PhantomAR: Gamified Mixed Reality System for Alleviating Phantom Limb Pain in Upper Limb Amputees – Design, Implementation, and Clinical Usability Evaluation

PhantomAR: Gamified Mixed Reality System for Alleviating Phantom Limb Pain in Upper Limb Amputees – Design, Implementation, and Clinical Usability Evaluation | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article PhantomAR: Gamified Mixed Reality System for Alleviating Phantom Limb Pain in Upper Limb Amputees – Design, Implementation, and Clinical Usability Evaluation Cosima Prahm, Korbinian Eckstein, Michael Bressler, Zhixing Wang, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4221472/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Feb, 2025 Read the published version in Journal of NeuroEngineering and Rehabilitation → Version 1 posted 11 You are reading this latest preprint version Abstract Background: Phantom limb pain (PLP) is a restrictive condition in which patients perceive pain in a limb that is no longer present, greatly reducing their quality of life. Mirror Therapy, wherein patients observe a mirror reflection of their intact limb, has demonstrated efficacy in alleviating PLP. However, its unilateral and seated nature presents limitations. To address these constraints while still reducing PLP, and evaluating the impact of different virtual limb representations (anthropomorphic vs. non-anthropomorphic) on the user's sense of ownership, agency, and embodiment, PhantomAR was developed. Leveraging wearable first-person augmented reality (AR) technology, PhantomAR extends traditional Mirror Therapy by enabling users to move freely and engage in bimanual tasks. Methods: The assistive mixed reality game application PhantomAR was deployed on the Microsoft HoloLens 2 and augmented the user’s residual limb by superimposing a virtual arm or tentacle that was controlled via residual muscles on their stump using an EMG electrode array. This setup allowed patients to engage in a first-person perspective and manipulate virtual objects with both the healthy and augmented limbs, free from the confines of a seated position. The study enrolled 10 able-bodied individuals and 8 individuals with unilateral, transradial amputation. All amputees experienced PLP. The usability of the PhantomAR application was evaluated using the System Usability Scale (SUS) and a user-centric survey. Additionally, the Game Experience was assessed on a 5-point Likert questionnaire (GEQ). Participants rated their phantom sensations using the Numerical Rating Scale and McGill Pain Questionnaire before, during, and after interaction with PhantomAR. The embodiment and agency of the virtual superimposed arm were evaluated with an altered Prosthesis Embodiment Scale. The study protocol included two sessions of 30 minutes each, during which participants experienced PhantomAR. Results: Participants (n=18) rated PhantomAR highly usable (SUS m=90.8%, SD=6.88). Feedback on the Game Experience Questionnaire was overwhelmingly positive, showing high immersion (m=4.46, SD=0.08) and positive affect (m=4.97, SD=0.05). PLP (n=8) significantly decreased post-intervention (NRS and McGill Pain Questionnaire, p<.001). Skin temperature in the residual limb increased significantly post-intervention (p<.01) but did not correlate with PLP (r=-0.08, p=0.83). Tentacle overlay yielded mixed ownership but high agency ratings. Conclusion: PhantomAR leverages extended reality to significantly reduce Phantom Limb Pain, enhance user engagement, and alter perceptions of ownership and agency of their augmented limb through dynamic, full-body interactions. upper limb amputation hand amputation mirror therapy gamification phantom limb pain prosthesis myoelectric control mixed reality extended reality Microsoft HoloLens 2 Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Background Many upper limb amputees report the sensation of a phantom limb, with some describing not only the presence but also various sensations associated with it. These sensations include proprioception of the phantom limb, awareness of its volume, spatial location, and occasional cramps or spasms [1], [2]. Another related phenomenon is known as telescoping, where patients perceive changes in the location, length and girth of their phantom limb [3]–[6]. Additionally, an estimated 80% of amputees perceive painful sensations in their missing limb, referred to as Phantom Limb Pain (PLP) [7], [8]. It significantly diminishes their quality of life, causing distress and hindering daily activities, mental well-being, and overall health [6], [9]–[12]. PLP manifests in diverse ways, with common descriptions including burning, gnawing, lacerating, pressure, and distorted positioning [13]–[15]. Some patients experience improvement over time, while others may continue to have persistent pain, making it an issue that requires ongoing treatment [16], [17]. Efforts to manage PLP have encompassed both pharmacological and non-pharmacological approaches, but they often fall short of providing complete relief [12], [18]–[20]. The drawbacks of pharmacological treatments, such as potential side effects like daytime fatigue and personality changes, highlight the need for effective non-pharmacological alternatives. As for these, Mirror Therapy is the predominant treatment modality for Phantom Limb Pain. This therapy involves the placement of a mirror in a sagittal position adjacent to the patient's intact limb, prompting the patient to visualize the reflection as a substitute for the contralateral amputated limb. This technique promotes a perception wherein the brain interprets the amputated limb as intact and mobile, effectively creating a non-painful illusion of the absent limb [3]. The efficacy of Mirror Therapy is largely attributed by neuroplasticity-based hypotheses of PLP to its provision of anthropomorphic visual feedback, which is recognized as a key factor in its therapeutic impact [21]–[23]. However, during Mirror Therapy, the patient is limited to only unilateral movements which, moreover, take place in a seated position. The patient does not have agency over the residual limb. These restrictive circumstances potentially limit the engagement, sustained motivation and embodiment of the patients, which are believed to be main driving factors of PLP reduction [22], [24]–[26]. Research has suggested that changes in skin temperature in the residual limb may correlate with the intensity of Phantom Limb Pain. Some studies have reported that increased pain intensity is associated with higher skin temperatures in the residual limb [27], while others have found no significant correlation [28], [29]. However, the amputation stump was almost always invariably colder than the corresponding point of the contralateral side [28], [30], [31]. Skin temperature is regulated by the body's vasomotor response, which adjusts blood flow and consequently, skin temperature through processes like vasodilation and vasoconstriction [32]. Physical activity has been shown to boost circulation to the limbs [32], which could either contribute to pain perception in those with PLP or offer temporary relief by promoting relaxation and reducing muscle tension. Recent advancements in PLP treatment increasingly leverage digital technologies such as Virtual Reality (VR), Augmented Reality (AR) and Mixed Reality (MR) using devices such as Meta Quest and Microsoft HoloLens to immerse users in virtual settings. In VR-based mirror therapy, the mirror image is substituted with a digital representation of the absent limb which is mirrored to the movements of the healthy limb [33]–[36]. AR extends this concept by superimposing virtual objects onto real-world views. This includes applications that project an augmented image of an intact limb over the residual limb on a computer screen using a camera and QR code [9], [37]–[40]. Some researchers developed a custom-made AR platform and augmented a VR headset with cameras [41], [42]. Previous research in screen-based AR has focused on myoelectric prosthesis control and the transferability of tasks from virtual environments to real-world settings, involving pick and place tasks [43] for pattern recognition control [44] or motor skill enhancement [45]. Mixed Reality advances this approach by allowing interactions between virtual and real objects, enhancing realism and engagement and spatial awareness, while first-person views via commercially available see-through glasses, such as the Microsoft HoloLens, Magic Leap or Google glasses, facilitate more accurate interactions and thus embodiment [46]–[54]. Immersive virtual reality technology is emerging as a successful nonpharmacologic adjunctive analgesic in reducing acute procedural pain. This is particularly evident in its application during dressing changes and in physical and occupational therapy [24]. In the context of healthcare gamification, research indicates that patient adherence to prescribed home rehabilitation exercises is often suboptimal, attributed to lack of motivation in absence of a supervising therapist [55], [56]. This challenge in motivation and compliance is a recurrent issue in clinical practice [57], [58]. Meta-analyses have highlighted the beneficial role of gamification strategies in enhancing health outcomes [59], [60]. Additionally, various studies have demonstrated the positive impact of gamification on therapy adherence, motivation, skill training, and learning in disease management [61], [62]. A systematic review of games for health also acknowledges their potential benefits while also underscoring the necessity for further methodologically sound studies in this [63]. Others emphasize to include the target population and observe these users to learn about their engagement with mixed reality technology [64]. Building upon mirror therapy, PhantomAR offers an immersive mixed reality experience for individuals with transradial amputations. While mirror therapy utilizes visual illusion of a complete limb for pain reduction, PhantomAR extends this concept. It liberates patients from a static position, allowing free exploration and bi-manual interaction through a non-mirrored virtual limb. This virtual limb augments the residual limb and operates independently from their unaffected limb. Additionally, PhantomAR incorporates gamified elements to stimulate curiosity and engagement. This study centered on designing, implementing, and evaluating PhantomAR, particularly focusing on: Evaluating the effectiveness and usability of PhantomAR, that allows free movement and bimanual interaction, on the intensity of Phantom Limb Pain and sensation in transradial amputees. Investigating the impact of different virtual limb representations (anthropomorphic vs. non-anthropomorphic) on ownership, agency, and embodiment. Exploring the potential relation between skin temperature changes and PLP. Methods Participant recruitment for the study was conducted in compliance with the Declaration of Helsinki and followed the ethical guidelines by the University of Tuebingen, Germany (181/2020BO1). Prior to the initiation of the study, informed consent was obtained from all participants. Participants consisted of a cohort of ten able-bodied individuals (7 males, 3 females, aged 29.6 ± 8.6 years) and eight individuals with unilateral, transradial amputations (6 males, 2 females, aged 45.1 ± 7.8 years). Out of these 8 patients, 5 had already received a prosthesis, however, all stated that they did not use it regularly. All patients experienced PLP. The usability of the PhantomAR application on the HoloLens 2 was assessed using the System Usability Scale (SUS). The SUS, a 10-item questionnaire using a 5-point Likert scale, is a widely accepted tool for evaluating a range of products, including software applications [65]. In addition, a user-centric survey comprising 10 questions was conducted to assess aspects such as immersion, ambience, sense of ownership, interaction with virtual and real objects, and the comfort of wearing the HoloLens 2. Participants' motivation in using PhantomAR was evaluated using the Game Experience Questionnaire (GEQ), which includes 5 main subscales (positive affect, negative affect, flow, challenge, immersion) and 2 additional subscales for control and non-anthropomorphic feedback, rated on a 5-point Likert scale with 1 meaning "completely disagree" and 5 meaning "completely agree" [66]. Prior mixed reality experience was limited, with 80% of able-bodied participants and all patients reporting no previous exposure. Patients were additionally asked to rate their phantom sensations before, during, and after the interaction using the Numerical Rating Scale ( NRS ). Phantom Limb Pain was assessed by the German version of the Short Form McGill Pain Questionnaire ( SF-MPQ ) [67] during baseline and post-intervention measurements. The McGill Pain Rating Index ( PRI ) is constructed by adding up the scores of 15 pain qualities which are rated on a scale of 0 (“none”) to 3 (“severe”). Therefore, the PRI score ranges from 0 to 45. Skin temperature was measured with a contactless infrared thermometer (MEM LEPU LFR30B) in the residual limb as well as in the uninjured limb, as it can be indicative of alterations in blood flow and muscle activity [31], [68], [69]. The embodiment and agency of the virtual superimposed arm was evaluated using an altered Prosthesis Embodiment Scale (PES) by Bekrater-Bodmann [70], in which “prosthesis” was swapped out for “virtual arm”, and which consists of 10 items across 3 subscales for ownership (feeling as if the virtual arm belongs to oneself), agency (feeling in control of the virtual arm), and anatomical plausibility (the virtual arm being in an anatomically correct position relative to the user), with ratings from -3 (strongly disagree) to +3 (strongly agree) [71], [72]. The usability evaluation of PhantomAR involved a single session of approximately 60 minutes being exposed to the application. The study protocol consisted of two sessions in which the participants were experiencing 4 randomized PhantomAR scenes, with the usability evaluation after both experiences and interleaved PLP NRS questionnaires (see Figure 1). The real arm of able-bodied participants was obscured with a sleeve to prevent hand recognition by the HoloLens 2. 