Abstract

Innovative Journal

http://www.innovativejournal.in/index.php/

Journal of Medical Research and Health Sciences

2589-9031 2589-9023

https://doi.org/10.15520/jmrhs.v4i3.322

Original Article

Olfactory Virtual Reality (OVR) for Wellbeing and Reduction of Stress, Anxiety and Pain

David Tomasi

Hannah Ferris, MS

Priscilla Booraem, MS, GT

Lindsay Enman, MSW, GT

Sheri Gates, MA, GT

Emily Reyns, MA, R-DMT, MHC, GT

University of Vermont Larner College of Medicine, Department of Pharmacology; University of Vermont University of Vermont Medical Center, Inpatient Psychiatry University of Vermont Integrative Health, College of Nursing and Health Sciences; University of Vermont Medical Center, Inpatient Psychiatry;

17 3 2021

4 3 1211 20 11 2020 4 3 2021 20 1 2021

The Authors. Published by Publisher. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/)

2021

Abstract

Background: As part of a consistent effort to examine and provide integrative medical approaches to the therapeutic offering for psychophysical health, this study investigates the utilization of Olfactory Virtual Reality (OVR) in an inpatient psychiatry unit, more specifically in the Shepardson 3 Inpatient Psychiatry Unit at the University of Vermont Medical Center, in Burlington, VT, USA.

Objectives: The purpose of this protocol is to explore the therapeutic value of olfactory virtual reality (OVR) in the above described population, and to collect statistically significant data to determine the feasibility of potential future OVR studies.

Method: Direct subject observation and monitoring in the context of Olfactory Virtual Reality (OVR) sessions and Qualitative data collection via the administration of subject surveys, subdivided in: a) Pre-OVR experience, b) Immediate post-OVR experience, and c) 1-to-3-hour post-OVR experience questionnaires.

Results: The research yielded positive outcomes in all areas investigated, despite challenges related to the utilization of the device itself, issues in individual olfactory threshold, and COVID-19 restrictions and limitations.

Conclusion: The outcome of this study indicates that the utilization of olfactory virtual reality technologies is a safe and effective integrative approach to target several aspects of psychological and physical health such as anxiety, stress, and pain, in combination with the psychotherapeutic and pharmacological standards of care in inpatient psychiatry.

Keywords Medicine Neuroscience Virtual Reality Olfactory System Stress Anxiety Pain Psychiatry Psychology

Introduction

The goal of this study is to use an OVR-Technology-developed Virtual and Altered Reality (VAR) device Figure 16 (image 1) that includes an olfactory stimulation (scent) component in addition to the traditional visual component of virtual reality.1 ,2 , 3 The OVR sessions engineered for this research protocol were focused on creating a more immersive, realistic, evocative, meaningful, and emotional VAR experience, and by allowing for the subjects enrolled therein to enter a calming and realistic environment, in order to decrease the amount of anxiety, stress, and pain experienced by study subjects. In multiple studies, the utilization of Virtual reality-based technologies has proven to be a useful tool in a range of medical issues connected with psycho-physical challenges including, but not limited to, distraction for pain and medical procedures, relaxation and calming, and immersion therapy for trauma, PTSD and phobias.4 ,5 ,6 ,7 ,8 ,9 ,10 ,11 Certainly, there are significant challenges and potential dangers in the utilization of digital-virtual technologies (with significant differences among the specific types of technology examined), often associated with decrease in cognitive and emotional capacity and understanding, focus vs. attention, as well as possible addictive properties of this type of intervention.12 ,13,14 , 15 ,16 These aspects are particularly relevant in a vulnerable population such as the one examined in this particular study, i.e. inpatient psychiatry patients.

However, due to the documented relationships between scent, memory, and emotion 17 , 18 , 19 ,20 ,21 ,22 the authors of this study wanted to verify the possible benefits of adding an olfactory stimulation component, following the current scientific evidence on emotion, cognition, attention, and memory in general, and more in detail on specific neural areas such as the olfactory-related afferents and efferents of the mediodorsal thalamic nucleus (MDT),23 ,24 ,25 to the virtual reality component of the experience, thereby monitoring the potential to increase the immersion and presence of such virtual environments, and to create a more therapeutically appropriate and nurturing emotional connection, in the broader context of wellbeing and health.

<bold id="s-cc67666ee983">Intervention</bold>

General Description

The OVR environment is an immersive, 3-dimensional, 6 DoF (Six Degrees of Freedom) environment in which the subject can freely move and interact with the virtual items presented therein (e.g. campfire, marshmallows, sticks/logs (wood), flowers, citronella candles, bacon, tree bark, soda-cola, with ambient scent of forest, as well as natural environment sounds such as leaves, etc.), to re-create a reality-like environment Figure 18 (Image 3). The "safety range" of approximately 10ft x 10ft in the selected study room has been cleared of any objects or furniture, so that subjects may move through the environment safely. These borders are defined by invisible walls in the OVR software, when the patient gets close to the edge of this safety range. More specifically, the environment is designed to simulate a relaxing camping experience including a tranquil campsite, tent, picnic table and fire pit cluster at the edge of rocks and trees overlooking the sunset. There are many objects in the OVR environment that the subject can interact with using two hand-held wands (virtual hands). These wands are tracked through HMD (head-mounted display)-mounted sensors to correspond with their movements and have buttons and grips that allow the user to interact with items (Image 2)Figure 17 . As the subject moves about and interacts with the environment, corresponding odors connected to the general environment as well as specific items and interactions are precisely released to give the environment an enhanced perception vs. proprioception of presence. Each subject spent on average 10 minutes in the OVR environment before the Inpatient psychiatry Group therapist (GT) assisted the patient in removing the Head-Mounted Display (HMD).

