwhich the ionic flux at the hair cells, the organ of Corti, gap junctions, the spiral ligaments, and the stria
vascularis are considered. Then, the mechanoelectrical transduction in the cochlea will be investigated using
the models.

We will also advance the developments of the implantable hearing aid and the apparatus formeasuring ossicular mobility toward commercialization.

2. Research Achievements
2. 1 Invited lectures(1) TAKANASHI Takuma，SAKAMOTO Hironori，SKALS Niels，FUKUI Shuji，MATSUI Yasuhiro，
KOIKE Takuji，NISHINO Hiroshi, Vibration sensitivity in longicorn beetles and biomimetic potential
for insect pest control, International Symposium on Engineering Neo-Biomimeteics VII, February 17(2017)(invited)

2.2 Patent(1) 2017-016331, System for evaluation of mobility and mobility evaluation method, Takuji Koike, Kai
Takakuwa, Yuka Irie, Sho Kanzaki, Chee Sze Keat, Takenobu Higo, Masaaki Hayashi, Univ. Electro
Communications, Keio Univ., Mechano Transformer Corp., Leadence Corp., Daiichi Medical Co.
(2) EP 2329802, Embedded audiphone, Takuji Koike, Naohito Hato, Kensei Yamamoto, Univ. Electro
Communications, Univ. Ehime.

2.3 Award(1) Sinyoung Lee, Outstanding Presentation Award, The Society for Bioacoustics, December 11, 2016
(2) Takuji Koike, JSME fellow 9141811.

2.4

Student guidance(1) Ryo Ebine, 2016 year, Bachelor(2) Takahiro Suzuki, 2016 year, Bachelor(3) Kenta Mito, 2016 year, Bachelor(4) Yohei Wagai, 2016 year, Bachelor(5) Nobutaka Hayashi, 2016 year, Bachelor(6) Sinyoung Lee, 2016 year, Master(7) Kai Takakuwa, 2016 year, Master48

2.5 Study abroad programs for students(1) Miho Sato, National Higher School of Mechanics and Microtechnology, Besanzon, France, Aug 22, 2016
– Sep 26, 2016.

3. Research funding
3.1 Grant-in-aid for scientific research(1) Takuji Koike, Grant-in-Aid for Scientific Research (C), 2015-2017

3.2. Competitive external research funding(1) Takuji Koike, Cross-ministerial Strategic Innovation Promotion Program, 2014-2017(2) Takuji Koike, Saitama Leading Edge Project (Medical Innovation), 2016

4. Collaboration
4.1 Outside UEC(1) Katsuhisa Ikeda, Department of Otorhinolaryngology, Jyuntendo University(2) Naohito Hato, Department of Otorhinolaryngology, Ehime University(3) Sho Kanzaki, Department of Otorhinolaryngology, Keio University

5. Outreach activities
5.1 Editor of academic journals(1) Journal of Biomechanical Science and Engineering, 2 years

5.2 Paper review of academic journals(1) Hearing Research(2) The Journal of the Acoustical Society of America(3) The Journal of the Association for Research in Otolaryngology(4) Acoustical Science & Technology

5.3 Other outreach activities(1) Scientific Committee, International Union of Theoretical and Applied Mechanics, Stuttgart, Germany,
2016

49

Yutaka KANO Laboratory
1. Outline of Research and Education
1. 1 Basic Policy in Research and Education
The loss of the muscle mass associated with non-active state such aging, bedridden or metabolic
disease (ex. diabetes) is a risk factor to be connected directly with Quality of Life (QOL) or health life
expectancy. However, adequate understanding is not obtained about the mechanism of the myocytes
adaptation to maintain muscle mass. This laboratory performs physiological analysis about biologicalresponse for various bio-stimulation (stress) in the locomotorium (skeletal muscle). The results ofresearch in our laboratory were demonstrated by in vivo bioimaging that we originally developed inrodent (rat, mouse) model. This research model attracts attention as the research model which isevaluable in intracellular molecules dynamics in real time by a living individual. The exercise acts onwhole body as combined vital stress. This stress is classified roughly into endogenous (including the
growth hormone) and exogenous (mechanical, hypoxia, heat) factors. Our research elucidates that thesevital stress factors change cytoplasmic ion balance and oxygen dynamics. The change of intracellularvarious ions and oxygen is important to elucidate an adaptation phenomenon of the skeletal muscle fiber.
Therefore, these basic research contributes to development of effective prophylaxis for the muscle
atrophy by bedridden/aging and development of the training method to maintain muscle mass.

1.2 Achievements and State of Progress (April, 2016 - March, 2017)
Our laboratory performed research subject about the homeostasis of the intracellular hydrogen ion+(H ) in this year. Most physiological processes are pH-sensitive, and pH within individual cells inskeletal muscles (pHi) must be carefully regulated to maintain normal cellular functioning. During
intensive exercise, and also in certain diseases, levels of a cationic form of hydrogen (H+) rise rapidly
within cells, causing pHi levels to plummet and become more acidic. There are three membranetransporters known to be involved in regulating pHi, but their precise individual roles are unclear.
Our research group conducted experiments using in vivo bioimaging models to verify the roles of thesetransporters in pHi regulation. The team tested the effects of an injection of H+ into single muscle fibers
in rats. They blocked each transporter involved in pHi regulation – namely, lactate/H+ cotransporter(MCT), Na+/ H+ exchange transporter (NHE) and Na+ / HCO3 cotransporter (NBC) – one at a time andthen all together. They compared their results with a control group with normal transporter functioning.
Their results showed that two stages exist in pHi recovery; an initial rapid stage followed by a second,
more gradual recovery stage. We discovered that the three transporters were not involved in the rapid
stage. While individual transporter inhibition did not impact on pHi recovery, blocking all threetransporters prevented the second stage (gradual recovery) from occurring.
The study also revealed that the pH of surrounding fibers changed following H+ injection, suggestingthat they take up excess H+ to alleviate stress in affected cells.

50

in vivo bio-imaging and muscle fiber function
Slow Fiber (TypeH+

Vascular

MCT1 andH+ utilization

CO2 + H2OInterstitium

H+ + HCO3)-

Transporters
H+ + B-

Fast Fiber (Type)

intracellular H+
buffering
H-B

1. 3 Future Plan
Currently, two research projects progress, 1: the new development of the Ca2+ evaluation procedure,
2: the evaluation of post-exercise Ca2+ dynamics. The new bioimaging method combined laser
microscope (2 photon and photothermal) with the in vivo model (Sonobe et al. 2008,2010, Eshima et al.
2013, 2015), and it is the highest system in the biology field (top efficiency of temporal, spatial
resolution). As a result, in addition to Ca2+ dynamics in cytoplasm, this method can evaluate Ca2+
dynamics with the endoplasmic reticulum - mitochondria simultaneously under in vivo environment.
This is the first in vivo animal experiment model highlighting regulatory mechanism of the Ca2+ at anorganelle level in myocytes.

2. Research Achievements
2. 1 Reviewed papers [〇: Impact factor greater than 4](1) Sudo M, Ando S, Kano Y. Repeated blood flow restriction induces muscle fiber hypertrophy.
Muscle Nerve. 2017 Feb;55(2):274-276. doi: 10.1002/mus.25415. Epub 2016 Oct 20. PubMed
PMID: 27668404. IF 2.713(2) Nakajima T, Yasuda T, Koide S, Yamasoba T, Obi S, Toyoda S, Sato Y, Inoue T, Kano Y.
Repetitive restriction of muscle blood flow enhances mTOR signaling pathways in a rat model.
Heart Vessels. 2016 Oct;31(10):1685-95. doi: 10.1007/s00380-016-0801-6. Epub 2016 Feb 1.
PubMed PMID: 26833042. IF 2.293(3) Tanaka Y, Inagaki T, Poole DC, Kano Y. pH buffering of single rat skeletal muscle fibers in the invivo environment. Am J Physiol Regul Integr Comp Physiol. 2016 May 15;310(10):R926-33. doi:
10.1152/ajpregu.00501.2015. Epub 2016 Mar 16. PubMed PMID: 26984893. IF 3.529(4) Tanaka Y, Poole DC, Kano Y. pH Homeostasis in Contracting and Recovering Skeletal Muscle:
Integrated Function of the Microcirculation with the Interstitium and Intramyocyte Milieu. Curr
Top Med Chem. 2016;16(24):2656-63. Review. PubMed PMID: 27072709. IF 2.95
2.2 Student guidance(1)

Naoki Nakada, Hiroshi Horikawa, Mutsumi Murase 2016 Bachelor (engineering)
51

(2)

Takuro Mashio. 2016, Master (engineering)(2)

Yoshinori Tanaka. 2016 Doctor (science)

2.3 Visit of oversea researchers and students(1) Leslie Carina Orozco Landa，Instituto Politecnico Nacional

3. Research funding
3.1 Grant-in-aid for scientific research(1) Yutaka Kano (representative), Change of the muscle fiber type as the multinucleate cell,

Grant-in-Aid for challenging Exploratory Research, 2015-2016, 3,770,000 yen(2) Yutaka Kano (representative), Importance of postexercise calcium ion dynamics to determine theadaptation of myocytes Grant-in-Aid for Scientific Research (B), 2016-2019, 17,030,000 yen
3.2. Competitive external research funding(1) The vehicle racing commemorative foundation, 2016, 1,500,000 yen

4. Collaboration
4.1 Inside BLSC
(1) Hidetaka Okada, Evaluation musculotendinous composition by the high speed camera, 2013-present(2) Takayoshi Kobayashi, Development of the bioimaging method with the high-powered laser,
2015-present
4.2 Outside BLSC in UEC(1) Hideki Shirakawa, Calcium ion and cell functions,

4.3 Outside UEC(1) Shinji Miura, University of Shizuoka, Myofunctional evaluation using the PGC1 model mouse,
2013-present(2) Toshiaki Nakajima, Dokkyo medical college Hospital heart center, Development of thepressurization load method to maintain skeletal muscle mass, 2013-present(3) Mikiyasu Shirai, Hirotsugu Tsuchimochi, Tadakatsu Inagaki, Department of Cardiac Physiology,
National Cerebral and Cardiovascular Center Research Institute, Evaluation of cardiovascular
dynamics under the hyperbaric hyperoxia environment, 2013-present(4) Kazuyoshi Yagishita, Clinical Center for Sports Medicine and Sports Dentistry, Hyperbaric
Medical Center/Sports Medicine Clinical Center, Medical Hospital of Tokyo Medical and Dental
University, Evaluation of cardiovascular dynamics under the hyperbaric hyperoxia environment,
2013-present52

(5) David C. Poole, Kansas state university College of veterinary medicine, Microcirculation andskeletal muscle function, 2003-present

5. Outreach activities
5.1 Paper review of academic journals(1) American Journal of Pathology, 2016
(2) Journal of Applied Physiology, 2016(3) Neurochemical Research, 2016(4) Physiological Reports, 2016
(5) Research in Veterinary Science, 2016
(6) Training Science, 201653

Hiroshi YOKOI/Yinlai JIANG Laboratory
1. Outline of Research and Education
1. 1 Basic Policy in Research and Education
The main aims of the Yokoi/Jiang lab are the redevelopment of the theoretical framework andperipheral technologies for human-based engineering, starting with the scientific study of humans and otherorganisms from an engineering perspective, and research into the natural interfaces between humans andmachines, society and machines and technologies integrating the two.
The lab engages in theoretical and technological developments in measurement and control in the fieldof robotics, as well as their applications, with a focus on the development of systems integrating humans andmachines. The theoretical backbone consists of artificial intelligence, bioelectrical measurements andanalysis, as well as design and development of coupled tendon-driven mechanisms, based on information
processing, learning, evolutionary computation and combinatorial optimization. The main areas ofapplication are the development of myoelectric prostheses, power assist devices, neural rehabilitation for therecovery of motor function with the goal of utilizing machines in the areas of welfare and medical carethrough medicine-engineering collaboration.