2.1 Study setup At the beginning of the study, participants sat comfortably in a chair in an examination room with ambient temperature of 22°C. Skin temperature was measured on the volar side of the stump and on the corresponding area on the contralateral, uninjured limb in patients and on the volar forearm in healthy participants. Patients were asked to rate their momentary PLP on the NRS scale. The mixed reality study required a setup that was quick to implement for effective use in daily clinical practice. The equipment included a Microsoft HoloLens 2 headset on which the holograms of the mixed reality were projected, one Myo electrode armband (Thalmic Labs, Toronto, Canada, Note: discontinued by Thalmic Labs) and two Mbient Lab MMRL inertial measurement units (MBIENTLAB INC, San Jose, USA). The Myo armband featured 8 EMG electrodes, and a vibration motor for haptic feedback. MMRL sensors incorporated a 9-axis IMU. The setup was entirely wireless and battery-operated. Participants wore the Myo armband and an MMRL sensor on the residual lower limb and another MMRL sensor on the upper arm (see Figure 2). Interaction scenes within the application were designed to automatically adjust to available room sizes and shapes, ideally within 10-20m². Upon wearing the HoloLens 2, the virtual arm and myoelectric controls were calibrated, saving the user’s profile, including scale and relative shoulder position, in the app. This initial setup took under 5 minutes and was only necessary once. Participants received no further information and were instructed simply to explore their environment using all available means. After navigating the first four interaction scenes, patients were asked about their PLP. After playing another set of 4 random interaction scenes, participants evaluated the PhantomAR application, completing the SUS, the User centered survey, the altered PES and the GEQ. Their temperature was taken again at the same location as during the beginning of the trial and they were asked one last time about their momentarily PLP. 2.2 Data analysis Data were processed in Matlab version R2022b (Natick, Massachusetts: The MathWorks Inc). The non-parametrical tests Wilcoxon signed-rank test was used to compare group means in related samples regarding NRS scores of PLP and the SF MPQ PRI, while Mann-Whitney U test was used for determining differences between independent samples as in the GEQ. Analysis of temperature correlating with PLP before and after the intervention was analyzed using the Pearson correlation coefficient. Because of the small sample size, the level of statistical significance was set at p < 0.01. Implementation We designed and implemented 7 different environments for users to explore, as well as a separate graphical user interface for therapists and patients, using the game development platform Unity 3D and the Microsoft Mixed Reality Toolkit. The PhantomAR application was installed on the Microsoft HoloLens 2 and connected via Bluetooth to the Thalmic Myo electrode armband and the MMRL IMU sensors. The optional graphical user interface (GUI) for therapists was running on a laptop and connected to the PhantomAR HoloLens session via WI- FI. 3.1 Game design and interaction scenes The game design focused on immersion while minimizing mental stress, frustration and discomfort for patients, which are factors that could adversely affect PLP and the EMG control due to high muscle tension. Therefore, a curiosity driven gameplay was chosen, where the patients can freely explore an interesting and interactive environment without the possibility of failure or underperforming. To allow patients to immerse themselves into the mixed reality experience, the rehabilitative exercises were integrated into various playful scenes (see Table 1). These scenes were designed without specific end goals, timers, or scoring systems. Instead, patients were encouraged to explore their surroundings with inquisitiveness, discovering the possibilities within each scene. This exploration involved touching, moving and resizing objects, interacting using one or both hands, and engaging with multiple objects simultaneously (see Figure 3). The focus was on experiential learning and interaction rather than achieving specific objectives, fostering a more immersive and less pressured environment. Table 1 Overview of the interactable scenes that were used in the study. Each scene contains a distinct environment and follows different rules and interaction mechanisms to sustain patient engagement and curiosity. The interactive elements within each scene can be manipulated using both the virtual and the physical hand. Scene Difficulty Description MyoControl Aqua 3 Underwater simulation with interactive elements such as fish, algae, and corals integrated into the room's spatial mapping environment. A treasure chest positions itself on any flat surface detected within the space. Participants are tasked with touching and combining virtual objects, which are designed to exhibit unexpected behaviors upon interaction. Interaction with both virtual and real hand simultaneously is possible, but not necessary. Liquid Creatures 3 Generation of sigils on the walls and a central virtual pillar on the actual floor. Participants interact with simulated liquids, eggs, and rune stones to initiate the spawning of various creatures within the space. Some of these virtual creatures are programmed to exhibit follower behavior, reacting to the participant's movements. Interaction with both virtual and real hand simultaneously is possible, but not necessary. Pipes 2-3 Virtual levers are algorithmically generated on the walls of the environment. When these levers are activated by the participant, a virtual pipe appears, necessitating connection to an existing network of pipes through a series of grab-and-rotate interaction. Successful connections trigger the release of steam clouds. Interaction with both hands simultaneously is required. Space Music 2 Set within a virtual space environment, this scenario creates interaction with planets that produce musical outputs. Participants can create simple melodies by engaging with objects they place in the planet’s orbit. Interaction with both hands simultaneously is required. Fruit Picking 2 Collecting of virtual fruits that are algorithmically spawned within the environment, including less conspicuous locations such as under tables. The system allows participants to manipulate the size of these fruits by using a bilateral hand grip, enabling the fruits to fit into a designated collection basket. Interaction with both virtual and real hand simultaneously is possible, but not necessary. Drawing 1 Create three-dimensional drawings within the virtual space or on surfaces. This interaction is predominantly unilateral, with the augmented hand designated for the act of drawing. The selection of colors is managed by the contralateral hand, providing a more complementary role. Predominantly unilateral interaction with the virtual hand. Shooting 1 Participants aim and fire at target objects, represented by virtual flowers that are programmed to wilt and respawn upon being hit. The system enhances hand-eye coordination through the implementation of an aiming ray, guiding the participant's actions. Predominantly unilateral interaction with the virtual hand. 3.2 Spatial mapping A unique feature of the HoloLens 2 is that it supports automatic spatial mapping, enabling it to scan floors, walls, and tangible objects such as tables or smaller sized objects. This scene understanding capability allows for the integration of virtual content with the real-world environment while adhering to height, width, or margin requirements with regard to these objects. This feature is instrumental in making PhantomAR an environmentally aware application and is used in various game mechanics, including the generation of plants on surfaces, the interaction of game elements with floors, walls and ceilings, i.e. bouncing a ball on the floor, and the placement of virtual objects onto physical ones during gameplay. However, Microsoft's toolkit provided only basic surface data, which could occasionally extend beyond the current room, thereby requiring a specialized wrapper layer. This layer aids in identifying suitable object placement locations and tracking these objects, thereby improving the game's integration and responsiveness to the surrounding environment. 3.3 Interaction with the virtual environment: Arm and hand movements Both the virtual and the intact hand were capable of interacting with virtual objects. To simulate the movements of a virtual arm as intended by the actual residual limb, we utilized EMG data from one Thalmic Myo Armband and IMU data of the two MMRL sensors placed on the upper and lower arm respectively. This comprehensive data collection enabled us to accurately determine the absolute orientation of the participants' forearm and upper arm. Previous horizontal drift over time could be addressed using these MMRL IMU sensors [50] instead of the Thalmic MyoArmband for spatial data. The position of the shoulder was fixed in relation to the head position and was adapted to match the individual user. The 3D orientation received from the sensors was applied to the respective arm segments representing the upper and lower arm and the head (which was the HoloLens 2). In case the virtual arm should not align with the patient’s residual limb anymore, the virtual arm could be reset to the calibrated position with a light tap on the MyoArmband. To enhance the naturalness of grasping movements with the virtual hand, we introduced auxiliary interaction mechanisms such as freezing the target object during grabbing and incorporating a two-handed interaction for larger objects, involving the use of the contralateral healthy hand. The HoloLens 2 tracked the healthy hand, capturing the positions of the fingers and palm. This feature enabled real fingers to interact with virtual objects. When an object was grasped with both hands, it allowed for ambidextrous interactions, such as rotating the object or resizing it. Successfully grabbing an object was accompanied by a short vibration of the Thalmic Myo armband, which was shown to reduce the time needed for grabbing [45]. The virtual hand had attached colliders that closely matched its shape, enabling physical interactions with virtual objects, such as pushing a ball. Smaller objects could pass between the virtual fingers to create an immersive interaction experience. To include all potential persons with transradial amputation in this study, we chose the conventional simple and robust threshold controller. Two electrodes on agonist/antagonist muscles recorded the activation, and when exceeding a threshold, the virtual hand either opened or closed with the speed proportional to the muscle activation. The path of the movement between the positions was calculated as an interpolation of the rotation of the individual bones/joints. The control algorithm, however, is modularly adaptable and any controller, such as pattern recognition, can be easily integrated into the PhantomAR application and chosen via the GUI. 3.4 Non-anthropomorphic feedback The virtual arm and hand were created as a rigged 3D model, consisting of bones connected by joints for natural-looking movements. Its visual aspect was a mesh render attached to the bone structure. Beyond just replicating a human arm, we allowed for the substitution of the arm model with a virtual tentacle (see Figure 4) Both the arm and tentacle were controlled using the same motion range via EMG. However, instead of the hand's opening and closing actions, the tentacle would extend and retract. Additionally, any wrist rotations or arm movements performed by the patients were correspondingly mirrored in the movements of the tentacle mesh. 3.5 GUI and remote connection for therapeutic supervision To facilitate therapist-led guidance and control over virtual scenarios, we developed a remote control application that operates on Microsoft Windows (Figure 5). This optional app communicates with the HoloLens 2 via Wi-Fi, providing therapists a live video stream that mirrors the patient's mixed reality view. It enhances versatility of