Primary Workflow and Timeline

This research study has been conducted over a 4-month period with Inpatient Psychiatry subjects (N= 60). Each patient participated in 2 sessions per week for a minimum of 2 weeks (with data being considered admissible after 2 sessions). Data have been recorded from each patient before, during, and after each session though Pre-, Immediate Post- and 1-to-3 hours Post- Questionnaires. After initial brief explanation, the clinician (Psychotherapist / Group Therapist) assisted the subject in securing the OVR/HMD device. More specifically, the HMD in this test was a Samsung Odyssey. This is a display device, worn on the head that covers both eyes and is secured via straps. The OVR device is mounted to the bottom of the mask and sits near the nose without making any skin contact to the user. As soon as the HMD is secured the clinician handed the subject the wands and ensured that they are comfortable. After this procedure has been completed, the OVR experience/session began through activation on a connected computer. Subjects have been monitored as they experienced the environment to ensure the absence of technical and/or clinical-medical issues and had the ability to turn off the environment from the connected computer at any time. After 8 to 12 minutes, at the conclusion of the OVR experience/session, the GT helped each subject individually remove the HMD and secure the device nearby, and turn off the environment via the attached computer. Following each session/single patient use, the device has been sanitized and examined for any loose connections or issues. The environment has then been rebooted in preparation of the next session with a new subject.

<bold id="s-f54e3ee5b514">Methods</bold>

Population and Eligibility

The subjects examined in this study were adult patients (18 and above, N=60) on the inpatient psychiatry unit Shepardson 3, University of Vermont Medical Center (UVMMC), over a 4-month study period (September-December 2020). More specifically, UVMMC Shepardson 3 presents a patient population with DSM-5 psychiatric diagnoses ranging from PTSD and other traumas, MDD, Bipolar Affective Disorder(s) (BPAD I vs II), Cluster A, B, and C Personality Disorders, other mood disorders, as well as Adjustment- and Generalized Anxiety Disorders, often in combination with other specified/unspecified psychiatric vs. general medical issues and comorbidities.

Qualitative and Quantitative Analysis

The pre-, immediate post-, and 1-to-3-hour post-session surveys addressed anxiety and stress levels, emotional and physical pain, psychological state, overall mood, level of enjoyment during the session, using a combination of binary (Yes/No) responses and Likert scales, with reported percentages and p-value from McNemar test and p-value from Wilcoxon Signed-Rank, in combination with open-ended question about the overall experience as subjectively perceived by the subject. The complete list of questions in the surveys administered to patients, with relative percentages and statistically relevant annotations, is reported in Section C - Questionnaires Figure 12 1, Figure 13 2, and Figure 14 3, respectively.

Inclusion Criteria

At the beginning of each OVR session, the Group Therapist read the informed consent information and procedure to the patients. Following informed consent documentation, every patient had the option to decline to take part in the exercise and nutrition education group.

Withdrawal Procedures

Following informed consent documentation, every patient had the option to decline session attendance, and to fill out the research survey.

Subjects had been allowed to withdraw from the study at any time, knowing that withdrawing from the study will have no impact on their clinical care. PI and multidisciplinary treatment team members (PhD, PsyD, MA, MD, MS, and MSW) assessed subjects to determine whether to withdraw subjects when clinically/medically inappropriate circumstances arise.

Safety, Privacy and Consent

All the information has been collected without any identifiers and used only for statistical purposes, and it will not be connected or linkable to clinical/medical records of single patients and/or groups / categories / diagnosis in the future. The hardcopy data has been archived in the locked group Therapist Office on Shepardson 529, separated from both Inpatient Psychiatry Units Shepardson 3 and Shepardson 6. Each GT documented on paper the number of subjects participating in the session and the number of subjects absent or subjects who declined to take part in the group.

Results

Positive Aspects

Examining the data obtained by analyzing subjects’ responses in the administered pre-, immediate post-, and 1-to-3-hour post-session surveys, the researchers have been able to identify multiple positive outcomes as direct results of the implementation of Olfactory Virtual Reality in Inpatient Psychiatry. Of note, as the study-related OVR sessions have been offered in combination with the pre-existing integrative therapeutic offerings conducted by the UVMMC psychotherapists / group therapists as part of the weekly schedule,26 ,27 all the subjects/patients involved in this research had the opportunity to further discuss their experiences in a nurturing, supportive and clinically appropriate environment for the whole duration of their admission, thereby providing them with constant opportunities for processing and cognitive, emotional improvement and overall well-being.

More specifically, the data yielded positive results across the spectrum of psycho-physical areas investigated. Utilizing a 1-10 scale (1-lowest, 10-highest value), Anxiety levels of 9 (16.2 %) or 10 (29.4 %) in the Before session, reported 1.8 % and 0 % respectively in the Immediately After session, and 0 % and 0% in the 1-to-3 hours After session, with a Relative Difference of -1.0 in both cases Figure 1 (Fig. 1a.). Similarly significant values were observed in the Stress area, with levels of 9 (16.4 %) and 10 (36.1 %) in the Before Session, 3.6 % and 0 % respectively in the Immediately After Session, and 5.0 % and 0% in the 1-to-3 hours After session with a Relative Difference of -0.7 for value 9 and -1.0 for value 10 Figure 4 (Fig. 2b). For the Pain–related responses, the values were 6.6 % in both 9 and 10 in the Before Session, 0 % and 0 % respectively in the Immediately After Session, and 0 % and 0% in the 1-to-3 hours After session, with a Relative Difference of -1.0 in both cases Figure 5 (Fig. 3a).

