Electrical stimulation shifts healing/scarring towards regeneration in a rat limb amputation model.

Different species respond differently to severe injury, such as limb loss. In species that regenerate, limb loss is met with complete restoration of the limbs' form and function, whereas in mammals the amputated limb's stump heals and scars. In in vitro studies, electrical stimulation (EStim) has been shown to promote cell migration, and osteo- and chondrogenesis. In in vivo studies, after limb amputation, EStim causes significant new bone, cartilage and vessel growth. Here, in a rat model, the stumps of amputated rat limbs were exposed to EStim, and we measured extracellular matrix (ECM) deposition, macrophage distribution, cell proliferation and gene expression changes at early (3 and 7 days) and later stages (28 days). We found that EStim caused differences in ECM deposition, with less condensed collagen fibrils, and modified macrophage response by changing M1 to M2 macrophage ratio. The number of proliferating cells was increased in EStim treated stumps 7 days after amputation, and transcriptome data strongly supported our histological findings, with activated gene pathways known to play key roles in embryonic development and regeneration. In conclusion, our findings support the hypothesis that EStim shifts injury response from healing/scarring towards regeneration. A better understanding of if and how EStim controls these changes, could lead to strategies that replace scarring with regeneration.

Common Synaptic Input to Motor Neurons and Neural Drive to Targeted Reinnervated Muscles.

We compared the behavior of motor neurons innervating their physiological muscle targets with motor neurons from the same spinal segment whose axons were surgically redirected to remnant muscles (targeted muscle reinnervation). The objective was to assess whether motor neurons with nonphysiological innervation receive similar synaptic input and could be voluntary controlled as motor neurons with natural innervation. For this purpose, we acquired high-density EMG signals from the biceps brachii in 5 male transhumeral amputees who underwent targeted reinnervation of this muscle by the ulnar nerve and from the first dorsal interosseous muscle of 5 healthy individuals to investigate the natural innervation of the ulnar nerve. The same recordings were also performed from the biceps brachii muscle of additional 5 able-bodied individuals. The EMG signals were decomposed into discharges of motor unit action potentials. Motor neurons were progressively recruited for the full range of submaximal muscle activation in all conditions. Moreover, their discharge rate significantly increased from recruitment to target activation level in a similar way across the subject groups. Motor neurons across all subject groups received common synaptic input as identified by coherence analysis of their spike trains. However, the relative strength of common input in both the delta (0.5-5 Hz) and alpha (5-13 Hz) bands was significantly smaller for the surgically reinnervated motor neuron pool with respect to the corresponding physiologically innervated one. The results support the novel approach of motor neuron interfacing for prosthesis control and provide new insights into the role of afferent input on motor neuron activity.SIGNIFICANCE STATEMENT Targeted muscle reinnervation surgically redirects nerves that lost their target in the amputation into redundant muscles in the region of the stump. The study of the behavior of motor neurons following this surgery is needed for designing biologically inspired prosthetic control strategies. Moreover, targeted muscle reinnervation offers a human experimental framework for studying the control and behavior of motor neurons when changing their target innervated muscle fibers and sensory feedback. Here, we show that the control of motor neurons and their synaptic input, following reinnervation, was remarkably similar to that of the physiological innervation, although with reduced common drive at some frequencies. The results advance our knowledge on the role of sensory input in the generation of the neural drive to muscles and provide the basis for designing physiologically inspired methods for prosthesis control.

Developing Non-Somatotopic Phantom Finger Sensation to Comparable Levels of Somatotopic Sensation through User Training With Electrotactile Stimulation.

Cutaneous electrical stimulation can provide tactile feedback for upper-limb amputees through somatotopic feedback (SF) or non-somatotopic feedback (NF). The SF delivers electrotactile stimulus to projection finger maps (PFMs) on the stumps of amputees, which outperforms NF that transfers stimulus to other human intact skin areas in general. However, the SF areas on stumps are very limited and often occupied by electromyography (EMG) sensors in application of myoelectric prosthesis. This work aims at improving NF performance on human upper arms through user training with electrotactile stimulation. The experiments were conducted over seven consecutive days on nine able-bodied subjects and two forearm amputees. The performance measures of NF/SF included the correct identification rates (CIRs), the response time and the NASA-TLX questionnaire. The between-day CIR s on NF sites increased logarithmically with a mean course of 3-day rapid-improving phase and plateaued in the relative-steady phase. The response time and NASA-TLX scores could also rapidly reduce to the comparable levels of the SF areas during the same mean period of 3-day rapid-improving phase, respectively. These results indicated that the performance of NF could be highly improved to the equivalent level as that of SF through 3-day electrotactile training, which we named as "3-day effect". It provides important insights that intact skin areas without phantom sensations can effectively replace SF sites to transfer tactile feedback after continuous user training, which validates effectiveness of non-invasive interfaces of tactile feedback for upper-limb amputees in practice.

