Progress Report
Realization of a society where people can live a forward-looking life in the face of adversity[2] Assistance and training for “Maemuki (Forward-looking mind)”
Progress until FY2024
1. Outline of the project
This research and development initiative aims to create training technologies that sustainably enhance "Maemuki" and assistive technologies that support such enhancement. The project also accumulates knowledge on pharmacological and chemogenetic manipulation of neurotransmitters in non-human primates, with the goal of establishing personalized and context-sensitive "Maemuki" assist and training technologies.
2. Outcome so far
Techniques for inducing psychological "Maemuki" through gait and posture interventions have been validated, and real-time feedback systems using sensory stimuli have been developed. In addition, molecular manipulation technologies targeting non-human primates have been established, forming a foundation for long-term and selective control of neural activity.
● Physical intervention target in gait for "Maemuki" assist and training
To investigate how changes in posture and movement during walking affect psychological "Maemuki", Dr. Natsuki Sado’s research group (University of Tsukuba) conducted experiments involving posture interventions. Their work focused on depressive gait patterns such as slouched posture and short strides, and tested interventions like gaze guidance and posture correction to elicit more positive movement patterns. Through comparative analysis of ballet dancers and general female participants, the group demonstrated that long-term posture training can influence specific body regions.
In parallel, Dr. Takahiro Hirao’s research group (QST) developed a biofeedback system that utilizes sensory inputs such as optical flow and rhythmic sounds. This system analyzes multidimensional biosignals—including EEG, heart rate, respiration, gaze, and ground reaction force—in real time and provides feedback through auditory and visual stimuli. The group also used fMRI to examine how different types and presentations of visual stimuli affect motor sensation and brain activity, contributing to the development of sensory-based methods for inducing "Maemuki".
● Development of molecular manipulation techniques for monkeys
In the domain of molecular manipulation, Dr. Takashi Minamoto’s research group (QST) applied chemogenetic techniques using DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) to control neural activity. They used PET imaging to evaluate long-term expression stability and validated the effectiveness of neural manipulation. The group also developed AAV vectors targeting serotonin and dopamine systems, enabling selective and stable activation of specific brain regions. Furthermore, they created shortened DREADD constructs and vectors with selective expression in serotonin neurons to support precise neural circuit manipulation.
Complementing this work, Dr. Kenichi Inoue’s research group (Kyoto University) pursued structural optimization of viral vectors to balance expression efficiency and specificity. They successfully developed shortened DREADD constructs that allow high-efficiency gene expression within size constraints. The group also established experimental systems to evaluate expression distribution and functional effects in the primate brain, and collaborated with Dr. Minamoto’s group to validate the effectiveness of these systems.
These achievements provide a strong biological and technological foundation for understanding the mechanisms of "Maemuki" and for advancing molecular-level research on psychiatric and neurological disorders. Future applications may include innovative therapeutic technologies based on neural manipulation.
3. Future plans
Comprehensive measurement of biosignals during walking—including gait, EEG, heart rate, respiration, and gaze—is currently underway to estimate individual levels of "Maemuki" from physical data. By integrating insights from this research and previous findings on gait and mental state, the development of a biofeedback system capable of adjusting "Maemuki" is anticipated.
In primate studies, cognitive tasks and motion capture systems will be used to examine the relationship between "Maemuki" and body posture, with the aim of generating knowledge applicable to humans. For DREADD validation, in addition to PET (Positron Emission Tomography)-based expression confirmation, behavioral changes related to "Maemuki" and electrophysiological changes in brain activity will also be assessed.