As observed in figures Figure 2 ,Figure 4 1b, 2b, and 3bFigure 6 the overall improvement (i.e. significant decrease) in these three areas was observed throughout the response provided. Subjects answering the quefstion “Is there anything bothering you today (mental or physical)” also selected their response on the same 1-10 scale (1-lowest, 10-highest value) in the case of a positive (“yes”) answer (Questionnaires 1, 2, and 3). The results yielded were 23 % for level 9 and 23 % for level 10 in the Before Session, with a significant decrease in the Immediately After Session, with 7.0 % for both value 9 and 10, and 0.0 % for both value 9 and 10 in the 1-to-3 hours After session Figure 8 (Fig. 4b). The Relative Difference to the same question in the comparison between Before, Immediately After, and 1-to-3 hours After Session yielded a 0.2 for “Yes” and 10.5 for “No” (Table 1)Table 1 . For the question “Did you enjoy the virtual reality experience?” the values observed were 0.02 for “Yes” and -1.0 for “No” (Table 2)Table 2 .

While these results are very significant, it is also important to note the impact of the decrease in the psychological factors in the context of complex diagnostic medical-psychiatric presentations, particularly in inpatient psychiatry. In this sense, multiple studies have also indicated that an overall amelioration of psychological wellbeing has resulted in an improvement of physical factors.28 ,29 ,30 ,31 This is evidenced by the results presented in Figure 9 Figure 10 Figure 11 Fig. 5, 6, and 7, with an overall significant decrease in the levels of anxiety and stress and the broader, bio-psycho-social model-based area investigated by the question “Is there anything bothering you today (mental or physical).” The aforementioned data thus indicated that Olfactory Virtual Reality, in conjunction with standard-of-care psychotherapeutic and pharmacological interventions, significantly resulted in a reduction of the subject-reported values for anxiety, stress and pain.

Negative Aspects

Some of the challenges encountered during the study were related to technical glitches and/or to the utilization of the VAR device itself, which proved to be somewhat difficult to utilize by the elder subjects in the study population examined. As an example of the above, once the subject already started the OVR process, if they had pressed on any other button on the “joystick/virtual hand” and they inadvertently exited the program, the software would open a new sub-menu, thus requiring, at times, the process to be started anew. Some more specific challenges were related to the medical presentation of the subject undergoing the OVR experience, for instance in regard to the need to re-adjust the virtual perimeter/boundaries and height for subjects who were experiencing the VAR scenario on a wheelchair (the VR cable often got stuck either under the wheels or the oxygen cylinder). Another potential issue lied in the very nature of the study presented, i.e. some decreased scores in olfactory threshold experienced by subjects affected by depressive disorders, as evidenced in multiple studies. 32 ,33 ,34 Of note, while similar clinical presentations regarding olfaction have been observed in COVID-19-positive individuals, all subjects who undertook this research study have been testing negative for SARS-Cov-2 Test prior to their admission to the Inpatient Psychiatry Unit Shepardson 3, where the study was conducted.

The current COVID-19 pandemic had of course added challenges, particularly in terms of the allotted number of subjects allowed in the OVR session room at any given time (N=1 + GT) and the required implementation of safety & hygiene restrictions, which contributed to the slowing down of the examination process in general.

Conclusions

Mounting evidence from current scientific research warrants the need for incorporating integrative methods to improve clinical outcomes across a wide range of physical and mental health disorders.35 ,36 ,37 ,38 39 ,40 ,41 ,42 ,43 Certainly, an attentive investigation of the specific approaches within integrative therapeutic modalities is warranted, especially in the context of the complexity of psycho-physical clinical presentations of individuals in an inpatient psychiatry unit. The results of this study indicates that the utilization of an integrative approach focused on olfactory virtual reality technologies in addition to the evidence-based standards of care within psychotherapy and pharmacology is a safe and effective strategy to target several aspects of psychological and physical health such as anxiety, stress, and pain.

Beside the observed decrease in self-reported levels of anxiety, stress, and pain, an important factor at the center of the application of olfactory virtual reality in inpatient psychiatry is its ability to provide an immersive psychological, physical, and (albeit to a lesser extent given the added restrictions of both technology and safety measures) social experience to those patients who are otherwise unable to engage in other integrative approaches to care, such as physical exercise, gentle movement or stretching, Yoga and T’ai Chi Chuan, Music Therapy or Dance Movement Therapy, due to physical problems or other medical comorbidities. This is especially true in the context of the current COVID-19 the pandemic which contributes to further self-isolation, a significant problem affecting, and in turn, affected, by a vast range of psychological issues, particularly depressive states and traumas. In other words, where physical proximity is not possible and or allowed, this type of technology allows the individual to experience a re-created environment in a safe, monitored, and measurable way.