the therapeutic process by enabling remote manipulation of virtual scenarios, such as manual creation or resetting of objects. Additionally, the GUI serves as a tool to simplify various configuration tasks, including Bluetooth connectivity setup, EMG controller calibration, and managing patient-specific parameters. However, everything can be adjusted within the HoloLens environment itself as well. Results System and game evaluation The application received an overall System Usability Scale (SUS) score of 90.8% (SD=6.88), as assessed by all 18 participants. This score reflects a high level of usability and user-friendliness, as all scores above 68 are considered above average [73]. The Game Experience Questionnaire results for the patients and able-bodied participants are depicted in Figure 6. The application received overwhelmingly positive feedback from all patients (m=4.85, SD=0.1), with no reported negative emotions (m=1.07, SD=0.07) or sensations of being overwhelmed during gameplay (m=1.93, SD=0.97). Additionally, both immersion (m=4.46, SD=0.08) and game flow (m=4.52, SD=0.38) received notably high ratings. The use of tentacle overlay instead of a virtual hand as anthropomorphic representation garnered a high agency score (m=4.42, SD=0.28), however, exhibited mixed ownership scores (m=3.12, SD=0.86). The game experience for able-bodied participants was similar, with equal scores in the subscales positive affect (m=4.97, SD=0.05), negative affect (m=1.0, SD=0), immersion (m=4.4, SD=0.18), flow (m=4.58, SD=0.42), and tentacle agency (m=4.89, SD=0.15). Tentacle ownership was rated slightly higher by able-bodied participants (m=3.58, SD=0.74), however, not significantly (p=0.45), and challenge was rated slightly lower (m=1.43, SD=0.37, p=0.74). According to the user centered survey, using a tentacle for a hand was a concept which was new to all patients, but they embraced the idea and stated, that it did not necessarily need to be their hand, or any hand for that matter. They reported it was fun to explore the PhantomAR application in real life and could see the room and their augmented arm. However, they preferred an anthropomorphic representation to a marine animal, which could further be shown by the high agency but low ownership (see Figure 6). PLP and physical reaction Initial PLP at baseline was rated with a mean of 5.25 (SD=1.2) on the NRS scale by all patients before the intervention. In the post-intervention user-centered survey, conducted after patients had completed the application, when questioned about their PLP during gameplay, all participants reported a decrease in their PLP while immersed in the application. However, when asked directly about their PLP during the break in between the two sessions, two patients reported an increase in pain (m=3.75; SD=2.3). After finishing the application patients reported a decrease of PLP (m=2.5; SD=1.2). Overall, a high variance can be observed during baseline PLP and during the intervention (see Figure 7). Similarly, the pairwise comparisons on the SF-MPQ Pain Rating Index (PRI) scores showed a significant reduction when analyzing the baseline and post-intervention scores (see Figure 8). The skin temperature shows a significant increase from before the intervention to afterwards in all conditions as presented in Table 2, its distribution can be found in Figure 9. The difference in skin temperature between the injured and unaffected arm was on average 3°C and temperature increased on average 1°C in the residual limb over the course of the intervention. There was a high variance in temperature in the residual limb of patients that ranged from 30.7°C to 34.1 °C before and from 31.7°C to 35.7°C after the intervention. There was no significant temperature difference between the patients’ uninjured arms and the arms of the able-bodied participants (p=0.61). A correlation analysis between PLP and the temperature of the residual limb before and after the intervention yielded a Pearson correlation coefficient of-0.09 and 0.19, respectively, indicating no significant linear relationship between these two variables (p=0.83 and p=0.64). Embodiment The modified Prosthesis Embodiment Scale, adapted to assess Virtual Arm Embodiment, revealed a high sense of agency, suggesting that participants felt a cohesive control over the superimposed virtual arm and regarded the executed movements as their own (see Figure 10). User centered survey Responses from all participants (n=18) in the user-centered survey further revealed the following key observations: Users described wearing the HoloLens as comfortable, and though initially the field of view felt restricted, they soon forgot about it. They described interactions with virtual game elements in the real environment as novel, interesting and challenging, increasingly perceiving these objects as convincingly real. None reported experiencing cyber (motion) sickness during the study. The introduction of haptic feedback through the Thalmic Myo armband greatly enhanced the immersive experience of grasping objects, and participants found the controls to be intuitive. Users commented that it was a long time since they could feel their hand and that they felt their phantom hand grow into the augmented hand. They said that they were surprised at how real everything looked and that they would like to just stay in this level (underwater level) and look around. There was not one comment that the HoloLens would be uncomfortable. When users “lost” their augmented arm, they could re-calibrate and would say “Ah, there is my hand again.” Discussion With PhantomAR we wanted to develop a wearable assistive therapy tool for PLP that extends traditional mirror therapy and not only liberates users from their restrictive position at a table, but also allows them to perform bi-manual tasks and freely interact with objects found in their virtual and actual environment. Addressing complex phenomena such as PLP equally requires flexibility in the treatment approach. The application is modularly built, so we can accommodate several control methods [74]. PhantomAR was not designed to be goal-oriented, but curiosity driven. There is no intended or evaluated task transfer from a virtual hand to an actual myoelectric prosthesis. Brasse et al. suggest, that augmented reality (AR) will play a significant role in future medical applications, enabling patients to perceive a fusion of virtual and real-world visuals [64]. By blending virtual projections with the real world, PhantomAR could serve as a bridge during the rehabilitation process. Specifically, it was designed to be used in the interim phase while the amputated limb is healing and before a permanent prosthetic is fitted, since using a prosthesis has been found to reduce PLP in most users [75]. Patient participation ensures clinical relevance by addressing real needs and challenges, fostering a user-centered approach. Their unique perspectives uncover limitations and refine design, functionality, and usability, ultimately improving the intervention. It was important to not only provide an application for research, but also transfer it to the clinic, with separate user interfaces for the clinician and the patient. Therefore, the patient only has to mount the devices and can start interacting. In addition, the whole system is portable and completely wireless and can thus be used anywhere in the clinic or even at home. The system automatically detects the room without any additional requirements. PLP There was a high variance in PLP sensation for patients and some incongruency. Some patients described a lessening of pain during active use but reported later that pain was actually increased during play and only decreased afterwards. All patients agreed that PLP was lower after using the application. Of course, this one-time proof of concept cannot provide a statement about the alleviation of PLP. Therefore, increasing the sample size can not only provide more insight on PLP but also on embodiment and their progress over time. Prospectively, a weekly assessment using the SF McGill Pain Questionnaire might be more indicative of the intervention's effectiveness. Anthropomorphic representation Literature pertaining to neuroplastic hypotheses for alleviating PLP highlight the relevance of prioritizing anthropomorphic visual feedback [22], [76]. The concept of stochastic entanglement as hypothesized by Ortiz-Catalan, however, predicts that pain reduction would be independent of the level of anthropomorphic visual representation [21]. However, while agency was high, ownership still received mixed scores. Temperature The increase in mean skin temperature in the post-condition phases, such as in the 'Post Residual Limb' and 'Post Proband' groups, could be indicative of increased blood flow to those areas. An elevation in skin temperature is often associated with vasodilation, where blood vessels widen to increase blood flow. This physiological response can be a result of various factors, including increased muscle activity. The difference in temperature between the residual limb and unaffected site of 3°C corresponds to previous findings in upper and lower limb amputees alike [69], [77] and was expected, because stump vascularization is affected by amputation and the limited activity of the residual limb. Our findings indicate that elevated PLP scores prior to the intervention correlate with increased temperatures in the residual limb. In the context of rehabilitation or physical therapy, variations in skin temperature may serve as markers for enhanced blood flow or elevated muscle engagement, aligning with common objectives of these therapeutic interventions [78], [79]. Bimanual interaction: myoelectric control PhantomAR could also be used as a tool to train myoelectric prosthetic control, even though it was not designed for that purpose. But since it offers the same functionality adapted to the control scheme that the patient will use, be it threshold control or machine learning, it would be possible due to the modularity of the application. The latency of the movement of the real arm to the visual representation of the corresponding virtual arm was not directly measured, but for arm movements, there is no noticeable lag. The latency is assumed to be below 50ms, as the data is received from the MMRL sensors in real-time every 10ms and translated to the virtual arm position within the next frame. A comparably low latency has not yet been reported in other studies, in which the latency was 500-800ms when controlling a virtual arm using custom IMU sensors [45]. Immersion could be increased from a technical perspective by creating a spatially coherent experience of the virtual and real world that are responsively interacting with each other and underlying it with haptic feedback. In a future study, to enhance the precision of arm tracking when rotating the head independently from the shoulders, a third MMRL sensor will be employed to monitor shoulder position, thereby creating a more accurate representation and adding additional Degrees of Freedom to the internal model of the patient's arm, which could further improve agency and embodiment. Currently, PhantomAR is exclusively available for transradial (forearm) amputees, but in the future, we plan to extend it to transhumeral (upper arm) amputees as well. Limitations A limitation may be that the findings presented here are based on a group of 8 patients, a longitudinal study is needed to further investigate. Reliance on self-reported measures for PLP intensity, embodiment, ownership, and agency might introduce a subjective bias. Consequently, the results and analyses should be considered in light of this. One of the key challenges of the Microsoft HoloLens 2, and AR glasses in general is the restrictive field of view, which might lead to reduced immersion when not operating in the center of vision. Conclusion This paper presented PhantomAR, a mixed reality application aimed to overcome the limitations of Mirror Therapy for addressing Phantom Limb Pain. Building on traditional methods, PhantomAR offers dynamic full-body interaction through the HoloLens 2 with human and non-anthropomorphic virtual limb representations. The study found significant PLP reduction, high usability, and an immersive experience. To further assess PhantomAR’s impact, a longitudinal intervention study is warranted, comparing PLP intensity, agency, and embodiment. Abbreviations GUI Graphical User Interface GEQ Game Experience Questionnaire IMU Inertial Measurement Unit IRT Infrared thermometer measurement NRS Numerical Rating Scale PES Prosthesis Embodiment Scale PLP Phantom Limb Pain PRI Pain Rating Index (SF McGill) SUS System Usability Scale Declarations Ethics approval and consent to participate Participant recruitment for the study was conducted in compliance with the Declaration of Helsinki and followed the ethical guidelines by the University of Tuebingen, Germany, under the positive vote number 181/2020BO1. Prior to the initiation of the study, informed consent was obtained from all participants. Trial Registration: DRKS00033208 (Jan. 5 th 2024) Consent for publication Consent on publishing any data, including images or videos, has been obtained from all participants via the institutional consent form. