For his work developing lower limb prostheses that can communicate critical sensory information back to the wearer, Stanisa Raspopovic is the 2021 grand prize winner of the Science & PINS Prize for Neuromodulation. By employing neurorobotic technologies, which interface directly with a wearer's peripheral nervous system, Raspopovic's research could inspire new prosthetic designs that can substantially improve quality of life, especially for lower limb amputees — the needs of whom have been overlooked relative to upper limb amputees.
In tests, users reported being able to feel when the foot of the prosthesis was touched and flexed — even when it was physically disconnected from the wearer's body and communicating with the neural interface through a wireless connection. The leg's sensors enabled the test users to avoid a number of obstacles when wearing special glasses to obscure their lower field of vision, and substantially enhanced their abilities to navigate stairs and sandy terrain, all while reducing their metabolic energy use.
By providing more realistic physical feedback and helping to alleviate phantom limb pain, Raspopovic's system led test users to report a greater sense of "embodiment," or the feeling that a prosthetic is a true extension of the wearer's body.
"Neurorobotic 'sensorized' prostheses could directly benefit patients with limb amputations in the near future, and the scientific philosophy we employed during this translational research is also applicable to other areas of neural interfacing and bioelectronics," said Raspopovic, a professor of neuroengineering in the department of health sciences and technology at ETH Zürich. "Our framework started with a deep understanding of a biological system achieved through computational modeling, which then informed the design and implementation of novel neural interfaces. The process concluded with clinical validation, which then fed back into deeper biological understanding."
Addressing the Unmet Needs of Lower Limb Amputees
There has been substantial progress in developing more sophisticated interfaces between prosthetic devices and their users in recent years. In particular, peripheral nervous system (PNS) interfaces, which connect prosthetic sensors directly to the remnant nerves in an amputee's limb stump, have been shown to provide users with nearly natural touch sensations and some relief from phantom limb pain. However, Raspopovic noted that much of this progress has been centered on the needs of upper limb amputees.
While this progress in upper limb prostheses has yielded the promise of restored abilities to grasp and manipulate objects, Raspopovic recognized an unmet clinical need, as roughly four out of every five amputees worldwide have lost a lower limb, he writes in his prize-winning essay. These people often experience a substantial lack of mobility, as traditional lower limb prosthetics can often be challenging and tiring for the wearer to manipulate. Although many prostheses can weigh less than the limbs they replace, users often report a feeling of carrying and moving an excessively heavy object. As a result, many users face a dilemma of succumbing to a more sedentary lifestyle, or regularly using their prostheses — which has been shown to exacerbate cardiovascular stress and increase the risk of heart attack.
Raspopovic and his colleagues have met this challenge with the design of a "sensing leg," imbued with sensors that can detect pressure and movement, communicating this information to the wearer through a PNS interface with an imperceptible delay. As described in Raspopovic's essay, they used computational modeling to determine the optimal number of connections to implant in a targeted nerve. They also added a wireless connection between the prosthesis and the PNS interface, addressing a longstanding issue of failures in hardwired connections.
In separate experiments, Raspopovic and his colleagues sought to assess the degree to which their neurorobotic prosthetic system integrates with the central nervous system. They noted that test users had fundamentally reshaped their gait to one that resembled walking with a natural leg, driven by an ability to control which channels their central nervous system activated in the PNS, and in what order. In tests where the users were asked to "drive" a simulated car, they could also perceive and react to subtle changes in pressure between foot and pedal.
"These studies not only provided clear evidence of the benefit of neuromodulation for lower-limb amputees but also provided insights into fundamental mechanisms of supraspinal integration of the restored sensory modalities," Raspopovic writes in his essay.
The PNS interface also includes a "neuro-pacemaker" mode that therapeutically stimulates the wearer's remnant nerves without connecting to the prosthesis. Here again, the precise targeting of neural pathways — informed by computational modeling — enabled the implant to reproduce more naturalistic nerve inputs, leading test wearers to report a notable reduction in phantom limb pain.
Neuromodulation’s Path to a Better Quality of Life
"The neuromodulation system triggered by lower limb prosthesis developed by Dr. Raspopovic and colleagues can allow more realistic sensations at lower metabolic cost and improved awareness of one's own actions, such as prosthesis control, potentially improving quality of life for millions of individuals with amputations," said Science Translational Medicine editors Mattia Maroso and Caitlin Czajka.
Since 2016, the annual Science & PINS Prize for Neuromodulation has honored scientists for excellent contributions to neuromodulation research with implications for translational medicine. The winner is awarded US$25,000 and publication of his or her essay in Science.
"As neuroscientists continue to decipher the human nervous system, and there are constantly new technologies such like optogenetics to interact with the nervous system, neuromodulation will be more and more commonly used to help patients recover health," said Chong Li, CEO of PINS Medical. "We are delighted to see that increasingly research results can emerge through the Science & PINS Prize for Neuromodulation."
Weijian Yang is the 2021 finalist for his essay, " Manipulating Neuronal Circuits, in Concert." Yang received his undergraduate degree from Peking University and a Ph.D. from the University of California, Berkeley. After completing his postdoctoral fellowship at Columbia University, he started his lab in the department of electrical and computer engineering at the University of California, Davis in late 2017. His research aims to develop advanced optical methods and neurotechnologies to interrogate and modulate brain activity, with a goal to understand how neural circuits organize and function, and how behaviors emerge from neuronal activity.