1. 2Achievements and State of Progress (April, 2016 - March, 2017)(1) Development of myoelectric prosthetic hand and application for registration of parts forcompletion
Myoelectric prosthetic hands are used to restore upper limb function. They therefore mustresemble human hands in fit, have the functionality to carry out necessary daily movements, be lightenough to minimize the burden on the body, and be usable by anyone. In FY 2016, the lab mainly
developed a myoelectric prosthetic hand equipped with a force magnification mechanism, apressure-sensitive cosmetic glove and a conductive silicon myoelectric sensor. An application was also
made to the Ministry of Health, Labor and Welfare for their registration as parts for completion.
a. Development of prosthetic hand with force magnification mechanism
The left image in Figure 1 shows the ball-chain driven force magnification device developed toincrease the grip function. In order to improve the mechanical adaptability when gripping, we
introduced an artificial tendon sheath mimicking a human hand. Furthermore, in order to increase therange of motion of the MP joint on the 4 fingers, we set the actuator to unlimited rotation and fitted alimit switch to the rotation axis of the MP joint. In order to compare the grip of each device, we selected
23 objects frequently used in daily life and carried out a pick-and-place experiment. The radar chart on
the right in Figure 1 shows the results of the experiment. The 4 types of myoelectric prosthesis areshown in different colors. The axis of the radar chart shows the number of successes. The larger thearea surrounded by the line, the more successfully the prosthetic hand performed. As shown by the redline, the prosthesis with unlimited rotation force magnification mechanism with artificial tendon sheath
had the greatest number of successes with almost every object, demonstrating the improved grip
function.
54

ダイレクト 倍⼒駆動
駆動

腱鞘付き
無限回転型
倍⼒駆動 腱鞘付き倍⼒駆動

Figure 1: prosthetic hand with ball-chain driven force magnification mechanism and evaluation resultsb. Development of pressure-sensitive glove for prosthetic hand

Figure 2: Glove fitted with conductive silicon (l) and pressure sensor fitted to prosthesis finger (r)Gloves for prostheses must reproduce the sensory functions of a human hand, as well as imitating its outerappearance, touch and texture. In order to produce tactile sensation, the lab has developed a thin, light andflexible pressure sensor by attaching conductive silicon to the inside surface of the prosthesis glove (Figure2). The material for the electrodes attached to the robotic prosthesis is conductive non-woven fabric. In order
to investigate the omni-directionality, force was applied from 4 directions to a prosthetic hand fitted withsensors. Omni-directionality was confirmed by the characteristics of the sensors. Furthermore, the fact thatthe sensors produced different outputs depending on the direction of force allowed us to determine thepressed face. In addition, by attaching pressure sensors to the front and right side of the thumb and index
fingers, we can detect the type of grip being undertaken by the prosthetic hand.
c.

Development of a myoelectric sensor using conductive silicon
For the smooth operation of myoelectric prosthetic hand, electrodes for sEMG (surface myoelectrogram)measurement must be resistant to sweat, pressure, and other causes of noise in users’ daily lives. In FY 2016,
we developed a conductive silicon-based myoelectric sensor (Figure 3). Test

55

amplifier and filter circuit

gold coating copper wire

insulating sheet
conductive non-woven fabricconductive silicon

Figure 3: Structure of myoelectric sensor using conductive silicon (left) and sensor band (right)
results showed that compared to electrodes made of conductive silicon alone and the conductive polymer
electrodes developed the previous year, electrodes made with gold plated wires and conductive siliconadhered more stably to the skin and reduced the effect of sweat. Furthermore, tests were carried out toinvestigate how the external force exerted on the electrodes influenced the myoelectric signal. This was doneby measuring the sEMG signal while periodically applying external force. This revealed that when pressure
is stable fluctuation in the sEMG signal is low, but when pressure is variable, fluctuation is high, particularly
at low frequencies (20~50Hz).
d. Application for registration as parts for completion（a）1 DoF myoelectric prosthetic hand for children (b) 2 DoF myoelectric prosthetic hand for adults
Figure 4: Prosthetic hand for registration as parts for completion and clinical trials
For the development of products acceptable from the perspective of design and functionality, we carriedout clinical trials using the myoelectric prostheses and received feedback to make improvements. Clinical
trials began in November 2015, after we had undergone an ethics examination with the cooperation of the
National Center for Child Health and Development and Tokai University Hospital. In FY 2016, we selectedsubjects suitable to take part in trials, based on the judgements of medical institutions. We carried out clinicaltests on 20 subjects, based on evaluations of ADL (Activities of Daily Living) while using a prosthesis andupper body function tests. Adult subjects took part in the trials at Tokai University Hospital and pediatricsubjects took part at the National Center for Child Health and Development. Both groups were supervised bydoctors during the trials (Figure 4). The ADL test evaluated how freely subjects could grip and move objects
around them. Even children with congenital defects were able to grip plates and throw building blocks and56

balls, and succeeded in many ADLs. Based on feedback from subjects about the manipulation of theprosthesis and the priority of finger movements, we carried out improvements in the myoelectric controller(movement prediction method), myoelectric sensor, and the user interface. In FY 2016, we madeimprovements to the prototype for a low-cost, high-safety myoelectric prosthetic hand. We also applied forregistration of parts for completion for mainstream distribution.
In addition to a~d mentioned above, we also conducted research and development of myoelectric
prosthetic hand for hand amputation and prosthetic arm for shoulder disarticulation, as well as support
systems for the guardians of pediatric amputees.
(2) Improvement of tendon-driven robot arm and construction of control system
We lightened and strengthened the tendon-driven arm designed in FY 2015. We achieved a balance
between low weight and high power: at the maximum reach of 0.8m, the arm can lift 1.5kg, despite weighing
under 2.5kg overall (excluding power supply). In addition, the maximum tangential speed of the fingertip is
2m/s, almost reproducing the speed of humans’ everyday movements. We developed an intelligent prosthesisthat automatically identifies the gripping object and determines the grip orientation, based on ROS (Figure 5).
In order to make the automatic gripping and moving of objects smoother, we implemented a route planningalgorithm for the selection of grip orientation and grip movement, by using an RGBD sensor toautomatically identify the target object and running a high speed simulation. We introduced a ROS simulator
for intelligent control at Osaka University, in preparation for the introduction of a BMI system for clinicalresearch.
RGBD Camera

Environment recognition andgrasping based on ROS

Figure 5: Gripping of objects by robot arm using ROS
In collaboration with Osaka University and Tokyo Institute of Technology, we proposed the strategies forswitching between autonomous control and BMI control depending on the distance from the object in anautonomous-BMI hybrid control system for the robot arm. We used an SSVEP system for the BMI control(Figure 6). Subjects control the arm to approach the object using SSVEP. When the object has been
identified through data from the RGBD sensor and the hand has entered the autonomous control area of theobject (within a radius of 15cm from the object), the robot arm switches to autonomous control, generates
the grip posture and trajectory and automatically grips and moves the object. Each test took 90 seconds, andwe were able to confirm that the task could be completed repeatedly.

57

Camera view

Robot arm

Hand position

LED flickerr = 15cm

Automatic control
regionBMI control region

Computer for robot arm control

Computer for
EEG analysis

Figure 6: Switch between BMI control and autonomous control based on distance from object(3) Motor point tracking functional electric stimulation using multiple surface electrodes
Functional electrical stimulation is effective as a form of rehabilitation for patients who have sufferedstrokes or spinal cord injuries, but there is the issue of it contributing to muscle fatigue that weakens muscle
contraction induced by the same signal. Stimulation of the motor point between nerve and muscle can inducemuscle contraction more effectively, so the laboratory developed a method of stimulation by following the
movement of the motor point through non-isometric muscle contraction (Figure 7). Stimulation electrodes
are applied to the motor points of the biceps in the upper arm during extension and flexion of the elbow. Two
methods were proposed: motor point tracking based on the angle of the scapula (JASS), and motor point
tracking based on the stimulation time (TSS). The experimental results with eight subjects revealed nosignificant difference between JASS and TSS. Both were shown to enable more stable maintenance ofmuscle contraction than conventional simultaneous stimulation.

CH2
CH1

Academic Defense for Master Degreein 2017

Joint Angle based Shifting Stimulation: JASS

Electrode (OFF)Electrode (ON)Motor point

Time Based Shifting Stimulation :TSS

Figure 7: Following motor point electrical stimulation based on joint angle (JASS) and time (TSS)58

Distance (cm)（4）Measurement of gait with proximity sensor during use of walking support machine

40
30
20
10

right
17
0

19
2

left
21
4

23
8

Time (s)

25
10

27
12

Gait pattern

Proximity sensor

Figure 8: Gait measurement using proximity sensor
When controlling walking machines to support the rehabilitation and movement in daily life of individuals
with gait disorders, it is necessary to detect the gait of the user and adjust the speed and/or direction
accordingly. Measurements from conventional environmental cameras have different accuracy depending on
the position of the subject, and measurements cannot be made when the subject is occluded due to movement
or obstacles. Moreover, measurements with motion sensors needs to attach and calibrate sensors on eachoccasion, which causes great inconvenience. The laboratory proposed a new method of detecting gait, by
attaching proximity sensors to the inside of the walking machine and measuring the movement of the lower
limbs in a 2D plane. In FY 2016 we developed a gait measuring system by attaching array proximity sensors(NSK Ltd.) to the area surrounding the feet in a walking support machine and measuring the distance
between the feet and the machine. Using this measurement system, we confirmed that the difference in gait
between the left and right leg increased in pseudo walking difficulty (through binding the knee joint).

