The World Health Organization estimates that traumatic brain injury (TBI) is and will remain the most important cause of neurodisability in the coming years (1). The search for neuroprotective therapies for severe TBI has been extensive but unfruitful over the last few decades, testified by more than 30 failed clinical trials, and we still have no specific neuroprotective therapy, that is, effective in clinical TBI. The burden of mortality and residual disability calls for new approaches to promote recovery of function of TBI patients in the acute and chronic phase (2, 3).
Classically described as a sudden event with short-term consequences, TBI induces dynamic pathological cascades that may persist for months or years after injury with a major impact on outcome (4, 5). Among dynamic mechanisms, the neuroinflammatory response and the accumulation of aberrant proteins may have a critical role in establishing a neuropathological link between acute mechanical injury and late neurodegeneration (6, 7). The close association between post-TBI neurological changes, persistent neuroinflammation, and late neuropathology highlights the fact that the window of opportunity for therapeutic intervention may be much wider than previously thought and that long-term treatment encompassing the acute and chronic phase should be tested to effectively interfere with this complex condition.
Importantly, next to the harmful processes, TBI also induces a neuro-restorative response that includes angiogenesis, neurogenesis, and brain plasticity (8, 9). These spontaneous regenerative mechanisms are short-lived and too weak to counteract damage progression but they could point the way to new therapeutic options if appropriately boosted and amplified. Physical and cognitive exercise increase repair and brain plasticity after injury in experimental models and patients (10, 11). Rehabilitative programs to provide inputs/stimuli to specific sensory or motor neural circuits, could in principle start very early on, and be finely tuned over time to account for the type and degree of injury and the level of motor and cognitive disability.
Virtual Reality (VR) for Rehabilitation after TBI
Cognitive and physical rehabilitation programs are fundamental instruments to improve the clinical outcome of TBI patients optimizing the activities, function, performance, productivity, participation, and quality of life (12). They are based on restitutional, compensatory, and adaptive strategies and vary in relation to the patient potential and disability degree (2, 12).
Traumatic brain injury encompasses heterogeneous etiology, as well as structural and molecular patterns of injury dictating different prognostic features and potential responses to rehabilitative therapy. Experimental studies indicate that depending on the degree of cognitive and sensorimotor impairment exercise may improve outcome with different window of opportunity, however, evidence supporting the optimal timing, type, and intensity of rehabilitative interventions in patients are scarce (12, 13). For example, rehabilitation is often delayed in patients with severe TBI until their discharge from the intensive care unit, or adopted in the most severe cases with only minimal goals aimed at limiting spasticity (14). Importantly, cognitive rehabilitation in the sub-acute stage of TBI is rarely considered. For these reasons, the use of innovative techniques is advocated to assess the TBI-related deficits and to develop and evaluate new rehabilitative interventions (12).
An emerging technology, VR, represents a new tool for this purpose and might provide TBI care teams with new neuro-restorative strategies readily available at the bedside. Since the late 1980s, this term has been used to describe a 3D synthetic environment created by computer graphics, where the user has the feeling of being inside (15). VR can be described as “an advanced form of human-computer interface that allows the user to interact with and become immersed in a computer-generated environment in a naturalistic fashion” (16). For its flexibility, sense of presence (i.e., the feeling of “being there”) and emotional engagement, VR has been tested in motor and cognitive rehabilitation, with good results. In stroke patients, the number of VR programs is rapidly increasing with compelling data showing an improvement in recovery of motor function and daily living activities (17).
Data on the effects of cognitive function and quality of life are more limited. As underlined by two recent systematic reviews (18, 19), VR allows a level of engagement and cognitive involvement, higher than the one provided by memory and imagination, but is more controlled and can be more easily measured than that offered by direct “real” experience. Its multisensory stimulation means VR can be considered an enriched environment that can offer functional and ecological real-world demands (e.g., finding objects, assembling things, and buying stuff) that may improve brain plasticity and regenerative processes (20–22).
There are several examples in the literature where VR has been successfully used both as assessment instrument and as therapeutic intervention. As assessment tool, VR has been used to detect visual-vestibular deficits in adults after concussion and mild TBI (23, 24). Wright WG et al., developed a Virtual Environment TBI Screen that allows subjects to explore a digitalized setting (i.e., outdoor Greek temple with columns, different kind of floor materials, etc.) performing postural tasks while the system collects data to detect visual-vestibular deficits. Besnard et al. (25) created a virtual kitchen to assess daily-life activity and evaluate executive dysfunctions in subjects with severe TBI. Robitaille et al. (26) developed a VR avatar interaction platform to assess residual executive functions in subjects with mild TBI. The platform can capture real-time subject’s movements translating them in to a virtual body, that is, therefore placed in a simulated environment (i.e., a village). The user is then allowed to explore the simulate surroundings which comprise different navigational obstacles to overcome. Similar approaches have been used by other authors, whereas simplified settings (i.e., 3D virtual corridor that the subject can explored with a joystick) have been proved useful to assess subclinical cognitive abnormalities in asymptomatic subjects that suffered a concussion (27).
As therapeutic instrument, Dahdah et al. (28) demonstrated that immersive VR intervention can be used as an effective neuro-rehabilitative tool to enhance executive functions and information processing in the sub-acute period, providing evidence of positive effects of a virtual Stroop task over traditional non-VR-based protocol. VR as therapeutic instrument has also been used for attention training in severe TBI with positive results in the early recovery stages (29) with a specific “augmented” task in which virtual and haptic feedbacks were used in a target-reaching exercise to enhance sustained attention. Finally, virtual protocols generated upon commercial available game solutions have been effective in addressing and treating balance deficits (30).
All these works suggest that VR could be useful as assessment instrument and in the rehabilitation of TBI, nonetheless a delineated pattern seems to emerge. VR assessment protocols appear to be primarily implemented for mild TBI, which induce subtle residual deficits hard to detect with traditional instruments (23). Conversely, VR treatment protocols for cognitive rehabilitation are used transversely from mild to severe conditions, although effectiveness of these kinds of interventions needs to be further explored (31).[…]