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This work has been supported by the Japan Society for the Promotion of Science (JSPS) SP20304 and SP20313 and AKF 453-0-0 by the University of Tuebingen, Germany. We acknowledge support by the Open Access Publishing Fund of the University of Tuebingen. Authors' contributions CP did the conceptualization, design, investigation of the study, conducted formal analysis, managed resources, curated data, developed software, created visualizations, administered the project, acquired funding, and drafted the manuscript. KE contributed to software development, formal analysis, and data curation, and acquired funding. MB contributed to software development, data curation, and providing a critical review of the manuscript. 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Supplementary Files PhantomARTrailer.mp4 Cite Share Download PDF Status: Published Journal Publication published 04 Feb, 2025 Read the published version in Journal of NeuroEngineering and Rehabilitation → Version 1 posted Editorial decision: Revision requested 10 May, 2024 Reviews received at journal 07 May, 2024 Reviews received at journal 03 May, 2024 Reviews received at journal 21 Apr, 2024 Reviewers agreed at journal 12 Apr, 2024 Reviewers agreed at journal 11 Apr, 2024 Reviewers agreed at journal 10 Apr, 2024 Reviewers invited by journal 10 Apr, 2024 Submission checks completed at journal 09 Apr, 2024 Editor assigned by journal 09 Apr, 2024 First submitted to journal 05 Apr, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4221472","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":290132400,"identity":"63e14195-5415-4d3b-bbf3-076f5e90b8e8","order_by":0,"name":"Cosima Prahm","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA70lEQVRIiWNgGAWjYJCCAxCKh4HhA5BiYydFC+MMkBZm4i3jYWDmAdGEtPC3tz88dKOGIc+8/ezRzTa/tsnzMTMwfviYg1uLxJkzBodzjjEUy5zJS7ud23fbsI2ZgVly5jbcWgwkchgO57AxJM5gyDG7ndtzmxGohY2ZF6+W9AeHc/4BtfC/Mbtt2XPbnggtCQaHc9uAWiSAtjD8uJ1IUAvYL7l9EsUSEm/MbvY23E5uY2ZsxusXYIg9/pzzzSZPgj/H7MaPP7dt57c3H/zwEY8WmGUJYIqxDUw2EFQPAhAtDH+IUjwKRsEoGAUjDAAAY7ZQ3/WfPrEAAAAASUVORK5CYII=","orcid":"","institution":"University of Tübingen","correspondingAuthor":true,"prefix":"","firstName":"Cosima","middleName":"","lastName":"Prahm","suffix":""},{"id":290132401,"identity":"bc01dc3e-e48e-4617-b78c-a0b6358e56fc","order_by":1,"name":"Korbinian Eckstein","email":"","orcid":"","institution":"University of Queensland","correspondingAuthor":false,"prefix":"","firstName":"Korbinian","middleName":"","lastName":"Eckstein","suffix":""},{"id":290132402,"identity":"ca08252c-f49d-40e1-9061-b86d83124303","order_by":2,"name":"Michael Bressler","email":"","orcid":"","institution":"University of Tübingen","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Bressler","suffix":""},{"id":290132403,"identity":"9994f2a0-a68d-4668-9895-3ef75867a042","order_by":3,"name":"Zhixing Wang","email":"","orcid":"","institution":"The University of Tokyo","correspondingAuthor":false,"prefix":"","firstName":"Zhixing","middleName":"","lastName":"Wang","suffix":""},{"id":290132404,"identity":"eec98eb9-adae-47dc-98cd-d5e785f7d6c0","order_by":4,"name":"Xiaotong Li","email":"","orcid":"","institution":"The University of Tokyo","correspondingAuthor":false,"prefix":"","firstName":"Xiaotong","middleName":"","lastName":"Li","suffix":""},{"id":290132405,"identity":"3244225f-e507-4007-842f-e6e5c1e94f19","order_by":5,"name":"Takashige Suzuki","email":"","orcid":"","institution":"The University of Tokyo","correspondingAuthor":false,"prefix":"","firstName":"Takashige","middleName":"","lastName":"Suzuki","suffix":""},{"id":290132406,"identity":"eac13ee9-3fa8-487c-aa1c-10d411154737","order_by":6,"name":"Adrien Daigeler","email":"","orcid":"","institution":"University of Tübingen","correspondingAuthor":false,"prefix":"","firstName":"Adrien","middleName":"","lastName":"Daigeler","suffix":""},{"id":290132407,"identity":"f08964bd-54ee-45c4-be29-28a6658db21d","order_by":7,"name":"Jonas Kolbenschlag","email":"","orcid":"","institution":"University of Tübingen","correspondingAuthor":false,"prefix":"","firstName":"Jonas","middleName":"","lastName":"Kolbenschlag","suffix":""},{"id":290132408,"identity":"e2bbb4ce-da4c-44e0-9575-607006622ef2","order_by":8,"name":"Hideaki Kuzuoka","email":"","orcid":"","institution":"The University of Tokyo","correspondingAuthor":false,"prefix":"","firstName":"Hideaki","middleName":"","lastName":"Kuzuoka","suffix":""}],"badges":[],"createdAt":"2024-04-05 07:57:17","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4221472/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4221472/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12984-025-01554-7","type":"published","date":"2025-02-04T15:57:05+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":54866069,"identity":"b0c9af5c-030b-425c-ad96-1e35e85767ba","added_by":"auto","created_at":"2024-04-17 20:50:25","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":58245,"visible":true,"origin":"","legend":"\u003cp\u003eFlow-chart of the study protocol. After the first PLP questionnaire the Set-Up required under 5 minutes, including the donning of the devices and calibration of the virtual arm. (PLP=Phantom Limb Pain, NRS=Numerical Rating Scale, IRT infrared thermometer measurement, SUS=System Usability Scale, GEQ=Game Experience Questionnaire, PES=Prosthesis Embodiment Scale)\u003c/p\u003e","description":"","filename":"Figure1Flowchart.png","url":"https://assets-eu.researchsquare.com/files/rs-4221472/v1/ab0bf7a25c1289af9f428c0a.png"},{"id":54866070,"identity":"f54c277c-3d48-4fb3-a13f-3701ff4dadad","added_by":"auto","created_at":"2024-04-17 20:50:26","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":5787034,"visible":true,"origin":"","legend":"\u003cp\u003eThe PhantomAR system set-up consists of the extended reality device Microsoft HoloLens 2, the Thalmic Myo electrode armband which transmits EMG signals, and 2 MMRL sensors for orientation data of the superimposed digital arm. The set-up is completely wireless and does not restrict movement while patients can explore the virtual environments.\u003c/p\u003e","description":"","filename":"figure2SetUp.png","url":"https://assets-eu.researchsquare.com/files/rs-4221472/v1/6c4a52e46c49ab2d7f95fc31.png"},{"id":54866075,"identity":"44baf138-c8fd-4f46-9192-8314907a03cc","added_by":"auto","created_at":"2024-04-17 20:50:27","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":8829276,"visible":true,"origin":"","legend":"\u003cp\u003eScreenshots of a) Scene Aqua, which presents the player with various underwater elements to encourage interaction, i.e. the coin can be grabbed by the virtual or healthy hand and used to trigger certain events. b) Scene Creature companion shows the interaction with a ball of lava that is bounced between the real and the virtual hand and can be evolved into a creature. The pillar is standing on the floor recognized by spatial recognition. c) Pipes can be placed on walls, floor, or desks and interconnected. More pipe parts can be released via a virtual lever automatically placed on a wall. d) Different fruits can be gathered and manipulated, such as resizing or squashing them.\u003c/p\u003e","description":"","filename":"Figure3Screenshots.png","url":"https://assets-eu.researchsquare.com/files/rs-4221472/v1/c5feb6b2f69adfa3c38ad8f2.png"},{"id":54866072,"identity":"9559224a-cbec-4cc7-958d-9f5f7130f228","added_by":"auto","created_at":"2024-04-17 20:50:26","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":3775887,"visible":true,"origin":"","legend":"\u003cp\u003eTentacle extending and retracting according to the myoelectric signals from the user to grasp a virtual game object.\u003c/p\u003e","description":"","filename":"Figure4Tentacle.png","url":"https://assets-eu.researchsquare.com/files/rs-4221472/v1/4cab56dc404220bfd1176a60.png"},{"id":54866076,"identity":"75e88cbf-564a-4b57-8204-3d6edb7fbf10","added_by":"auto","created_at":"2024-04-17 20:50:27","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":519705,"visible":true,"origin":"","legend":"\u003cp\u003eRemote connected GUI. The interface has different sections for managing the user data, settings, scene control and EMG calibration. In the selected Scene section, the left side provides control over the running session, while the live stream on the right side is used to monitor the patient experience. In the lower left corner of the live stream window, the patient's stump can be seen, which is superimposed by the virtual arm.\u003c/p\u003e","description":"","filename":"Figure5GUI1.png","url":"https://assets-eu.researchsquare.com/files/rs-4221472/v1/8f7f10e7379fb74ac98f27da.png"},{"id":54866071,"identity":"29757af2-795e-4725-b720-e1b616c88e2c","added_by":"auto","created_at":"2024-04-17 20:50:26","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":262999,"visible":true,"origin":"","legend":"\u003cp\u003eThe results of the game experience questionnaire on a 5-point Likert scale as rated by patients (n=8) and able-bodied participants (n=10) show 5 subscales for positive and negative affect, immersion, flow, and challenge, as well as for rating the ownership and agency of operating a virtual tentacle instead of a realistic arm.\u003c/p\u003e","description":"","filename":"Figure6GEQ.png","url":"https://assets-eu.researchsquare.com/files/rs-4221472/v1/adab8ba07c502e9af8a2e85f.png"},{"id":54866073,"identity":"d2a406a3-c7e3-416d-87cc-e479f79550f0","added_by":"auto","created_at":"2024-04-17 20:50:26","extension":"png","order_by":7,"title":"Figure 7","display":"","copyAsset":false,"role":"figure","size":160688,"visible":true,"origin":"","legend":"\u003cp\u003eProgression of PLP (n=8) as assessed with NRS showing a significant reduction indicated * p\u0026lt;0.001 between the baseline and post-intervention measurement. High variance in PLP NRS score was observed both at the baseline and during the intervention.\u003c/p\u003e","description":"","filename":"Figure7PLPsign.png","url":"https://assets-eu.researchsquare.com/files/rs-4221472/v1/d23a3fb6f56b8987c5a2d2e2.png"},{"id":54866077,"identity":"bc408f91-758e-485b-9a4a-c4686867f6d2","added_by":"auto","created_at":"2024-04-17 20:50:27","extension":"png","order_by":8,"title":"Figure 8","display":"","copyAsset":false,"role":"figure","size":89043,"visible":true,"origin":"","legend":"\u003cp\u003ePain Rating Index (PRI) of the patients’ PLP (n=8) as assessed by the SF McGill questionnaire (SF-MPQ) showing a significant reduction from the baseline to after the PhantomAR experience (p\u0026lt;0.01).\u003c/p\u003e","description":"","filename":"Figure8PRI.png","url":"https://assets-eu.researchsquare.com/files/rs-4221472/v1/ea6d7b8995a83676e0792c86.png"},{"id":54866074,"identity":"d458d4e0-e8ae-4ecb-9181-2f1b939d3d62","added_by":"auto","created_at":"2024-04-17 20:50:26","extension":"png","order_by":9,"title":"Figure 9","display":"","copyAsset":false,"role":"figure","size":19120,"visible":true,"origin":"","legend":"\u003cp\u003eSkin temperature measured on the residual limb and the unaffected contralateral limb of patients (n=8), and in able-bodied participants (n=10) before and after the intervention, respectively.\u003c/p\u003e","description":"","filename":"Figure9Temperature.png","url":"https://assets-eu.researchsquare.com/files/rs-4221472/v1/cc0f8a5b3f57bb1f9a78dedb.png"},{"id":54866078,"identity":"f8439510-5641-4edc-a9c5-1dd4193b0e1b","added_by":"auto","created_at":"2024-04-17 20:50:27","extension":"png","order_by":10,"title":"Figure 10","display":"","copyAsset":false,"role":"figure","size":12840,"visible":true,"origin":"","legend":"\u003cp\u003eThe 3 subscales of the adapted Prosthesis Embodiment Scale for all patients (n=8). Questions about their prosthesis had been replaced by questions about the augmented virtual arm. Agency subscale was rated highest, indicating a feeling of congruent control during movement of their virtual arm and hand. Ownership and Anatomical plausibility scales showed higher variance.\u003c/p\u003e","description":"","filename":"Figure10ARarmEmbodimentScale.png","url":"https://assets-eu.researchsquare.com/files/rs-4221472/v1/7a49a817f16f88e967d540be.png"},{"id":75930526,"identity":"3e5d5415-f2ec-4ab1-808d-940f7d40983e","added_by":"auto","created_at":"2025-02-10 16:12:53","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":33273701,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4221472/v1/b6ca63ea-32ce-4bea-af3a-5a257bc4d6fb.pdf"},{"id":54866174,"identity":"cb07acba-d4a8-4b68-aa5b-e5bf7dc8f11d","added_by":"auto","created_at":"2024-04-17 20:50:48","extension":"mp4","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":375535151,"visible":true,"origin":"","legend":"","description":"","filename":"PhantomARTrailer.mp4","url":"https://assets-eu.researchsquare.com/files/rs-4221472/v1/3478ee09679d5c54593ef1a7.mp4"}],"financialInterests":"No competing interests reported.","formattedTitle":"PhantomAR: Gamified Mixed Reality System for Alleviating Phantom Limb Pain in Upper Limb Amputees – Design, Implementation, and Clinical Usability Evaluation","fulltext":[{"header":"Background","content":"\u003cp\u003eMany upper limb amputees report the sensation of a phantom limb, with some describing not only the presence but also various sensations associated with it. These sensations include proprioception of the phantom limb, awareness of its volume, spatial location, and occasional cramps or spasms [1], [2]. Another related phenomenon is known as telescoping, where patients perceive changes in the location, length and girth of their phantom limb [3]\u0026ndash;[6]. Additionally, an estimated 80% of amputees perceive painful sensations in their missing limb, referred to as Phantom Limb Pain (PLP) [7], [8]. It significantly diminishes their quality of life, causing distress and hindering daily activities, mental well-being, and overall health [6], [9]\u0026ndash;[12]. PLP manifests in diverse ways, with common descriptions including burning, gnawing, lacerating, pressure, and distorted positioning [13]\u0026ndash;[15]. Some patients experience improvement over time, while others may continue to have persistent pain, making it an issue that requires ongoing treatment [16], [17].