The Paper
By simply implanting electrode chips in the brain and spinal cord to build a "nerve bypass" between the brain and spinal cord, paralyzed patients may regain autonomous control of muscles and regain the ability to stand and walk in the lower limbs.
On October 5, the surging news (www.thepaper.cn) reporter learned from Fudan University that the team of young teachers from Fudan Institute of Brain-like Intelligence Science and Technology has developed a new generation of implantable cerebrospinal interface equipment for patients with spinal cord injury, bringing hope for patients with spinal cord injury to stand and walk. Recently, the related project "Development of Key Technologies and Systems for Implantable Cerebrospinal Interface" stood out among about 1,400 entries and won the winning award of the 2024 National Disruptive Technology Innovation Competition, and the first clinical trial is expected to be carried out by the end of the year.
Minimally invasive electrodes are implanted, and paralyzed patients are expected to walk smoothly
As a "high-speed channel" connecting the brain to the peripheral nervous system, if the spinal cord is damaged, the instructions from the brain cannot be transmitted to the muscles, and the patient loses the ability to move independently. How to restore the exercise ability of patients paralyzed by spinal cord injury has always been a major problem in the medical field.
Due to the irreversible nature of nerve injury, current treatments for patients with spinal cord injury have limited efficacy. Until recent years, studies have confirmed that spinal epidural electrical stimulation can reactivate neuromuscular activity and significantly promote sports rehabilitation after spinal cord injury - in 2023, the team of Dr. Grégoire Courtine at the Ecole Polytechnique Fédérale de Lausanne, Switzerland, carried out a brain-spinal interface study, which connects the brain and spinal cord nerve pathways by collecting and decoding brain signals and electrically stimulating relevant areas of the lower limbs of the spinal cord, so that quadriplegic patients can walk autonomously, and even realize synaptic remodeling at the site of spinal cord injury. Allows the patient to control the paralyzed muscles autonomously without stimulation.
Although the Switzerland team has preliminarily verified the possibility of cerebrospinal interface to achieve functional recovery in patients with spinal cord injury, there are still many shortcomings in EEG exercise decoding, individualized reconstruction of spinal cord nerve roots, system integration and clinical application. In response to these problems, the Jiafumin team has carried out the research and development of a new generation of cerebrospinal interface technology, which has the characteristics of "high precision, high throughput, high integration, and low latency".
The first core challenge is how to accurately stimulate the nerve roots of the spinal cord and alternately activate the corresponding muscle groups of the lower limbs to reconstruct the walking gait. To solve this problem, the Jiafumin team used the 3T magnetic resonance imaging equipment of Zhangjiang Imaging Center to innovatively design an imaging scheme containing a variety of scanning sequences, and built an automatic reconstruction algorithm model based on manual labels, so as to accurately capture the structural characteristics of the spinal cord nerve root in the lumbosacral segment. The relevant data and the generated individualized spinal cord nerve root model have recently been open-sourced, which provides support for experts in the field of neurorehabilitation to carry out basic research on spinal cord neuromodulation.
3D model of spinal cord nerve root image reconstruction. The pictures in this article are all from the WeChat official account of "Fudan University".
In addition, the ideal walking process requires real-time optimization and adjustment of spinal cord spatiotemporal stimulation parameters according to the movement results of lower limb posture, which requires real-time monitoring of gait. The Jiafumin team uses multi-modal technologies such as infrared motion capture, electromyography, inertial sensors, and plantar pressure pads to construct healthy gait and a variety of abnormal gait datasets, establish algorithm models, and achieve high-performance tracking of continuous gait trajectories across populations, modalities, and types, laying the foundation for brain-spinal interface technology.
Multi-modal real-time monitoring of gait trajectory
The existing brain-spinal interface solution adopts a multi-device implantation model, which requires the implantation of two EEG acquisition devices in the left and right motor cortex of the brain, and the implantation of a spinal cord stimulation device in the spinal cord. The Jiafumin team proposed a "three-in-one" system design scheme, integrating the three devices into a skull implantable miniature device, which can reduce the postoperative wound of the patient, and realize the integration of collection and stimulation, and carry out closed-loop regulation of the patient's voluntary movement. This solution can transfer the decoding process from the outside to the body, improve the stability and efficiency of EEG signal acquisition, and finally achieve a decoding speed and stimulation instruction output at the level of 100 milliseconds - the reaction time of a normal person is about 200 milliseconds, which means that in the future, the walking gait of patients with spinal cord injury will be more natural and smooth.
