NTT Research Develops Closed-Loop Control of Innervated Tissue

SUNNYVALE, Calif.

NTT Research, Inc., a division of NTT (TYO:9432), today announced that the collaboration between its Medical & Health Informatics (MEI) Lab and the Technical University of Munich (TUM) has produced a novel technique for closed-loop control of innervated tissue of a live insect. The results were published on June 27 in Scientific Reports, part of the Nature portfolio, in an article titled “In vivo closed-loop control of a locust’s leg using nerve stimulation.” The paper’s co-authors are affiliated with the MEI Lab, the Neuroelectronics Group within TUM’s Munich Institute of Biomedical Engineering (MIBE) and TUM’s Chair of Zoology. Professor Bernhard Wolfrum leads the Neuroelectronics Group. The article describes implantable electrodes that stimulate an extensor motor nerve in an insect, Locusta migratoria, using a closed circuit of feedback control. The paper’s lead author is Francisco Zurita, a Ph.D. candidate at TUM, who is one of the team members contributing to NTT Research’s project. This work is part of a joint research program between TUM and NTT Research.

Neurotechnology-based diagnosis and treatments already impact a wide range of medical conditions. This work reaches into two relatively unexplored areas: implantable electrodes and closed-loop control. First, instead of applying electrical current to stimulate muscle tissue from outer areas, as is conventional in insect or rodent tests or in human trials, this study uses electrodes that interface directly with peripheral nerves. Second, whereas the most common method of modulating neural activity is in an open-loop fashion, these researchers have developed a technique that takes feedback into account, thereby allowing for some degree of control over what would otherwise consist of more variable outputs. The paper describes a cuff electrode for an extensor motor nerve, fabricated using a 3D-printed mold, which elicits leg movement in the live locust. A flexible resistor senses the leg angle, and a connected microcontroller directs a train of digital-level voltage pulses to control the movement in real time given a selected angle set point. Offered as a model for other researchers exploring neural control of biological systems, this work has several potential applications involving manipulation of the body in acute and chronic conditions, as well as prosthesis and cyborg systems, such as the cardiovascular bio digital twin (CVbioDT), a research objective of the MEI Lab.

“The development of cuff electrodes is applicable for implantation in vagus nerves,” said Dr. Tetsuhiko Teshima, a Visiting Researcher at the Neuroelectronics Group, Research Scientist in the MEI Lab, and one of the paper’s co-authors. “Vagus nerves that connect to the heart tissue will be stimulated or recorded using our cuff electrodes or circuits and then it becomes possible to regulate heart functions, creating a regulatory system that aligns with the MEI Lab’s digital twin project. Another promising application is sciatic nerve stimulation for prosthesis.”

The collaboration between the MEI Lab and the Neuroelectronics Group officially began in early 2020, following the signing of a multi-year joint research agreement between NTT Research and TUM. The original scope of work covered the screening and optimization of functional materials for implantable electrodes, as well as their assembly and biocompatibility. In June 2020, NTT Research opened an office in Munich in support of the joint research. At its founding in 2019 as part of NTT Research, the MEI Lab embarked on a bio digital twin initiative focused initially on the cardiovascular system. In July 2021, Joe Alexander, M.D., Ph.D., who was leading this effort, became director of the Lab. Professor Wolfrum’s lab is focused on designing and fabricating bioelectronic interfaces and sensor arrays for stimulating and recording signals in vivo and in vitro. In addition to Mr. Zurita, and Drs. Teshima and Wolfrum, the paper’s co-authors include Fulvia Del Duca and Lukas Hiendlmeier, two other Ph.D. candidates supported by NTT Research, Dr. Michael Gebhardt and Professor Harald Luksch, chair of the Department of Zoology at TUM.

“To help realize the shared goals of our work with NTT Research, I was able to bring together several specialists in material science, zoology and circuit development,” said Dr. Wolfrum. “We are encouraged by the results and anticipating follow-up work on new materials and further development of cuff electrode systems.”

Along with this work with TUM, the MEI Lab is also engaged with the Disease Biophysics Group in Harvard University’s John A. Paulsson School of Engineering and Applied Physics and the National Cerebral and Cardiovascular Center (NCVC) in Japan. The MEI Lab’s ongoing research includes work on multi-scale precision cardiology platforms, such as the CVbioDT and heart-on-a-chip technology, aimed at developing the infrastructure for a digital replica of an individual’s heart.

About NTT Research

NTT Research opened its offices in July 2019 as a new Silicon Valley startup to conduct basic research and advance technologies that promote positive change for humankind. Currently, three labs are housed at NTT Research facilities in Sunnyvale: the Physics and Informatics (PHI) Lab, the Cryptography and Information Security (CIS) Lab, and the Medical and Health Informatics (MEI) Lab. The organization aims to upgrade reality in three areas: 1) quantum information, neuroscience and photonics; 2) cryptographic and information security; and 3) medical and health informatics. NTT Research is part of NTT, a global technology and business solutions provider with an annual R&D budget of $3.6 billion.

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