Improving the Performance Against Force Variation of EMG Controlled Multifunctional Upper-Limb Prostheses for Transradial Amputees.

We investigate the problem of achieving robust control of hand prostheses by the electromyogram (EMG) of transradial amputees in the presence of variable force levels, as these variations can have a substantial impact on the robustness of the control of the prostheses. We also propose a novel set of features that aim at reducing the impact of force level variations on the prosthesis controlled by amputees. These features characterize the EMG activity by means of the orientation between a set of spectral moments descriptors extracted from the EMG signal and a nonlinearly mapped version of it. At the same time, our feature extraction method processes the EMG signals directly from the time-domain to reduce computational cost. The performance of the proposed features is tested on EMG data collected from nine transradial amputees performing six classes of movements each with three force levels. Our results indicate that the proposed features can achieve significant reductions in classification error rates in comparison to other well-known feature extraction methods, achieving improvements of ≈ 6% to 8% in the average classification performance across all subjects and force levels, when training with all forces.

Characterization of evoked tactile sensation in forearm amputees with transcutaneous electrical nerve stimulation.

OBJECTIVE: The goal of this study is to characterize the phenomenon of evoked tactile sensation (ETS) on the stump skin of forearm amputees using transcutaneous electrical nerve stimulation (TENS). APPROACH: We identified the projected finger map (PFM) of ETS on the stump skin in 11 forearm amputees, and compared perceptual attributes of the ETS in nine forearm amputees and eight able-bodied subjects using TENS. The profile of perceptual thresholds at the most sensitive points (MSPs) in each finger-projected area was obtained by modulating current amplitude, pulse width, and frequency of the biphasic, rectangular current stimulus. The long-term stability of the PFM and the perceptual threshold of the ETS were monitored in five forearm amputees for a period of 11 months. MAIN RESULTS: Five finger-specific projection areas can be independently identified on the stump skin of forearm amputees with a relatively long residual stump length. The shape of the PFM was progressively similar to that of the hand with more distal amputation. Similar sensory modalities of touch, pressure, buzz, vibration, and numb below pain sensation could be evoked both in the PFM of the stump skin of amputees and in the normal skin of able-bodied subjects. Sensory thresholds in the normal skin of able-bodied subjects were generally lower than those in the stump skin of forearm amputees, however, both were linearly modulated by current amplitude and pulse width. The variation of the MSPs in the PFM was confined to a small elliptical area with 95% confidence. The perceptual thresholds of thumb-projected areas were found to vary less than 0.99 × 10(-2) mA cm(-2). SIGNIFICANCE: The stable PFM and sensory thresholds of ETS are desirable for a non-invasive neural interface that can feed back finger-specific tactile information from the prosthetic hand to forearm amputees.

Somatotopical feedback versus non-somatotopical feedback for phantom digit sensation on amputees using electrotactile stimulation.

BACKGROUND: Transcutaneous electrical stimulation can provide amputees with tactile feedback for better manipulating an advanced prosthesis. In general, there are two ways to transfer the stimulus to the skin: somatotopical feedback (SF) that stimulates the phantom digit somatotopy on the stump and non-somatotopical feedback (NF) that stimulates other positions on the human body. METHODS: To investigate the difference between SF and NF, electrotactile experiments were conducted on seven amputees. Electrical stimulation was applied via a complete phantom map to the residual limb (SF) and to the upper arm (NF) separately. The behavior results of discrimination accuracy and response time were used to examine: 1) performance differences between SF and NF for discriminating position, type and strength of tactile feedback; 2) performance differences between SF and NF for one channel (1C), three channels (3C), and five channels (5C). NASA-TLX standardized testing was used to determine differences in mental workload between SF and NF. RESULTS: The grand-averaged discrimination accuracy for SF was 6% higher than NF, and the average response time for SF was 600 ms faster than NF. SF is better than NF for position, type, strength, and the overall modality regarding both accuracy and response time except for 1C modality (p<0.001). Among the six modalities of stimulation channels, performance of 1C/SF was the best, which was similar to that of 1C/NF and 3C/SF; performance of 3C/NF was similar to that of 5C/SF; performance of 5C/NF was the worst. NASA-TLX scores indicated that mental workload increased as the number of stimulation channels increased. CONCLUSIONS: We quantified the difference between SF and NF, and the influence of different number of stimulation channels. SF was better than NF in general, but the practical issues such as the limited area of stumps could constrain the use of SF. We found that more channels increased the amount and richness of information to the amputee while fewer channels resulted in higher performance, and thus the 3C/SF modality was a good compromise. Based on this study, we provide possible solutions to the practical problems involving the implementation of tactile feedback for amputees. These results are expected to promote the application of SF and NF tactile feedback for amputees in the future.

