Faculty Bibliography

Introduction: Virtual reality (VR) can be used to manage symptomatic burden in people with neurological disorders. VR treatment can be both distracting and immersive and can effectively reorient subjective attention. People with multiple sclerosis (MS) can experience a high symptomatic burden and present with comorbidities that can be managed by VR treatment. This study investigates whether VR rehabilitation can be feasible and efficacious for people with MS. Method(s): People with MS were recruited to complete 8 weekly VR sessions using the HTC Vive Pro VR System. Participants completed one of two treatment schedules: Schedule A which consisted of interactive VR exercises and Schedule B which consisted of passively viewed 360degree videos. Participant completed self-report measures before and after each treatment session. Result(s): Four participants have been enrolled in the study to date with two participants assigned to each treatment schedule. A single participant experience motion sickness during Schedule B's 360degree videos and was stopped during that treatment session but remains in the study and interested in future treatments. All other participants tolerated the stimulation well with no adverse events. All participants experienced improved affect following the VR treatment. Conclusion(s): VR treatment is feasible for MS patients and leads to enhanced affect and mood. 2 Introduction: Virtual reality (VR) is an emerging technology that presents tremendous opportunities for the modulation of a person's perceptive input. For decades, VR has been presented as the future of technological interface but had remained largely impractical. Recent advances in computer processing and engineering have yielded commercially available VR headsets that are relatively inexpensive, highly immersive, and capable of running on medium to high end personal computers. VR has been shown to be efficacious in distracting post-surgical and burn patients from pain they may experience through the use of interactive virtual environments. One of the initial studies that investigated the analgesic effect of VR utilized VR software titled "SnowWorld", where users interact with penguins in a snowy environment, and led to a reduction of perceived pain in a cohort of pediatric burn patients. The theory of limited conscious attention helps to explain why such a distraction is beneficial to perceived pain; humans have a limited amount of attention that can be attributed to any given stimulus and by consuming as much of the attention as possible with VR, the self-appraisal of pain is thereby limited. In sum, VR is a potentially powerful tool for distraction from physical and emotional trauma. Beyond distraction, VR can be used to reorient one's sense of subjective presence or the feeling of actually residing in an environment. The ability to look in 360degree establishes a convincing illusion of reality and one's presence in the illusion can be further magnified when one can interact with the virtual environment with the use of their hands or body. A fully immersive experience can fundamentally alter one's perception and mindset and can even affect one's physiological state. People with multiple sclerosis (MS) experience significant symptomatic burden, often including chronic pain, fatigue, and depressed mood. Those with MS stand to gain from such a treatment, as reduction of perceived symptoms can lead to enhancements of quality of life. To determine whether patients with multiple sclerosis can tolerate and benefit from immersive VR, we have initiated a study at NYU Langone Health's Department of Neurology. Here, we present the study design and initial results. 3 Methods: This study is currently ongoing and all procedures have been approved by NYULH's institutional review board. All participants have provided informed consent. Eligibility criteria included a diagnosed neurological disorder and no current or uncontrolled epilepsy, vertigo, mood disorders, psychosis, or schizophrenia. Patients diagnosed with MS were recruited to complete eight sessions of guided VR over eight weeks (one session per week). Participants were assigned to either complete interactive VR exercises in which they used handheld controllers and the headset to interact with a virtual setting (schedule A) or to passively watch 360degree videos (schedule B). Both schedules were experienced through use of the HTC Vive Pro VR system. Schedule A utilized Virtual Embodiment TrainingTM software by Karuna Labs, Inc. which emphasizes reduction of physical symptoms through instructed rehabilitation exercises. For example, one such exercise instructs participants to operate a ballista and fire it at targets that appear nearby the participant. As participants perform the task, they must rotate toward their left or right while the program assesses the range of motion exhibited by the participant to determine how far the target will be placed. The exercises were conducted in VR for 30 minutes with a final five minutes of passive, guided meditation at the close of each session. [Figure presented] Schedule B consisted of passively viewed 360degree videos for 30 minutes each session. No video was repeated to any participant over the course of the study. Similar to schedule