Interspecies Comparison: AMED Brain/MINDS Beyond (Kokusai Nou) Program

Mental and psychiatric disorders are characterized by impairment of higher cognitive functions. To elucidate the neural basis of this deficit, we need to identify the underlying neural mechanisms, based on fMRI scanning of patients with these disorders. To demonstrate the causal relationship in experimental models, it is also necessary to perform animal studies. In this study, we will use macaque and marmoset monkeys because they are closely related to humans in evolutionary terms, and thus provide an excellent and irreplaceable model of human disorders. Using the 7T MRI scanner, we will investigate anatomical and functional similarities and differences between these monkey species and humans. Specific goals include the following:

(1) To establish procedures for the acquisition and analysis of ultrafine functional and anatomical 7T MRI scan images of humans and monkeys, along with standardized data formats and analytical procedures.

(2) To investigate the neural basis for social cognitive functions, ultrafine anatomical and functional 7T MRI scans will be obtained for disease-related and other regions of macaque monkeys. These scans will be compared with human scans acquired using the same sequence, and homologous neural regions and functional regionalization will be compared between species.

(3) Healthy macaque and marmoset monkeys will be subjected to 7T MRI scanning to obtain ultrafine anatomical and functional images of the basal ganglia and other deep brain structures. These scans will be integrated with the results of electrophysiological and neuroanatomical brain mapping and connectivity analysis. Similar procedures will be used for the basal ganglia dysfunction model.

(4) To study recovery of manual dexterity, visual motor, cognitive, and other functions in macaque models of neural injury by (i) cervical insult, (ii) primary visual cortex lesion, and (iii) selective neural transfection by double virus vector infection. In particular, a large volume of data on neural functional and structural changes will be collected using electrocorticography and depth electrodes, and the obtained data will be applied to machine learning analysis of neural network architecture. In addition, high-sensitivity viral tracers will be used for neuroanatomical analysis. These results will be projected onto 7T fMRI scan maps.

(5) Physiological findings made in nonhuman primates will be combined with their 7T fMRI scan data, and an interspecies linkage database will be created that describes the relationship between these nonhuman findings and 3T MRI scan data collected from a cohort of patients with brain diseases. The 7T MRI technology will play a critical role in creating the interspecies linkage database. This database will greatly advance the understanding of the functional anatomy of the basal ganglia, a key organ involved in social behavior control, brain plasticity, and mental or neurological disorders.

Our proposal has been accepted as a 6-year project (FY 2018 to FY 2023) under the AMED Brain/MINDS Beyond (Kokusai Nou) Program Research Cluster No. 2: Interspecies Comparison of the Brain Between Humans and Nonhuman Primates.

Contributions to Applied Brain Sciences

Foreign Language Learning Process

In collaboration with Prof. Hirokazu Yokokawa of the Kobe University, we used neuroscientific approaches and investigated the process of learning English as a second language in a project entitled “An Investigation of the Automatization Process in Second Language Processing With Respect to Noticing, Attention, and Interactive Alignment” (Grant-in-Aid for Scientific Research [A] Program). We will shift our focus from the automatization of language processing to the association between social interactions and language skill improvements. The methodologies explained above will be an asset to our future research.

Contributions to Affective Neuroscience

Along with NTT Data Institute of Management Consulting, Inc., Yokohama National University, and other institutions, NIPS has been participating in the Center of Innovation Science and Technology–based Radical Innovation and Entrepreneurship Program (COI STREAM) since FY 2013. NIPS is positioned as a satellite institution to the Center of Kansei Innovation Nurturing Mental Welfare (hereinafter referred to as the “Center of Kansei Innovation”).

This vision-driven program fostering industry–academia collaboration aims to establish innovation platforms that cannot be developed by industry or academia alone. In this program, the goals of the ideal society and lifestyle will be articulated in the form of program visions taking note of latent needs for future growth, and these program visions chart the course for innovative research and development that should be achieved within a decade. The COI STREAM program is run by the JST under the sponsorship of the Science and Technology Policy Bureau, MEXT. The program visions are three-fold:

-Vision No. 1: Secure sustainability, as a country with an aging population and declining birth rate;

-Vision No. 2: Create a living environment with a high quality of life, as a prosperous and reputable country; and

-Vision No. 3: Establish a sustainable society with vitality.

