A multi-dimensional framework for prosthetic embodiment: a perspective for translational research.

The concept of embodiment has gained widespread popularity within prosthetics research. Embodiment has been claimed to be an indicator of the efficacy of sensory feedback and control strategies. Moreover, it has even been claimed to be necessary for prosthesis acceptance, albeit unfoundedly. Despite the popularity of the term, an actual consensus on how prosthetic embodiment should be used in an experimental framework has yet to be reached. The lack of consensus is in part due to terminological ambiguity and the lack of an exact definition of prosthetic embodiment itself. In a review published parallel to this article, we summarized the definitions of embodiment used in prosthetics literature and concluded that treating prosthetic embodiment as a combination of ownership and agency allows for embodiment to be quantified, and thus useful in translational research. Here, we review the potential mechanisms that give rise to ownership and agency considering temporal, spatial, and anatomical constraints. We then use this to propose a multi-dimensional framework where prosthetic embodiment arises within a spectrum dependent on the integration of volition and multi-sensory information as demanded by the degree of interaction with the environment. This framework allows for the different experimental paradigms on sensory feedback and prosthetic control to be placed in a common perspective. By considering that embodiment lays along a spectrum tied to the interactions with the environment, one can conclude that the embodiment of prosthetic devices should be assessed while operating in environments as close to daily life as possible for it to become relevant.

Prosthetic embodiment: systematic review on definitions, measures, and experimental paradigms.

The term embodiment has become omnipresent within prosthetics research and is often used as a metric of the progress made in prosthetic technologies, as well as a hallmark for user acceptance. However, despite the frequent use of the term, the concept of prosthetic embodiment is often left undefined or described incongruently, sometimes even within the same article. This terminological ambiguity complicates the comparison of studies using embodiment as a metric of success, which in turn hinders the advancement of prosthetics research. To resolve these terminological ambiguities, we systematically reviewed the used definitions of embodiment in the prosthetics literature. We performed a thematic analysis of the definitions and found that embodiment is often conceptualized in either of two frameworks based on body representations or experimental phenomenology. We concluded that treating prosthetic embodiment within an experimental phenomenological framework as the combination of ownership and agency allows for embodiment to be a quantifiable metric for use in translational research. To provide a common reference and guidance on how to best assess ownership and agency, we conducted a second systematic review, analyzing experiments and measures involving ownership and agency. Together, we highlight a pragmatic definition of prosthetic embodiment as the combination of ownership and agency, and in an accompanying article, we provide a perspective on a multi-dimensional framework for prosthetic embodiment. Here, we concluded by providing recommendations on metrics that allow for outcome comparisons between studies, thereby creating a common reference for further discussions within prosthetics research.

Spectral-temporal-spatial customization via modulating multimodal nonlinear pulse propagation.

Multimode fibers (MMFs) are gaining renewed interest for nonlinear effects due to their high-dimensional spatiotemporal nonlinear dynamics and scalability for high power. High-brightness MMF sources with effective control of the nonlinear processes would offer possibilities in many areas from high-power fiber lasers, to bioimaging and chemical sensing, and to intriguing physics phenomena. Here we present a simple yet effective way of controlling nonlinear effects at high peak power levels. This is achieved by leveraging not only the spatial but also the temporal degrees of freedom during multimodal nonlinear pulse propagation in step-index MMFs, using a programmable fiber shaper that introduces time-dependent disorders. We achieve high tunability in MMF output fields, resulting in a broadband high-peak-power source. Its potential as a nonlinear imaging source is further demonstrated through widely tunable two-photon and three-photon microscopy. These demonstrations provide possibilities for technology advances in nonlinear optics, bioimaging, spectroscopy, optical computing, and material processing.

Reducing phantom limb pain using phantom motor execution enabled by augmented and virtual reality: participants' perspectives on an innovative treatment.

PURPOSE: Phantom limb pain (PLP) is a condition that greatly diminishes quality of life. Phantom motor execution (PME), enabled by myoelectric pattern recognition combined with virtual and augmented reality, is a novel treatment for PLP. Here we, aimed to describe patients' experiences of this treatment. MATERIAL AND METHODS: Qualitative, using semi-structured interviews one month after completed PME treatment. Twenty-one Swedish and Dutch patients (mean age 57, 16 males, 16 lower limb amputations) participated. The analysis followed the framework approach. RESULTS: The main themes were 1) treatment effects on the perception of the phantom limb, 2) living with PLP before and after treatment, and 3) facilitators and barriers to treatment. Most participants learned to control their phantom limb, perceived it more positively and as more complete. This control over the phantom limb became a tool for managing PLP. Most participants' outlook on life and energy levels improved after treatment. Being mentally focused during treatment was important. Therapists were pivotal to the success of the treatment. CONCLUSION: Controlling the phantom limb improved their perception of it and pain management, self-agency, and quality of life. The therapists' role was invaluable. We suggest training for patients in phantom limb control before and after amputation.