1.3 Future Plan
We will engage with the following issues regarding research into myoelectric prostheses, robot arms,
functional electrical stimulation, and walking support.
(1) Increasing the functionality and practicality of myoelectric prostheses
In order to increase the freedom of prostheses, we will develop a wire-driven module that can be fitted
inside the structure of the prosthesis. Furthermore, in order to realize a greater number of grip postures
without increasing the number of motors, we will add finger joints that move passively and optimize theangle of the finger joints. In order to realize a myoelectric hand that possesses tactile function as well as
replicating the motor function of the fingers, we will develop omni-directional pressure sensors that fit to thefingers and sensory feedback equipment using functional electrical stimulation and oscillations. These will
be adapted for use by shoulder, upper arm, lower arm and hand amputees. In order to evaluate the59effectiveness of myoelectric prostheses, we will, in addition to performance tests, use fNIRS and fMRI to
take brain measurements of the brain activity of users and evaluate the degree to which the prosthesis feels
like it belongs to the body, as well as observing the changes in patterns of brain activity through long termuse.
(2) Optimization of robot arm and motor control
We will improve the mechanism and autonomous system of the wire-driven robot arm, combine this with
the BMI controller developed at Osaka University and carry out clinical trials. On the hardware side, grip
power, control precision and maintainability will be improved by reducing the weight of the mechanism andmodularizing it. The safety of movements will be improved by introducing motors capable of speed andtorque control. On the software side, we will design an interface for the combination with BMI control andequip a system for switching between BMI control and autonomous control.
(3) Investigation of electrical stimulation signals and patterns
We will investigate stimulation signals that effectively induce sensation and muscle contraction
respectively. In order to construct an algorithm that can efficiently investigate the stimulation patterns offunctional electrical stimulation utilizing multi-point surface electrodes, we will develop a high speed
method of exploring stimulation patterns and a clustering method for finger posture.
(4) Motion control for a gait-adjusted walking support machine
We will attempt to realize versatile methods of measuring and analyzing gait, which will serve as theunderlying technologies increasing the intelligence and safety of the walking machine. We will extract thecharacteristics of lower limb movement from data measured by proximity sensors and develop a method of
distinguishing gait patterns. The proximity sensors utilize the reflection intensity of infrared light, so in orderfor them not to be affected by light in the environment, we will develop a data processing algorithm using
active sensing. In addition, we will develop a method of inferring the shape and posture of the target using
distance information from multiple sensor arrays.

2. Research Achievements
2. 1 Reviewed papers [〇: Impact factor greater than 4]
Journal articles(1) Yinlai Jiang, Takeru Togane, Baoliang Lu, Hiroshi Yokoi sEMG Sensor Using Polypyrrole-coatednonwoven fabric sheet for practical control of prosthetic hand. Frontiers in Neuroscience 11/ 33,
2017/02/06, 10.3389/fnins.2017.00033 .
(2) Tatsuhisa Takahashi, Yinlai Jiang, Shuoyu Wang, Masanaga Ikegami, Akihito Yoshimura, Shinichi
Watanabe, Takashi Matsuo, Hirotaka Yanagida Identification of fragmented letters throughminimum-distance interpolation. Therapeutic Research 37/ 8, 795-802, 2016.
(3) Rintaro Kamihira, Misato Kasuya, Yinlai Jiang, Shunta Togo, Masao Sugi, Hiroshi Yokoi Maintenanceof muscle contraction improves during dynamic exercise by multi-channel functional electricalstimulation with time shifting stimulation. International Journal of Bioscience, Biochemistry andBioinformatics (IJBBB) 7 (1) 30-40, 2017.

60

(4) Takufumi Yanagisawa, Ryohei Fukuma, Ben Seymour, Koichi Hosomi, Haruhiko Kishima, Takeshi
Shimizu, Hiroshi Yokoi, Masayuki Hirata, Toshiki Yoshimine, Yukiyasu Kamitani, Youichi Saitoh
Induced sensorimotor brain plasticity controls pain in phantom limb patients. Nature Communications 7
Article number: 13209 (2016) doi:10.1038/ncomms13209.
(5) Xiaoxiao Zhu, Qixin Cao, Hiroshi Yokoi, Yinlai Jiang Large scale indoor 3D mapping using RGB-D
sensor. Intelligent Robotics and Applications 313-321, 2016.
(6) Yoshiko Yabuki, Kazumasa Tanahashi, Masahaku Ishihara, Suguru Hoshikawa, Tatsuhiro Nakamura,
Yinlai Jiang, Ryu Kato, Hiroshi Yokoi Development of new cosmetic gloves for a myoelectric
prosthetic hand by using elastomer, Bulletin of the Japanese Society of Prosthetic and Orthotic
Education, Research and Development 32, 177-185, 2016 (in Japanese).

International conference journals(1) Hesong Ye, Xiang Feng, Yoshiko Yabuki, Shunta Togo, Yinlai Jiang and Hiroshi Yokoi,"Force-magnification mechanism with artificial tendon sheath for myoelectric prosthetic hand forchildren", IEEE International Conference on robotics and biomimetics (ROBIO2016), SuC04.1,
Qingdao China, 2016.
(2) Rintaro Kamihira, Misato Kasuya, Yinlai Jiang, Shunta Togo, Masao Sugi and Hiroshi Yokoi,"Maintenance of Muscle Contraction Improves during Dynamic Exercise by Multi-channel Functional
Electrical Stimulation with Time Shifting Stimulation", International Conference on Biomedical Signal
and Bioinformatics (ICBSB), AUT University, New Zealand, 2016.
(3) Yoshiko Yabuki, Kazumasa Tanahashi, Yuta Suzuki, Tatsuhiro Nakamura, Ryu Kato, Yinkai Jiang andHiroshi Yokoi, "Development of Artificial Skin for the Myoelectric Prosthetic Hand by using Hyper
Elastic Materials with tactile sensor", The International Workshop on modern Science and Technology
2016(IWMST2016), pp.26-32, Taichung, Taiwan, 2016.
(4) Hesong Ye, Shintaro Sakoda, Yinlai Jiang, Soichiro Morishita and Hiroshi Yokoi, "Prosthetic Hand with
Wire-Driven Force-Magnification Mechanism for Children", The International Workshop on modern
Science and Technology 2016(IWMST2016), pp.40-45, Taichung, Taiwan, 2016.
(5) Mai Nozakura, Soichiro Morishita, Misato Ohdaira, Yinlai Jiang and Hiroshi Yokoi, "A method forevaluation of dependency between diseased side and opposite side of hemiplegia patient during
FES-Cycling by using transfer entropy", XXI International Society of Electrophysiology andKinesiology (ISEK) Congress, Chicago, USA, 2016.
(6) Yoshiko Yabuki, Kazumasa Tanahashi, Suguru Hoshikawa, Tatsuhiro Nakamura, Ryu Kato, Yinkai
Jiang and Hiroshi Yokoi, "Development of new Cosmetic Gloves for Myoelectric Prosthetic Hand byusing Thermoplastic Styrene Elastomer", The 14th International Conference on Intelligent Autonomous
Systems (IAS-14), Shanghai,China, 2016.
(7) Yuta Murai, Suguru Hoshikawa, Shintaro Sakoda, Yoshiko Yabuki, Masahiro Ishihara, Tatsuhiro
Nakamura, Takehiko Takagi, Shinichiro Takayama, Yinlai Jiang and Hiroshi Yokoi, "Development of a
Myoelectric Hand Incorporating a Residual Thumb for Transmetacarpal Amputees", The 14th
International Conference on Intelligent Autonomous Systems (IAS-14), Shanghai, China, 2016.

2. 3 Invited lectures(1) Hiroshi Yokoi Human-machine fusion systems and their applications, Robot engineering seminar,
2016/10/31

2. 4 Media releases(1) Super J Channel Information News Show, Toretate, Akita Asahi Broadcasting，2017/3/22

61

(2) Myoelectric Prosthetic Hand, Grasp the future～ Low cost domestic newest technology to be inpractical use～，The Asahi Shimbun，2016/11/24(3) Read and Understand the Electrical Signals of Brain and Muscle，Yomiuri Lecture at the University ofElectro-Communications, Yomiuri Shimbun, 2016/06/10，2016/06/12

2. 5 Patent(1) Hiroshi Yokoi，Yinlai Jiang，Shunta Togo, Yoshiko Yabuki, Yuta Murai, Signal measurement device, andsignal measurement method, The University of Electro-Communications ， Patent application
No.2017-029981，2017/2/21．

(2) Hiroshi Yokoi，Yinlai Jiang，Manipulator，The University of Electro-Communications，Patent application
No.2016-109120, 2016/5/31.

2. 6 Awards(1) Excellent Paper Award: Rintaro Kamihira, Misato Kasuya, Yinlai Jiang, Shunta Togo, Masao Sugiand Hiroshi Yokoi 2016 International Conference on Biomedical Signal and Bioinformatics (ICBSB
2016) 2016/11/22(2) Best Conference Paper Award Finalist: Yoshiko Yabuki, Kazumasa Tanahashi, Suguru Hoshikawa,
Tatsuhiro Nakamura, Ryu Kato, Yinlai Jiang and Hiroshi Yokoi The 14th International Conference onIntelligent Autonomous Systems 2016/07/06

2. 7 Student guidance(1) Daiki Ikuzawa，2016，Bachalor（engineering）(2) Taihei Kuwahara，2016，Bachalor（engineering）(3) Yuki Kojoma，2016，Bachalor（engineering）(4) Akane Fujimoto，2016，Bachalor（engineering）(5) Kentaro Maeda，2016，Bachalor（engineering）(6) Yasuhiro Mouri，2016，Bachalor（engineering）(7) Rintaro Kamihira，2016，Master（engineering）(8) Mai Nozakura，2016，Master（engineering）(9) Yuya Sakai，2016，Master（engineering）(10) Hesong Ye, 2016，Master（engineering）

2.8 Visit of oversea researchers and students(1) Xiaoxiao Zhu，Postdoctoral researcher, Shanghai Jiaotong University, 2016.7.1～2017.1.31.
(2) Baiqing Sun, Associate professor, Shenyang University of Technology, 2016.6.28～2016.7.15(3) Dianchun Bai, Lecturer, Shenyang University of Technology, 2016.6.26～2016.7.3

62

3.Research funding
3.1 Grant-in-aid for scientific research(1)

Hiroshi Yokoi (PI) Artificial hand with conductive silicon skin, Challenging Exploratory Research,
2016/4/1～2019/3/31.

