A05 Research Group

A05-1 A closed-loop brain stimulation for reinforcing hyper-adaptability

Research Outline

Functional network reorganization in the brain can lead to positive outcomes for example a recovery from functional disability after brain injuries, whereas it can lead to negative outcomes as well for example phantom limb pain as a result of maladaptation. However, there was no brain stimulation technology that properly guides functional network reorganization in the brain properly so far. Therefore, in this study we will develop a brain stimulation technology that reinforces a target brain state by precisely-timed stimulation of the brain reward system for positive outcomes.

Members

Principal Investigator	Yuichi TAKEUCHI	Associate Professor, Hokkaido University
Co-investigators	Michele Chan	Specially Appointed Assistant Professor, Hokkaido University

A05-2 Comprehensive understanding of the mechanism of adaptive changes in brain, body consciousness and arm use underlying upper limb recovery in stroke patients

Research Outline

This study aims to comprehensively understand the mechanism of adaptive changes in brain, body consciousness and arm use underlying upper limb recovery in stroke patients. We longitudinally investigate plastic changes in functional and structural brain networks in subacute stroke patients using resting-state fMRI and DTI. In addition, we measure arm use and body-specific attention by using accelerometers and psychophysical methods, respectively, to elucidate the causal relationship and neural basis of these changes. We expect to investigate the neural basis of hyper-adaptation in the rehabilitation of stroke upper limb paralysis and to contribute to the elucidation of the relationship between behavioral execution and neural reorganization.

Members

Principal Investigator	Shinichi IZUMI	Professor, Tohoku University
Co-investigators	Shintaro SEKI	Part-time Lecturer, Tohoku University
	Ryoji OTAKI	Ph.D Student, Tohoku University
	Tamami SUDO	Researcher, Oouchi Hospital / Part-time Lecturer, Tohoku University
	Ryuko ISHIMODA	Assistant Technical Staff, Tohoku University
	Naoki AIZU	Assistant Professor, Fujita Health University
	Juan WU	Graduate Student, Tohoku University
	Kouta ATAKA	Graduate Student, Tohoku University

A05-3 Elucidation of neural circuits for optimal adaptation to the external environment

Research Outline

Blindly over-adapting to the external environment or failing to adapt to it often leads to mental and physical illness and, in many cases, a decline in our quality of life. It is thought that optimal adaptation is essential to improving our quality of life. Using rats and mice performing visual discrimination tasks, we would like to clarify how the adaptation of the input-output relationship to the changes in visual stimulus contrast is influenced by mental stress and developmental disorders. By examining the visual responses in the multidimensional brain systems across multiple regions, we aim to understand the neural basis of optimal adaptation to the external environment.

Members

Principal Investigator

Rie KIMURA

Specially Appointed Assistant Professor, The University of Tokyo

A05-4 Neural substrate of unified learning theory for adaptive behavior

Our adaptive behavior is based on multiple strategies. For example, let s think about Rock-paper-scissors which is one of the most popular game s in Japan. In this game , one decides the choice (rock, paper , scissors) (i) based on its favorites choice or (ii) by estimating the opponent’s choice. How does the brain generate such complex decisions? One hypothesis is that the brain keeps multiple learning strategies in parallel and decides which strategy to use. Another hypothesis is that the brain keeps only one learning strategy but generates flexible behavior with the non linear neuronal circuit. Our study is to investigate the hypotheses by combining mouse behavioral task, neural recording and neural manipulation and behavioral modeling with artificial neural network (AI). Accomplishment of our study leads to understand the neural mechanism of adaptive behavior. In future, I hope that our study contributes to build a brain-like AI.