Phantom limb pain is a common and chronic problem after amputation. When informing patients about the phantom limb phenomenon it is important to use positive wording and to acknowledge its existence as normal.Controlling the phantom limb is a key for the success of the phantom motor execution (PME) treatment and should therefore receive clinicians' attention from the early stages after surgery and onwards.The role of the therapist is invaluable in teaching, supporting and coaching patients receiving PME treatment.In order to facilitate successful outcome of the PME treatment it is important to consider and reduce potential barriers to patient adherence to the treatment.

General anesthesia activates a central anxiolytic center in the BNST.

Low doses of general anesthetics like ketamine and dexmedetomidine have anxiolytic properties independent of their sedative effects, but the underlying mechanisms remain unclear. We discovered a population of GABAergic neurons in the oval division of the bed nucleus of the stria terminalis that are activated by multiple anesthetics and the anxiolytic drug diazepam (ovBNSTGA). The majority of ovBNSTGA neurons express neurotensin receptor 1 (Ntsr1) and form circuits with brain regions known to regulate anxiety and stress responses. Optogenetic activation of ovBNSTGA or ovBNSTNtsr1 neurons significantly attenuated anxiety-like behaviors in both naive animals and mice with inflammatory pain, while inhibition of these cells elevated anxiety. Activation of these neurons decreased heart rate and increased heart rate variability, suggesting that they reduce anxiety by modulating autonomic responses. Our study identifies ovBNSTGA/ovBNSTNtsr1 neurons as a common neural substrate mediating the anxiolytic effect of low-dose anesthetics and a potential therapeutic target for treating anxiety-related disorders.

Extended reality used in the treatment of phantom limb pain: a multicenter, double-blind, randomized controlled trial.

ABSTRACT: Phantom limb pain (PLP) represents a significant challenge after amputation. This study investigated the use of phantom motor execution (PME) and phantom motor imagery (PMI) facilitated by extended reality (XR) for the treatment of PLP. Both treatments used XR, but PME involved overt execution of phantom movements, relying on the decoding of motor intent using machine learning to enable real-time control in XR. In contrast, PMI involved mental rehearsal of phantom movements guided by XR. The study hypothesized that PME would be superior to PMI. A multicenter, double-blind, randomized controlled trial was conducted in 9 outpatient clinics across 7 countries. Eighty-one participants with PLP were randomly assigned to PME or PMI training. The primary outcome was the change in PLP, measured by the Pain Rating Index, from baseline to treatment cessation. Secondary outcomes included various aspects related to PLP, such as the rate of clinically meaningful reduction in pain (CMRP; >50% pain decrease). No evidence was found for superiority of overt execution (PME) over imagery (PMI) using XR. PLP decreased by 64.5% and 68.2% in PME and PMI groups, respectively. Thirty-seven PME participants (71%) and 19 PMI participants (68%) experienced CMRP. Positive changes were recorded in all other outcomes, without group differences. Pain reduction for PME was larger than previously reported. Despite our initial hypothesis not being confirmed, PME and PMI, aided by XR, are likely to offer meaningful PLP relief to most patients. These findings merit consideration of these therapies as viable treatment options and alternatives to pharmacological treatments.

Interplay Between Innovation and Intersubjectivity: Therapists Perceptions of Phantom Motor Execution Therapy and Its Effect on Phantom Limb Pain.