(2) Yinlai Jiang (PI) Bio-adaptive sEMG measurement method for control of welfare machines ,Scientific Research (C) 2016/4/1～2019/3/31.
(3) Hiroshi Yokoi (CI) Understanding brain plasticity on body representations to promote their adaptivefunctions (Posture/walking rehabilitation using sensory intervention), Scientific Research on Innovative
Areas, 2014/4/1～2019/3/31.
(4) Hiroshi Yokoi（CI）Research on control technology of welfare robots that induce body-fusion in the brain,

Scientific Research (A) 2014/4/1～2017/3/31.
(5) Hiroshi Yokoi（CI）Development of BMI devices for rebuilding body function that can enhance senses ofagency and ownership. Scientific Research (B) 2015/4/1～2018/3/31.

(6) Hiroshi Yokoi (CI) Information gain assistive technologies for the deafblindness using tactile
fingerspelling robot. Scientific Research (C) 2014/4/1～2017/3/31.

3.2 Competitive external research funding(1) Hiroshi Yokoi (PI) Integrated research and development of BMI utilizing Japanese strengths(development of technology for input and output type devices and examination of cranial nerve
ethics for the purposes of BMI). Japan Agency for Medical Research and Development 2012-2017.
(2) Hiroshi Yokoi (PI) Development and commercial distribution of 5 digit myoelectric prosthesis forchildren and infants. Japan Science and Technology Agency (Ａ-STEP) 2012-2016.
(3) Hiroshi Yokoi (PI) Development of adaptive myoelectric prosthetic hand for children. Takahashi
Industrial and Economic Research Foundation 2014～2016.

4. Collaboration
4.1 Inside BLSC
(1) Analysis method of fNIRS data（with Tanaka Lab）

4.2 Outside BLSC in UEC(1) Control method of robot arm（with Kurihara Lab）

4.3 Outside UEC(1) Development of multi-channel electrical stimulation device for neural rehabilitation, with System

Instruments Co. Ltd, private enterprise. 2014/11/1-2017/3/31.
(2) Development of myoelectric prosthesis, with Meltin MMI, private enterprise. 2015/3/1-2017/2/28.
(3) sEMG sensor using stretchable wiring technology，Panasonic Corporation， 2016/11/1～2017/9/30.

63

5. Outreach activities
5.1 Editor of academic journals(1)Yinlai Jiang，Journal of Advanced Computational Intelligence and Intelligent Informatics,editorial
member, 2016.3～(2) Yinlai Jiang，Journal of Japan Society for Fuzzy Theory and Intelligent Informatics，2015.9～

5.2 Peer review of academic journals(1) PLOS ONE, Sensors, Industrial Robot, Mechatronics, Mobile Information Systems, Control Engineering
Practice, Neural Networks, Journal of Advanced Computational Intelligence and Intelligent Informatics

5.3 Other outreach activities(1) Host of the 29th symposium on autonomous distributed system，2017/ 1/30～3164

Hidetaka OKADA Laboratory
1. Outline of Research and Education
1. 1 Basic Policy in Research and Education
The organs of our body such as locomotive system, cardiorespiratory system and so on consequently
produce physical movement as results of their functional activities. In our laboratory, we are studying basic
human movement in order to send new findings that can be useful for maintenance of the activities of dailyliving (ADL) or the coaching of athletes.
We are mainly analyzing human movement mechanically. Specifically we are describing thekinematics of each body segment during physical movement and calculating internal forces such as joint
torques by using inverse dynamics method (Figure 1).
Applying the results from these biomechanical analyses, it is possible to develop a new training
method for obtaining superior motor skills and to evaluate the degree of aging of basic human movement.
In the education, I hope to bring up a talented person contributing to the society and the affluent life of theindividuals based on scientific knowledge and technique. I want students to acquire basic knowledge ofengineering and to cultivate practical ability to conduct the researches of biomechanical area. However, I
think that it is more important to learn the problem solving procedures acquired through the process ofConstruction of rigid-link model

Kinematics
Displacement of center of mass，segment
angle，joint angular velocity.…etc.

HeadShoulderNeck

Upper arm
Elbow

Trunk

Wrist

Hip

Forearm
hand

Thigh

Knee

Shank

Ankle

Foot

Inverse dynamics
ai
αi
Force platform

Mid

rid

Segment i+1

Fip
rip Mip

Segment i
mi･g

Fid

Kinetics

Segment i-1
Fid + Fip + mi･ g = mi･ ai

Joint torque, joint torque power, work
done by joint …etc.

Mid + Mip + rid×Fid + rip×Fip = Ii･αi

Figure 1 Outline of motion analysis
65pursuit of studies, the surge of the thought provided from repetition of deep consideration, and teamwork by
the collaboration with the colleagues. Acquiring these would be certainly demanded in the various studies orthe various areas other than study.

1.2 Achievements and State of Progress (April, 2016 - March, 2017)
We conducted the research focusing on the analysis of gait motion. The outline and results are as
follows.
(1) Effect of physical fitness factors change with aging on the variability of walking motion
In Japan, the declining birthrate and aging population is progressing, and it is an important task tosupport the elderly so that they can live their lives without needing care. In order to send a healthy old age, it
is indispensable that ADL (Activities of Daily Living) can be carried out without trouble. Among the ADLs,
walking, which is the basis of various behaviors, plays a crucial role. Previous studies have compared theelderly and young people to know the characteristics of walking motion of the elderly, but in comparison
with the study of walking motion itself, a study reporting the variability (stability) of walking motion issmall. It is thought that observing the variability of walking motion is effective in evaluating the ease oftripping, the presence of a disorder, bilateral coordination of limbs, and the like. In addition, since it is
known that the physical functions supporting ADLs are known to decrease with age, it is thought that ameasure for the maintenance and improvement of independent walking can be indicated by clarifying therelationship between the physical fitness factors and the variability of walking motion.
In this study, walking motion, muscle strength, physical fitness, balance ability, and range of joint movement
were measured for adult females of a wide range of age from young people to the elderly. The purposes ofthis study were 1) to clarify the effect of aging on the variability of walking motion and 2) to examine therelationship between the variability of walking motion and the various physical fitness factors. The subjects
were 35 healthy females from 19 to 82 years old, divided into three groups according to age. MEXT's new
physical fitness test, muscle strength measurement, and ROM measurement were conducted. In addition,
walking motion was measured using a motion capture system, and the stride characteristics andthree-dimensional kinematics during walking were calculated.
As a result of investigating the relationship between the variability of walking motion and physicalfunctions, significant negative correlation with the dynamic balance ability was observed in the variability ofthe step length and the step frequency, and the variability of the phase time had a significant negative
correlation with the static balance ability. As the static balance ability tended to decrease with age, thevariability of the phase time among the stride characteristics seems to be strongly influenced by aging. The
variabilities of the joint angles at the heel contact and the toe-off had significant negative correlation withstatic balance function, ankle plantar flexor strength, and hip flexion ROM. As described above, it issuggested that the deterioration of physical functions due to aging may affect the variabilities of phase time
and the lower limb joint angles at the heel contact and the toe-off.
(2) Effect of difference of marker-set on the results of lower limb motion analysis
Motion analysis is performed in various research fields, and roughly divided into two methods,

66

two-dimensional motion analysis and three-dimensional motion analysis. There are various marker sets inthree-dimensional analysis and also there is a method for analyzing in three-dimensional as a simplified.
Since there are several methods for marker set and analysis method, differences are occurred in each study.
We do not know how much these differences will affect our research results. Nevertheless, comparison ofdifferent research results is frequently done. The influence of the differences of such methods on the results
is an important factor underlying the validity of the study, so it will be necessary to quantify and evaluate.
Moreover, by clarifying the influence due to the difference of the method, it is thought that it is possible topropose a simpler analysis method and experiment method even for the same content measurement. In thisstudy, we analyzed the walking motion of adult males using different methods. The purposes of this study
were 1) to quantify the influence of difference of marker set and difference of analysis method on the motion
analysis results, 2) to recommend a suitable marker set and analysis method for aim and accuracy desired ina study.
Ten healthy males in their twenties participated as subjects. Sixty-four retroreflective markers wereattached to the body of the subjects. Two typical marker sets, plug-in-gait (PiG) marker set and IOR marker
set were used for the motion analysis. Subjects were asked to walk at two speeds (normal walk(NW) and fast
walk(FW) ) on a walkway of about 8 m. Three-dimensional coordinates of markers were measured at 200 Hz
by a motion capture system comprising eleven infrared cameras. Local coordinate system for each lower
limb segment was defined from each of PiG marker set (3DP) and IOR marker set (3DI). From these local
coordinate systems, lower limb joint angles (ankle, knee, and hip) about three axes (extension-flexion,
abduction-adduction, and external rotation-internal rotation) were calculated. In addition, similar analysis
was carried out using the method of Yuki (1996) using only the marker coordinates of the joint point (3DY).
In addition, two-dimensional coordinates in the sagittal plane were extracted from the three-dimensional
coordinates of the joint point marker and a two-dimensional motion analysis (2D) was performed. From thecomparison of the results by each method, the following conclusions were obtained.
1) Pattern similarity of the joint angle of y axis (anterior-posterior axis) and z axis (longitudinal axis) is low
amongst the methods, so it is necessary to pay attention to the measuring method for the joint angles
about these axes.
2) The hip joint angle about the x axis (medial-lateral axis) was different in the 2D method from othermethods, but the difference amongst the 3D methods was small. Therefore, it can be said that there is no
problem in analyzing with the 3DY method (simplified 3D method) in a restricted measuring
environment.
3) The knee joint angle about the x axis is different between (3DP, 3DI) and (3DY, 2D). Therefore,
measurement by 3DP method and 3DI method, which can be said to be generally high accuracy, isrecommended.
4) It can be said that there is no big difference in the ankle joint angle about the x axis amongst any methods.
(3) Effect of components of ground reaction force on the ankle joint torque during walking
In normal walking motion analysis, the lower limb joint torque is calculated using motion capturesystem (or video image) and force platform measurements. However, there are limitations on the67