Furthermore, the ability of the olfactory-visual stimulation provided by OVR to positively affect emotion and memory can be an important aide and support in the complex process of mitigating the negative effects of the aforementioned psychological and social issues (e.g. MDD, PTSD, as well as Addiction disorders, etc.) affecting such vulnerable populations and could promote a better understanding of the psychological functioning in the general public during a times of epidemiological challenges and increased risks for further medical and psychological problems.

<bold id="s-e67868b185e5">Limitations and Future Studies</bold>

The primary limitations of this study are the specific population investigated, the total number of participants, the limited technical glitches encountered during the setting up portion of the OVR session, the specific challenges linked to the diagnostic presentation of the subjects examined, and the limitations in terms of clinical safety and exposure parameters for clinical research subjects, following COVID-19 taskforce recommendations. Future EBM double-blind RCTs and biostatistical-epidemiological analysis are recommended to verify the empirical validity of the results and outcomes discussed herein.

Declaration of Conflicting Interests

The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Funding

The authors received no financial support for authorship, and/or publication of this article.

Acknowledgments

Gratitude extended to all staff, students, faculty at the University of Vermont Medical Center and the University of Vermont

Images

A) General Results

Figure 1a.

Figure 1 </caption> <graphic id="g-df9b1f9669a8" xlink:href="https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/ca68f5a4-5719-4cbd-aa1b-0b61f6af9277/image/40a06a03-00b5-4acb-b537-f22496df5894-uimage.png"/> </fig> The Wilcoxon Signed Rank test was completed between the Before and Immediately After time points, z = -6.528, p < 0.001 and the Before and 1-3h After time points, z = -5.550, p < 0.001. <bold id="s-cbc0d250bc4b">Figure 1b.</bold> <bold id="s-7f07e9bfcd98"> </bold> <fig id="f-1e73e16b69d8" position="anchor" orientation="portrait" fig-type="graphic"> <label>Figure 2 </label> <caption id="c-21b988c2de1b"> <title id="t-9d4502adfe54">Time point comparison inpercent of responses per level of Anxiety subdivided into Before, ImmediatelyAfter, and 1-to-3 hours-After

Figure 2a.

Figure 3 </caption> <graphic id="g-1f70de3b7e72" xlink:href="https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/ca68f5a4-5719-4cbd-aa1b-0b61f6af9277/image/dab801af-bdeb-4d35-a6c0-0ffb5f0c794b-uimage.png"/> </fig> The Wilcoxon Signed Rank test was completed between the Before and Immediately After time points, z = -6.437, p < 0.001, and the Before and 1-3h After time points, z = -5.415, p < 0.001. <bold id="s-879e2bbb1e04">Figure 2b.</bold> <bold id="s-98b9066fc1ec"> </bold> <fig id="f-0f9d738b5cb4" position="anchor" orientation="portrait" fig-type="graphic"> <label>Figure 4 </label> <caption id="c-76bd99c7db77"> <title id="t-e1d6c7a7a5d9">Time point comparison inpercent of responses per level of Stress subdivided into Before, ImmediatelyAfter, and 1-to-3 hours-After

Figure 3a.

Figure 5 </caption> <graphic id="g-e739e8938516" xlink:href="https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/ca68f5a4-5719-4cbd-aa1b-0b61f6af9277/image/69b884d1-dcdd-42e8-91c2-e532ed86a257-uimage.png"/> </fig> The Wilcoxon Signed Rank test was completed between the Before and Immediately After time points, z = -1.534, p = 0.125, and the Before and 1-3h After time points, z = -4.439, p < 0.001. Figure 3b <fig id="f-a84504b7316e" position="anchor" orientation="portrait" fig-type="graphic"> <label>Figure 6 </label> <caption id="c-14d49d9c22a5"> <title id="t-2ca5a45a5422">Time point comparison inpercent of responses per level of Pain subdivided into Before, ImmediatelyAfter, and 1-to-3 hours-After

Figure 4a.

Figure 7 </caption> <graphic id="g-dd8f8e82a9cf" xlink:href="https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/ca68f5a4-5719-4cbd-aa1b-0b61f6af9277/image/176f10e4-69e5-4c8d-ae1d-17ae21b4083b-uimage.png"/> </fig> The Wilcoxon Signed Rank test was completed between the Before and Immediately After time points, z = -5.452, p < 0.001, and the Before and 1-3h After time points, z = -3.759, p < 0.001. <bold id="s-60ccb5d69851">Figure 4b.</bold> <bold id="s-ceeeba1c9657"> </bold> <fig id="f-bb0a1257b022" position="anchor" orientation="portrait" fig-type="graphic"> <label>Figure 8 </label> <caption id="c-e0a6b63adc60"> <title id="t-b59fc0f464e2">Time point comparison inpercent of responses per level of Anything bothering [you] subdivided intoBefore, Immediately After, and 1-to-3 hours-After

Figure 5.

Figure 9 Pie Charts of responsesBefore OVR session, per level of Anxiety, Stress, Pain, and Anything bothering[you] in Percent (%).

Figure 6.

Figure 10 Pie Charts of responsesImmediately After OVR session, per level of Anxiety, Stress, Pain, and Anythingbothering [you] in Percent (%).

Missing levels have values = 0.

Figure 7.

Figure 11 Pie Charts of responses1-to-3 Hours After OVR session, per level of Anxiety, Stress, Pain, andAnything bothering [you] in Percent (%).

Missing levels have values = 0.

B) Comparative Tables

Table 1.