Purpose: Interpersonal processes, including therapeutic alliance, may modulate the impact of interventions on pain experience. However, the role of interpersonal context on the effects of technology-enhanced interventions remains underexplored. This study elicited therapists' perspectives on how a novel rehabilitative process, involving Phantom Motor Execution (PME), may impact phantom limb pain. The mediating role of therapeutic alliance, and the way PME influenced its formation, was investigated. Methods: A qualitative descriptive design, using a framework method, was used to explore therapists' (n=11) experiences of delivering PME treatment. Semi-structured online-based interviews were conducted. Results: A 3-way interaction between therapist, patient, and the PME device was an overarching construct tying four themes together. It formed the context for change in phantom limb experience. The perceived therapeutic effects (theme 1) extended beyond those initially hypothesised and highlighted the mediating role of the key actors and context (theme 2). The therapeutic relationship was perceived as a transformative journey (theme 3), creating an opportunity for communication, collaboration, and bonding. It was seen as a cause and a consequence of therapeutic effects. Future directions, including the role of expertise-informed adaptations and enabling aspects of customised solutions, were indicated (theme 4). Conclusion: This study pointed to intrapersonal, interpersonal, and contextual factors that should be considered in clinical implementation of novel rehabilitative tools. The results demonstrated that therapists have unique insights and a crucial role in facilitating PME treatment. The study highlighted the need to consider the biopsychosocial model of pain in designing, evaluating, and implementing technology-supported interventions.

Statistical analysis plan for an international, double-blind, randomized controlled clinical trial on the use of phantom motor execution as a treatment for phantom limb pain.

BACKGROUND: Phantom limb pain (PLP) is a detrimental condition that can greatly diminish the quality of life. Purposeful control over the phantom limb activates the affected neural circuitry and leads to dissolution of the pathological relationship linking sensorimotor and pain processing (which gives rise to PLP). An international, double-blind, randomized controlled clinical trial (RCT) on the use of phantom motor execution (PME) as a treatment for PLP is currently undertaken, where PME is compared to an active placebo treatment, namely phantom motor imagery (PMI). METHODS AND DESIGN: Sixty-seven subjects suffering from PLP in upper or lower limbs are randomly assigned in 2:1 ratio to PME or PMI interventions respectively. Subjects allocated to either treatment receive 15 interventions where they are exposed to the same VR-AR environments using the same device. The only difference between interventions is whether phantom movements are performed (PME) or imagined (PMI). RESULTS: The primary outcome of the study is to examine whether 15 sessions of PME can induce a greater PLP relief, compared to PMI. The secondary objectives are to examine whether 15 sessions of PME provide a greater improvement in different aspects related to PLP compared to PMI, such as pain duration, pain intensity as measured by other metrics, and the patient's own impression about the effect of treatment. Long-term retention of treatment benefits will be assessed as change in all the variables (both primary and secondary) between baseline and follow-up timepoints (at 1, 3, and 6 months post-treatment). CONCLUSION: This manuscript serves as the formal statistical analysis plan (version 1.0) for the international, double-blind, randomized controlled clinical trial on the use of PME as a treatment for PLP. The statistical analysis plan was completed on 3 August 2021. TRIAL REGISTRATION: ClinicalTrials.gov NCT03112928 . Registered on April 13, 2017 SAP version: version: 1.0, date: 2021/08/03 Protocol version: This document has been written based on information contained in the study protocol published in Lendaro et al. (BMJ Open 8:e021039, 2018), in July 2018. SAP revisions: Not applicable.

Common Spatial Pattern EEG decomposition for Phantom Limb Pain detection.

Phantom Limb Pain (PLP) is a chronic condition frequent among individuals with acquired amputation. PLP has been often investigated with the use of functional MRI focusing on the changes that take place in the sensorimotor cortex after amputation. In the present study, we investigated whether a different type of data, namely electroencephalographic (EEG) recordings, can be used to study the condition. We acquired resting state EEG data from people with and without PLP and then used machine learning for a binary classification task that differentiates the two. Common Spatial Pattern (CSP) decomposition was used as the feature extraction method and two validation schemes were followed for the classification task. Six classifiers (LDA, Log, QDA, LinearSVC, SVC and RF) were optimized through grid search and their performance compared. Two validation approaches, namely all-subjects validation and leave-one-out cross-validation (LOOCV), resulted in high classification accuracy. Most notably, the 93.7% accuracy achieved with SVC in LOOCV holds promise for good diagnostic capabilities using EEG biomarkers. In conclusion, our findings indicate that EEG data is a promising target for future research aiming at elucidating the neural mechanisms underlying PLP and its diagnosis.

Out of the Clinic, into the Home: The in-Home Use of Phantom Motor Execution Aided by Machine Learning and Augmented Reality for the Treatment of Phantom Limb Pain.