measurement place and the number of steps in the measurement using these, so a foot pressure sensor may
be used as a substitute for the force platform. However, the foot pressure sensor has the convenience of notchoosing the measurement location, but since it can measure only the vertical ground reaction force, it has
not been used conventionally for inverse dynamics. Therefore, if it is possible to estimate the ankle joint
torque component due to the horizontal ground reaction force, it can be considered that it is possible to use
the foot pressure sensor for the inverse dynamics analysis. In this study, we aimed to clarify the effect ofeach component of the ground reaction force on the ankle joint torque during walking and to examine theestimation method of the ankle joint torque component due to the horizontal ground reaction force.
Subjects were 266 healthy adults from 21 to 86 years old. Subjects were asked to walk at four walking
speeds (Normal Walk (NW), Slow Walk (SW), Fast Walk (FW), and Maximum-speed Walk (MW)) on awalkway of about 8 m. Retroreflective markers were attached to 7 body landmarks of the right lower limb
(toe, head of the 5th metatarsal, heel, ankle joint, knee joint, hip joint, suprasternal), and walking motion wasvideotaped at 60fps from the right side of subjects. The ground reaction force acting on the right foot of thesubject was measured at 200 Hz using a force platform embedded in the walkway.
Based on the two-dimensional inverse dynamics method, the ankle joint torque and the breakdowns inthe sagittal plane (term obtained by the horizontal ground reaction force, term obtained by the verticalground reaction force, terms obtained by the acceleration of the center of mass of the foot, and term obtainedby the angular acceleration of the foot) were calculated. In addition, among the breakdowns, a method for
estimating the term due to horizontal ground reaction force was examined. As a result, it was shown thatusing either of the walking speed, ankle joint torque component due to the vertical ground reaction force,
step length, and step frequency, the ankle joint torque component due to the horizontal ground reaction force
was estimated with an RMS error of about 4%.

1. 3 Future Plan
Based on the accumulated walking motion data, we plan to establish the standard gait motion (standard
value) of each age of Japanese adult males and females and to examine the aging degree evaluation methodof gait motion based on the standard motion change by aging. We are also developing a system for feedingback the gait motion in real time with the aim of promoting learning of gait motion.

2. Research Achievements
2. 1 Reviewed papers [〇: Impact factor greater than 4](1) Yokozawa T, Tsujimura R, Kubo Y, Takahashi H, Okada H. (2016) Body segment inertial parameters
for Japanese elite athletes in various competitive events. Japanese Journal of Elite Sports Support 8:
11-27. (in Japanese)

2.2

Student guidance(1) Niitsu, T., 2017, Bachelor of Engineering(2) Matsumoto, T., 2017, Bachelor of Engineering(3) Sugimoto, T., 2017, Master of Engineering683. Research funding
3.1 Competitive external research funding(1) Joint research (with Univ. of Tsukuba), Study on development of a special strength training appliancespecialized in Judo, ¥2,727,273

4. Collaboration
4.1 Outside UEC(1) Okada, H., University of Tsukuba, Study on development of a special strength training appliancespecialized in Judo, Fiscal Year 2010-2015

5. Outreach activities
5.1 Paper review of academic journals(1) Journal of the Society of Biomechanisms(2) The Japan Journal of Coaching Studies

5.3 Other outreach activities(1) Participation in administrative agencies as an academic expert･Chofu Sports Promotion Council, vice-chairperson(2) Diffuse awareness raising activity at local governments and schools･Japan Association of Athletic Federations Spread Nurturing Committee, member･Chofu city kids running classroom (4 times. Total 105 kids)

69

Norihiro KOIZUMI Laboratory
1. Outline of Research and Education
1. 1 Basic Policy in Research and Education
Promote the digitization of medicine (medical diagnosis) by deploying robot technology to medicalcare. Medical knowledge, expertise and skills closed among some experts are commonly shared byreproducing the doctor's view of the world and medical skills using digital (especially robot) technology andby copying it, Leading to new innovation in medical care. In this laboratory, we will promote the use ofultrasound diagnostic and therapeutic skills as medical targets for medical diagnosis. We collaborate withmedical institutions and medical device manufacturers to develop high quality medical devices and train
medical students and fusion personnel capable of developing them.

Concept of Medical DigITalization (Me-DigIT)
1.2 Achievements and State of Progress (April, 2016 - March, 2017)
Papers were published / accepted in the first class journals: International topic journal International
Journal of Endocrinology (IJE, IF = 2.4), International Journal of Medical Robotics and Computer Assisted
Surgery (IJMRCAS, IF = 1.5), Advances in Experimental Medicine and Biology (IF = 2.0). We exhibited at
JST Innovation Japan 2016, exhibited 2017 degrees and presented lectures at the new technology briefing(12 out of 400). A paper on the development project of visceral fat area measurement techniques using70

ultrasonic waves carried out jointly with Hitachi, Ltd. was published in MEDIX magazine (issued by Hitachi,Ltd.).

1. 3 Future Plan
Promote Medical DigITalization (Me-DigIT) using ultrasound diagnosis / treatment skills as the main
target. We collaborate with medical institutions and medical device manufacturers to develop high quality
medical devices and train medical students and fusion personnel capable of developing them.

2. Research Achievements
2. 1 Reviewed papers [〇: Impact factor greater than 4](1) Takeharu asano, Naoto Kubota, Norihiro Koizumi, Kazunori Itani, Tsuyoshi Mitake, Kazuhito Yuhashi,
Hongen Liao, Mamoru Mitsuishi, Shigemi Takeishi, Toshiaki Takahashi, Shin Ohnishi, Shiro Sasaki,
Ichiro Sakuma and Takashi Kadowaki , "Novel and simple ultrasonographic methods for estimating theabdominal visceral fat area," International Journal of Endocrinology (IJE), Accepted, IF=2.4 Preprint(2) Tatsuya Fujii, Norihiro Koizumi, Atsushi Kayasuga, Dongjun Lee, Hiroyuki Tsukihara, Hiroyuki Fukuda,
Kiyoshi Yoshinaka, Takashi Azuma,Hideyo Miyazaki, Naohiko Sugita, Kazushi Numata, Yukio Honma,
Yoichiro Matsumoto, Mamoru Mitsuishi, "Servoing performance enhancement by respiratory organ
motion prediction model for non-invasive ultrasound theragnostic system," Journal of Robotics andMechatronics (JRM), Vol.29, No.2, pp.434-446, DOI: 10.20965/jrm.2017.p0434, 2017.
(3) Joonho Seo, Norihiro Koizumi, Mamoru Mitsuishi, and Naohiko Sugita, "Ultrasound image based visual
servoing for moving target ablation by high intensity focused ultrasound," International Journal of
Medical Robotics and Computer Assisted Surgery (IJMRCAS), e1793, DOI: 10.1002/rcs.1793, 2016.
IF=1.5(4) Teiichiro Ikeda, Shin Yoshizawa, Norihiro Koizumi, Mamoru Mitsuishi, and Yoichiro Matsumoto,"
Focused ultrasound and Lithotripsy," Advances in Experimental Medicine and Biology (ADV EXP MED
BIOL), Vol.880, pp.113-129, 2016 (DOI: 10.1007/978-3-319-22536-4 ). IF=2.0

2.2 Book, non-refereed articles and translation(1) Hirofumi Namba, Motohiro Kawasaki, Tomonari Kato, Toshikazu Tani, Takahiro Ushida, and Norihiro
Koizumi Evaluation of the pain and local tenderness in bone metastasis treated with magnetic
resonance-guided focused ultrasound surgery (MRgFUS). AIP Conference Proceedings 1821, 160007(2017); doi: http://dx.doi.org/10.1063/1.4977660.
(2) Dongjun Lee, Norihiro Koizumi, Hiroyuki Tsukihara, Akira Nomiya, Kiyoshi Yoshinaka, Naohiko
Sugita, Yukio Homma, Yoichiro Matsumoto, and Mamoru Mitsuishi Construction of kidney phantom
model with acoustic shadow by rib bones and respiratory organ motion. AIP Conference Proceedings
1821, 150007 (2017); http://doi.org/10.1063/1.4977651.
712.3 Invited lectures
4 Japanese lectures.

2.4 Media release(1) Rad Fan Online "The 41st Ultrasonic Doppler and New Technical Studies Conference", 2017.03.31.

2.5 Patent
Japanese Patent Application No. 2017-040348, 2017.3.3

2.6 Award
2 Japanese awards (For students)
2.7 Student guidance
Fumio Eura，FY2016，Bachelor (Eng.)
Tatsuya Genda，FY2016，Bachelor (Eng.)
Ryosuke Kondo，FY2016，Bachelor (Eng.)
Kyouhei Tomita，FY2016，Bachelor (Eng.)
Izumu Hosoi，FY2016，Bachelor (Eng.)

3. Research funding
3.1 Grant-in-aid for scientific research(1) FY2017 - FY2020 Grant-in-Aid for Scientific Research (17H03200) Grant-in-Aid for Scientific Research(B).
(2) FY2014 - 2016 Grant-in-Aid for Scientific Research of the Ministry of Education, Culture, Sports,
Science and Technology (26289061) Basic Research (B).
(3) Grant-in-Aid for Scientific Research, Ministry of Education, Culture, Sports, Science and Technology,
FY2015 - FY2016 Grant-in-Aid for Scientific Research (15K15557) Challenging sprouts research.

3.2. Competitive external research funding(1) Ministry of Education, Culture, Sports, Science and Technology JST Research Outcomes Development
Project Matching Planner Program(2) Saitama prefecture new technology and Product development subsidy

4. Collaboration
None

72

5. Outreach activities(1) Norihiro Koizumi, Medical robotics: Technological and digital transfer of medical skills.
Gunma-prefectural Kiryu High School, Gunma, Dec. 7, 2016.

73

Guanghao SUN Laboratory
1. Outline of Research and Education
1. 1 Basic Policy in Research and Education
Due to the most competitive advantage in allowing users fully unconstrained, noncontact
bio-measurement technology will play a vital role in future clinical practice. Guanghao SUN Laboratory
focus on developing novel medical devices based on noncontact bio-measurement technology, such as,
infection screening system, home healthcare monitoring system, and etc.

