Researchers believe that the entry of the metaverse into clinical practice will be achieved through notable innovation and the development of new technological devices useful for offering deeper immersive experiences (Figure 1). This new era of innovation could help to overcome the actual limitations reported with VR applications in clinical practice, boosting the efficacy of VR-based treatments with respect to traditional approaches. According to a recent review ^[1][30], numerous studies have shown that altering patients’ internal body representations by using the sense of embodiment in a virtual body is a potent tool for modulating some clinical disorders (such as motor, pain or psychiatric disorders). For this reason, rwesearchers believe that the translation from the metaverse of tools based on the integration of different embodied technologies (e.g., haptic and interoceptive technologies mediated by AI algorithms via digital avatar) will increase the transposition of users’ first-/third-person perspectives, thus enhancing immersive experience. Here, researcherswe propose a list of possible neurological disorders where a new generation of advanced VR-based treatment could potentially be applied for overcoming previous technological limitations.

RWesearchers hypothesize that the metaverse-related technology could be applied in neurological disorders where the body schema representation is damaged. Body representation (BR) is a multifaceted concept that is related to the perception, memory and cognition of your body. BR is continuously updated by the different sensory inputs coming from the skin, joint and muscle receptors and flowing to the cerebral cortex through the brain stem, thalamus and cerebellum. At the cerebral cortex level (e.g., in the temporal–parietal cortex) the signals from the visual, vestibular and primary sensory cortices are integrated into an internal body schema. BR consists of both body image (the conscious representation of the body) and body scheme (the dynamic representation of the spatial properties of the body). It is noteworthy that BR is constantly evolving and affects life and interpersonal and social relationships ^[2][31]. These premises pave the way for the use of the metaverse in the rehabilitation of both motor and cognitive deficits in patients with different neurological disorders. Indeed, metaverse patients may experience the so-called “embodied cognition”, which has a large spectrum of potentiality in the rehabilitation setting ^[3][32].

From a neurorehabilitation point of view, metaverse might also give the opportunity to boost motor recovery by exploiting cognitive pathways/resources in a more tailored and sophisticated manner. Motor imagery and action observation are two clear examples of training opportunities that are more powerful when boosted by immersive virtual reality, both for motor recovery after stroke, ^[4][33] and improving the motor control of a body powered prosthesis ^[5][34]. Moreover, coordination and skill transfer (two important components in sports and in neuromotor rehabilitation) can also be better trained through mental training performed with immersive virtual reality ^[6][7][35,36]

The metaverse can represent an even greater opportunity in consideration of the senses of agency, body ownership and self-location. The possibility of modifying the first-person vision into a third-person vision and the interaction with other avatars could accelerate processes related to motor learning during rehabilitation by playing even more clearly with the attention based on an internal focus and/or an external focus ^[8][37]. The internal focus during rehabilitation is more suitable when the aim is to improve sensory-motor feedback and feedforward components during motor rehabilitation, while the external focus is more suitable when there is a pain maladaptive mechanism that reduces movement intention and action. Therefore, thanks to the metaverse, key aspects of both orthopedic and neurological rehabilitation like attention will be recalled. In fact, to learn motor behavior efficiently, humans rely on interaction of learning and attention, and that might be manipulated in the metaverse ^[9][38].

One field that could largely benefit from the arrival of the metaverse is cognitive rehabilitation (CR). CR is a way to rehabilitate individuals with brain damage and cognitive problems to compensate for the impairment or recover their normal functioning. CR may be provided in clinical practice in two ways, using either restorative methods or compensative ones. Restorative CR allows the patient to regain their lost cognitive domains by means of specific cognitive training, whereas compensatory CR is based on the use of aids and tools to overcome the deficits. CR is also classified as conventional (when it is based on paper/pencil exercises) or computer-assisted (if innovative devices and software are used) ^[10][39].

Generally, individuals immersed in a multisensory stimulation of augmented feedback are more able to obtain both knowledge of results and performance of their training, which are fundamental to reinforcement learning as well as neuroplasticity, and functional recovery ^[11][40]. This latter is boosted by the repetitive, intensive and task-oriented training provided by VR. Indeed, VR has been positively applied to different neurological disorders, promoting the recovery of different cognitive functions, including memory, attention, visuospatial cognition, executive processes, and planning ^[11][40]. In detail, a recent meta-analysis of 21 studies (1149 participants), VR led to better outcomes (such as MMSE, MoCa, ADL/IADL and FIM scores) than conventional training in patients with different cognitive dysfunction following stroke ^[12][41]. This data was corroborated by changes in the event-related potential 300 (P300) amplitude ^[13][42]. Concerning multiple sclerosis, it has been demonstrated that the use of VR-exergaming exceeded conventional training for improving cognitive abilities as well as psychosocial status and fatigue ^[14][43]. Moreover, VR interventions may be considered beneficial for improving cognitive as well as motor function in individuals with mild cognitive impairment or dementia. This improvement was evident for global cognition, attention/executive function and memory and balance, but VR was not superior in visuospatial ability and gait ability ^[15][44]. On the contrary, no conclusive data are available concerning the positive effect of VR in improving motor, cognitive and behavioral function in patients with Parkinson’s disease ^[16][45].

Unilateral spatial neglect is another neurological deficit that would benefit from the improvement of VR-related immersive experiences. Indeed, thanks to the possibility to boost embodied cognition using different virtual environments, this may lead to better outcomes in improving neglect and associated symptoms ^[17][18][22,46]. The use of the metaverse, thanks to the realistic experience of “being there” with the therapist, might better work on the attention deficit, not only by potentiating the visual and spatial neglect but also by acting on the body representation, thus potentially improving anosognosia and personal neglect.

