Investigating Phantom Motor Execution as treatment of Phantom Limb Pain

Phantom Limb Pain (PLP) is commonly suffered by people with amputations and even though it has been studied for centuries, it remains a mysterious object of debate among researchers. For one thing, despite the vast number of proposed PLP treatments, no therapy has so far proved to be reliably effective. For another, studies attempting to provide a mechanistic explanation of the condition have produced mixed and inconsistent results, thus providing unreliable guidance for devising new treatment approaches. Phantom Motor Execution (PME) – exertion of voluntary phantom limb movements – aims at restoring control over the phantom limb and the exercise of such control has been hypothesized to reverse neural changes implicated in PLP. Preliminary evidence supporting this hypothesis has been provided by clinical investigations on upper limb amputees. The main purpose of this doctoral thesis was to provide high quality and unbiased evidence for the use of PME as a treatment of PLP, by probing its efficacy with a Randomized Controlled Trial (RCT) on both upper and lower limb amputees. However, the implementation of this clinical investigation required of additional technology development related the extraction of motor volition via Myoelectric Pattern Recognition (MPR). In practice, this doctoral work consisted in the extension of PME technology to lower limb amputations by proposing and validating a new and more user-friendly recording method to acquire myoelectric signals. The use of PME was then shown to be efficacious in relieving PLP even in the lower limb population with a case study.Another necessity for providing unbiased evidence was to ensure that the highest standards were met when designing, conducting, analysing and reporting the results of the RCT. For this reason, the protocol for the RCT and the prospective Statistical Analysis Plan (SAP) were designed and published. The RCT was established as an international, multi-center effort in 2017 and it is expected to reach its conclusion in September 2021. Preliminary results of the RCT regarding the primary outcome showed reduction of PLP above what is considered clinically relevant, and whereas a higher reduction was obtained with PME, this was not statistically significant over the control treatment. The available evidence at this stage indicates that the RCT will not be able to rule out the role of contextual factors other than PME in providing pain relief. Having at hand a way to alleviate PLP provided a unique opportunity to investigate and identify its neural correlates, therefore this became a secondary aim of this thesis. In particular, patients suffering from PLP were followed regarding their pain trajectory through the therapy and brain imaging studies with functional Magnetic Resonance Imaging (fMRI) and electroencephalography (EEG) were performed. The present doctoral thesis reports part of this work by showing the early results of a cross-sectional study on the EEG correlates of PLP. The results show that it is possible to use machine-learning techniques to discriminate EEG recorded from patients with and without PLP. The findings further point to this technique as a promising target for future longitudinal research aiming at elucidating the neural mechanisms underlying PLP

On the use of Phantom Motor Execution for the treatment of Phantom Limb Pain

Phantom limb pain (PLP) is a common complaint among amputees and despite having been studiedfor centuries, it remains a mysterious object of debate among researcher. To date, a vast number ofways to treat PLP has been proposed in the literature, however none of them has proven to beuniversally effective, thus creating uncertainty on how to operate clinically. The uncertainty is largelyattributable to the scarcity of well conducted randomized controlled trials (RCTs) to prove the efficacyof PLP treatments.Phantom Motor Execution (PME) -exertion of voluntary phantom limb movements – aims at restoringthe control over the phantom limb and the exercise of such control has been hypothesized to reverseneural changes implicated in PLP. Preliminary evidence supporting this hypothesis has been providedby clinical investigations on upper limb amputees. The main purpose of this Licentiate thesis was toenable a RCT on the use of PME for the treatment of PLP in order to provide robust and unbiasedevidence for clinical practice. However, the implementation and kick-off of this clinical investigationrequired to complete few preparatory steps. For example, most amputees and PLP patients have lowerlimb amputation, thus PME needed to be adapted and validated for this population. Further, the RCTprotocol needed to be carefully planned and made openly accessible, as per guidelines for conductingand publishing clinical RCT. Finally, a secondary aim of this thesis emerged with the need of providinglong term relief from PLP to patient. Preliminary evidence seemed to indicate that in order to maintainpain relief, periodic rehearsal of the phantom motor skills acquired through PME is necessary. Thisraised the question of whether it is beneficial and possible to translate the technology from clinic tohome use, question that was explored employing both quantitative and qualitative methods fromengineering, medical anthropology, and user interface design.The work conducted within this thesis resulted in the extension of PME to lower limb patients byproposal and validation of a new and more user-friendly recording configuration to record EMG signals.The use of PME was then shown to be efficacious in relieving PLP with a case study on a patient. Theprotocol for the RCT was then designed and published. These two first steps permitted theestablishment of the RCT, which is currently ongoing and expected to close in March 2021. With regardto the secondary aim of this thesis, the work conducted enabled PME to be used by the patients in thecomfort of their home, while it also allowed investigate the benefits and challenges generally faced(not only by PME) in the transition from the clinic to home and its effects on treatment adherence. Thework conducted is presented in the three appended publications.Future work includes the presentation of the results of the RCT. Further, having a way to modulate PLPis an incredibly useful tool to study the neural basis of PLP. By capitalizing on this tool, we are currentlyconducting brain imaging studies using fMRI and electroencephalography that are the main focus ofthe work that lies ahead

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