1.2 Achievements and State of Progress (April, 2016 - March, 2017)
To promote the widespread use of infection screening system, we have been working on systems withminimum hardware requirements to achieve a system that is more suitable for real world settings. The mostreliable solution is to enhance the functionality of the conventional infrared thermography systems that are
already installed at international airports. By incorporating the latest advances in image processing
techniques, these infrared thermography systems can acquire thermal and visible images together byintegrating visible and thermal cameras. In this study, we used high image and temperature resolution
infrared thermography that combines visible and thermal images to acquire multiple vital sign measurementsfrom facial images using remote sensing. The benefit of this approach is that it only requires a CMOS
camera that is equipped with IRT rather than a large-scale system. As shown in Figure 1, we simultaneously
measured peoples’ respiration rates by monitoring temperature changes around the nasal areas, and facialskin temperatures from thermal images. Facial blood circulation causes tiny color changes in visible facial
images that enable the determination of heart rates. A logistic regression discriminant function predicted thelikelihood of infection within 10 s, based on the measured vital signs.

Figure 1. Schematic representation of the visible and thermal image processing method that remotely senses
multiple vital signs and the multiple logistic regression function that predicts the possibility of infection.

74

2. Research Achievements
2. 1 Reviewed papers [〇: Impact factor greater than 4](1) Guanghao Sun, Yosuke Nakayama, Sumiyakhand Dagdanpurev, Shigeto Abe, Hidekazu Nishimura,
Tetsuo Kirimoto, Takemi Matsui Remote sensing of multiple vital signs using a CMOS
camera-equipped infrared thermography system and its clinical application in rapidly screening patientswith suspected infectious diseases. International Journal of Infectious Diseases, 55, 113-117, 2017.
(2) Guanghao Sun, Toshikazu Shinba, Tetsuo Kirimoto, and Takemi Matsui An Objective Screening Method
for Major Depressive Disorder Using Logistic Regression Analysis of Heart Rate Variability Data
Obtained in a Mental Task Paradigm. Frontiers in Psychiatry, 2016.
(3) Enrique Dorronzoro Zubiete, Keigo Nakahata, Nevrez Imamoglu, Masashi Sekine, Guanghao Sun, Isabel
María Gómez and Wenwei Yu Evaluation of a home bio-monitoring autonomous mobile robot.
Computational Intelligence and Neuroscience, 2016.
(4) Guanghao Sun, Masahiko Akanuma, Takemi Matsui Clinical Evaluation of the Newly Developed
Infectious Disease/Fever Screening Radar System Using the Neural Network and Fuzzy Grouping
Method for Travellers with Suspected Infectious Diseases at Narita International Airport Clinic.
Journal of Infection, 72(1), 121-123, 2016.
(5) Yu Yao, Guanghao Sun, Takemi Matsui, Yukiya Hakozaki, Stefan van Waasen, Michael Schiek Multiple
Vital-sign Based Infection Screening Outperforms Thermography Independent of the Classification
Algorithm. IEEE Transactions on Biomedical Engineering, 63(5), 1025-1033, 2016.

Conference proceedings paper(1) Xiaofeng Yang, Guanghao Sun, Koichiro Ishibashi Non-Contact Acquisition of Respiration andHeart Rates Using Doppler Radar with Time Domain Peak-Detection Algorithm. The 39th Annual
International Conference of the IEEE Engineering in Medicine and Biology Society, 2017, Jeju
Island, Korea.
(2) Mai Kobayashi, Guanghao Sun, Toshikazu Shinba, Takemi Matsui, Tetsuo Kirimoto Simple andObjective Screening of Major Depressive Disorder by Heart Rate Variability Analysis During Paced
Respiration and Mental Task Conditions. The 39th Annual International Conference of the IEEE
Engineering in Medicine and Biology Society, 2017, Jeju Island, Korea.
(3) Guanghao Sun, Wenwei Yu Development of an EMG-based Human-Machine Interface on
Open-source Linux Platform for Evaluating the Motor Skill Acquisition Process. The 16th
International Conference on Biomedical Engineering, 2016, Singapore.
(4) Guanghao Sun, Yu Yao, Sumiyakhand Dagdanpurev, Satoshi Suzuki, Takemi Matsui, Tetsuo
Kirimoto A Comparative Study between Piezoelectric Pressure Sensor and Doppler Radar for
Noncontact Monitoring of Respiration Rate. The 16th International Conference on Biomedical75

Engineering, 2016, Singapore.
(5) Takemi Matsui, Guanghao Sun, Bazarragchaa Ts., Sumiyakhand D., Yukiya Hakozaki, Lodoiravsal
Ch., Buyanjargal Ya., Odmaa E., Myagmarjav Z., Suvdmaa N., Batsukh B. The rapid screening ofpatients with suspected infection in Mongolia using infection screening system with a compact
radar, a thermopile array and a pulse photo-sensor. International Scientific Conference on Tackling
Infectious Diseases: Information for Action, 2016, Ulaanbaatar, Mongolia.

2.2 Book, non-refereed articles and translation(1) 小型マイクロ波レーダーによる心拍、呼吸の計測技術 第2章第2節：生体情報センシングとヘルスケアへの最新応用 ～ウェアラブル、非侵襲・非接触計測、連続モニタリング～, 2017.

(2) Guanghao Sun, Takemi Matsui, Tetsuo Kirimoto, Yu Yao, Shigeto Abe Applications of Infrared
Thermography for Noncontact and Noninvasive Mass Screening of Febrile International Travelers at
Airport Quarantine Stations. Chapter: Application of Infrared to Biomedical Sciences, 347-358, Springer,
2017.

2.3 Media release
新聞 日刊工業新聞 感染症、AIで即時特定 2017/02/23
2.4

Student guidance(1)

Mai Kobayashi (Bachelor)

3. Research funding
3.1 Grant-in-aid for scientific research(1). 若手研究(B) :大規模な生体情報データ計測に基づくリアルタイム感染症サーベイランスシステムの開発(2). 基盤研究(B)一般:マイクロ波を用いた非接触による血圧変動推定方法の開発(3). 基盤研究(C)一般:ニューラルネットワークを用いた完全非接触-感染症・熱中症スクリーニ
ングシステム4. Collaboration
None

5. Outreach activities
5.1 Editor of academic journals(1)

Journal of Sensors
765.2 Paper review of academic journals(1)

Measurement(2)

Frontiers in Bioengineering and Biotechnology(3)

Journal of the Royal Society Interface(4)

Informatics in Medicine Unlocked(5)

Computers in Biology and Medicine

77Yoshiki KASHIMORI Laboratory
1. Outline of Research and Education
1. 1 Basic Policy in Research and Education
Research
We study the neural mechanisms of information processing in sensory systems such as visual,auditory, gustatory, and electrosensory systems. Our approach is based on modeling and simulation studies.
In our study, we adopt two viewpoints of the brain systems, as shown in Fig. 1. One is a viewpoint of asystem, providing the idea that the brain is a complex system consisting of feedforward and feedback flows
of information. Another is a viewpoint of dynamic system, providing the intriguing idea that dynamic
properties of neuronal ensembles have crucial roles in sensory coding and memory formation. With the two
viewpoints, we are working on modeling studies on the neural mechanisms of sensory perception andrecognition.
Education
Under my mentorship, 2 graduate students took master’s degrees in 2016. I would like to continue toguide graduate school students who can play an active part in the research field of computational
neuroscience.

Fig.1 Two viewpoints in our work78

1.2 Achievements and State of Progress (April, 2016 - March, 2017)
We studied the neural mechanisms of four types of sensory systems. A first research is on the best
frequency (BF) shifts in bat’s auditory system. Experimental studies have demonstrated that in themustached bat, auditory neurons have a BF shifting away from a stimulated frequency, or centrifugal BF
shift. To explore address the neural mechanism of the centrifugal BF shift, we developed a neural model ofthe bat’s auditory system. Using our model, we showed the centrifugal BF shifts (Fig. 2) and found thereceptive field properties of feedback signals from the auditory cortex to the inferior colliculus, necessary forthe centrifugal BF shift. Second is the research on taste perception. Taste perception is significantly affectedby other sensory modalities such as vision, smell, and somatosensation. Such taste sensation elicited byintegrating gustatory and other sensory information is referred to as flavor. We developed network models of
primary gustatory cortex (GC) and orbitofrontal cortex (OFC), and presented the neural mechanism of how
flavor emerges from the interaction between GC and OFC (Fig. 3). Third is the research on top-down
influence on V1 responses in perceptual learning. Experimental studies have shown that V1 responses are
modulated depending on task contexts. This suggests that early visual areas such as V1 could be involved invisual recognition, via top-down signals from higher visual areas. To elucidate the neural mechanism
underlying the modulations of V1 responses, we developed a neural model that consists of V1 network and ahigher area, and explored the neural mechanism of the top-down influence. Forth is the research on GPGPU
calculation of large sizes of neural systems. This research is a preliminary work for studying the neuralmechanism of electrosensory processing of a weakly electric fish. We developed a GPGPU-calculation
system, and evaluated the computation time and accuracy for simulations of neuronal populations
constructed with various neuron models. We found that CUDA calculation was an effective method for
calculating large systems, compared with Open-MP method.

Fig.2 Centrifugal BF shift in the tuning

Fig. 3 Dynamic states of GC network incurves of IC neurons.

the space of Hamming distance.

791. 3 Future Plan
Brain rhythms have crucial roles in gating of sensory information and enhancement of neuronal
responses to stimulus features relevant to behaviors. Interareal interactions, mediated by slower oscillations
such as alpha and beta rhythms, have a pivotal role in gating of sensory information relevant to behaviors. In
contrast, intracortical interactions, mediated by faster oscillations such as gamma rhythms, are involved in
representation of sensory information. However, how the brain rhythms contribute to sensory processing andrecognition is poorly understood. To address this issue, we study top-down influence on V1 responses inperceptual learning. The top-down influence may be mediated by the brain rhythms. We will explore theneural mechanism by which task-relevant information is gated by top-down signals and multiple brain
oscillations. We also focus on taste perception in taste preference and avoidance behaviors. orbitofrontal
cortex (OFC) is known to contribute to value evaluation and decision making, and is closely involved inbehavior evoked by taste perception. Moreover, amygdala plays a pivotal role in associative learning ofmultisensory information. As a next step towards understanding the neural mechanism of taste recognition,
we will study how taste preference and avoidance behaviors emerge from the interaction between gustatory,
olfactory cortices, OFC, and amygdala. Furthermore, we have a project on the study in electrosensory
systems (Grant-in-aid for scientific research). Electrosensory systems have simpler circuit structurescompared with those in visual and auditory systems, and the sensory coding of electrosensory systems iswell-defined. Therefore, they provide an ideal system for studying sensory processing mechanism by meansof a large-scale parallel computing method such as GPGPU computing. We developed a GPGPU-calculation
system and showed the usefulness of GPGPU method for the calculation in neural populations constructedwith various neuron models. As a next step, we will study the geometry of electric field around a fish andsensory processing mechanism of central nervous systems.