High-frequency electrical nerve block for postamputation pain: a pilot study.

OBJECTIVES: This study aimed to assess the analgesic effect of kilohertz alternating current applied to the severed nerves in amputees afflicted by intractable limb pain. METHODS: Ten lower-limb amputees with chronic and severe residual limb pain or phantom limb pain who attained significant pain reduction after local nerve block injection were enrolled. A cuff electrode was wrapped around the sciatic or tibial nerve. An external waveform generator was used for the main part of the study, while an implantable generator was developed and implanted in the responders after 9 to 12 months. Sinusoidal waveforms of 10 kHz and up to 10 V were applied for 30 min during each subject-initiated treatment session. A diary was used to record pain intensities before and after each session. RESULTS: Among the seven subjects who received treatment, the average pain reduction was 75% at the three-month primary end point. These subjects were responders per predefined criterion of achieving ≥50% pain reduction in ≥50% of treatment sessions for the three-month end point. Pain medication use and interference of pain on functions was significantly reduced. The treatment efficacy was sustained through the follow-up period of up to 12 months. Besides dislodgement and loss of function for one electrode in one subject, all other devices functioned as intended. No changes of residual motor and sensory function were observed. CONCLUSION: This pilot study generated preliminary evidence on the efficacy and safety of kilohertz electrical nerve block for postamputation pain, justifying a pivotal study for regulatory approval.

Providing time-discrete gait information by wearable feedback apparatus for lower-limb amputees: usability and functional validation.

Here we describe a novel wearable feedback apparatus for lower-limb amputees. The system is based on three modules: a pressure-sensitive insole for the measurement of the plantar pressure distribution under the prosthetic foot during gait, a computing unit for data processing and gait segmentation, and a set of vibrating elements placed on the thigh skin. The feedback strategy relies on the detection of specific gait-phase transitions of the amputated leg. Vibrating elements are activated in a time-discrete manner, simultaneously with the occurrence of the detected gait-phase transitions. Usability and effectiveness of the apparatus were successfully assessed through an experimental validation involving ten healthy volunteers.

Novel targeted sensory reinnervation technique to restore functional hand sensation after transhumeral amputation.

We present a case study of a novel variation of the targeted sensory reinnervation technique that provides additional control over sensory restoration after transhumeral amputation. The use of intraoperative somatosensory evoked potentials on individual fascicles of the median and ulnar nerves allowed us to specifically target sensory fascicles to reroute to target cutaneous nerves at a distance away from anticipated motor sites in a transhumeral amputee. This resulted in restored hand maps of the median and ulnar nerve in discrete spatially separated areas. In addition, the subject was able to use native and reinnervated muscle sites to control a robotic arm while simultaneously sensing touch and force feedback from the robotic gripper in a physiologically correct manner. This proof of principle study is the first to demonstrate the ability to have simultaneous dual flow of information (motor and sensory) within the residual limb. In working towards clinical deployment of a sensory integrated prosthetic device, this surgical method addresses the important issue of restoring a usable access point to provide natural hand sensation after upper limb amputation.

Sensory feedback in upper limb prosthetics.

One of the challenges facing prosthetic designers and engineers is to restore the missing sensory function inherit to hand amputation. Several different techniques can be employed to provide amputees with sensory feedback: sensory substitution methods where the recorded stimulus is not only transferred to the amputee, but also translated to a different modality (modality-matched feedback), which transfers the stimulus without translation and direct neural stimulation, which interacts directly with peripheral afferent nerves. This paper presents an overview of the principal works and devices employed to provide upper limb amputees with sensory feedback. The focus is on sensory substitution and modality matched feedback; the principal features, advantages and disadvantages of the different methods are presented.

Role of myofascial trigger points in post-amputation pain: causation and management.