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Efforts to manage PLP have encompassed both pharmacological and non-pharmacological approaches, but they often fall short of providing complete relief [12], [18]\u0026ndash;[20]. The drawbacks of pharmacological treatments, such as potential side effects like daytime fatigue and personality changes, highlight the need for effective non-pharmacological alternatives. As for these, Mirror Therapy is the predominant treatment modality for Phantom Limb Pain. This therapy involves the placement of a mirror in a sagittal position adjacent to the patient\u0026apos;s intact limb, prompting the patient to visualize the reflection as a substitute for the contralateral amputated limb. This technique promotes a perception wherein the brain interprets the amputated limb as intact and mobile, effectively creating a non-painful illusion of the absent limb [3]. The efficacy of Mirror Therapy is largely attributed by neuroplasticity-based hypotheses of PLP to its provision of anthropomorphic visual feedback, which is recognized as a key factor in its therapeutic impact [21]\u0026ndash;[23]. However, during Mirror Therapy, the patient is limited to only unilateral movements which, moreover, take place in a seated position. \u0026nbsp;The patient does not have agency over the residual limb. These restrictive circumstances potentially limit the engagement, sustained motivation and embodiment of the patients, which are believed to be main driving factors of PLP reduction [22], [24]\u0026ndash;[26].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Research has suggested that changes in skin temperature in the residual limb may correlate with the intensity of Phantom Limb Pain. Some studies have reported that increased pain intensity is associated with higher skin temperatures in the residual limb [27], while others have found no significant correlation [28], [29]. However, the amputation stump was almost always invariably colder than the corresponding point of the contralateral side [28], [30], [31]. Skin temperature is regulated by the body\u0026apos;s vasomotor response, which adjusts blood flow and consequently, skin temperature through processes like vasodilation and vasoconstriction [32]. Physical activity has been shown to boost circulation to the limbs [32], which could either contribute to pain perception in those with PLP or offer temporary relief by promoting relaxation and reducing muscle tension.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Recent advancements in PLP treatment increasingly leverage digital technologies such as Virtual Reality (VR), Augmented Reality (AR) and Mixed Reality (MR) using devices such as Meta Quest and Microsoft HoloLens to immerse users in virtual settings. In VR-based mirror therapy, the mirror image is substituted with a digital representation of the absent limb which is mirrored to the movements of the healthy limb [33]\u0026ndash;[36]. AR extends this concept by superimposing virtual objects onto real-world views. This includes applications that project an augmented image of an intact limb over the residual limb on a computer screen using a camera and QR code [9], [37]\u0026ndash;[40]. Some researchers developed a custom-made AR platform and augmented a VR headset with cameras [41], [42]. Previous research in screen-based AR has focused on myoelectric prosthesis control and the transferability of tasks from virtual environments to real-world settings, involving pick and place tasks [43] for pattern recognition control [44] or motor skill enhancement [45].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Mixed Reality advances this approach by allowing interactions between virtual and real objects, enhancing realism and engagement and spatial awareness, while first-person views via commercially available see-through glasses, such as the Microsoft HoloLens, Magic Leap or Google glasses, facilitate more accurate interactions and thus embodiment [46]\u0026ndash;[54]. Immersive virtual reality technology is emerging as a successful nonpharmacologic adjunctive analgesic in reducing acute procedural pain. This is particularly evident in its application during dressing changes and in physical and occupational therapy [24].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;In the context of healthcare gamification, research indicates that patient adherence to prescribed home rehabilitation exercises is often suboptimal, attributed to lack of motivation in absence of a supervising therapist [55], [56]. This challenge in motivation and compliance is a recurrent issue in clinical practice [57], [58]. Meta-analyses have highlighted the beneficial role of gamification strategies in enhancing health outcomes [59], [60]. Additionally, various studies have demonstrated the positive impact of gamification on therapy adherence, motivation, skill training, and learning in disease management [61], [62]. A systematic review of games for health also acknowledges their potential benefits while also underscoring the necessity for further methodologically sound studies in this [63]. Others emphasize to include the target population and observe these users to learn about their engagement with mixed reality technology [64]. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eBuilding upon mirror therapy, PhantomAR offers an immersive mixed reality experience for individuals with transradial amputations. While mirror therapy utilizes visual illusion of a complete limb for pain reduction, PhantomAR extends this concept. It liberates patients from a static position, allowing free exploration and bi-manual interaction through a non-mirrored virtual limb. This virtual limb augments the residual limb and operates independently from their unaffected limb. Additionally, PhantomAR incorporates gamified elements to stimulate curiosity and engagement.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;This study centered on designing, implementing, and evaluating PhantomAR, particularly focusing on:\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Evaluating the effectiveness and usability of PhantomAR, that allows free movement and bimanual interaction, on the intensity of Phantom Limb Pain and sensation in transradial amputees.\u0026nbsp;\u003c/p\u003e\n\u003cul\u003e\n \u003cli\u003eInvestigating the impact of different virtual limb representations (anthropomorphic vs. non-anthropomorphic) on ownership, agency, and embodiment.\u003c/li\u003e\n \u003cli\u003eExploring the potential relation between skin temperature changes and PLP.\u003c/li\u003e\n\u003c/ul\u003e"},{"header":"Methods","content":"\u003cp\u003eParticipant recruitment for the study was conducted in compliance with the Declaration of Helsinki and followed the ethical guidelines by the University of Tuebingen, Germany (181/2020BO1). Prior to the initiation of the study, informed consent was obtained from all participants. Participants consisted of a cohort of ten able-bodied individuals (7 males, 3 females, aged 29.6 \u0026plusmn; 8.6 years) and eight individuals with unilateral, transradial amputations (6 males, 2 females, aged 45.1 \u0026plusmn; 7.8 years). Out of these 8 patients, 5 had already received a prosthesis, however, all stated that they did not use it regularly. All patients experienced PLP.\u003c/p\u003e\n\u003cp\u003eThe usability of the PhantomAR application on the HoloLens 2 was assessed using the \u003cstrong\u003eSystem Usability Scale\u003c/strong\u003e (SUS). The SUS, a 10-item questionnaire using a 5-point Likert scale, is a widely accepted tool for evaluating a range of products, including software applications\u0026nbsp;[65]. In addition, a \u003cstrong\u003euser-centric survey\u003c/strong\u003e comprising 10 questions was conducted to assess aspects such as immersion, ambience, sense of ownership, interaction with virtual and real objects, and the comfort of wearing the HoloLens 2.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eParticipants\u0026apos; motivation in using PhantomAR was evaluated using the \u003cstrong\u003eGame Experience Questionnaire (GEQ),\u003c/strong\u003e which includes 5 main subscales (positive affect, negative affect, flow, challenge, immersion) and 2 additional subscales for control and non-anthropomorphic feedback, rated on a 5-point Likert scale with 1 meaning \u0026quot;completely disagree\u0026quot; and 5 meaning \u0026quot;completely agree\u0026quot;\u0026nbsp;[66]. Prior mixed reality experience was limited, with 80% of able-bodied participants and all patients reporting no previous exposure.\u003c/p\u003e\n\u003cp\u003ePatients were additionally asked to rate their phantom sensations before, during, and after the interaction using the Numerical Rating Scale (\u003cstrong\u003eNRS\u003c/strong\u003e). Phantom Limb Pain was assessed by the German version of the Short Form McGill Pain Questionnaire (\u003cstrong\u003eSF-MPQ\u003c/strong\u003e)\u0026nbsp;[67]\u0026nbsp;during baseline and post-intervention measurements. The McGill Pain Rating Index (\u003cstrong\u003ePRI\u003c/strong\u003e) is constructed by adding up the scores of 15 pain qualities which are rated on a scale of 0 (\u0026ldquo;none\u0026rdquo;) to 3 (\u0026ldquo;severe\u0026rdquo;). Therefore, the PRI score ranges from 0 to 45.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSkin temperature\u003c/strong\u003e was measured with a contactless infrared thermometer (MEM LEPU LFR30B) in the residual limb as well as in the uninjured limb, as it can be indicative of alterations in blood flow and muscle activity\u0026nbsp;[31], [68], [69].\u003c/p\u003e\n\u003cp\u003eThe embodiment and agency of the virtual superimposed arm was evaluated using an altered \u003cstrong\u003eProsthesis Embodiment Scale (PES)\u0026nbsp;\u003c/strong\u003eby Bekrater-Bodmann\u0026nbsp;[70], in which \u0026ldquo;prosthesis\u0026rdquo; was swapped out for \u0026ldquo;virtual arm\u0026rdquo;, and which consists of 10 items across 3 subscales for ownership (feeling as if the virtual arm belongs to oneself), agency (feeling in control of the virtual arm), and anatomical plausibility (the virtual arm being in an anatomically correct position relative to the user), with ratings from -3 (strongly disagree) to +3 (strongly agree)\u0026nbsp;[71], [72].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe usability evaluation of PhantomAR involved a single session of approximately 60 minutes being exposed to the application. The study protocol consisted of two sessions in which the participants were experiencing 4 randomized PhantomAR scenes, with the usability evaluation after both experiences and interleaved PLP NRS questionnaires (see Figure 1). The real arm of able-bodied participants was obscured with a sleeve to prevent hand recognition by the HoloLens 2.\u003c/p\u003e\n\u003cp\u003e2.1 Study setup \u003c/p\u003e\n\u003cp\u003eAt the beginning of the study, participants sat comfortably in a chair in an examination room with ambient temperature of 22\u0026deg;C. Skin temperature was measured on the volar side of the stump and on the corresponding area on the contralateral, uninjured limb in patients and on the volar forearm in healthy participants. Patients were asked to rate their momentary PLP on the NRS scale.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The mixed reality study required a setup that was quick to implement for effective use in daily clinical practice. The equipment included a Microsoft HoloLens 2 headset on which the holograms of the mixed reality were projected, one Myo electrode armband (Thalmic Labs, Toronto, Canada, Note: discontinued by Thalmic Labs) and two Mbient Lab MMRL inertial measurement units (MBIENTLAB INC, San Jose, USA). The Myo armband featured 8 EMG electrodes, and a vibration motor for haptic feedback. MMRL sensors incorporated a 9-axis IMU. The setup was entirely wireless and battery-operated. Participants wore the Myo armband and an MMRL sensor on the residual lower limb and another MMRL sensor on the upper arm (see Figure 2).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Interaction scenes within the application were designed to automatically adjust to available room sizes and shapes, ideally within 10-20m\u0026sup2;. Upon wearing the HoloLens 2, the virtual arm and myoelectric controls were calibrated, saving the user\u0026rsquo;s profile, including scale and relative shoulder position, in the app. This initial setup took under 5 minutes and was only necessary once.