2. Research Achievements
2. 1 Reviewed papers [〇: Impact factor greater than 4](1) K. Kamiyama, K. Fujita, Y. Kashimori (2016). A neural mechanism of dynamic gating of task-relevant
information by top-down influence in primary visual cortex. BioSystems, 150:138-148.
(2) Takahiro Shimemura, Kazuhisa Fujita, Yoshiki Kashimori (2016). A neural mechanism of taste
perception modulated by odor information. Chemical Senses. 41:579-589(3) Kazuhisa Fujita and Yoshiki Kashimori (2016). Neural mechanism of corticofugal modulation of tuning
property in frequency domain of bat's auditory system. Neural Processing Letters, 43:537-551(4) Kazuhisa Fujita and Yoshiki Kashimori (2016). GPU-accelerated simulation of an electric stimulus andneural activities in electrolocation. Lecture Notes in Computer Science, 9950, 213-220(5) Yuki Abe, Kazuhisa Fujita, Yoshiki Kashimori (2016). A neural model for retaining object information
required in a categorization task. Lecture Notes in Computer Science, 9948, 391-398

2.2

Student guidance(1) Bachelors

80Reira Antake
Eiki Hayashi
Miyuki Asanuma(2) Master’s degree:
Yuuki Abe
Koya Onodera

3. Research funding
3.1 Grant-in-aid for scientific research(1) Yoshiki Kashimori (Principal investigator). A theoretical study aimed at the system-level understandingof information processing mechanism of electrosensory systems. Scientific research (C), 2015-2017,
4,420,000 yen

4. Collaboration
4.1 Outside UEC(1) Kazuhisa Fujita, Tsuyama National College of Technology (see subsection 3.1)

5. Outreach activities
5.1 Editor of academic journals(1) Cognitive Neurodynamics 2006~

5.2 Paper review of academic journals(1) Cognitive Neurodynamics, May. 2016
(2) Cognitive Neurodynamics, June. 201681

Shigeru TANAKA Laboratory
1. Outline of Research and Education
1. 1 Basic Policy in Research and Education
The basic policy of this laboratory is to provide students with opportunity to learn how to solve
problems in the contemporary society through the education of theoretical research in neurosciences. For
research, towards the understanding of information representation and processing in the visual and auditory
cortices, brain mechanisms underlying working memory, attention and consciousness, we are carrying out
theoretical research on (1) the self-organization of visual cortical maps during development, (2) neuraldynamics in auditory continuity illusion, (3) zero-lag remote synchronization, (4) tripartite synapses underneuron-glia interaction and (5) the establishment of functional near infrared spectroscopy measurement andanalysis methods for future research on human working memory. Figure 1 illustrates major targets of ourtheoretical studies.

Figure 1 Overview of our laboratory’s research

1.2 Achievements and State of Progress (April, 2016 - March, 2017)(1) Elaboration of our model for the self-organization of visual cortical maps
Based on the elaboration of our model for the activity-dependent self-organization of geniculo-corticalafferent inputs, we derived the free energy Fokker-Planck equation that describes receptive field formation oforientation and direction selective simple cells in the primary visual cortex. This provides a solid basis ofmathematical explanation of not only simple cell receptive fields but also visual cortical feature
representations formed during development. We also elaborated a spin-glass theory that can describe thetransition between the orderly map representation and salt-and-pepper-like random representation ofpreferred orientations. Using this theory, we can explain the reason why the number of82

orientation-unselective neurons increased markedly in addition to the emergence of salt-and-pepper-likerandom orientation representation in the rodent visual cortex.
(2) Neural dynamics in auditory continuity illusion
The auditory continuity illusion is a well-known phenomenon: When a continuous melody ispartially replaced with periodic silent periods (gaps), we feel the melody to be unpleasantly fragmented.
However, when the periodic gaps are further replaced with noise, we hear the continuous melody as a
background of the periodic noise. That is, the insertion of noise recovers the sensation of continuity in theoriginal melody although it is still fragmented. To elucidate the neural mechanisms underlying this illusion
theoretically, we examined dynamic activities of a neural network in the primary auditory cortex (AI)composed of spiking neuron models. Each neuron in the model received self-organized inputs from the
MGB and excitatory and inhibitory lateral inputs from other AI neurons. The following three types of stimuli
were presented: (a) continuous 800-Hz pure tone, (b) 800-Hz pure tone periodically fragmented with gaps,and (c) 800-Hz pure tone with a periodic insertion of the band-pass noise into the gaps in (b). For stimulus(b), the spike responses of 800-Hz pure tone selective neurons were observed only during the presentation of
the pure tone but not generated in the gaps. On the other hand, the same neurons elicited spikes continuallyin response to stimulus (c), and temporal patterns of firing were similar to those for stimulus (a).
Furthermore, we carried out dynamic simulations without lateral interactions in the model AI in response to
the three types of stimuli. Firing rate of model AI neurons in the noise periods was six-fold higher than thatin the melody periods for stimulus (c), whereas the level of activation was almost the same for the other two
types of stimuli irrespective of the presence or absence of the lateral interactions. These results indicate thatthe lateral interactions are involved in the gain control of neuronal responses in AI. Next, we examined thesimilarity of temporal firing patterns of model neurons in response to stimulus (c) between those to stimulus(a), changing the noise intensity. The dependence of the similarity on the noise intensity showed an excellent
agreement with a human psychometric function representing the dependence of the sensation of continuityon the noise intensity. Taken together, it is suggested that the topographic map and lateral interactions in AI
contribute to the generation of auditory continuity illusion.
(3) Elucidation of the mechanisms underlying zero-lag remote synchronization
Synchronous firing of neurons
has received much attention in relation
to the generation of brain wave rhythms,
and information processing at various
aspects in the neuronal systems, such asfeature binding, cognition, memory
processes,

odor

perception,etc.

Synchronization with zero phase lag has
been observed between remote areas inhuman brains despite that time from

Figure 2 Zero-lag synchronization among three neurons

83spike generation at a presynaptic neuron to the change of membrane potential at a postsynaptic neuron after
spike conduction along the axon can amount to several tens of milliseconds. We started a theoretical study toelucidate mechanisms of how neurons between remote regions can form neural populations that fire at thesame timing despite non-negligible temporal delays. We obtained simulation results that phenomenologically
reproduced such zero-lag synchronization in the two excitatory and 1 inhibitory neurons whose reciprocal
connections had different conduction delays (Fig. 2).
(4) Mathematical modeling of tripartite synapses
We built a mathematical modelof neuron-glia interaction, which gives apossible interpretation that tripartite
synapses enhance signal-to-noise ratio in
neuronal

informationtransmission

mediated by the elevation of intracellular
calcium

concentrationinastrocytes

under the secretion of neuromodulator
noradrenaline.

We

used

the

Hodgkin-Huxley model as a neuronmodel.

We

exocytosis

added
of

modelsglutamateoftheFigure 3 Sharpening of orientation tuning under the effect ofnoradrenaline via tripartite synapses

containing

vesicles from the presynaptic neuron andof ATP and D-serine containing vesicles from astrocytes surrounding the synaptic junction, which are alldependent on the intracellular calcium concentration. We also took into account metabotropic glutamate
receptors expressed on the cell surface of astrocytes, which generate IP3 (inositol trisphosphate) to bind to
specific receptors on the endoplasmic reticulum (ER) activating the Ca2+-permeable channel and thus
causing the release of stored Ca2+ to the cytoplasm. Carrying out computer simulations based on this set ofmodels, we observed the enhanced signal-to-noise ratio in the transmission at tripartite synapses. When weapplied the same set of models to the activation of an orientation selective neuron in the primary visualcortex, orientation tuning became sharper under the volume transmission of noradrenaline, due to thestronger activation of postsynaptic NMDAR by increased release of D-serine and suppression of theexocytosis of glutamate-containing vesicles at presynaptic sites by increased release of ATP from astrocytes(Fig. 3).
(5) Establishment of functional near-infrared spectroscopy for brain activity measurements
It is still likely that in the data analysis of functional near-infrared spectroscopy (fNIRS) for humanbrain activity measurement reliable methods have not yet been established. So we are trying to develop asuite in Matlab environment for the processing of raw data obtained from fNIRS measurement to eliminate
periodic artifacts arising from oscillatory systemic processes and motion artifacts. Figure 4 shows across-correlogram which displays a pseudo-color map of the correlation in measured signals among different

84channels. The channels identified by the numbers are reordered and grouped by how correlated they are witheach other using the k-nearest neighbor algorithm.

1. 3 Future Plan
We will continue to elaborate the mathematicaltheory of the activity-dependent self-organization ofafferent inputs, and consequently the formation ofreceptive field profiles and feature maps in the visualcortex, because the theory provides a firm basis for amathematical study of neural network dynamics. Also

Figure 4 Cross-correlogram of NIRS signals

we will extend a mathematical model of tripartite

among different channels

synapses, taking into account glutamate release as one ofgliotransmitters. We have a hypothesis that glutamate released from astrocytes enhances dendritic
excitability mediated by extrasynaptic NMDARs. Integrating the self-organized visual cortical functional
maps and neuronal information processing through tripartite synapses, we will try to figure out themechanisms of the expansion of a neuronal responsive range of stimulus spatial frequencies in the primaryvisual cortex of awake animals. Furthermore, we will construct a mathematical model of neuronal networks
in the visual cortex taking into account complex cells, chandelier cells and double bouquet cells as well as
simple cells, and carry out computer simulations to understand neural mechanisms of dynamic sparse coding.
Also, we will investigate a simple network composed of a small number of spiking neuron models to
elucidate how the zero-lag synchronization is generated among remote neuronal clusters. Continuing theeffort to develop the fNIRS signal analysis method, we will attempt to use fNIRS measurement to obtain abetter understanding of the mechanisms of human working memory functions.