A, each session of schedule B also closed out with an additional five minutes of passive, guided meditation. It should be noted that both Schedule A and B may benefit patients with neurological disorders equally as the literature suggests that either schedule will lead to symptomatic benefit. However, we expect that schedule A will lead to a higher subjective presence in the virtual environment due to the interactive nature of the schedule, and therefore greater symptom reduction. Participants completed a battery of self-report questionnaires and cognitive measures at baseline and treatment end visits and a small set of measures pre- and post- session over the course of the study. Of relevance, participants completed a measure of positive and negative affect (Positive and Negative Affect Schedule or PANAS) before and after each treatment session. 4 Results: To date, n=4 participants have been recruited to the study and n=2 participants have been assigned to schedule A while n=2 participants have been assigned to schedule B. The VR treatment has been well-tolerated in n=3 participants while a single participant experienced motion sickness and was subsequently discontinued from that treatment session (but remains interested in returning for additional treatments). While no participant has completed the entirety of their eight week schedule yet, changes in pre- and post-session PANAS data is available and can provide signals of the acute effects of the VR treatment. Effect size analysis shows that participants immediately felt an increase in their positive affect (PA, Cohen's d = 0.27) and a large decrease in their negative affect (NA, Cohen's d =1.95) following VR. Participants in Schedule A (which consisted of the interactive virtual exercises) particularly experienced a larger improvement in positive affect than those in schedule B (which consisted of the passive 360degree videos). [Figure presented] 5 Discussion and Conclusion(s): A small cohort of participants with MS completed VR treatments with only a single instance of an adverse event that quickly resolved following removal of the VR headset. Additionally, affect improvements were observed in all 4 participants after VR treatment, with the strongest improvements in those that completed the VR exercises that involved interaction with the virtual environment. All participants indicated satisfaction with the treatment and a desire to continue. Importantly, all participants were highly immersed in their treatment and often remarked so following the treatment. As previously described, immersion is essential to an effective VR treatment session. In the future, we hope to incorporate objective measures of immersion such as eye tracking that may provide insight into processing and engagement of the participant. A scalable and quantifiable objective measure of immersion may reveal which VR techniques and software promote the greatest level of symptomatic benefit. While our findings are limited by a small cohort of participants that have completed a single VR treatment session, the initial signals of efficacy and tolerability are promising. This study remains active and will continue to recruit participants in hopes of collecting pilot data that could be used for power calculations in future clinical trials. References: [1] Hoffman, H.G., et al. Effectiveness of virtual reality-based pain control with multiple treatments. Clin J Pain; 2001; 17(3): p. 229-35. [2] Schmitt, YS., et al. A randomized, controlled trial of immersive virtual reality analgesia, during physical therapy for pediatric burns. Burns: journal of the International Society for Burn Injuries; 2011; 37:61-8.

BACKGROUND AND PURPOSE/OBJECTIVE:Pediatric-onset multiple sclerosis (POMS) is a demyelinating disorder with unique clinical challenges. A brief computer-administered cognitive screening battery measuring processing speed (Cogstate) and the Brief International Cognitive Assessment in MS (BICAMS) detect cognitive impairment in POMS. The neuroanatomic correlates of these deficits are incompletely understood. The purpose of this study is to define the neuroanatomic underpinnings of deficits identified with cognitive screening batteries in POMS. METHODS:Participants with POMS and age-matched healthy controls (HCs) were screened with Cogstate and BICAMS. Diffusion tensor imaging assessed region-wise and tractography-based fractional anisotropy (FA). RESULTS:The POMS (n = 15) and HC (n = 21) groups were matched on age (mean ages 17.9 ± 3.2 vs. 17.8 ± 3.3 years, respectively) and on an estimate of general intellectual functioning. The Cogstate composite revealed significant slowing in POMS relative to HCs (P = .004), but the BICAMS composite did not significantly distinguish the groups (P = .10). The Cogstate composite showed moderate-to-strong correlations with regional FA (r = -.67 to -.82) and significantly associated with uncinate fasciculus FA following multiple comparisons correction (P = .002) in POMS. However, the BICAMS composite measure showed only weak-to-moderate correlations with FA in POMS (r = -.19 to -.57), with none surviving multiple comparisons correction. CONCLUSIONS:Computer-administered measures of cognitive processing are particularly sensitive in POMS and are closely linked to white matter FA.