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Participants received no further information and were instructed simply to explore their environment using all available means. After navigating the first four interaction scenes, patients were asked about their PLP. After playing another set of 4 random interaction scenes, participants evaluated the PhantomAR application, completing the SUS, the User centered survey, the altered PES and the GEQ. Their temperature was taken again at the same location as during the beginning of the trial and they were asked one last time about their momentarily PLP.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;2.2 Data analysis\u003c/p\u003e\n\u003cp\u003eData were processed in Matlab version R2022b (Natick, Massachusetts: The MathWorks Inc). The non-parametrical tests Wilcoxon signed-rank test was used to compare group means in related samples regarding NRS scores of PLP and the SF MPQ PRI, while Mann-Whitney U test was used for determining differences between independent samples as in the GEQ. Analysis of temperature correlating with PLP before and after the intervention was analyzed using the Pearson correlation coefficient. Because of the small sample size, the level of statistical significance was set at p \u0026lt; 0.01.\u003c/p\u003e"},{"header":"Implementation","content":"\u003cp\u003eWe designed and implemented 7 different environments for users to explore, as well as a separate graphical user interface for therapists and patients, using the game development platform Unity 3D and the Microsoft Mixed Reality Toolkit. The PhantomAR application was installed on the Microsoft HoloLens 2 and connected via Bluetooth to the Thalmic Myo electrode armband and the MMRL IMU sensors. The optional graphical user interface (GUI) for therapists was running on a laptop and connected to the PhantomAR HoloLens session via WI- FI.\u003c/p\u003e\n\u003cp\u003e3.1 Game design and interaction scenes\u003c/p\u003e\n\u003cp\u003eThe game design focused on immersion while minimizing mental stress, frustration and discomfort for patients, which are factors that could adversely affect PLP and the EMG control due to high muscle tension. Therefore, a curiosity driven gameplay was chosen, where the patients can freely explore an interesting and interactive environment without the possibility of failure or underperforming.\u003c/p\u003e\n\u003cp\u003eTo allow patients to immerse themselves into the mixed reality experience, the rehabilitative exercises were integrated into various playful scenes (see Table 1). These scenes were designed without specific end goals, timers, or scoring systems. Instead, patients were encouraged to explore their surroundings with inquisitiveness, discovering the possibilities within each scene. This exploration involved touching, moving and resizing objects, interacting using one or both hands, and engaging with multiple objects simultaneously (see Figure 3). The focus was on experiential learning and interaction rather than achieving specific objectives, fostering a more immersive and less pressured environment.\u003c/p\u003e\n\u003cp\u003eTable\u0026nbsp;1\u0026nbsp;Overview of the interactable scenes that were used in the study. Each scene contains a distinct environment and follows different rules and interaction mechanisms to sustain patient engagement and curiosity. The interactive elements within each scene can be manipulated using both the virtual and the physical hand.\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"616\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.85899513776337%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eScene\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.53484602917342%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDifficulty\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"59.48136142625608%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eDescription\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.124797406807133%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eMyoControl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.85899513776337%\" valign=\"top\"\u003e\n \u003cp\u003eAqua\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.53484602917342%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"59.48136142625608%\" valign=\"top\"\u003e\n \u003cp\u003eUnderwater simulation with interactive elements such as fish, algae, and corals integrated into the room\u0026apos;s spatial mapping environment. A treasure chest positions itself on any flat surface detected within the space. Participants are tasked with touching and combining virtual objects, which are designed to exhibit unexpected behaviors upon interaction.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.124797406807133%\" valign=\"top\"\u003e\n \u003cp\u003eInteraction with both virtual and real hand simultaneously is possible, but not necessary.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.85899513776337%\" valign=\"top\"\u003e\n \u003cp\u003eLiquid Creatures\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.53484602917342%\" valign=\"top\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"59.48136142625608%\" valign=\"top\"\u003e\n \u003cp\u003eGeneration of sigils on the walls and a central virtual pillar on the actual floor. Participants interact with simulated liquids, eggs, and rune stones to initiate the spawning of various creatures within the space. Some of these virtual creatures are programmed to exhibit follower behavior, reacting to the participant\u0026apos;s movements.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.124797406807133%\" valign=\"top\"\u003e\n \u003cp\u003eInteraction with both virtual and real hand simultaneously is possible, but not necessary.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.85899513776337%\" valign=\"top\"\u003e\n \u003cp\u003ePipes\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.53484602917342%\" valign=\"top\"\u003e\n \u003cp\u003e2-3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"59.48136142625608%\" valign=\"top\"\u003e\n \u003cp\u003eVirtual levers are algorithmically generated on the walls of the environment. When these levers are activated by the participant, a virtual pipe appears, necessitating connection to an existing network of pipes through a series of grab-and-rotate interaction. Successful connections trigger the release of steam clouds.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.124797406807133%\" valign=\"top\"\u003e\n \u003cp\u003eInteraction with both hands simultaneously is required.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.85899513776337%\" valign=\"top\"\u003e\n \u003cp\u003eSpace Music\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.53484602917342%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"59.48136142625608%\" valign=\"top\"\u003e\n \u003cp\u003eSet within a virtual space environment, this scenario creates interaction with planets that produce musical outputs. Participants can create simple melodies by engaging with objects they place in the planet\u0026rsquo;s orbit.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.124797406807133%\" valign=\"top\"\u003e\n \u003cp\u003eInteraction with both hands simultaneously is required.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.85899513776337%\" valign=\"top\"\u003e\n \u003cp\u003eFruit Picking\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.53484602917342%\" valign=\"top\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"59.48136142625608%\" valign=\"top\"\u003e\n \u003cp\u003eCollecting of virtual fruits that are algorithmically spawned within the environment, including less conspicuous locations such as under tables. The system allows participants to manipulate the size of these fruits by using a bilateral hand grip, enabling the fruits to fit into a designated collection basket.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.124797406807133%\" valign=\"top\"\u003e\n \u003cp\u003eInteraction with both virtual and real hand simultaneously is possible, but not necessary.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.85899513776337%\" valign=\"top\"\u003e\n \u003cp\u003eDrawing\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.53484602917342%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"59.48136142625608%\" valign=\"top\"\u003e\n \u003cp\u003eCreate three-dimensional drawings within the virtual space or on surfaces. This interaction is predominantly unilateral, with the augmented hand designated for the act of drawing. The selection of colors is managed by the contralateral hand, providing a more complementary role.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.124797406807133%\" valign=\"top\"\u003e\n \u003cp\u003ePredominantly unilateral interaction with the virtual hand.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"10.85899513776337%\" valign=\"top\"\u003e\n \u003cp\u003eShooting\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"10.53484602917342%\" valign=\"top\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"59.48136142625608%\" valign=\"top\"\u003e\n \u003cp\u003eParticipants aim and fire at target objects, represented by virtual flowers that are programmed to wilt and respawn upon being hit. The system enhances hand-eye coordination through the implementation of an aiming ray, guiding the participant\u0026apos;s actions.\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"19.124797406807133%\" valign=\"top\"\u003e\n \u003cp\u003ePredominantly unilateral interaction with the virtual hand.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u0026nbsp;3.2 Spatial mapping\u003c/p\u003e\n\u003cp\u003eA unique feature of the HoloLens 2 is that it supports automatic spatial mapping, enabling it to scan floors, walls, and tangible objects such as tables or smaller sized objects. This scene understanding capability allows for the integration of virtual content with the real-world environment while adhering to height, width, or margin requirements with regard to these objects. This feature is instrumental in making PhantomAR an environmentally aware application and is used in various game mechanics, including the generation of plants on surfaces, the interaction of game elements with floors, walls and ceilings, i.e. bouncing a ball on the floor, and the placement of virtual objects onto physical ones during gameplay. However, Microsoft\u0026apos;s toolkit provided only basic surface data, which could occasionally extend beyond the current room, thereby requiring a specialized wrapper layer. This layer aids in identifying suitable object placement locations and tracking these objects, thereby improving the game\u0026apos;s integration and responsiveness to the surrounding environment.\u003c/p\u003e\n\u003cp\u003e3.3\u0026nbsp; Interaction with the virtual environment: Arm and hand movements\u003c/p\u003e\n\u003cp\u003eBoth the virtual and the intact hand were capable of interacting with virtual objects. To simulate the movements of a virtual arm as intended by the actual residual limb, we utilized EMG data from one Thalmic Myo Armband and IMU data of the two MMRL sensors placed on the upper and lower arm respectively. This comprehensive data collection enabled us to accurately determine the absolute orientation of the participants\u0026apos; forearm and upper arm. Previous horizontal drift over time could be addressed using these MMRL IMU sensors\u0026nbsp;[50]\u0026nbsp;instead of the Thalmic MyoArmband for spatial data. The position of the shoulder was fixed in relation to the head position and was adapted to match the individual user. The 3D orientation received from the sensors was applied to the respective arm segments representing the upper and lower arm and the head (which was the HoloLens 2). In case the virtual arm should not align with the patient\u0026rsquo;s residual limb anymore, the virtual arm could be reset to the calibrated position with a light tap on the MyoArmband.\u003c/p\u003e\n\u003cp\u003eTo enhance the naturalness of grasping movements with the virtual hand, we introduced auxiliary interaction mechanisms such as freezing the target object during grabbing and incorporating a two-handed interaction for larger objects, involving the use of the contralateral healthy hand. The HoloLens 2 tracked the healthy hand, capturing the positions of the fingers and palm. This feature enabled real fingers to interact with virtual objects. When an object was grasped with both hands, it allowed for ambidextrous interactions, such as rotating the object or resizing it. Successfully grabbing an object was accompanied by a short vibration of the Thalmic Myo armband, which was shown to reduce the time needed for grabbing\u0026nbsp;[45]. The virtual hand had attached colliders that closely matched its shape, enabling physical interactions with virtual objects, such as pushing a ball. Smaller objects could pass between the virtual fingers to create an immersive interaction experience.