Hand amputation is a traumatic event that dramatically and permanently changes the life of any person who undergoes one. After surgery, the amputee requires a prosthetic device to perform activities of daily living— in particular, tasks requiring grasping and manipulation functions. According to the Washington, D.C.-based Amputee Coalition, there are 1.9 million amputees who use limb prosthetic services and products, and it is estimated that, among them, 500,000 are upper-limb amputees, with approximately 185,000 new amputations every year. The Center for Orthotic and Prosthetic Care, a consortium of providers in Kentucky, Indiana, North Carolina, and New York, says that upper-limb amputations represent 14% of all amputations. Based on these statistics, we can estimate that, in the European Union, there are a total of 3 million amputees, with 290,000 new cases each year; among these, 40,000 are upper-limb amputations.
There are three main types of upper-limb protheses for amputees. Hand-passive (cosmetic) prostheses have no functionality and are biomimetically designed to give amputees an artificial limb that is an aesthetic replacement for the one that is missing. In contrast, active body-powered devices use the energy produced by remnant joint movements to drive their motion. Finally, more sophisticated myoelectric prostheses use the superficial electrical activity of muscles [superficial electromyogram (sEMG)] recorded over the arm or the forearm to decode the user’s intentions and to generate motor actuations (i.e., prosthesis movements). Among these possibilities, myoelectric prostheses are, presently, the most promising devices, offering a complete restoration of hand motor function because they can provide more intuitive control for the user with respect to the body-powered prostheses.
Unfortunately, however, the abandonment rate of currently available myoelectric prostheses (such as those commercialized by companies like Ottobock, Touch Bionics, and RSL Steeper) in favor of body-powered or cosmetic prostheses is still very high. The main reasons for this tendency are unclear, but their heavy weight, the limited dexterity of the hand prosthesis, and a complete absence of sensory feedback provided to users have played a role.
Limitations of Myoelectric Prostheses
Indeed, current myoelectric prostheses allow amputees only one or two degrees of freedom (DoF) (opening/closing the hand and pronosupination, i.e., simple rotation) controlled by homologous or nonhomologous strategies (a homologous strategy involves a muscle contraction, executed by the amputee, that drives a prosthetic movement corresponding to the one that would have been produced by the contraction itself). These DoF are not enough to satisfy the needs of most amputees in performing tasks such as household maintenance (car repairs, shoveling snow, gardening, electrical work) or hobbies (playing an instrument, riding a bike). Moreover, these prostheses constrain the user to visually monitor every task they execute in the absence of any kind of sensory feedback.
The lack of these functionalities may also be the cause of the low level of embodiment (i.e., the prosthesis is perceived as a foreign body) reported by amputees. Moreover, 50–80% of amputees experience neuropathic pain from the missing part of the limb, and drugs do not provide adequate relief (strong evidence indicates that pain can be alleviated when close-to-natural peripheral sensory feedback is provided).
The restoration of the natural flow of sensory information should, therefore, lead to a higher-performance use of hand prostheses, without requiring continuous visual monitoring. Furthermore, by exploiting the preserved residual motor networks and pathways to close the prosthetic control loop, a significant decrease in the associated cognitive burden compared to any nonnatural approach should be obtained.
Enhancing Sensory Feedback
Sensory feedback can be restored using different approaches . For example, patients undergoing targeted muscle reinnervation (TMR) can gather a certain amount of sensory feedback , but because the sEMG used as a control signal is recorded from the same area that needs to be mechanically stimulated to provide feedback, TMR subjects are unable to contract muscles and simultaneously perceive a touch sensation. By contrast, the use of electrodes implanted into the peripheral nerves is a quite attractive alternative for amputees because in such cases it is possible to exploit the remnant neural structures to increase the efficacy of the neuroprosthetic device .
Recently, very interesting results have been achieved by exploiting this approach. Our group first showed  that by stimulating the median and ulnar nerve fascicles using transversal multichannel intrafascicular electrode (TIME) interfaces , the information transmitted by the artificial sensors embedded in a hand prosthesis (see figure below) can provide physiologically appropriate (near-natural) sensory information to an amputee during the real-time decoding of different grasping tasks to control a dexterous hand prosthesis. In our studies, this feedback enabled the participant to effectively modulate the grasping force of the prosthesis with no visual or auditory feedback. Three different force levels were distinguished and consistently used by the subject.
The results also demonstrated that a high complexity of perception can be obtained, which can allow the subject to identify the stiffness and shape of three different objects by exploiting the temporal variation of the strength of the elicited sensations. This approach could improve the efficacy and “lifelike” quality of hand prostheses, resulting in a keystone strategy for the new generation of prosthetic devices. It should be noted, however, that this study was conducted on one participant over a limited amount of time.
Later, Tan and colleagues at Case Western Reserve University and Ortiz-Catalan ,  have shown the possibility of delivering sensory feedback using epineural electrodes and that such an approach can be usable over a prolonged period of time with amputees.
After these very interesting results, two main challenges lie ahead. First, it will be interesting to understand to which extent different types of tactile information can be restored (such as vibration and texture discrimination). This result can likely be achieved by using more sophisticated stimulation approaches that are able to fully exploit the potential of neural interfaces. For example, Tan and colleagues  showed that different sensations can be elicited by using a complex stimulation profile that is probably able to “play” with different sensory afferents in a more natural way.
We also recently showed  that a neuromorphic intraneural stimulation delivered to the human median nerve can restore more sophisticated features such as the ability to judge spatial coarseness of a textured surface. This finding was achieved via percutaneous microstimulation in four healthy subjects and also via implanted intrafascicular stimulation in one transradial amputee. It represents a novel step toward the reestablishment of the sensory skills of the natural hand, and it extends our previous achievements. In fact, in this case, a complementary and challenging dimension of the tactile experience was targeted. Peripheral neural stimulation seems to be able to open up a window inside the sensory neural path, which can be exploited in several interesting ways. For example, it will be possible to use these kinds of studies to provide evidence to address specific neuroscientific questions about the neuronal mechanisms of the human sense of touch.
However, the main challenge for the next few years is to make the results achieved in testing available for largescale clinical application. To reach this goal, it will be necessary to develop new components (such as implantable stimulators that allow the flexible control of different stimulation parameters) and to extensively investigate the long-term biocompatibility and stability of the implanted neural interfaces (this is especially true for intraneural interfaces). For example, novel materials must be developed to create a more intimate and natural interface with the nervous system.
Various different funding agencies—including the Defense Advanced Research Projects Agency in the United States and the Future and Emerging Technologies program in the European Union (specifically, the NEBIAS project coordinated by the author)—are providing support right now to make this dream come true in the next few years.
The author wishes to thank DAS (the anonymous subject involved in the studies cited in the manuscript) and the many scientists who have been involved in these activities, in particular, P.M. Rossini, T. Stieglitz, S. Raspopovic, F. Petrini, M. Capogrosso, C.M. Oddo, A. Mazzoni, and F. Artoni.
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