Ten years of sharpening the sword, facing the world's problems "creeping forward"
From 2010 to 2020, as one of the core members of the National Engineering Research Center for Neuromodulation led by Academician Li Luming, Jia Fumin participated in the R&D and clinical transformation of the first generation of implantable neuromodulation equipment in mainland China, and developed the world's first inverter brain pacemaker under the guidance of Academician Li Luming to solve the clinical problems of Parkinson's complex symptom regulation. As a first-hand witness to witness the whole process of neuromodulation in mainland China from "tracking", "parallel" to "leading", Jia Fumin deeply experienced the hardships from clinical needs to the transformation of scientific research achievements.
"In life, you should choose to do difficult but right things, and write your thesis on the land of the motherland." Deeply influenced by this concept, Jia Fumin set his sights on the field of cerebrospinal interface research, which is also a "world problem", hoping to apply his past experience to patients with spinal cord injury.
According to the 2023 edition of the Survey Report on the Quality of Life and Disease Burden of Spinal Cord Injury in China, there are 3.74 million spinal cord injury patients in China, and about 90,000 new spinal cord injury patients are added every year. "If a paralyzed patient can stand up, it's a breakthrough from 0 to 1." However, it will not be easy to overcome this major conundrum. Jia Fumin predicts that it will take at least ten years for the cerebrospinal interface technology to be transformed from basic research to clinical translation, and he is ready to fight a protracted battle.
Professor Jia Fumin
The Institute of Brain-inspired Intelligence Science and Technology of Fudan University (hereinafter referred to as the "Brain-like Institute") is one of the earliest interdisciplinary research institutions of brain science and brain-like frontiers established in domestic universities, aiming to carry out major original innovations, cutting-edge technology research and application transformation of brain and brain-like basic theories for the world's major scientific and technological frontiers and national strategies. In 2020, Jia Fumin joined the Institute of Brain-like Sciences full-time, and continued to carry out research in an international academic environment that encourages originality, free exploration, and multidisciplinary cooperation. "I have benefited a lot from Fudan's profound background in basic medicine, artificial intelligence, and neuroimaging." Gafumin said.
At the supervisor double selection meeting, Liu Jionghui, a 2022 doctoral student in biomedical engineering, chose to join the Jiafumin team and became the first student in the team. "I hope to do something meaningful to society during my Ph.D. and realize my value in the process." Liu Jionghui is currently mainly responsible for MRI image reconstruction, individualized modeling, and neuromusculoskeletal model simulation and calculation of spinal nerve roots, providing patients with high-precision nerve root construction and personalized stimulation programs.
Liu Jionghui, a 2022 Ph.D. student in biomedical engineering, joined the Jiafumin team
Since then, Jia Fumin has taken one or two students to silently "tinker" with the brain-spinal interface, and now the industry-university-research team has nearly 30 people. He describes these years of research as "creeping forward", "studying silently away from outside voices until he sees a paralyzed patient walk again". With the strong support of the Fudan-Baoshan Science and Technology Innovation Center and the Brain-like Institute, Jia Fumin has actively established a cerebrospinal interface laboratory, whose main research direction is the recovery and reconstruction of lower limb walking function in patients with spinal cord injury, and on this basis, to explore the application potential of neuromodulation technology in a variety of indications.
In the past four years, the team has simultaneously carried out basic research, software development, algorithm iteration, experimental verification, etc., and has preliminarily completed the accumulation of key technologies of spinal cord spatiotemporal stimulation and cerebrospinal interface, and achieved proof of concept on animals, which has the necessary conditions for clinical application. It is expected that by the end of this year, the team will cooperate with relevant experts from tertiary hospitals in China to carry out the first clinical trial.
In the next stage, Jiafumin plans to complete the product development and clinical transformation of the key technology of the implantable cerebrospinal interface. At the same time, we will continue to develop a series of new neuromodulation methods and technologies for patients with spinal cord injury, such as the development of wearable neuromodulation equipment and multimodal motion monitoring systems for patients with mild symptoms, so as to reduce the burden of family and social medical care on patients with spinal cord injury on a larger scale.
In the longer term, with the vision of "original technology to serve the world", the Jiafumin team hopes to establish an independent intellectual property system for intelligent cerebrospinal interface through the research and development of three types of active implantable innovative medical devices, so as to benefit 20 million spinal cord injury patients around the world.