\u003c/p\u003e\n\u003cp\u003eTo include all potential persons with transradial amputation in this study, we chose the conventional simple and robust threshold controller. Two electrodes on agonist/antagonist muscles recorded the activation, and when exceeding a threshold, the virtual hand either opened or closed with the speed proportional to the muscle activation. The path of the movement between the positions was calculated as an interpolation of the rotation of the individual bones/joints. The control algorithm, however, is modularly adaptable and any controller, such as pattern recognition, can be easily integrated into the PhantomAR application and chosen via the GUI.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;3.4 Non-anthropomorphic feedback\u003c/p\u003e\n\u003cp\u003eThe virtual arm and hand were created as a rigged 3D model, consisting of bones connected by joints for natural-looking movements. Its visual aspect was a mesh render attached to the bone structure. Beyond just replicating a human arm, we allowed for the substitution of the arm model with a virtual tentacle (see\u0026nbsp;Figure 4) Both the arm and tentacle were controlled using the same motion range via EMG. However, instead of the hand\u0026apos;s opening and closing actions, the tentacle would extend and retract. Additionally, any wrist rotations or arm movements performed by the patients were correspondingly mirrored in the movements of the tentacle mesh.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;3.5 GUI and remote connection for therapeutic supervision\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo facilitate therapist-led guidance and control over virtual scenarios, we developed a remote control application that operates on Microsoft Windows (Figure 5). This optional app communicates with the HoloLens 2 via Wi-Fi, providing therapists a live video stream that mirrors the patient\u0026apos;s mixed reality view. It enhances versatility of the therapeutic process by enabling remote manipulation of virtual scenarios, such as manual creation or resetting of objects. Additionally, the GUI serves as a tool to simplify various configuration tasks, including Bluetooth connectivity setup, EMG controller calibration, and managing patient-specific parameters. However, everything can be adjusted within the HoloLens environment itself as well.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eSystem and game evaluation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe application received an overall System Usability Scale (SUS) score of 90.8% (SD=6.88), as assessed by all 18 participants. This score reflects a high level of usability and user-friendliness, as all scores above 68 are considered above average [73].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The Game Experience Questionnaire results for the patients and able-bodied participants are depicted in Figure 6. The application received overwhelmingly positive feedback from all patients (m=4.85, SD=0.1), with no reported negative emotions (m=1.07, SD=0.07) or sensations of being overwhelmed during gameplay (m=1.93, SD=0.97). Additionally, both immersion (m=4.46, SD=0.08) and game flow (m=4.52, SD=0.38) received notably high ratings. The use of tentacle overlay instead of a virtual hand as anthropomorphic representation garnered a high agency score (m=4.42, SD=0.28), however, exhibited mixed ownership scores (m=3.12, SD=0.86).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe game experience for able-bodied participants was similar, with equal scores in the subscales positive affect (m=4.97, SD=0.05), negative affect (m=1.0, SD=0), immersion (m=4.4, SD=0.18), flow (m=4.58, SD=0.42), and tentacle agency (m=4.89, SD=0.15). Tentacle ownership was rated slightly higher by able-bodied participants (m=3.58, SD=0.74), however, not significantly (p=0.45), and challenge was rated slightly lower (m=1.43, SD=0.37, p=0.74).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAccording to the user centered survey, using a tentacle for a hand was a concept which was new to all patients, but they embraced the idea and stated, that it did not necessarily need to be their hand, or any hand for that matter. They reported it was fun to explore the PhantomAR application in real life and could see the room and their augmented arm. However, they preferred an anthropomorphic representation to a marine animal, which could further be shown by the high agency but low ownership (see\u0026nbsp;Figure 6).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003ePLP and physical reaction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInitial PLP at baseline was rated with a mean of 5.25 (SD=1.2) on the NRS scale by all patients before the intervention. In the post-intervention user-centered survey, conducted after patients had completed the application, when questioned about their PLP during gameplay, all participants reported a decrease in their PLP while immersed in the application. However, when asked directly about their PLP during the break in between the two sessions, two patients reported an increase in pain (m=3.75; SD=2.3). After finishing the application patients reported a decrease of PLP (m=2.5; SD=1.2). Overall, a high variance can be observed during baseline PLP and during the intervention (see\u0026nbsp;Figure 7).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Similarly, the pairwise comparisons on the SF-MPQ Pain Rating Index (PRI) scores showed a significant reduction when analyzing the baseline and post-intervention scores (see Figure 8).\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The skin temperature shows a significant increase from before the intervention to afterwards in all conditions as presented in Table 2, its distribution can be found in Figure 9. The difference in skin temperature between the injured and unaffected arm was on average 3\u0026deg;C and temperature increased on average 1\u0026deg;C in the residual limb over the course of the intervention. There was a high variance in temperature in the residual limb of patients that ranged from 30.7\u0026deg;C to 34.1 \u0026deg;C before and from 31.7\u0026deg;C to 35.7\u0026deg;C after the intervention. There was no significant temperature difference between the patients\u0026rsquo; uninjured arms and the arms of the able-bodied participants (p=0.61).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA correlation analysis between PLP and the temperature of the residual limb before and after the intervention yielded a Pearson correlation coefficient of-0.09 and 0.19, respectively, indicating no significant linear relationship between these two variables (p=0.83 and p=0.64).\u0026nbsp;\u003cbr\u003e\u003cimg 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\"\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEmbodiment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe modified Prosthesis Embodiment Scale, adapted to assess Virtual Arm Embodiment, revealed a high sense of agency, suggesting that participants felt a cohesive control over the superimposed virtual arm and regarded the executed movements as their own (see Figure 10).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eUser centered survey\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eResponses from all participants (n=18) in the user-centered survey further revealed the following key observations: Users described wearing the HoloLens as comfortable, and though initially the field of view felt restricted, they soon forgot about it. They described interactions with virtual game elements in the real environment as novel, interesting and challenging, increasingly perceiving these objects as convincingly real. None reported experiencing cyber (motion) sickness during the study. The introduction of haptic feedback through the Thalmic Myo armband greatly enhanced the immersive experience of grasping objects, and participants found the controls to be intuitive.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eUsers commented that it was a long time since they could feel their hand and that they felt their phantom hand grow into the augmented hand. They said that they were surprised at how real everything looked and that they would like to just stay in this level (underwater level) and look around. There was not one comment that the HoloLens would be uncomfortable. When users \u0026ldquo;lost\u0026rdquo; their augmented arm, they could re-calibrate and would say \u0026ldquo;Ah, there is my hand again.\u0026rdquo;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eWith PhantomAR we wanted to develop a wearable assistive therapy tool for PLP that extends traditional mirror therapy and not only liberates users from their restrictive position at a table, but also allows them to perform bi-manual tasks and freely interact with objects found in their virtual and actual environment.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAddressing complex phenomena such as PLP equally requires flexibility in the treatment approach. The application is modularly built, so we can accommodate several control methods\u0026nbsp;[74].\u003c/p\u003e\n\u003cp\u003ePhantomAR was not designed to be goal-oriented, but curiosity driven. There is no intended or evaluated task transfer from a virtual hand to an actual myoelectric prosthesis.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Brasse et al. suggest, that augmented reality (AR) will play a significant role in future medical applications, enabling patients to perceive a fusion of virtual and real-world visuals [64]. By blending virtual projections with the real world, PhantomAR could serve as a bridge during the rehabilitation process. Specifically, it was designed to be used in the interim phase while the amputated limb is healing and before a permanent prosthetic is fitted, since using a prosthesis has been found to reduce PLP in most users [75].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;Patient participation ensures clinical relevance by addressing real needs and challenges, fostering a user-centered approach. Their unique perspectives uncover limitations and refine design, functionality, and usability, ultimately improving the intervention. It was important to not only provide an application for research, but also transfer it to the clinic, with separate user interfaces for the clinician and the patient. Therefore, the patient only has to mount the devices and can start interacting. In addition, the whole system is portable and completely wireless and can thus be used anywhere in the clinic or even at home. The system automatically detects the room without any additional requirements.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003ePLP\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThere was a high variance in PLP sensation for patients and some incongruency. Some patients described a lessening of pain during active use but reported later that pain was actually increased during play and only decreased afterwards. All patients agreed that PLP was lower after using the application. Of course, this one-time proof of concept cannot provide a statement about the alleviation of PLP. \u0026nbsp;Therefore, increasing the sample size can not only provide more insight on PLP but also on embodiment and their progress over time. Prospectively, a weekly assessment using the SF McGill Pain Questionnaire might be more indicative of the intervention\u0026apos;s effectiveness.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAnthropomorphic representation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eLiterature pertaining to neuroplastic hypotheses for alleviating PLP highlight the relevance of prioritizing anthropomorphic visual feedback [22], [76]. The concept of stochastic entanglement as hypothesized by Ortiz-Catalan, however, predicts that pain reduction would be independent of the level of anthropomorphic visual representation [21]. However, while agency was high, ownership still received mixed scores.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTemperature\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe increase in mean skin temperature in the post-condition phases, such as in the \u0026apos;Post Residual Limb\u0026apos; and \u0026apos;Post Proband\u0026apos; groups, could be indicative of increased blood flow to those areas. An elevation in skin temperature is often associated with vasodilation, where blood vessels widen to increase blood flow. This physiological response can be a result of various factors, including increased muscle activity. The difference in temperature between the residual limb and unaffected site of 3\u0026deg;C corresponds to previous findings in upper and lower limb amputees alike\u0026nbsp;[69], [77]\u0026nbsp;and was expected, because stump vascularization is affected by amputation and the limited activity of the residual limb. Our findings indicate that elevated PLP scores prior to the intervention correlate with increased temperatures in the residual limb. In the context of rehabilitation or physical therapy, variations in skin temperature may serve as markers for enhanced blood flow or elevated muscle engagement, aligning with common objectives of these therapeutic interventions\u0026nbsp;[78], [79].