BACKGROUND: Post-amputation pain is a multifactorial issue and thus necessitates multiple treatment strategies. Myofascial trigger points-related pain remains under diagnosed and hence not addressed. This study investigates causation and management. OBJECTIVES: To identify the presence and role of myofascial trigger points in post amputation pain. STUDY DESIGN: Post-amputation pain clinic review and recruitment. METHODS: Twenty one identified patients in the post-amputation pain clinic with myofascial trigger points were recruited, of which 13 were transtibial and eight transfemoral and all had phantom limb pain and stump pain. The trigger points were identified and injected with long-acting local anaesthetic on a weekly basis and patients were followed up on an ongoing basis. RESULTS: There was significant resolution of pain on the Visual Analogue Scale in the majority of these patients within five weeks, though some of the transtibial cohort needed further eight injections on a weekly basis for resolution of the pain. CONCLUSION: Identification of myofascial trigger points in amputation stumps and their role in post-amputation pain, followed by appropriate intervention is an important facet of management of this complex chronic pain. Clinical relevance Myofascial trigger points in amputation stumps can lead to ongoing chronic post-amputation pain and our results indicate that identification and intervention of these trigger points does lead to notable resolution of this pain.

Artificial redirection of sensation from prosthetic fingers to the phantom hand map on transradial amputees: vibrotactile versus mechanotactile sensory feedback.

This work assesses the ability of transradial amputees to discriminate multi-site tactile stimuli in sensory discrimination tasks. It compares different sensory feedback modalities using an artificial hand prosthesis in: 1) a modality matched paradigm where pressure recorded on the five fingertips of the hand was fed back as pressure stimulation on five target points on the residual limb; and 2) a modality mismatched paradigm where the pressures were transformed into mechanical vibrations and fed back. Eight transradial amputees took part in the study and were divided in two groups based on the integrity of their phantom map; group A had a complete phantom map on the residual limb whereas group B had an incomplete or nonexisting map. The ability in localizing stimuli was compared with that of 10 healthy subjects using the vibration feedback and 11 healthy subjects using the pressure feedback (in a previous study), on their forearms, in similar experiments. Results demonstrate that pressure stimulation surpassed vibrotactile stimulation in multi-site sensory feedback discrimination. Furthermore, we demonstrate that subjects with a detailed phantom map had the best discrimination performance and even surpassed healthy participants for both feedback paradigms whereas group B had the worst performance overall. Finally, we show that placement of feedback devices on a complete phantom map improves multi-site sensory feedback discrimination, independently of the feedback modality.

A running controller for a powered transfemoral prosthesis.

This paper describes a running controller for a powered knee and ankle prosthesis. The running controller was implemented on a powered prosthesis prototype and evaluated by a transfemoral amputee subject running on a treadmill at a speed of 2.25 m/s (5.0 mph). The ability of the prosthesis and controller to provide the salient features of a running gait was assessed by comparing the kinematics of running provided by the powered prosthesis to the averaged kinematics of five healthy subjects running at the same speed. This comparison indicates that the powered prosthesis and running controller are able to provide essential features of a healthy running gait.

A comparison of direct and pattern recognition control for a two degree-of-freedom above elbow virtual prosthesis.

Individuals with a transhumeral amputation have a large functional deficit and require basic functions out of their prosthesis. Myoelectric prostheses have used amplitude control techniques for decades to restore one or two degrees of freedom to these patients. Pattern recognition control has also been investigated for transhumeral amputees, but in recent years, has been more focused on transradial amputees or high-level patients who have received targeted muscle reinnervation. This study seeks to use the most recent advances in pattern recognition control and investigate techniques that could be applied to the majority of the transhumeral amputee population that has not had the reinnervation surgery to determine if pattern recognition systems may provide them with improved control. In this study, able-bodied control subjects demonstrated that highly accurate two degree-of-freedom pattern recognition systems may be trained using four EMG channels. Such systems may be used to better control a prosthesis in real-time when compared to conventional amplitude control with mode switching.

Phantom limb pain and bodily awareness: current concepts and future directions.

PURPOSE OF REVIEW: Phantom pain is a frequent consequence of amputation or deafferentation. There are many possible contributing mechanisms, including stump-related pathology, spinal and cortical changes. Phantom limb pain is notoriously difficult to treat. Continued consideration of the factors associated with phantom pain and its treatment is of utmost importance, not only to advance the scientific knowledge about the experience of the body and neuropathic pain, but also fundamentally to promote efficacious pain management. RECENT FINDINGS: This review first discusses the mechanisms associated with phantom pain and summarizes the current treatments. The mechanisms underlying phantom pain primarily relate to peripheral/spinal dysfunction, and supraspinal and central plasticity in sensorimotor body representations. The most promising methods for managing phantom pain address the maladaptive changes at multiple levels of the neuraxis, for example, complementing pharmacological administration with physical, psychological or behavioural intervention. These supplementary techniques are even efficacious in isolation, perhaps by replacing the absent afferent signals from the amputated limb, thereby restoring disrupted bodily representations. SUMMARY: Ultimately, for optimal patient outcomes, treatments should be both symptom and mechanism targeted.