Principal Investigator	Akihiro FUNAMIZU	Lecturer, The University of Tokyo
Co-investigators	Maria Ines de Sa Ribeiro	Research Technician, The University of Tokyo

A05-5 Enhanced neuronal circuits for vocal learning with extensive experiences during development

Neuronal circuits are intensively shaped or modified depending on experiences during development. It is reported that excessive experiences in juvenile period extends the ability to adapt to new environment in adult barn owl sound localization behavior.
Like humans leaning to speak, songbirds learn to sing by listening and memorizing, and then mimicking adult tutor’s song exclusively during development. We reported that memories of tutor’s song form in the higher auditory cortex in zebra finches, a premiere modeling of songbirds. Recent our study further showed that auditory cortical neurons related to song auditory memory project to motor brain areas for song learning only in the developmental song learning period. We also suggest in adult zebra finches which leaned two songs sequentially from two tutors, neuronal connection from auditory to motor area retains. Here in this project, we will elucidate how extensive learning retain the neuronal circuits for song learning, and further seek possibilities of re-leaning in adults.

Members

SUGIYAMA

Principal Investigator

Yoko YAZAKI-SUGIYAMA

Associate Professor, The Okinawa Institute of Science and Technology Graduate University / Project Associate Professor, The University of Tokyo

A05-7 Mechanism of Hyper-Adaptivity of the human premotor area: electrophysiological connectomes analysis with electrocorticogram

Research Outline

It remains a challenge in 2020’s to predict whether higher motor impairments, such as tool use, will remain or recover after surgical resection of motor-related areas. It is essential to understand the network, including not only cortical regions but also connections between the regions. We have created a cortical ECoG connectome, based on effective connectivity analysis using comprehensive low-frequency electrical stimulation in the previous project. We demonstrated the structural features of the brain networks associated with higher brain functions. In this project, we hypothesized that change of structural features has impact on the degree of higher motor deficits and recovery after cortical resection. We also hypothesized that circuits not normally used (“alternative or hibernated circuits”) are activated during recovery from deficits (hyperadaptation). Using our database of ECoG connectomes, we will simulate and quantify the structural network changes after brain resection, using parameters such as graph-theoretical parameters. This study aims to elucidate the association between the simulated network changes after surgery and the degree of impairment and recovery for tailor-made prediction of the functional prognosis on higher motor functions.

Members

Principal Investigator	Riki MATSUMOTO	Professor, Kobe University
Co-investigators	Takashi SASAYAMA	Professor, Kobe University
	Yosuke FUJIMOTO	Assistant Professor, Kobe University
	Masaya TOGO	Assistant Professor, Kobe University
	Kento MATOBA	Assistant Professor, Kobe University
	Takayuki KIKUCHI	Lecturer, Kyoto University
	Akihiro SHIMOTAKE	Assistant Professor, Kyoto University
	Kiyohide USAMI	Assistant Professor, Kyoto University
	Hirofumi TAKEYAMA	Visiting researcher, Kyoto University
	Masamune KIMURA	Graduate Student, Kobe University
	Kozue HAYASHI	Graduate Student, Kyoto University

A05-8 Interregional brain network dynamics enabling hyper-adaptation from a fear-memory induced maladaptive state.

Research Outline

Due to memories of excessive fear, animals fall into a maladaptation state in which the animal cannot take optimal behaviors. Extinction learning of the fear memory induces hyper-adaptation through which the animals recover optimal behaviors. By using multi-regional large-scale electrophysiology on freely moving rats, we have revealed that inter-regional coactivation emerged after the transition to the maladaptation state, however, it remains unknown how inter-regional network changes through hyper-adaptation. In this study, we will investigate how hyper-adaptation changes the inter-regional networks and how the changes are regulated by using large-scale electrophysiology, optogenetics, and behavioral analyses.

Members

Principal Investigator

Hiroyuki MIYAWAKI

Lecturer, Osaka Metropolitan University

A05-9 Research on developing a cognitive rehabilitation method for neurological and psychiatric diseases thorough improving precision on the sense of agency

Research Outline

Our research project aims to reveal neural mechanisms of the sense of agency (SoA) from the standpoint of functional connectivity. The SoA is the feeling that a person controls his/her own actions and their effects on the environment, it is one of the important self-awareness during actions. Moreover, we intend to study pathophysiology of neurological and psychiatric illnesses from the stand of neural dysconnection. We have originally created a cognitive rehabilitation method for improving precision on the SoA. Our approach intends to intervene and re-organize nervous systems for facilitating recovery processes of these diseases.