\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eBimanual interaction: myoelectric control\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePhantomAR could also be used as a tool to train myoelectric prosthetic control, even though it was not designed for that purpose. But since it offers the same functionality adapted to the control scheme that the patient will use, be it threshold control or machine learning, it would be possible due to the modularity of the application.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe latency of the movement of the real arm to the visual representation of the corresponding virtual arm was not directly measured, but for arm movements, there is no noticeable lag. The latency is assumed to be below 50ms, as the data is received from the MMRL sensors in real-time every 10ms and translated to the virtual arm position within the next frame. A comparably low latency has not yet been reported in other studies, in which the latency was 500-800ms when controlling a virtual arm using custom IMU sensors\u0026nbsp;[45].\u003c/p\u003e\n\u003cp\u003eImmersion could be increased from a technical perspective by creating a spatially coherent experience of the virtual and real world that are responsively interacting with each other and underlying it with haptic feedback.\u003c/p\u003e\n\u003cp\u003eIn a future study, to enhance the precision of arm tracking when rotating the head independently from the shoulders, a third MMRL sensor will be employed to monitor shoulder position, thereby creating a more accurate representation and adding additional Degrees of Freedom to the internal model of the patient\u0026apos;s arm, which could further improve agency and embodiment. Currently, PhantomAR is exclusively available for transradial (forearm) amputees, but in the future, we plan to extend it to transhumeral (upper arm) amputees as well.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eLimitations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA limitation may be that the findings presented here are based on a group of 8 patients, a longitudinal study is needed to further investigate. Reliance on self-reported measures for PLP intensity, embodiment, ownership, and agency might introduce a subjective bias. Consequently, the results and analyses should be considered in light of this. One of the key challenges of the Microsoft HoloLens 2, and AR glasses in general is the restrictive field of view, which might lead to reduced immersion when not operating in the center of vision.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis paper presented PhantomAR, a mixed reality application aimed to overcome the limitations of Mirror Therapy for addressing Phantom Limb Pain. Building on traditional methods, PhantomAR offers dynamic full-body interaction through the HoloLens 2 with human and non-anthropomorphic virtual limb representations. The study found significant PLP reduction, high usability, and an immersive experience. To further assess PhantomAR\u0026rsquo;s impact, a longitudinal intervention study is warranted, comparing PLP intensity, agency, and embodiment.\u003c/p\u003e\n"},{"header":"Abbreviations","content":"\u003cp\u003eGUI \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Graphical User Interface\u003c/p\u003e\n\u003cp\u003eGEQ\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Game Experience Questionnaire\u003c/p\u003e\n\u003cp\u003eIMU \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Inertial Measurement Unit\u003c/p\u003e\n\u003cp\u003eIRT\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Infrared thermometer measurement\u003c/p\u003e\n\u003cp\u003eNRS\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Numerical Rating Scale\u003c/p\u003e\n\u003cp\u003ePES\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Prosthesis Embodiment Scale\u003c/p\u003e\n\u003cp\u003ePLP\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;Phantom Limb Pain\u003c/p\u003e\n\u003cp\u003ePRI\u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;Pain Rating Index (SF McGill)\u003c/p\u003e\n\u003cp\u003eSUS \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; System Usability Scale\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eParticipant recruitment for the study was conducted in compliance with the Declaration of Helsinki and followed the ethical guidelines by the University of Tuebingen, Germany, under the positive vote number 181/2020BO1. Prior to the initiation of the study, informed consent was obtained from all participants.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eTrial Registration:\u003c/strong\u003e DRKS00033208 (Jan. 5\u003csup\u003eth\u003c/sup\u003e 2024)\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConsent on publishing any data, including images or videos, has been obtained from all participants via the institutional consent form.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work has been supported by the Japan Society for the Promotion of Science (JSPS) SP20304 and SP20313 and AKF 453-0-0 by the University of Tuebingen, Germany. We acknowledge support by the Open Access Publishing Fund of the University of Tuebingen.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCP did the conceptualization, design, investigation of the study, conducted formal analysis, managed resources, curated data, developed software, created visualizations, administered the project, acquired funding, and drafted the manuscript. KE contributed to software development, formal analysis, and data curation, and acquired funding. MB contributed to software development, data curation, and providing a critical review of the manuscript. ZW, XL, and TS were dedicated to software development. HK, AD, and JS provided critical reviews, supervision, and funding acquisition. All authors have read and approved the final manuscript for publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur gratitude extends to the individuals with limb amputations and the able-bodied participants for their invaluable contribution to this research.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eSupplementary Materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSupplementary information on the application PhantomAR can be found at www.playbionic.org/phantom-ar.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eT. S. Jensen, B. Krebs, J. Nielsen, and P. Rasmussen, \u0026ldquo;Phantom limb, phantom pain and stump pain in amputees during the first 6 months following limb amputation,\u0026rdquo; \u003cem\u003ePain\u003c/em\u003e, 1983, doi: 10.1007/BF01402796.\u003c/li\u003e\n\u003cli\u003eT. S. Jensen, B. Krebs, J. 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Zijlstra, \u0026ldquo;Regulation of peripheral blood flow in Complex Regional Pain Syndrome: clinical implication for symptomatic relief and pain management,\u0026rdquo; \u003cem\u003eBMC Musculoskelet. Disord.\u003c/em\u003e, vol. 10, no. 1, p. 116, Dec. 2009, doi: 10.1186/1471-2474-10-116.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"journal-of-neuroengineering-and-rehabilitation","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jner","sideBox":"Learn more about [Journal of NeuroEngineering and Rehabilitation](http://jneuroengrehab.biomedcentral.com/)","snPcode":"12984","submissionUrl":"https://submission.nature.com/new-submission/12984/3","title":"Journal of NeuroEngineering and Rehabilitation","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"upper limb amputation, hand amputation, mirror therapy, gamification, phantom limb pain, prosthesis, myoelectric control, mixed reality, extended reality, Microsoft HoloLens 2","lastPublishedDoi":"10.21203/rs.3.rs-4221472/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4221472/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Phantom limb pain (PLP) is a restrictive condition in which patients perceive pain in a limb that is no longer present, greatly reducing their quality of life. Mirror Therapy, wherein patients observe a mirror reflection of their intact limb, has demonstrated efficacy in alleviating PLP. However, its unilateral and seated nature presents limitations. To address these constraints while still reducing PLP, and evaluating the impact of different virtual limb representations (anthropomorphic vs. non-anthropomorphic) on the user's sense of ownership, agency, and embodiment, PhantomAR was developed. Leveraging wearable first-person augmented reality (AR) technology, PhantomAR extends traditional Mirror Therapy by enabling users to move freely and engage in bimanual tasks.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e The assistive mixed reality game application PhantomAR was deployed on the Microsoft HoloLens 2 and augmented the user’s residual limb by superimposing a virtual arm or tentacle that was controlled via residual muscles on their stump using an EMG electrode array. This setup allowed patients to engage in a first-person perspective and manipulate virtual objects with both the healthy and augmented limbs, free from the confines of a seated position. The study enrolled 10 able-bodied individuals and 8 individuals with unilateral, transradial amputation. All amputees experienced PLP. The usability of the PhantomAR application was evaluated using the System Usability Scale (SUS) and a user-centric survey. Additionally, the Game Experience was assessed on a 5-point Likert questionnaire (GEQ). Participants rated their phantom sensations using the Numerical Rating Scale and McGill Pain Questionnaire before, during, and after interaction with PhantomAR. The embodiment and agency of the virtual superimposed arm were evaluated with an altered Prosthesis Embodiment Scale. The study protocol included two sessions of 30 minutes each, during which participants experienced PhantomAR.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Participants (n=18) rated PhantomAR highly usable (SUS m=90.8%, SD=6.88). Feedback on the Game Experience Questionnaire was overwhelmingly positive, showing high immersion (m=4.46, SD=0.08) and positive affect (m=4.97, SD=0.05). PLP (n=8) significantly decreased post-intervention (NRS and McGill Pain Questionnaire, p\u0026lt;.001). Skin temperature in the residual limb increased significantly post-intervention (p\u0026lt;.01) but did not correlate with PLP (r=-0.08, p=0.83). Tentacle overlay yielded mixed ownership but high agency ratings.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e PhantomAR leverages extended reality to significantly reduce Phantom Limb Pain, enhance user engagement, and alter perceptions of ownership and agency of their augmented limb through dynamic, full-body interactions.\u003c/p\u003e","manuscriptTitle":"PhantomAR: Gamified Mixed Reality System for Alleviating Phantom Limb Pain in Upper Limb Amputees – Design, Implementation, and Clinical Usability Evaluation","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-17 20:50:20","doi":"10.21203/rs.3.rs-4221472/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-10T18:53:05+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-07T21:55:50+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-03T23:18:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-04-21T17:37:54+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"6355168a-32fd-4327-a199-d0489575568d_SNPRID","date":"2024-04-12T15:53:37+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"923e20c4-876e-4b82-a2f8-2b70a05e299a","date":"2024-04-11T13:12:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"0e31f713-035f-4df7-b103-03a9b29e41d5","date":"2024-04-10T20:04:26+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-04-10T17:52:42+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-04-09T15:03:18+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-04-09T15:03:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"Journal of NeuroEngineering and Rehabilitation","date":"2024-04-05T07:55:37+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"journal-of-neuroengineering-and-rehabilitation","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"jner","sideBox":"Learn more about [Journal of NeuroEngineering and Rehabilitation](http://jneuroengrehab.biomedcentral.com/)","snPcode":"12984","submissionUrl":"https://submission.nature.com/new-submission/12984/3","title":"Journal of NeuroEngineering and Rehabilitation","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"c4d87d98-01e3-44aa-8b2a-2ad472440d28","owner":[],"postedDate":"April 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2025-02-10T16:05:03+00:00","versionOfRecord":{"articleIdentity":"rs-4221472","link":"https://doi.org/10.1186/s12984-025-01554-7","journal":{"identity":"journal-of-neuroengineering-and-rehabilitation","isVorOnly":false,"title":"Journal of NeuroEngineering and Rehabilitation"},"publishedOn":"2025-02-04 15:57:05","publishedOnDateReadable":"February 4th, 2025"},"versionCreatedAt":"2024-04-17 20:50:20","video":"","vorDoi":"10.1186/s12984-025-01554-7","vorDoiUrl":"https://doi.org/10.1186/s12984-025-01554-7","workflowStages":[]},"version":"v1","identity":"rs-4221472","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4221472","identity":"rs-4221472","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}