PURPOSE: Phantom motor execution (PME) facilitated by augmented/virtual reality (AR/VR) and serious gaming (SG) has been proposed as a treatment for phantom limb pain (PLP). Evidence of the efficacy of this approach was obtained through a clinical trial involving individuals with chronic intractable PLP affecting the upper limb, and further evidence is currently being sought with a multi-sited, international, double blind, randomized, controlled clinical trial in upper and lower limb amputees. All experiments have been conducted in a clinical setting supervised by a therapist. Here, we present a series of case studies (two upper and two lower limb amputees) on the use of PME as a self-treatment. We explore the benefits and the challenges encountered in translation from clinic to home use with a holistic, mixed-methods approach, employing both quantitative and qualitative methods from engineering, medical anthropology, and user interface design. PATIENTS AND METHODS: All patients were provided with and trained to use a myoelectric pattern recognition and AR/VR device for PME. Patients took these devices home and used them independently over 12 months. RESULTS: We found that patients were capable of conducting PME as a self-treatment and incorporated the device into their daily life routines. Use patterns and adherence to PME practice were not only driven by the presence of PLP but also influenced by patients' perceived need and social context. The main barriers to therapy adherence were time and availability of single-use electrodes, both of which could be resolved, or attenuated, by informed design considerations. CONCLUSION: Our findings suggest that adherence to treatment, and thus related outcomes, could be further improved by considering disparate user types and their utilization patterns. Our study highlights the importance of understanding, from multiple disciplinary angles, the tight coupling and interplay between pain, perceived need, and use of medical devices in patient-initiated therapy.

Seamless Integrated Textrode-Band for Real-time Lower Limb Movements Classification to Facilitate Self-Administrated Phantom Limb Pain Treatment.

Phantom Motor Execution (PME) is a mechanism-based approach for the treatment of Phantom Limb Pain (PLP), which could potentially be self-administered in the home environment. However, the placement of electrodes aimed to acquire myoelectric signals from the residual stump muscles can be regarded as a difficult and time-consuming process by the patient. Thus, to increase patient compliance, the process must be made easier, faster, and cost effective. In this study, we developed and investigated a seamless integrated textrode-band for myoelectric recordings. The textrode-band can be easily donned/doffed, is reusable and washable. We demonstrated the viability of such concept by analyzing the signal-to-noise ratio (SNR), as well as offline and real time motion decoding performance, that in our experience are compatible with the PME treatment.

Differential Activation of Biceps Brachii Muscle Compartments for Human-Machine Interfacing.

A central challenge for myoelectric limb prostheses resides in the fact that, as the level of amputation becomes more proximal, the number of functions to be replaced increases, while the number of muscles available to collect input signals for control decreases. Differential activation of compartments from a single muscle could provide additional control sites. However, such feat is not naturally under voluntary control. In this study, we investigated the feasibility of learning to differentially activate the two heads of the bicep brachii muscle (BBM), by using biofeedback via high-density surface electromyography (HD-sEMG). Using a one degree of freedom Fitts' law test, we observed that eight subjects could learn to control the center of gravity of BBM's myoelectric activity. In addition, we examined the activations patterns of BBM that allow for the decoding of distal hand movements. These patterns were found highly individual, but different enough to allow for decoding of motor volition of distal joints. These findings represent promising venues to increase the functionality of myoelectrically controlled upper limb prostheses.

An Alternative Myoelectric Pattern Recognition Approach for the Control of Hand Prostheses: A Case Study of Use in Daily Life by a Dysmelia Subject.

The functionality of upper limb prostheses can be improved by intuitive control strategies that use bioelectric signals measured at the stump level. One such strategy is the decoding of motor volition via myoelectric pattern recognition (MPR), which has shown promising results in controlled environments and more recently in clinical practice. Moreover, not much has been reported about daily life implementation and real-time accuracy of these decoding algorithms. This paper introduces an alternative approach in which MPR allows intuitive control of four different grips and open/close in a multifunctional prosthetic hand. We conducted a clinical proof-of-concept in activities of daily life by constructing a self-contained, MPR-controlled, transradial prosthetic system provided with a novel user interface meant to log errors during real-time operation. The system was used for five days by a unilateral dysmelia subject whose hand had never developed, and who nevertheless learned to generate patterns of myoelectric activity, reported as intuitive, for multi-functional prosthetic control. The subject was instructed to manually log errors when they occurred via the user interface mounted on the prosthesis. This allowed the collection of information about prosthesis usage and real-time classification accuracy. The assessment of capacity for myoelectric control test was used to compare the proposed approach to the conventional prosthetic control approach, direct control. Regarding the MPR approach, the subject reported a more intuitive control when selecting the different grips, but also a higher uncertainty during proportional continuous movements. This paper represents an alternative to the conventional use of MPR, and this alternative may be particularly suitable for a certain type of amputee patients. Moreover, it represents a further validation of MPR with dysmelia cases.

