Phantom motor execution facilitated by machine learning and augmented reality as treatment for phantom limb pain: a single group, clinical trial in patients with chronic intractable phantom limb pain.

BACKGROUND: Phantom limb pain is a debilitating condition for which no effective treatment has been found. We hypothesised that re-engagement of central and peripheral circuitry involved in motor execution could reduce phantom limb pain via competitive plasticity and reversal of cortical reorganisation. METHODS: Patients with upper limb amputation and known chronic intractable phantom limb pain were recruited at three clinics in Sweden and one in Slovenia. Patients received 12 sessions of phantom motor execution using machine learning, augmented and virtual reality, and serious gaming. Changes in intensity, frequency, duration, quality, and intrusion of phantom limb pain were assessed by the use of the numeric rating scale, the pain rating index, the weighted pain distribution scale, and a study-specific frequency scale before each session and at follow-up interviews 1, 3, and 6 months after the last session. Changes in medication and prostheses were also monitored. Results are reported using descriptive statistics and analysed by non-parametric tests. The trial is registered at ClinicalTrials.gov, number NCT02281539. FINDINGS: Between Sept 15, 2014, and April 10, 2015, 14 patients with intractable chronic phantom limb pain, for whom conventional treatments failed, were enrolled. After 12 sessions, patients showed statistically and clinically significant improvements in all metrics of phantom limb pain. Phantom limb pain decreased from pre-treatment to the last treatment session by 47% (SD 39; absolute mean change 1·0 [0·8]; p=0·001) for weighted pain distribution, 32% (38; absolute mean change 1·6 [1·8]; p=0·007) for the numeric rating scale, and 51% (33; absolute mean change 9·6 [8·1]; p=0·0001) for the pain rating index. The numeric rating scale score for intrusion of phantom limb pain in activities of daily living and sleep was reduced by 43% (SD 37; absolute mean change 2·4 [2·3]; p=0·004) and 61% (39; absolute mean change 2·3 [1·8]; p=0·001), respectively. Two of four patients who were on medication reduced their intake by 81% (absolute reduction 1300 mg, gabapentin) and 33% (absolute reduction 75 mg, pregabalin). Improvements remained 6 months after the last treatment. INTERPRETATION: Our findings suggest potential value in motor execution of the phantom limb as a treatment for phantom limb pain. Promotion of phantom motor execution aided by machine learning, augmented and virtual reality, and gaming is a non-invasive, non-pharmacological, and engaging treatment with no identified side-effects at present. FUNDING: Promobilia Foundation, VINNOVA, Jimmy Dahlstens Fond, PicoSolve, and Innovationskontor Väst.

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.

Upper limb amputees can be induced to experience a rubber hand as their own.

We describe how upper limb amputees can be made to experience a rubber hand as part of their own body. This was accomplished by applying synchronous touches to the stump, which was out of view, and to the index finger of a rubber hand, placed in full view (26 cm medial to the stump). This elicited an illusion of sensing touch on the artificial hand, rather than on the stump and a feeling of ownership of the rubber hand developed. This effect was supported by quantitative subjective reports in the form of questionnaires, behavioural data in the form of misreaching in a pointing task when asked to localize the position of the touch, and physiological evidence obtained by skin conductance responses when threatening the hand prosthesis. Our findings outline a simple method for transferring tactile sensations from the stump to a prosthetic limb by tricking the brain, thereby making an important contribution to the field of neuroprosthetics where a major goal is to develop artificial limbs that feel like a real parts of the body.

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.

"Pulling telescoped phantoms out of the stump": manipulating the perceived position of phantom limbs using a full-body illusion.

Most amputees experience phantom limbs, or the sensation that their amputated limb is still attached to the body. Phantom limbs can be perceived in the location previously occupied by the intact limb, or they can gradually retract inside the stump, a phenomenon referred to as "telescoping". Telescoping is relevant from a clinical point of view, as it tends to be related to increased levels of phantom pain. In the current study we demonstrate how a full-body illusion can be used to temporarily revoke telescoping sensations in upper limb amputees. During this illusion participants view the body of a mannequin from a first person perspective while being subjected to synchronized visuo-tactile stimulation through stroking, which makes them experience the mannequin's body as their own. In Experiment 1 we used an intact mannequin, and showed that amputees can experience ownership of an intact body as well as referral of touch from both hands of the mannequin. In Experiment 2 and 3 we used an amputated mannequin, and demonstrated that depending on the spatial location of the strokes applied to the mannequin, participants experienced their phantom hand to either remain telescoped, or to actually be located below the stump. The effects were supported by subjective data from questionnaires, as well as verbal reports of the perceived location of the phantom hand in a visual judgment task. These findings are of particular interest, as they show that the temporary revoking of telescoping sensations does not necessarily have to involve the visualization of an intact hand or illusory movement of the phantom (as in the rubber hand illusion or mirror visual feedback therapy), but that it can also be obtained through mere referral of touch from the stump to the spatial location corresponding to that previously occupied by the intact hand. Moreover, our study also provides preliminary evidence for the fact that these manipulations can have an effect on phantom pain sensations.