Members

Principal Investigator	Takaki MAEDA	Lecturer, Keio University
Co-investigators	Yuichi YAMASHITA	Section Chief, National Center of Neurology and Psychiatry
	Tsukasa OKIMURA	School of Medicine, Keio University
	Hiroki OI	School of Medicine, Keio University

A05-10 Adaptive mechanisms for perturbations in the neural manifold.

Research Outline

A hallmark of our motor system is the adaptability to the drastic changes in the body and nervous systems, that is called “hyper-adaptability”. The goal of this project is to understand what neural mechanisms differentiate the hyper-adaptation and the normal adaptation. Our approach is multidisciplinary, including 1) brain-machine interface to manipulate motor systems and 2) constructing an artificial neural network model to reproduce the hyper-adaptation. By taking advantage of these diverse techniques, we aim to identify the neural basis for the “hyper-adaptability”.

Members

Principal Investigator	Tomohiko TAKEI	Associate Professor, Brain Science Institute, Tamagawa University
Co-investigators	Akihiro MASAOKA	Adjunct Research Fellow, Tamagawa University

A05-11 Spatio-temporal modulation of disinhibition for super-recovery from motor dysfunction in the chronic phase of stroke

Research Outline

We hypothesize that sustained disinhibition of neural activity blocks the recovery of motor function after stroke. In this study, we will develop a method to induce ‘super-recovery’ after stroke by controlling the disinhibition properly. For this aim, we combine several methods: 1. Advanced analysis of Motor function with 3D posture of animals using DeepLabCutTM. 2. Electrophysiological recording of neural activity related to motor function. 3. High-speed wide-field imaging of neural activity. 4. Controlling the neural activity of specific regions by optogenetics. Being aware of the gap between rodents and humans, we will conduct this study to provide knowledge that will lead to a new therapeutic way for recovery from motor dysfunction after stroke.

Members

Principal Investigator	Hironobu OSAKI	Program-Specific Associate Professor, Doshisha University
Co-investigators	Yoshito MASAMIZU	Professor, Doshisha University
	Kaneyasu NISHIMURA	Associate professor, Doshisha University
	Kotaro TEZUKA	Graduate student, Doshisha University

A05-12 Hyper adaptive changes in spatial recognition

Research Outline

Impairments in the right hemisphere of the brain due to stroke or other deficits sometimes cause unilateral spatial neglect; the patients ignore the visual space on the left side of the body, even though vision is intact. Even though this symptom is relatively frequent, effective rehabilitations are limited, and “not noticing” the left side of the space can interfere with ADL. Therefore, we aim to obtain insight into the neural mechanisms of spatial attention to help recover from unilateral spatial neglect through hyper-adaptive intervention using augmented reality (AR) and a robotic interface.

Members

Principal Investigator	Rieko OSU	Professor, Waseda University
Co-investigators	Kento HIRAYAMA	Ph.D Student(Assistant), Waseda University
	Yuki ITO	Master Student, Waseda University
	Taiki YOSHIDA	Assistant Professor, Fujita Health University
	David Franklin	Prof. Dr., Technical University of Munich

A05-13 Creation of hyper-adaptability by synthetic synaptic organizers and micro-environmental control of neural reconstruction

Research Outline

TSpinal cord injury（SCI）causes permanent dysfunction in the body movement and sensation. We are using new techniques and methodologies as ” Synthetic synaptic connectors” and “Regulation of neural microenvironments”. Furthermore, we have introduced an analysis system using AI deep- learning to analyze the process of recovery of physiological functions. We aim to create a system that analyzes the Hyper-adaptive process of neural and motor functions by synthetic-synapse organizers, and to construct a throughput system that can evaluate the function improvement in detail.