Another example of a possible condition where the metaverse could be positively applied is frailty. Although this condition is not a disease per se, aging of the brain and other systems may induce behavioral complications that need to be treated for avoiding more severe outcome. In this context, the metaverse would allow for a motivating and multidimensional rehabilitation and socialization. Thanks to the metaverse, older frail individuals could train motor and cognitive problems at the same time, and those individuals with social restriction due to geographical/physical and behavioral/cognitive barriers may benefit from this tool. To this end, the metaverse could be applied during pandemics, like COVID-19, to avoid isolation and treat all kinds of patients in a safer manner. In this case, the adjunctive use of sensors might give clinical staff information regarding the online and offline patients’ performance during training (amount and quality of the movement).

Of particular interest could be the rehabilitation of developmental pathologies such as mild-moderate cerebral palsy. The disease represents the synthesis of the cognitive, sensory, motor and behavioral developmental deficits of a child and would find in the metaverse an opportunity to carry out a true multidimensional rehabilitation, thanks to a well-tested and customized rehabilitation protocol. Many studies have already reported positive results of clinical trials based on digital gaming technologies ^[19][47] and virtual reality ^[20][21][48,49] in children with cerebral palsy, as well as studies with the therapist not in person ^[22][50]. However, a recent systematic review found that the effect of VR in the rehabilitation of the upper limb of children with CP remains unclear ^[23][51]. Although caution is needed for children with cerebral palsy for their risk of epilepsy, this population seems to be an important target for metaverse activities as well as for improving their participation, based on an active inclusion, in schooling and clinical programs based on the new approaches of e-learning, edutainment, gamification ^[22][50].

Other clinical conditions in which the metaverse should be used are chronic pain syndromes such as regional complex pain syndrome, where rehabilitation with an external focus can give great benefit, as well as chronic nonspecific cervical and lumbar pain syndrome, where the sharing and awareness of current problems could be learned by the patient through the metaverse (e.g., first lesson of postural cognitive-behavioral re-education such as Back School).

Last but not least, the metaverse could be used for the motor and emotional recovery of injured athletes to better prepare them to return to play by simulating and accustoming them to the stressful conditions of a race.

Finally, the influence of the metaverse for health care digitalization and artificial intelligence in support of prevention and/or early diagnosis should not be underestimated. In fact, the digital avatar based on biometric data and implemented with other medical information such as blood analysis and imaging tests (Rx, CT, MRI, PET, etc.), could facilitate the aforementioned objectives.

The immersion of the patient in the metaverse could be useful not only during the rehabilitation sessions. Patients spent most of their time inactive, alone and confined to their beds during the hospitalization period ^[24][52]. Conversely, an enriched environment may favor physical, cognitive and social activities of patients with stroke ^[25][53]. The metaverse could provide a virtual enriched environment allowing patients to interact with their relatives at home, with friends and even with other patients in a more stimulating environment. Among the many potential applications, it has been shown as a virtual tour of a museum could improve social inclusion, physical and mental health in older adults ^[26][54]. Another interesting application is the possibility of virtually visiting different hospitals before deciding the preferred one ^[27][55].

A further aspect of the metaverse is its possibility for initial treatment education, during for example a robot-assisted rehabilitation or when learning to use a prosthesis for walking, in order to reduce the time of the learning curve; such education could begin even while the patients are still confined to their beds. Likewise, it is impossible to deny the potential of the metaverse in the education of specialists, particularly in surgery and in medical education at all ^[28][56].

In the past, the aim of neurorehabilitation has always been the reduction of harmful effects of motor or cognitive impairments, working on a single deficit using a single device/protocol. In the last ten years, this mono-therapeutic approach has been coupled together with a multidisciplinary approach where the main target is shifted to the patient’s awareness and ability to take motor/cognitive impairments into account in daily living. This holistic approach, which considers the patient’s cognitive, emotional, and psychosocial status, has been regarded as the best rehabilitation approach ^[29][30][57,58].

This goal could be achieved through a multidisciplinary strategy where the clinical team participated in the patient’s needs and therapists’ assessment of problems (mobility, self-care ADL, communication, daily occupations, and social interactions). Several studies demonstrated that this kind of inpatient or outpatient rehabilitation programs may reduce disability and bladder dysfunction, and improve participation in neurological patients ^[31][59].

Participation is another concept that could be considered in the future application of the metaverse technology in clinical rehabilitation. RWesearchers here use the term in the context of the World Health organization’s ^[32][60] differentiation of “health-related states,” into separate domains: (a) impairment is distinguished from (b) activity limitations (activities) and (c) participation restrictions (participation). Participation is defined as “involvement in life situations,” whereas participation restrictions are defined as “problems an individual may experience in involvement in life situations.” In medical rehabilitation, the degree of participation during neurorehabilitation protocols or at discharge is often neglected. Instead, the new guidelines highlight the need to include participation as one of the main milestones in designing the rehabilitative protocols. Working together improves mood and motivation. This is also called social group work or group therapy, where patients who have similar deficits work together to solve them. This approach is widely employed in the psychiatric domain (i.e., eating disorders, addiction ^[33][61]), but in neurological rehabilitation, this is generally neglected. The development of a new technology able to provide a “deep feeling of presence” through a multisensory experience shared by multi users, will revolutionize the employment of medical devices for rehabilitation enhancing the degree of participation in neurological patients, which in turn will promote neural plasticity as well as wellbeing.

Although social participation and return to work are primary objectives during neuromotor rehabilitation, to date, none of the common rehabilitation strategies is implemented to pursue this objective due to obvious difficulties. The metaverse can represent an optimal environment by simulating scenarios of social and work participation, facilitating the process of integration and the acceptance of one’s different abilities following a trauma of the central nervous system or an amputation, for instance.