Percent (%) of responses to “Is anything bothering you today?” Before, Immediately After, 1-to-3 hours After, and relative difference

Table 1 </caption> <table id="table-1" rules="rows"> <colgroup/> <tbody id="table-section-1"> <tr id="table-row-1"> <td id="table-cell-1" colspan="5" align="left"> Table 1. Percent (%) of responses to “Is anything bothering you today?” Before, Immediately After, 1-to-3 hours After, and relative difference </td> </tr> <tr id="table-row-2"> <td id="table-cell-2" align="left"> Timing of Survey </td> <td id="table-cell-3" align="left"> Yes </td> <td id="table-cell-4" align="left"> No </td> <td id="table-cell-5" align="left"> </td> <td id="table-cell-6" align="left"> p value </td> </tr> <tr id="table-row-3"> <td id="table-cell-7" align="left"> Before </td> <td id="table-cell-8" align="left"> 98.3 </td> <td id="table-cell-9" align="left"> 1.7 </td> <td id="table-cell-10" align="left"> </td> <td id="table-cell-11" align="left"> </td> </tr> <tr id="table-row-4"> <td id="table-cell-12" align="left"> Immediately After </td> <td id="table-cell-13" align="left"> 82.1 </td> <td id="table-cell-14" align="left"> 17.9 </td> <td id="table-cell-15" align="left"> </td> <td id="table-cell-16" align="left"> 0.002 </td> </tr> <tr id="table-row-5"> <td id="table-cell-17" align="left"> 1-3h After </td> <td id="table-cell-18" align="left"> 80.5 </td> <td id="table-cell-19" align="left"> 19.5 </td> <td id="table-cell-20" align="left"> </td> <td id="table-cell-21" align="left"> 0.008 </td> </tr> <tr id="table-row-6"> <td id="table-cell-22" align="left"> Relative difference </td> <td id="table-cell-23" align="left"> 0.2 </td> <td id="table-cell-24" align="left"> 10.5 </td> <td id="table-cell-25" align="left"> </td> <td id="table-cell-26" align="left"> </td> </tr> </tbody> </table> </table-wrap> The McNemar test was completed between the Before and Immediately After responses, N = 56, p = 0.002, and the Before and 1-3h After responses, N = 41, p = 0.008. <bold id="s-871553b1b42c">Table 2.</bold> Percent (%) of responses to “Did you enjoy the virtual reality experience?” Before, Immediately After, 1-to-3 hours After, and relative difference <table-wrap id="tw-62a8f1d144ea" orientation="portrait" position="anchor"> <label>Table 2</label> <caption id="c-c8bdda7d3705"> <title id="t-c2b7f00cbc23"/> </caption> <table id="t-a172b894e63e" rules="rows"> <colgroup/> <tbody id="ts-9b3ad7518134"> <tr id="tr-2f284d379c29"> <td id="tc-920ecd716991" colspan="6" align="left"> Table 2. Percent (%) of responses to “Did you enjoy the virtual reality experience?” Before, Immediately After, 1-to-3 hours After, and relative difference </td> </tr> <tr id="tr-bf2cffc2fd32"> <td id="tc-0543e8c05576" align="left"> Timing of Survey </td> <td id="tc-c34db271cd51" align="left"> Yes </td> <td id="tc-ff808f815b12" align="left"> No </td> <td id="tc-83832796df02" align="left"> </td> <td id="tc-49ae7861ec78" align="left"> p value </td> <td id="tc-ee08a56a0668" align="left"> </td> </tr> <tr id="tr-1db8ff402d2f"> <td id="tc-d048cb11a4fa" align="left"> Immediately After </td> <td id="tc-ea07c07fcb8c" align="left"> 98.1 </td> <td id="tc-154b01d762a2" align="left"> 1.9 </td> <td id="tc-065c482bef76" align="left"> </td> <td id="tc-2c96d7862de6" align="left"> </td> <td id="tc-a92c6222c4de" align="left"> </td> </tr> <tr id="tr-141fe0f1e60c"> <td id="tc-e0fc4f2f156f" align="left"> 1-3h After </td> <td id="tc-c8719e25a35f" align="left"> 100 </td> <td