Periodic Reporting for period 4 - FeelAgain (Restoring natural feelings from missing or damaged peripheral nervous system by model-driven neuroprosthesis)
Berichtszeitraum: 2022-10-01 bis 2024-03-31
Leg amputees wear commercial prosthetic devices that do not give proper sensory information back to the brain, about the interaction of the device with the ground or its movement. Diabetic patients with peripheral neuropathy suffer the altered information arriving from the periphery to the brain. Amputees, relying on a very limited haptic information from the stump-socket interaction, face grave impairments: risk of falls, decreased mobility, perception of the prosthesis as an extraneous body (low embodiment) and increased cognitive burden during walking with consequent psychological distress and device abandonments. Diabetic patients suffer neuropathic pain, poor balance and mobility. Peripheral nerve electrical stimulation (PNES) of the sensory fibers proximal to hand amputation can reactivate sensations from the missing extremity in the brain. For the fist time, we explore if physiologically plausible recruitment of an appropriate portion of proximal residual nerve, through optimized implanted neural interfaces, is amenable to recreate the missing or partial sensation from foot.
We created and validated a computational model of nerves, comprising receptors and electrical stimulation effects, usable in wide context of neuro-computational science. This project proposes a conceptual and technological framework for model-guided design and use of neuroproshetic devices, together with tailored measurements definition of long-term clinical benefits, which will be commonly used for future devices development. On the socio-economical level, we provide a therapy against neuropathic pain, today iunavailable. It would enable the full work reintegration of diabetic and amputee patients for whom working is impossible because of the impairment produced by pain, together with cost savings for a society by elimination of present (inefficient) drug-based treatments. All these aspects will allow the creation of a new neuromodulation market, which will guarantee new job positions. In an historical moment in which neuromodulation technologies are becoming clinical reality (e.g. vagal or cochlear stimulation), the development of a conceptual framework to assist the design of smart technologies become of paramount importance
For the first time, an implant of intrafascicular electrodes into the residual sciatic nerve of diabetics and amputees is performed. It last more than a month (chronic) and allows, by means of an innovative surgery procedure to maximize the efficiency of stimulation. During clinical trial a carefully designed experiments enable the measurement of embodiment, pain suppression, fall avoidance and walking ability. This metrics is used to evaluate the impact of the introduction of developed neuroprosthetic intervention and its comparison with others. This strategy can be summarized in the following 5 objectives:
1. Design and implementation of a computational model of EPNS effects on nervous system
2. Exploitation of the model for the design of the optimal neural interfaces and stimulation strategies (encoding algorithms)
3. Development of a sensing prostheses
4. Development of assessment-interventional tools (AIT) to boost and measure the: neuropathic pain diminishment, the level of embodiment, fall avoidance and walking quality, integration of the sensory feedback involved in movement control.
5. Proof-of-concept in a humans with amputation and diabetic foot
We created and validated a computational model of nerves, comprising receptors and electrical stimulation effects, usable in wide context of neuro-computational science. This project proposes a conceptual and technological framework for model-guided design and use of neuroproshetic devices, together with tailored measurements definition of long-term clinical benefits, which will be commonly used for future devices development. On the socio-economical level, we provide a therapy against neuropathic pain, today iunavailable. It would enable the full work reintegration of diabetic and amputee patients for whom working is impossible because of the impairment produced by pain, together with cost savings for a society by elimination of present (inefficient) drug-based treatments. All these aspects will allow the creation of a new neuromodulation market, which will guarantee new job positions. In an historical moment in which neuromodulation technologies are becoming clinical reality (e.g. vagal or cochlear stimulation), the development of a conceptual framework to assist the design of smart technologies become of paramount importance
For the first time, an implant of intrafascicular electrodes into the residual sciatic nerve of diabetics and amputees is performed. It last more than a month (chronic) and allows, by means of an innovative surgery procedure to maximize the efficiency of stimulation. During clinical trial a carefully designed experiments enable the measurement of embodiment, pain suppression, fall avoidance and walking ability. This metrics is used to evaluate the impact of the introduction of developed neuroprosthetic intervention and its comparison with others. This strategy can be summarized in the following 5 objectives:
1. Design and implementation of a computational model of EPNS effects on nervous system
2. Exploitation of the model for the design of the optimal neural interfaces and stimulation strategies (encoding algorithms)
3. Development of a sensing prostheses
4. Development of assessment-interventional tools (AIT) to boost and measure the: neuropathic pain diminishment, the level of embodiment, fall avoidance and walking quality, integration of the sensory feedback involved in movement control.
5. Proof-of-concept in a humans with amputation and diabetic foot
We pioneered a human-machine system whereby prosthetic sensors readouts are translated into the language of the nervous system of three amputees, achieving significant health and functional benefits. In detail, natural sensory feedback can be restored in above-knee amputees and can be exploited by them to improve the use of the leg prosthesis during different ambulation tasks and to promote its integration in their body schema. We designed a neuroprosthesis to restore sensory feedback referred on the phantom lower limb of transfemoral amputees and triggered from the bionic leg by stimulating the residual tibial branch of the sciatic nerve through implanted neural interfaces (more than 10 Journal articles, including Nat Med, Sci Trans Med, Curr Bio, Sci Advances, Biomaterials, Nat Com).