Members

Principal Investigator	Kosei TAKEUCHI	Professor, Aichi Medical University
Co-investigators	Hiroyuki SASAKURA	Assistant Professor, Aichi Medical University
	Masashi IKENO	Associate Professor, Aichi Medical University
	Satoko HATTORI	Associate Professor, Aichi Medical University
	Yuki MORIOKA	Research Technician, Aichi Medical University

A05-14 Brain reorganization in stroke patients with hyper-recovery by measuring EEG modulation induced by static and dynamic magnetic fields.

Research Outline

Based on the hypothesis that “miraculous healing” in stroke can be viewed as a dramatic expression of hyper-adaptation , clinical studies will be conducted on such post-stroke people with “hyper-recovery”, focusing on the reorganization of neural networks.
The purpose of this study is to measure functional neural networks by TMS/tSMS-EEG and to elucidate the specificity of neural network reorganization in hyper-recovery, and to search for neural connections that are latent in normal subjects but become active during the process of hyper-adaptation

Members

Principal Investigator	Tatsuya MIMA	Professor, Ritsumeikan University
Co-investigators	Sumiya SHIBATA	Professor, Niigata University of Health and Welfare
	Satoko KOGANEMARU	Program-specific Associate Professor, Kyoto University

A05-15 Brain adaptation after limb loss

Research Outline

If we lose a part of our body because of accident or disease, how does our brain adapt and overcome difficulties? After losing our upper or lower limb, we can still sense our lost limb as it is still attached (phantom limb) and sometimes experience severe pain (phantom limb pain). Our brain, especially somatomotor and somatosensory cortices show one-to-one correspondence between our brain and body (somatotopy). How does our somatotopy change after losing our limb? To answer these questions, we will use macaque monkeys who lost their upper limb by accident and map these cortical areas by direct recording and manipulation.

Members

Principal Investigator	Atsushi NAMBU	Professor, National Institute for Physiological Sciences
Co-investigators	Nobuhiko HATANAKA	Assistant professor, National Institute for Physiological Sciences
	Satomi CHIKEN	Assistant professor, National Institute for Physiological Sciences
	Pimpimon NONDHALEE	Research fellow, National Institute for Physiological Sciences

A05-16 Adaptive mechanism occurring in both hemispheres after unilateral brain damage

Research Outline

The brain has “adaptability” to reconstruct neural structures and functions to compensate for the brain lesions caused by stroke. Our recent study using a macaque model of unilateral internal capsular infarcts reported compensatory changes in motor cortical activity after recovery of dexterous hand movements. The results are consistent with stroke patients in that the cortex contralateral to stroke plays a greater role in recovery when lesions are more severe. This research project aims to investigate key factors that determine the hemisphere involved in functional recovery after infarction in the posterior internal capsule using the macaque model. Moreover, this project will reveal changes of brain structure that underlie compensatory adaptation of brain function in each hemisphere.

Members

Principal Investigator	Noriyuki HIGO	Group Leader, National Institute of Advanced Industrial Science and Technology
Co-investigators	Toru YAMADA	Senior Researcher, National Institute of Advanced Industrial Science and Technology
	Hiroshi KAWAGUCHI	Senior Researcher, National Institute of Advanced Industrial Science and Technology

A05-17 Functional reorganization of motor and somatosensory cortices during recovery of motor functions after the loss of peripheral sensory inputs

Research Outline

The somatosensory system plays an important role in the execution of movement. Indeed, patients who cannot receive somatosensory information due to peripheral sensory neuropathy exhibit not only sensory but also motor impairment. In this study, we make monkeys that selectively lack somatosensory input from the upper limb to the central nervous system by cutting the dorsal roots of the cervical cord. Such a monkey with somatosensory paralysis exhibits motor impairment of the upper limbs, but the motor function gradually recovers within several weeks. By recording and analyzing ECoG signals in the cerebral motor-related and somatosensory areas during the recovery, we aim to clarify the adaptive process of cerebral cortical activity underlying the recovery of motor function.

Members

Principal Investigator

Osamu YOKOYAMA

Senior Researcher, Tokyo Metropolitan Institute of Medical Science