id="tc-c4612f5a10f7" align="left"> 0 </td> <td id="tc-f960493309e4" align="left"> </td> <td id="tc-4b6e454d5e6f" align="left"> </td> <td id="tc-9dafb7a11c72" align="left"> </td> </tr> <tr id="tr-da4d31fc73e2"> <td id="tc-88aa638aa99a" align="left"> Relative difference </td> <td id="tc-01214b77c2cc" align="left"> 0.02 </td> <td id="tc-bd685aced8dc" align="left"> -1.0 </td> <td id="tc-9b43730db52f" align="left"> </td> <td id="tc-1cff5965f1dd" align="left"> </td> <td id="tc-f623a0bb8d2a" align="left"> </td> </tr> </tbody> </table> </table-wrap> The McNemar test was completed between the Immediately after and 1-3 hours after responses, N = 38, p = 1.000. <bold id="s-5a36439f9820">C) Questionnaires </bold> <fig id="f-06257d78578c" position="anchor" orientation="portrait" fig-type="graphic"> <label>Figure 12 </label> <caption id="c-8de75e8a9838"> <title id="t-ffe8ee4c4873"/> </caption> <graphic id="g-d2296b1fd5db" xlink:href="https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/ca68f5a4-5719-4cbd-aa1b-0b61f6af9277/image/3b56c115-2799-4a96-9b7d-3650127c3304-uimage.png"/> </fig> <bold id="s-3c9853b96f5d">Questionnaire 1.</bold><bold id="s-1297683f5a74"> </bold>The pre-session survey <fig id="f-a445c381e3df" position="anchor" orientation="portrait" fig-type="graphic"> <label>Figure 13 </label> <caption id="c-e6293800af75"> <title id="t-79cb51f67b02"/> </caption> <graphic id="g-311a72e56480" xlink:href="https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/ca68f5a4-5719-4cbd-aa1b-0b61f6af9277/image/15af5654-dc62-4e9a-87f0-7ea1c128e66e-uimage.png"/> </fig> <bold id="s-d9bfcda01963">Questionnaire 2.</bold><bold id="s-7b6b15aa0161"> </bold>The immediate post-session survey. <fig id="f-ee9d5d0b5ef3" position="anchor" orientation="portrait" fig-type="graphic"> <label>Figure 14 </label> <caption id="c-992d86c1b0f4"> <title id="t-df9e672b3244"/> </caption> <graphic id="g-ced3af235ca3" xlink:href="https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/ca68f5a4-5719-4cbd-aa1b-0b61f6af9277/image/117e392d-6a7a-4e72-8f90-bb7a75861aa4-uimage.png"/> </fig> Questionnaire 3. The 1-to-3-hour post-session survey <bold id="s-6a8fa0dd0501">D) Patients’ Narratives</bold> <fig id="f-97ac3428c6e9" position="anchor" orientation="portrait" fig-type="graphic"> <label>Figure 15 </label> <caption id="c-e53722946079"> <title id="t-a3235e03da5f"/> </caption> <graphic id="g-85d0f6f44596" xlink:href="https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/ca68f5a4-5719-4cbd-aa1b-0b61f6af9277/image/ae307ea7-19e9-461b-8f5f-c7b2eff527c1-uimage.png"/> </fig> <bold id="s-86d623f5ffa3">Table 4.</bold><bold id="s-651757fff4ae"> </bold>Subjects’ Narratives (Abstracts) <bold id="s-4616edded653">E) Software and Hardware</bold> <fig id="f-a3ff856a2db4" position="anchor" orientation="portrait" fig-type="graphic"> <label>Figure 16 </label> <caption id="c-48145ca91ae0"> <title id="t-6660c91d6ab1">TheHMD-mounted ION on-mask, wifi / USB scent Device, Headset, Cartridges (foreground)and scent extracts (background) developed by OVR Technology. The Architectureof Scent® framework translates VR movements and inputs into real-time scentoutput, allowing for .1 millisecond bursts of scent and change between scentsin 20 milliseconds. Figure 17 Frontalview of the installed version of the HMD-mounted ION on-mask, wifi / USB scentDevice, Headset, and Cartridges utilized in this study. Figure 18 AVirtual reality scenario / 3D rendering developed by OVR Technology utilized inthis study.