The neuroprosthesis is constituted by alower limb prosthesis equipped with sensors under the foot sole and in the knee, a controlling microcomputer and a stimulating system. The policy of the biomimetic current injection in the nerve is designed with help of sophisticated computational models (published in several Journal articles, Nat Com, iScience etc.) which emulate the neurophysiology of the peripheral nerve fibers transmission of the information. Then, nature does the rest: the signals from the residual nerves are conveyed to the brain of the person, to perceive what happens at the prosthesis and to adjust the walking accordingly. The machine and the body are finally re-connected. Together with the functional outcomes, we assessed the cognitive (brain) integration of the device into the body schema of the subjects through measurements of prosthesis embodiment and cognitive effort while using the artificial leg. Then, thanks to the full portability and real-time operation of our novel hardware and software system, amputees stepped out form the lab to the ecological environment, proving that our approach promoted mobility over sand, diminished metabolic cost and therefore overall usability fo the device. The results from these proof-of-concept provide the rationale for larger population studies .
Analogous system has been developed then for the diabetic neuropathy, and tested with several patients. We have modified the stimulating device into the non-invasive, easy to wear smart-stimulating sock, with several active electrodes. By means of the properly developed AI-based policy of stimulation (published in JNE, JNER, NatCom) we enabled the restoration of missing sensations from the diabetic feet, and their proper integration within body schema of patients.
Overall, FeelAgain project delivered 1. several computational models of the human nervous system (sciatic nerve, pudendal nerve, vagus nerve), usable in research and clinical applications worldwide, 2. novel sophisticate assessment tools for clinical research, 3. first in-human neuroprostheses with their clinical validation. All these pave the way for further research about how the brain interpretation of artificial feedback and for the development of sensory-enhanced leg neuroprostheses, which could drastically ameliorate life quality in people with disability.
The neuroprosthesis is constituted by alower limb prosthesis equipped with sensors under the foot sole and in the knee, a controlling microcomputer and a stimulating system. The policy of the biomimetic current injection in the nerve is designed with help of sophisticated computational models (published in several Journal articles, Nat Com, iScience etc.) which emulate the neurophysiology of the peripheral nerve fibers transmission of the information. Then, nature does the rest: the signals from the residual nerves are conveyed to the brain of the person, to perceive what happens at the prosthesis and to adjust the walking accordingly. The machine and the body are finally re-connected. Together with the functional outcomes, we assessed the cognitive (brain) integration of the device into the body schema of the subjects through measurements of prosthesis embodiment and cognitive effort while using the artificial leg. Then, thanks to the full portability and real-time operation of our novel hardware and software system, amputees stepped out form the lab to the ecological environment, proving that our approach promoted mobility over sand, diminished metabolic cost and therefore overall usability fo the device. The results from these proof-of-concept provide the rationale for larger population studies .
Analogous system has been developed then for the diabetic neuropathy, and tested with several patients. We have modified the stimulating device into the non-invasive, easy to wear smart-stimulating sock, with several active electrodes. By means of the properly developed AI-based policy of stimulation (published in JNE, JNER, NatCom) we enabled the restoration of missing sensations from the diabetic feet, and their proper integration within body schema of patients.
Overall, FeelAgain project delivered 1. several computational models of the human nervous system (sciatic nerve, pudendal nerve, vagus nerve), usable in research and clinical applications worldwide, 2. novel sophisticate assessment tools for clinical research, 3. first in-human neuroprostheses with their clinical validation. All these pave the way for further research about how the brain interpretation of artificial feedback and for the development of sensory-enhanced leg neuroprostheses, which could drastically ameliorate life quality in people with disability.
We advanced different aspects of science and technology beyond the state of the art:
- Computational models of erves and mechano-nerve transduction are novel and valuable tool for neuroprosthetic design and also for the neuro-scientific purposes.
- We achieved the first sensory neuroprosthesis for the highly disabled above-knee amputees
- We executed unique detailed battery of carefully designed assessments for the health and functionality of the neuroprosthesis, which could became the "golden standard" for similar technologies.
- We designed the first neuroprosthesis for the clinically more relevant and also more complicated category of diabetic neuropathic patients.
- Computational models of erves and mechano-nerve transduction are novel and valuable tool for neuroprosthetic design and also for the neuro-scientific purposes.
- We achieved the first sensory neuroprosthesis for the highly disabled above-knee amputees
- We executed unique detailed battery of carefully designed assessments for the health and functionality of the neuroprosthesis, which could became the "golden standard" for similar technologies.
- We designed the first neuroprosthesis for the clinically more relevant and also more complicated category of diabetic neuropathic patients.