NIPS operates under Vision No. 2 as a satellite institution to the Center of Kansei Innovation, jointly led by Hiroshima University and Mazda Motor Corporation. Dr. Takahide Nouzawa of Mazda and Dr. Shigeto Yamawaki of the Department of Psychiatry and Neurosciences, Hiroshima University Graduate School of Biomedical and Health Sciences, are the project leaders of the Center of Kansei Innovation. This project aims to propose a new product development method that comprises quantification of kansei, or the perception of inherent affective and cognitive quality. This method is expected to surpass the conventional ‘hunch-based’ approach to commercial development. In collaboration with private companies, our Division is conducting research to visualize, and construct a model of, the human perception process. This research is entitled “The Sense of Sharing in Social Interactions.”

Participation in Government-Funded National Projects

AMED Brain/MINDS

See also " Technological Development of 7T MRI"

The AMED Brain/MINDS project was launched to elucidate the mechanisms of micro-scale neural circuit formation and how signal processing contributes to sustaining macro-scale brain integrity. This project will provide a basis for understanding the mechanisms of higher human brain functions, and will thereby assist in overcoming mental and psychiatric disorders. Several researchers in our Division are among the members of the Clinical Research Group (leader: Dr. Kiyoto Kasai, Prof. of the University of Tokyo Graduate School of Medicine), which is in charge of developing ultrahigh-field (7T) MRI scanning and analysis protocols for human neural circuitry. The specific objective of our team is to help advance connectomics through (i) three-dimensional reconstruction of the human cortical architecture and neural circuits at resolutions of a few hundred microns, and (ii) acquisition and integration of ultrahigh-resolution scan images of brain activity during higher-order cognitive tasks. In FY 2016, a signal detection coil system was created for use in macaque monkeys. Brain MRI scans obtained in this species will assist in extrapolating marmoset data to humans.

AMED Integrative Research on Depression, Dementia, and Development Disorders

Yuugou Nou, See also "MRI Research Using Japanese Monkeys"

The AMED SRPBS program aims to advance brain science towards positive social contributions and to thereby overcome a variety of challenges to our rapidly diversifying society. With the ultimate goal of understanding the vast complexity of functional networks in the human brain, ongoing research seeks to provide the basis for overcoming psychiatric and neurological problems. Under this umbrella program, a new initiative entitled “Integrative Research on Depression, Dementia, and Development Disorders (IR 3D, Yuugou Nou)” was started. Under the guidance of Associate Prof. Fukunaga, our Division participated in the study entitled “Development of Combination Therapy Consisting of BMI Technology and Biological Compounds to Promote Restoration of the Injured Central Nervous System” (principal investigator: Dr. Toshihide Yamashita, Prof., Osaka University). Our team’s task was to find a new biomarker for functional recovery through resting-state fMRI measurement and large-scale connectivity analysis.

AMED SRPBS (Nou Puro) Decision Making

The AMED SRPBS Decision-Making initiative was started in November 2016 under the leadership of Prof. Tadashi Isa of the Kyoto University. A group of NIPS researchers led by Prof. Masaki Isoda participated in this research. Dr. Isoda was in charge of a project entitled “Towards a System-Level Understanding of Social Decision-Making and Behavioral Control,” and Prof. Sadato became a subproject leader of the project entitled “Integrative Studies on Neural Circuit Basis of Flexible Decision Making in Humans and Nonhuman Primates” (project leader: Dr. Isa). The goal of Dr. Sadato’s study was to develop a method for evaluating the effects of face-to-face verbal interactions through simultaneous measurements and modeling of the neural representations of two mutually engaged individuals.

In preparation for the study of the neural basis of decision-making in social contexts, preliminary work was carried out in FY 2017 to establish the methodologies for concurrent fMRI and EEG measurements of the brain activities of dyads. Specifically, measurement conditions were optimized by using electric shields to reduce the noise from the EEG device located in the MRI system. In addition, to obtain simultaneous, high–temporal resolution fMRI scans of two individuals, a new instrument was introduced to reconstruct the scan data at an ultrahigh speed. This instrument was applied to simultaneous fMRI measurement of two persons engaged in a joint task. Moreover, using the 7T MRI system, we developed a technique for removing noise during resting-state functional imaging, and obtained high-resolution diffusion-weighted scans.

AMED Brain/MINDS Beyond

Kokusai Nou, See also the top of the page

In close coordination with the AMED Brain/MINDS (Kakushin Nou) and other existing national research projects, the AMED Brain/MINDS Beyond (Kokusai Nou) promotes international collaboration for early detection and treatment of psychiatric and neurological illnesses. The specific objectives of this project include the following: longitudinal analysis of fMRI scans at different stages of pathology, interspecies comparison of the brain activity between humans and nonhuman primates, and clarification of human brain function at the neural circuit level.