References Amores J Richer R Zhao N Maes P Eskofier B Promoting relaxation using virtual reality, olfactory interfaces and wearable EEG 2018 IEEE 15th International Conference on Wearable and Implantable Body Sensor Networks (BSN) 2018 Las Vegas, NV 98 101 Micaroni Lorenzo Carulli Marina Ferrise Francesco Gallace Alberto Bordegoni Monica An Olfactory Display to Study the Integration of Vision and Olfaction in a Virtual Reality Environment Journal of Computing and Information Science in Engineering 2019 19 3 31015 31015 1530-9827, 1944-7078 10.1115/1.4043068 ASME International https://dx.doi.org/10.1115/1.4043068 OVR Technology presentation, research and description https://ovrtechnology.com/ Cieślik Błażej Mazurek Justyna Rutkowski Sebastian Kiper Paweł Turolla Andrea Szczepańska-Gieracha Joanna Virtual reality in psychiatric disorders: A systematic review of reviews Complementary Therapies in Medicine 2020 52 102480 102480 0965-2299 10.1016/j.ctim.2020.102480 Elsevier BV https://dx.doi.org/10.1016/j.ctim.2020.102480 Pourmand Ali Davis Steven Marchak Alex Whiteside Tess Sikka Neal Virtual Reality as a Clinical Tool for Pain Management Current Pain and Headache Reports 2018 22 8 53 53 1531-3433, 1534-3081 10.1007/s11916-018-0708-2 Springer Science and Business Media LLC https://dx.doi.org/10.1007/s11916-018-0708-2 Abhinav RP Sweta VR Ramesh Asha Role of virtual reality in pain perception of patients following the administration of local anesthesia Annals of Maxillofacial Surgery 2019 9 1 110 110 2231-0746 10.4103/ams.ams_263_18 Medknow https://dx.doi.org/10.4103/ams.ams_263_18 Fodor Liviu A. Coteț Carmen D. Cuijpers Pim Szamoskozi Ștefan David Daniel Cristea Ioana A. The effectiveness of virtual reality based interventions for symptoms of anxiety and depression: A meta-analysis Scientific Reports 2018 8 1 10323 10323 2045-2322 10.1038/s41598-018-28113-6 Springer Science and Business Media LLC https://dx.doi.org/10.1038/s41598-018-28113-6 Rizzo Albert ‘Skip’ Shilling Russell Clinical Virtual Reality tools to advance the prevention, assessment, and treatment of PTSD European Journal of Psychotraumatology 2017 8 sup5 1414560 1414560 2000-8198, 2000-8066 10.1080/20008198.2017.1414560 Informa UK Limited https://dx.doi.org/10.1080/20008198.2017.1414560 Hassan C Antonelli G 2020) ‘I want to have virtual reality distraction during my colonoscopy! Endoscopy International Open 08 10 1389 1391 Wittkopf Priscilla G. Lloyd Donna M. Coe Olivia Yacoobali Shafiyyah Billington Jac The effect of interactive virtual reality on pain perception: a systematic review of clinical studies Disability and Rehabilitation 2020 42 26 3722 3733 0963-8288, 1464-5165 10.1080/09638288.2019.1610803 Informa UK Limited https://dx.doi.org/10.1080/09638288.2019.1610803 Gebara Cristiane M. Barros-Neto Tito P. de Gertsenchtein Leticia Lotufo-Neto Francisco Virtual reality exposure using three-dimensional images for the treatment of social phobia Revista Brasileira de Psiquiatria 2015 38 1 24 29 1516-4446, 1809-452X 10.1590/1516-4446-2014-1560 FapUNIFESP (SciELO) https://dx.doi.org/10.1590/1516-4446-2014-1560 Sabelman Eric E. Lam Roger The real-life dangers of augmented reality IEEE Spectrum 2015 52 7 48 53 0018-9235 10.1109/mspec.2015.7131695 Institute of Electrical and Electronics Engineers (IEEE) https://dx.doi.org/10.1109/mspec.2015.7131695 Kenwright Ben Virtual Reality: Ethical Challenges and Dangers [Opinion], IEEE Technology and Society Magazine 2018 37 4 20 25 0278-0097, 1937-416X 10.1109/mts.2018.2876104 Institute of Electrical and Electronics Engineers (IEEE) https://dx.doi.org/10.1109/mts.2018.2876104 Sharma A Bajpai P Singh S Khatter K Virtual Reality: Blessings and Risk Assessment, Human-Computer Interaction (cs.HC) Ithaca, NY 2017 Urueña López Alberto Mateo Fernando Navío-Marco Julio Martínez-Martínez José María Gómez-Sanchís Juan Vila-Francés Joan José Serrano-López Antonio Analysis of computer user behavior, security incidents and fraud using Self-Organizing Maps Computers & Security 2019 83 38 51 0167-4048 10.1016/j.cose.2019.01.009 Elsevier BV https://dx.doi.org/10.1016/j.cose.2019.01.009 Hicks Tyler M Digital Detox - Addressing the Issue of Screen Addiction in Millennials" (2019). Undergraduate Honors Theses. Paper 513. https://dc.etsu.edu/honors/513 Digital Detox - Addressing the Issue of Screen Addiction in Millennials 2019 https://dc.etsu.edu/honors/513 Croy Ilona Hummel Thomas Olfaction as a marker for depression Journal of Neurology 2017 264 4 631 638 0340-5354, 1432-1459 10.1007/s00415-016-8227-8 Springer Science and Business Media LLC https://dx.doi.org/10.1007/s00415-016-8227-8 Abramowitz Eitan G. Lichtenberg Pesach Hypnotherapeutic Olfactory Conditioning (HOC):Case Studies of Needle Phobia, Panic Disorder, and Combat-Induced PTSD International Journal of Clinical and Experimental Hypnosis 2009 57 2 184 197 0020-7144, 1744-5183 10.1080/00207140802665450 Informa UK Limited https://dx.doi.org/10.1080/00207140802665450 Amores J Maes P Essence: Olfactory interfaces for unconscious influence of mood and cognitive performance ACM SIGCHI 2017 28 34 Tomasi D Critical Neuroscience and Philosophy. A Scientific Re-examination of the Mind-body Problem Palgrave Macmillan Basingstoke, UK 2020 Munyan Benson G. Neer Sandra M. Beidel Deborah C. Jentsch Florian Olfactory Stimuli Increase Presence in Virtual Environments PLOS ONE 2016 11 6 e0157568 e0157568 1932-6203 10.1371/journal.pone.0157568 Public Library of Science (PLoS) https://dx.doi.org/10.1371/journal.pone.0157568 