A05 Research Group

A05-1 Elucidation of the hyper-adaptation mechanism of upper limb recovery in stroke patients

Research Outline

This study aims to elucidate the hyper-adaptation mechanism of upper limb recovery in stroke patients. We longitudinally investigate relationship among frequency of upper limb use, body-specific attention and brain activities in stroke patients by using accelerometers, psychophysical methods, and fMRI, respectively. We expect the elucidation of the adaptation mechanism underlying upper limb recovery after stroke could contribute to understanding the hyper-adaptation mechanism of body-brain system.

Members

Principal Investigator	Shinichi IZUMI	Professor, Tohoku University
Co-investigators	Ryoji OTAKI	Ph.D Student/Occupational therapist, Tohoku University
	Tamami SUDO	Researcher (Part-time Lecturer), Oouchi Hospital(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
	Shintaro SEKI	Part-time Lecturer, Tohoku University

A05-3 Mechanism of Hyper-Adaptivity of the human premotor area: electrophysiological connectome analysis with electrocorticogram

Research Outline

In order to elucidate the Hyper-Adaptivity mechanism of motor function under aging and pathological condition, it is essential to understand hyper-adaptability of the premotor cortex that integrates the information top down from the prefrontal cortex and bottom up from the parietal lobe.
We record electrocorticogram (ECoG) in epilepsy patients who undergo intracranial electrode implantation in the frontal and parietal lobes for preoperative evaluation of epilepsy surgery. We probe neural signatures of higher-order motor control by recording wide-band ECoG activities during higher-order motor tasks. In order to understand the brain network associated with motor control, we make an electrophysiological connectome by using cortico-cortical evoked potentials (CCEPs) as an index of effective connectivity, which were obtained by systemic evaluation of the whole implanted electrodes. We extract structural features such as cluster coefficient or centrality, and attempt to clarify modifications of the connectome by epilepsy pathology or variations by different strategies for higher-order motor tasks.
In order to clarify how the brain hyper-adapts to the intervention to the premotor cortex, we investigate the impact of high frequency electrical stimulation and brain surgery on hyper-adaptation. We apply high frequency electrical stimulation to the cortex for clinical functional cortical mapping. Stimulation of the premotor areas has effect on the execution of higher-order motor tasks to a variable degree. To investigate the immediate modulation, we use this opportunity to study the relationship between the mode of behavior impairment and network impairment by combining quantitative motion analysis and ECoG signal analysis during stimulation. To investigate the acute and subacute (hyper)adaptation at the network level, we investigate the impact of the resection of the premotor area by simulating the virtual lesion using the electrophysiological connectome, and comparing it with the movement disability and its recovery after surgery.

Members

Principal Investigator	Riki MATSUMOTO	Professor, Kobe University
Co-investigators	Akihiro SHIMOTAKE	Assistant Professor, Kyoto University
	Takayuki KIKUCHI	Assistant Professor, Kyoto University
	Kiyohide USAMI	Assistant Professor, Kyoto University
	Hirofumi TAKEYAMA	Assistant Professor, Kyoto University
	Masaya TOGO	Assistant Professor, Kobe University
	Kozue HAYASHI	Graduate Student, Kyoto University
	Kento MATOBA	Graduate Student, Kobe University

A05-5 Development of non-invasive brain stimulation techniques that can increase recruitment of the corticospinal motor indirect pathway during acquisition of hand motor skills.

Research Outline

Hand movement is controlled mainly by two corticospinal pathways: the direct pathway and the indirect pathway. The direct pathway sends monosynaptic efferents from the primary motor cortex (M1) to motoneurons in the spinal cord through the corticospinal tract. The indirect pathway originates from bilateral M1, and relays inputs to motoneurons through the reticulospinal or propriospinal tract in the brainstem and spinal cord. Although the indirect pathway had long been considered necessary for gross forelimb movements in lower mammals, recent evidence suggests a role for the indirect pathway in controlling dexterous hand movement in higher primates. We found asymmetric organization of the direct and indirect pathway for preferred hand and nonpreferred hand movement. In this project we will develop non-invasive brain stimulation techniques that can increase recruitment of the indirect pathway during motor skill learning. We will apply dual stimulation techniques for the aim to activate the indirect pathway by facilitating or suppressing activity in bilateral M1s.

Members

Principal Investigator	Mitsunari ABE	Section Chief, National Center of Neurology and Psychiatry
Co-investigators	Kazumasa UEHARA	Assistant Professor, National Institute for Physiological Sciences

A05-6 Analysis of motor control system in the recovery of forelimb function by rehabilitation after intracerebral hemorrhage

Research Outline

Constraint-induced movement therapy (CIMT) is known as an effective rehabilitation by forcing the use of damaged forelimb after the cerebrovascular disorder. Using model rats that show relatively big motor deficits with a small hemorrhage near the internal capsule (ICH), we are trying to clarify the mechanism of forced-limb use (FLU) that represents CIMT in rats. We revealed that FLU after ICH improves the recovery of disturbed forelimb function by ICH, cortico-rubral pathway is involved in the functional recovery by FLU, and cortico-reticular pathway has a potential to substitute the recovery of cortico-rubral pathway when needed. However, dynamic change of the adaptive mechanism via the cerebellum in the functional recovery by FLU is still unknown. In this study, we will try selective blockade of rubro-spinal tract or rubro-olive tract using the double virus vector infection, clarifying the adaptive changes of the regulatory system mediated by the cerebellum on the functional recovery by FLU after ICH.