2. Research Achievements
2. 1 Book, non-refereed articles and translation(1) Tanaka S. Topology inherent in the visual cortical information representation. Journal of Japanese
Neural Network Society 23 (2): 60-67, 2016.
(2) Tanaka S, Miyashita M. Theory of the formation of columnar organization. Clinical Neuroscience 34(August): 880-884, 2016.
(3) Ishikawa S, Miyashita M, Horikawa J, Tanaka S．Functional roles of orientation representation for visual
information preservation. 39th Annual meeting of Japanese Society for Neuroscience（Yokohama） 7.21,
2016.
(4) Miyashita M, Tanaka S. Theoretical study of regularity in orientation representation and preservation ofvisual information. 20th Visual Science Forum（Osaka） 8.26, 2016.
(5) Endo T, Miyashita M, Horikawa J, Tanaka S. A computational study of neural dynamics in the auditory
cortex for the generation of auditory continuity illusion. 3rd Annual meeting of Bioacoustic Society85

（Irago）12.10-11, 2016.
(6) Tanaka S. Ten years after receiving research grant. Public Relations Magazine of The Naito

Foundation 99（March）2017.
2.2

Student guidance(1) Masaki Hayashi，FY2016, Bachelor degree（Engineering）(2) Shuhei Okawa，FY2016，Bachelor student

3. Research funding
3.1 Grant-in-aid for scientific research(1) Shigeru Tanaka （PI）fMRI study for the understanding of sound symbolism and common sense.
Challenging Exploratory Research, 2014-2016, 3,770,000 yen.
(2) Shigeru Tanaka (CI) Understanding of complementary motor learning with multiple plasticity sites
distributed in the cerebellum. Scientific Research (C), 2014-2016, 5,070,000 yen.
(3) Shigeru Tanaka（CI）A study of mathematical modeling of auditory cortical information representation:
Auditory continuity illusion. Scientific Research (C), 2016-2018, 5,200,000 yen.

4. Collaboration
4.1 Inside BLSC
(1) Tadashi Yamazaki, Theoretical study of the cerebellum, 2013/04(2) Hiroshi Yokoi, Yinlai Jiang, Establishment of basic methods for fNIRS measurement and analysis,
2016/4(3) Vasileios Tserolas, Mathematical study of zero-lag remote synchronization, 2015/4- , Establishment ofbasic methods for fNIRS measurement and analysis, 2016/4-

4.2 Outside BLSC
(1) Masaki Hisano, fMRI measurement for understanding of the mechanisms of sound symbolism, 2014/4-

4.3 Outside UEC(1) Masanobu Miyashita (Numazu National College of Technology) Neural dynamics in the auditory
continuity illusion 2015/4-, Self-organization of visual cortical receptive fields and related maps,
2013/4(2) Tomoki Fukai (RIKEN Brain Science Institute) fMRI measurement for understanding of the mechanismsof sound symbolism, 2014/4-

86

5. Outreach activities
5.1 Editor of academic journals(1) ISRN Neuroscience, 2012-present(2) Science Postprint, 2013-present
5.2 Paper review of academic journals(1) Neuroscience 2016/8

87

Tadashi YAMAZAKI Laboratory
1. Outline of Research and Education

1. 1 Basic Policy in Research and Education
We are conducting research in the interdisciplinary area between neuroscience and high-performancecomputing. Specifically, we are engaged with theoretical modeling of neural networks of the brain andlarge-scale computer simulation on supercomputers. Our final goal is to understand the neural mechanismsof human-specific higher-order functions such as bipedal locomotion and language. Currently as an initiative
project, we are working on the following projects: (1) building a whole-brain-scale functional model for
motor learning and control, (2) development of high-performance neurocomputing methods for acceleratorssuch as graphics processing units (GPUs), and (3) applications of an artificial brain for controllingmusculoskeletal models and humanoid robots, and for rehabilitation.
Students in the lab participate to one of the above projects. In other words, they take part of aworld-class advanced research project from the beginning as an on-the-job training to gain practicalexperience on research. We stress the importance of publishing results to students. Master course students
must present their results in international conferences at least once. We also strongly encourage students topublish a research paper. To achieve these, we have generous research funds and provide the best
environment and equipment for students.
We also have a research scientist and a technical staff in the lab who are leading our science88

aggressively and helping management.

1.2 Achievements and State of Progress (April, 2016 - March, 2017)
We have achieved the following:(1) In our NEDO project, we built a computational model of cerebro-basal ganglia loop for motor leaning,
representation and generation. We studied the network dynamics empirically, and demonstrated the ability
using a small humanoid robot. We also built a unified model of a basal ganglia model and a cerebellar model
for representation of time, and studied the dynamics analytically and empirically. We submitted a paper onrobust representation of time by feedback signals to an international journal. We successfully passed thestage gate of NEDO project.
(2) We achieved realtime simulation of a spiking network model of the cerebellum composed of 1 billion
neurons on Shoubu, an energy-efficient supercomputer installed at RIKEN ACCC. We implemented
synaptic plasticity so that the model can perform online learning. We submitted a paper to an international
journal. Our project was accepted for MEXT Post-K Supercomputing Project.
(3) We built a brain-musculoskeletal model composed of a cerebellar model and a bipedal locomotion model
for stable walk against proprioceptive feedback delays. Specifically, we assumed that the cerebellar modelcompensates the feedback delay, and replaced a feedback control with a feedforward control. We submitted
a paper on the model to a Japanese journal. We also started to acquire parameters for robust locomotion of asmall humanoid robot using genetic algorithms.

1. 3 Future Plan
(1)

We continue our NEDO project. In particular, to obtain a large amount of human motion data, wedevelop a method to extract human body motion data from movies on YouTube. We also develop aspiking neuron version of our basal ganglia model that can perform reinforcement learning.

(2) We plan to build a human-scale cerebellar model composed of 100 billion neurons on thenext-generation PEZY-SC chips. We also continue MEXT Post-K Supercomputing Project.
(3)

We realize locomotion control of a humanoid robot using our cerebellar model. We also conduct
computer simulation of abnormal walking by cerebellar patients.

2. Research Achievements
2. 1 Reviewed papers [〇: Impact factor greater than 4](1) Tsukasa Tsuyuki, Yuki Yamamoto, Tadashi Yamazaki(2016), Efficient numerical simulation of neuronmodels with spatial structure on graphics processing units, A. Hirose et al. (Eds.), ICONIP 2016, Part IV,
LNCS 9950(279–285), DOI: 10.1007/978-3-319-46681-1 34(2) Ohki Katakura, Tadashi Yamazaki(2016), Computational model of the cerebellum and the basal ganglia
for interval timing learning, A. Hirose et al. (Eds.), ICONIP 2016, Part IV, LNCS 9950(244–251),
89

DOI: 10.1007/978-3-319-46681-1 30

2.2 Book, non-refereed articles and translation(1) Tadashi Yamazaki. Cerebellar clocks. Annual Review Shinkei 2016. Chugai Igakusha. 1-6, 2016.
(Japanese article)(2) Tadashi Yamazaki, Junichiro Makino, Toshikazu Ebisuzaki. Perceptron and cerebellum. Rinsho
Shinkeigaku 34(8):889–891, 2016 (Japanese article).

2.3 Invited lectures(1) Tadashi Yamazaki, Toward building an artificial cerebellum, Advances in Neuroinformatics 2016,
RIKEN, 2016/5/28-29(2) Tadashi Yamazaki, A cat-scale artificial cerebellum on Shoubu (In Japanese), RIKEN Symposium“Supercomputer HOKUSAI and Shoubu, advances in computational science”, RIKEN, 2016/6/8(3) Tadashi Yamazaki, Cat-scale artificial cerebellum on an energy-efficient supercomputer Shoubu,
Workshop on Brain-inspired Hardware, The Artificial Intelligence Research Center, 2017/3/30

2.4 Media release(1) Nikkei technology online, Reproducing a cat cerebellum on a supercomputer (In Japanese), 2016/6/13(2) My Navi News, A cat cerebellum on supercomputer Shoubu (In Japanese), 2016/6/20(3) UEC:Report, Can a Next-generation Supercomputer Reveal How the Brain Works? , 2016/7/6

2.5 Award(1) Toshiki Kusano，Hiroki Kurashige，and 5 more persons. Research Award, Japanese Neurol Network
Society, 2016/10/19
2.6

Student guidance(1) Ohki Katakura, 2014, Master (Engineering)(2) Daisuke Ichimura, 2014, Master (Engineering), now in Doctor course(3) Tsukasa Tsuyuki, 2015, Bachelor (Engineering), now in Master course(4) Wataru Furusho, 2016, Bachelor (Engineering), now in Master course

3. Research funding
3.1 Grant-in-aid for scientific research(1) Tadashi Yamazaki (PI), Study on Synergistic Motor Control Mechanisms of Distributed Plasticity in the
Cerebellum, Grant-in-Aid for Scientific Research (C), 2014/4/1-2017/3/3

90

3.2. Competitive external research funding(1) Tadashi Yamazaki (PI), R&D of Artificial Motor Cortices, NEDO Next-Generation Artificial
Intelligence R&D, 2015/7/1-2018/3/31(2) Tadashi Yamazaki (PI), MEXT Post-K Supercomputing Project, 2016/8/1-2017/3/31

4. Collaboration
4.1 Inside BLSC
(1) Shigeru Tanaka, Theoretical study on the cerebellum, 2013/04-

4.2 Outside BLSC in UEC(1) Adjunct member, Artificial Intelligence eXploration Research Center, 2016/07-

4.3 Outside UEC(1) Neuroinformatics Japan Center, RIKEN, Study on Neural Network Simulation, 2013(2) AI Research Center, AIST, R&D of Brain-style Artificial Intelligence, 2015(3) Junichiro Makino, Kobe University, Large-Scale Simulation of the Cerebellum on PEZY-SC, 2015(4) Toshikazu Ebisuzaki, RIKEN, Large-Scale Simulation of the Cerebellum on PEZY-SC, 2015(5) Jun Igarashi, RIKEN, Computer Simulation of the Cerebellar Network Model on GPUs, 2013(6) Tmagawa Hospital, Computer Simulation of Rehabilitation with Neuromusculoskeletal models, 2014(7) Chung Tin, City Universyty of HongKong, Cerebellar circuit simulation on FPGAs, 2013-

5. Outreach activities
5.1 Editor of academic journals(1) Review Editor, Frontiers in Computational Neuroscience, 2012/05(2) Action Editor, Neural Networks, 2016/01-

5.2 Paper review of academic journals
Many times from prestigious journals including PNAS and Science to technical journals including
Neural Networks and Frontiers in Computational Neuroscience.

91