Rochet Marion El-Hage Wissam Richa Sami Kazour François Atanasova Boriana Depression, Olfaction, and Quality of Life: A Mutual Relationship Brain Sciences 2018 8 5 80 80 2076-3425 10.3390/brainsci8050080 MDPI AG https://dx.doi.org/10.3390/brainsci8050080 Mitchell A S The mediodorsal thalamus as a higher order thalamic relay nucleus important for learning and decision-making Neurosci. Biobehav. Rev 2015 54 76 88 Courtiol Emmanuelle Wilson Donald A. The olfactory thalamus: unanswered questions about the role of the mediodorsal thalamic nucleus in olfaction Frontiers in Neural Circuits 2015 9 1662-5110 10.3389/fncir.2015.00049 Frontiers Media SA https://dx.doi.org/10.3389/fncir.2015.00049 Jacobson Green Haase Szajer Murphy Differential Effects of BMI on Brain Response to Odor in Olfactory, Reward and Memory Regions: Evidence from fMRI Nutrients 2019 11 4 926 926 2072-6643 10.3390/nu11040926 MDPI AG https://dx.doi.org/10.3390/nu11040926 The Inpatient Psychiatry Unit at UVM Medical Center https://www.uvmhealth.org/medcenter/departments-and-programs/inpatient-psychiatry UVMMC) Shepardson 3, department of inpatient psychiatry https://www.uvmhealth.org/medcenter/location/inpatient-psychiatry-shepardson-3 Meng S L Tak E W Li W C & L The Longitudinal Associations between Physical Health and Mental Health among Older Adults Aging & Mental Health 1990 24 12 12 Carrigan N Dysch Salkovskis A Replication and Treatment Case Series', Behavioural and Cognitive Psychotherapy The Impact of Health Anxiety in Multiple Sclerosis: A Replication 2018 46 2 148 167 https://doi.org/10.1017/S135246581700056X Lupien Sonia J. McEwen Bruce S. Gunnar Megan R. Heim Christine Effects of stress throughout the lifespan on the brain, behaviour and cognition Nature Reviews Neuroscience 2009 10 6 434 445 1471-003X, 1471-0048 10.1038/nrn2639 Springer Science and Business Media LLC https://dx.doi.org/10.1038/nrn2639 Stanton Robert To Quyen G. Khalesi Saman Williams Susan L. Alley Stephanie J. Thwaite Tanya L. Fenning Andrew S. Vandelanotte Corneel Depression, Anxiety and Stress during COVID-19: Associations with Changes in Physical Activity, Sleep, Tobacco and Alcohol Use in Australian Adults International Journal of Environmental Research and Public Health 2020 17 11 4065 4065 1660-4601 10.3390/ijerph17114065 MDPI AG https://dx.doi.org/10.3390/ijerph17114065 Kamath Vidyulata Paksarian Diana Cui Lihong Moberg Paul J Turetsky Bruce I Merikangas Kathleen R Olfactory processing in bipolar disorder, major depression, and anxiety Bipolar Disorders 2018 20 6 547 555 1398-5647 10.1111/bdi.12625 Wiley https://dx.doi.org/10.1111/bdi.12625 Kohli Preeti Soler Zachary M. Nguyen Shaun A. Muus John S. Schlosser Rodney J. The Association Between Olfaction and Depression: A Systematic Review Chemical Senses 2016 41 6 479 486 0379-864X, 1464-3553 10.1093/chemse/bjw061 Oxford University Press (OUP) https://dx.doi.org/10.1093/chemse/bjw061 Croy Ilona Hummel Thomas Olfaction as a marker for depression Journal of Neurology 2017 264 4 631 638 0340-5354, 1432-1459 10.1007/s00415-016-8227-8 Springer Science and Business Media LLC https://dx.doi.org/10.1007/s00415-016-8227-8 Eisenberg D M Kaptchuk T J Post D E Hrbek A L O'connor B B Osypiuk K Wayne P M Buring J E Levy D B Establishing an Integrative Medicine Program Within an Academic Health Center: Essential Considerations. Academic medicine : journal of the Association of American Medical Colleges 2016 91 9 1223 1230 Gartlehner G Gaynes B N Amick H R Asher G N Morgan L C Coker-Schwimmer E Comparative benefits and harms of antidepressant, psychological, complementary, and exercise treatments for major depression: an evidence report for a clinical practice guideline from the American College of Physicians Ann Intern Med 2016 Tomasi D Mind-Body Medicine in Inpatient Psychiatry. New York, NY: Ibidem Verlag / Columbia University Press 2019 Ibidem Verlag / Columbia University Press New York, NY Bastos Andre Goettems Pinto Guimarães Luciano Santos Trentini Clarissa Marceli Neurocognitive changes in depressed patients in psychodynamic psychotherapy, therapy with fluoxetine and combination therapy Journal of Affective Disorders 2013 151 3 1066 1075 0165-0327 10.1016/j.jad.2013.08.036 Elsevier BV https://dx.doi.org/10.1016/j.jad.2013.08.036 Hohmann Louisa Bradt Joke Stegemann Thomas Koelsch Stefan Effects of music therapy and music-based interventions in the treatment of substance use disorders: A systematic review PLOS ONE 2017 12 11 e0187363 e0187363 1932-6203 10.1371/journal.pone.0187363 Public Library of Science (PLoS) https://dx.doi.org/10.1371/journal.pone.0187363 Wang J Hodes G E Zhang H Epigenetic modulation of inflammation and synaptic plasticity promotes resilience against stress in mice Nature Communications 2018 9 1 477 477 Mitchell K S Am D Dimartino D M A pilot study of a randomized controlled trial of yoga as an intervention for PTSD symptoms in women J Trauma Stress 2014 27 2 121 129 Motraghi Terri E. Seim Richard W. Meyer Eric C. Morissette Sandra B. Virtual Reality Exposure Therapy for the Treatment of Posttraumatic Stress Disorder: A Methodological Review Using CONSORT Guidelines Journal of Clinical Psychology 2014 70 3 197 208 0021-9762 10.1002/jclp.22051 Wiley https://dx.doi.org/10.1002/jclp.22051 Regev Dafna Cohen-Yatziv Liat Effectiveness of Art Therapy With Adult Clients in 2018—What Progress Has Been Made? Frontiers in Psychology 2018 9 1664-1078 10.3389/fpsyg.2018.01531 Frontiers Media SA https://dx.doi.org/10.3389/fpsyg.2018.01531