Members

Principal Investigator	Hideki HIDA	Professor, Nagoya City University
Co-investigators	Naoki TAJIRI	Associate Professor, Nagoya City University
	Takeshi SHIMIZU	Lecturer, Nagoya City University
	Kenta KOBAYASHI	Associate Professor, National Institute for Physiological Sciences

A05-7 Regulatory mechanisms of inter-regional network changes underlying hyper-adaptation from mal-adaptation state caused by fear memory.

Research Outline

Excessive fear memories prevent animals to take optimal behaviors, which are refered as to mal-adaptation states. Extinction learning induces hyper-adaptation through which the animals recover optimal behaviors. By using multi-regional large-scale electrophysiology on freely moving rats, we investigate the network changes underlying the hyper-adaptation and regulatory mechanisms of the changes.

Members

Principal Investigator

Hiroyuki MIYAWAKI

Assistant Professor. Osaka Metropolitan University

A05-8 Facilitating hyper-adaptation in neurological and psychiatric diseases thorough improving precision on the sense of agency

Research Outline

The sense of agency (SoA) is the feeling that a person initiates and controls his/her own actions and their effects on the outside world, it is one of the important self-awareness during actions. We have originally created the rehabilitation method for improving precision on the SoA for patients with neurological and psychiatric diseases. Our approach intends to intervene and re-organize nervous systems for facilitating hyper-adaptation in recovery processes of those diseases.

Members

Principal Investigator	Takaki MAEDA	Assistant Professor/Senior Assistant Professor, 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

A05-9 The role of inhibitory neurons related to skilled hand movements after spinal cord injury.

Research Outline

The ability to learn new motor skills or recovery after stroke is supported by plasticity in the structural and functional reorganisation of the primary motor cortex. Inhibitory neurons are thought to play an important role in the regulation of these plasticity. There are also numerous reports on the reorganization of the brain during the recovery of motor function after spinal cord injury, but little is known about the relevance of inhibitory neurons. Here, using in vivo calcium imaging or DREADD in marmoset spinal cord injury model, we examine rehabilitation-induced activity change of inhibitory neurons.

Members

Principal Investigator	Takahiro KONDO	Assistant Professor, Keio University
Co-investigators	Yuta SATO	Ph.D Student, Keio University

A05-11 Activating preference network for affected side by neural and behavioral modulation.

Research Outline

To improve ADL after stroke impairments, it is necessary, not only to promote recovery of impaired functions but also to facilitate the attention to the affected side and to induce the preference for the affected side so that the patients are willing to utilize the affected side of the body in their daily life. Therefore, we will try to activate the neural networks that are responsible for inducing preference for the affected side by neural modulation and manipulation of the body space.

Members

Principal Investigator	Rieko OSU	Professor, Waseda University
Co-investigators	Taiki YOSHIDA	Ph.D Student, Waseda University
	Kento HIRAYAMA	Ph.D Student, Waseda University

A05-12 Hyper-adaptability from inducing synapse connection and regulation of extracelluar matrix. -Spinal cord injury and AI-based motion capture-

Research Outline

Spinal cord injury (SCI) causes permanent dysfunction in the body movement and sensation. Many studies in both animal tests and clinical trials have been conducted, however established methods for recovery are currently limited. To achieve the substantial recovery from SCI, a combined method to down-regulate a repulsive factor (the regulation of Chodroitin-sulfate: Takeuchi, et.al., Nature commun.) and promote re-wiring (the injection of the synthetic synaptic organizer protein: Suzuki, et.al., Science) would be useful. We investigated the effects of the individual factors and next examined the combined effect by using the AI-based motion-capture system for mice models. Our approach represents a promising strategy to amelioration from SCI and further analysis are undergoing.

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
	Yuki MORIOKA	Research Technician, Aichi Medical University

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

Research Outline

This research project aims to investigate key factors that determine the hemisphere involved in functional recovery after infarction in the unilateral posterior internal capsule, using a macaque model of internal capsular stroke we developed. 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 Animal model of unilateral spatial neglect in marmosets

Research Outline

Unilateral spatial neglect (USN) is a characteristic failure to explore the side of space contralateral to a brain lesion, which cannot be explained by primary sensory or motor disorders. To establish an animal model of USN in marmosets, we will conduct the following experiments. 1) A surgical lesion is made to the right TPO of marmosets and the monkeys’ behavior is examined whether they exhibit symptoms of USN. 2) ECoG electrodes are implanted to measure cortical network activity. 3) Local cortical activities are measured with a Ca imaging system with an endoscope. 4)These findings are modeled by computational models. 5) The marmosets’ circuit is intervened based on the predictions made by the model.

Members

Principal Investigator	Masatoshi YOSHIDA	Specially Appointed Associate Professor, Hokkaido University
Co-investigators	Hiroshi MATSUI	Postdoctoral Fellow, Hokkaido University
Co-investigators	Polyakova Zlata	Postdoctoral Fellow, Hokkaido University