Individual differences in response to phantom limb movement therapy.

PURPOSE: Phantom limb pain (PLP) is a distressing condition experienced by many amputees. The purpose of this study was to investigate whether motor imagery could be used to treat PLP. METHOD: Four single case studies were conducted. The participants kept a pain diary in which they recorded the intensity of their PLP during a baseline period, general motor imagery training, phantom limb movement therapy and a follow-up period. Qualitative and quantitative (i.e. interrupted time series) analyses were employed to determine whether phantom limb movement therapy had a significant effect on PLP intensity. RESULTS: Phantom limb movement therapy significantly reduced intensity of PLP in one participant. One participant gained occasional relief by doing phantom limb movement therapy exercises but did not experience an overall reduction in PLP intensity. The third participant did not experience any relief and the fourth participant reported experiencing the re-emergence of an old pain. CONCLUSION: The results display individual differences in response to phantom limb movement therapy. Individual differences are discussed in the context of motor imagery ability and the phantom limb phenomenon as a multi-dimensional disorder.

Complementary limb motion estimation for the control of active knee prostheses.

To restore walking after transfemoral amputation, various actuated exoprostheses have been developed, which control the knee torque actively or via variable damping. In both cases, an important issue is to find the appropriate control that enables user-dominated gait. Recently, we suggested a generic method to deduce intended motion of impaired or amputated limbs from residual human body motion. Based on interjoint coordination in physiological gait, statistical regression is used to estimate missing motion. In a pilot study, this complementary limb motion estimation (CLME) strategy is applied to control an active knee exoprosthesis. A motor-driven prosthetic knee with one degree of freedom has been realized, and one above-knee amputee has used it with CLME. Performed tasks are walking on a treadmill and alternating stair ascent and descent. The subject was able to walk on the treadmill at varying speeds, but needed assistance with the stairs, especially to descend. The promising results with CLME are compared with the subject's performance with her own prosthesis, the C-Leg from Otto Bock.

Robotic touch shifts perception of embodiment to a prosthesis in targeted reinnervation amputees.

Existing prosthetic limbs do not provide amputees with cutaneous feedback. Tactile feedback is essential to intuitive control of a prosthetic limb and it is now clear that the sense of body self-identification is also linked to cutaneous touch. Here we have created an artificial sense of touch for a prosthetic limb by coupling a pressure sensor on the hand through a robotic stimulator to surgically redirected cutaneous sensory nerves (targeted reinnervation) that once served the lost limb. We hypothesize that providing physiologically relevant cutaneous touch feedback may help an amputee incorporate an artificial limb into his or her self image. To investigate this we used a robotic touch interface coupled with a prosthetic limb and tested it with two targeted reinnervation amputees in a series of experiments fashioned after the Rubber Hand Illusion. Results from both subjective (self-reported) and objective (physiological) measures of embodiment (questionnaires, psychophysical temporal order judgements and residual limb temperature measurements) indicate that returning physiologically appropriate cutaneous feedback from a prosthetic limb drives a perceptual shift towards embodiment of the device for these amputees. Measurements provide evidence that the illusion created is vivid. We suggest that this may help amputees to more effectively incorporate an artificial limb into their self image, providing the possibility that a prosthesis becomes not only a tool, but also an integrated body part.

A method to determine the optimal features for control of a powered lower-limb prostheses.

Lower-limb prostheses are rapidly advancing with greater computing power and sensing modalities. This paper is an attempt to begin exploring the trade-off between extrinsic and intrinsic control modalities. In this case, between electromyographic (extrinsic) and several internal sensors that can be used for intrinsic control. We propose a method that will identify the particular features, taken from two trans-femoral amputee and one trans-tibial amputee, during locomotion on varying terrain, that perfectly discriminate between locomotion modes. From this we are able to identify the source of the discriminability from a large-set of features that does not depend on the type of amputation. Also, we comment on the use of this algorithm in selecting the most discriminatory and least encumbering sensor/feature combination for transitions when the ground underneath the foot is unknown for trans-tibial amputees.