Phantom motor execution as a treatment for phantom limb pain: protocol of an international, double-blind, randomised controlled clinical trial.

INTRODUCTION: Phantom limb pain (PLP) is a chronic condition that can greatly diminish quality of life. Control over the phantom limb and exercise of such control have been hypothesised to reverse maladaptive brain changes correlated to PLP. Preliminary investigations have shown that decoding motor volition using myoelectric pattern recognition, while providing real-time feedback via virtual and augmented reality (VR-AR), facilitates phantom motor execution (PME) and reduces PLP. Here we present the study protocol for an international (seven countries), multicentre (nine clinics), double-blind, randomised controlled clinical trial to assess the effectiveness of PME in alleviating PLP. METHODS AND ANALYSIS: Sixty-seven subjects suffering from PLP in upper or lower limbs are randomly assigned to PME or phantom motor imagery (PMI) interventions. Subjects allocated to either treatment receive 15 interventions and are exposed to the same VR-AR environments using the same device. The only difference between interventions is whether phantom movements are actually performed (PME) or just imagined (PMI). Complete evaluations are conducted at baseline and at intervention completion, as well as 1, 3 and 6 months later using an intention-to-treat (ITT) approach. Changes in PLP measured using the Pain Rating Index between the first and last session are the primary measure of efficacy. Secondary outcomes include: frequency, duration, quality of pain, intrusion of pain in activities of daily living and sleep, disability associated to pain, pain self-efficacy, frequency of depressed mood, presence of catastrophising thinking, health-related quality of life and clinically significant change as patient's own impression. Follow-up interviews are conducted up to 6 months after the treatment. ETHICS AND DISSEMINATION: The study is performed in agreement with the Declaration of Helsinki and under approval by the governing ethical committees of each participating clinic. The results will be published according to the Consolidated Standards of Reporting Trials guidelines in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT03112928; Pre-results.

Real-time Classification of Non-Weight Bearing Lower-Limb Movements Using EMG to Facilitate Phantom Motor Execution: Engineering and Case Study Application on Phantom Limb Pain.

Phantom motor execution (PME), facilitated by myoelectric pattern recognition (MPR) and virtual reality (VR), is positioned to be a viable option to treat phantom limb pain (PLP). A recent clinical trial using PME on upper-limb amputees with chronic intractable PLP yielded promising results. However, further work in the area of signal acquisition is needed if such technology is to be used on subjects with lower-limb amputation. We propose two alternative electrode configurations to conventional, bipolar, targeted recordings for acquiring surface electromyography. We evaluated their performance in a real-time MPR task for non-weight-bearing, lower-limb movements. We found that monopolar recordings using a circumferential electrode of conductive fabric, performed similarly to classical bipolar recordings, but were easier to use in a clinical setting. In addition, we present the first case study of a lower-limb amputee with chronic, intractable PLP treated with PME. The patient's Pain Rating Index dropped by 22 points (from 32 to 10, 68%) after 23 PME sessions. These results represent a methodological advancement and a positive proof-of-concept of PME in lower limbs. Further work remains to be conducted for a high-evidence level clinical validation of PME as a treatment of PLP in lower-limb amputees.

Classification of non-weight bearing lower limb movements: towards a potential treatment for phantom limb pain based on myoelectric pattern recognition.

Research in myoelectric pattern recognition (MPR) for the prediction of motor volition has primarily focused on the upper limbs. Recent studies in the lower limbs have mainly concentrated on prosthetic control, while MPR for lower limb rehabilitation purposes has received little attention. In this work we investigated the viability of a MPR system for the prediction of four degrees of freedom controlled in a near natural or physiologically appropriate fashion. We explored three different electrode configurations for acquiring electromyographic (EMG) signals: two targeted (bipolar and monopolar) and one untargeted (electrodes equally spaced axially). The targeted monopolar configuration yielded overall lower signal-to-noise ratios (SNR) but similar accuracy than those of the targeted bipolar configuration. The targeted bipolar and untargeted monopolar configurations were comparable in terms of SNR and offline accuracy when the same number of channels was used. However, the untargeted configuration tested with twice the channels yielded the best results in terms of accuracy. An advantage of the untargeted configuration is that it offers a simpler and more practical electrode placement. This work is the first step in our long-term goal of implementing a phantom limb pain (PLP) treatment for lower limb amputees based on MPR and augmented/virtual reality.