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  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JSG</journal-id>
      <journal-id journal-id-type="nlm-ta">JMIR Serious Games</journal-id>
      <journal-title>JMIR Serious Games</journal-title>
      <issn pub-type="epub">2291-9279</issn>
      <publisher>
        <publisher-name>JMIR Publications</publisher-name>
        <publisher-loc>Toronto, Canada</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">v9i4e13124</article-id>
      <article-id pub-id-type="pmid">34813485</article-id>
      <article-id pub-id-type="doi">10.2196/13124</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Paper</subject>
        </subj-group>
        <subj-group subj-group-type="article-type">
          <subject>Original Paper</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Using a 360° Virtual Reality or 2D Video to Learn History Taking and Physical Examination Skills for Undergraduate Medical Students: Pilot Randomized Controlled Trial</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Zary</surname>
            <given-names>Nabil</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Birckhead</surname>
            <given-names>Brandon</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Gallagher</surname>
            <given-names>Steve</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Clavier</surname>
            <given-names>Thomas</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Lin</surname>
            <given-names>Yu-Hsuan</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Jonas</surname>
            <given-names>Stephan</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib id="contrib1" contrib-type="author">
          <name name-style="western">
            <surname>Chao</surname>
            <given-names>Yi-Ping</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff01" ref-type="aff">1</xref>
          <xref rid="aff02" ref-type="aff">2</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-1681-5410</ext-link>
        </contrib>
        <contrib id="contrib2" contrib-type="author">
          <name name-style="western">
            <surname>Chuang</surname>
            <given-names>Hai-Hua</given-names>
          </name>
          <degrees>MD</degrees>
          <xref rid="aff03" ref-type="aff">3</xref>
          <xref rid="aff04" ref-type="aff">4</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-7394-4016</ext-link>
        </contrib>
        <contrib id="contrib3" contrib-type="author">
          <name name-style="western">
            <surname>Hsin</surname>
            <given-names>Li-Jen</given-names>
          </name>
          <degrees>MD</degrees>
          <xref rid="aff04" ref-type="aff">4</xref>
          <xref rid="aff05" ref-type="aff">5</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-9201-0270</ext-link>
        </contrib>
        <contrib id="contrib4" contrib-type="author">
          <name name-style="western">
            <surname>Kang</surname>
            <given-names>Chung-Jan</given-names>
          </name>
          <degrees>MD, PhD</degrees>
          <xref rid="aff04" ref-type="aff">4</xref>
          <xref rid="aff05" ref-type="aff">5</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-5333-9396</ext-link>
        </contrib>
        <contrib id="contrib5" contrib-type="author">
          <name name-style="western">
            <surname>Fang</surname>
            <given-names>Tuan-Jen</given-names>
          </name>
          <degrees>MD</degrees>
          <xref rid="aff04" ref-type="aff">4</xref>
          <xref rid="aff05" ref-type="aff">5</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-7805-3458</ext-link>
        </contrib>
        <contrib id="contrib6" contrib-type="author">
          <name name-style="western">
            <surname>Li</surname>
            <given-names>Hsueh-Yu</given-names>
          </name>
          <degrees>MD</degrees>
          <xref rid="aff04" ref-type="aff">4</xref>
          <xref rid="aff05" ref-type="aff">5</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-9016-8098</ext-link>
        </contrib>
        <contrib id="contrib7" contrib-type="author">
          <name name-style="western">
            <surname>Huang</surname>
            <given-names>Chung-Guei</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff06" ref-type="aff">6</xref>
          <xref rid="aff07" ref-type="aff">7</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-0598-5684</ext-link>
        </contrib>
        <contrib id="contrib8" contrib-type="author">
          <name name-style="western">
            <surname>Kuo</surname>
            <given-names>Terry B J</given-names>
          </name>
          <degrees>MD, PhD</degrees>
          <xref rid="aff08" ref-type="aff">8</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-7107-3632</ext-link>
        </contrib>
        <contrib id="contrib9" contrib-type="author">
          <name name-style="western">
            <surname>Yang</surname>
            <given-names>Cheryl C H</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff08" ref-type="aff">8</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-1053-997X</ext-link>
        </contrib>
        <contrib id="contrib10" contrib-type="author">
          <name name-style="western">
            <surname>Shyu</surname>
            <given-names>Hsin-Yih</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff04" ref-type="aff">4</xref>
          <xref rid="aff09" ref-type="aff">9</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-7723-5498</ext-link>
        </contrib>
        <contrib id="contrib11" contrib-type="author">
          <name name-style="western">
            <surname>Wang</surname>
            <given-names>Shu-Ling</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff04" ref-type="aff">4</xref>
          <xref rid="aff10" ref-type="aff">10</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-7486-8051</ext-link>
        </contrib>
        <contrib id="contrib12" contrib-type="author">
          <name name-style="western">
            <surname>Shyu</surname>
            <given-names>Liang-Yu</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff11" ref-type="aff">11</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-6994-4603</ext-link>
        </contrib>
        <contrib id="contrib13" contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Lee</surname>
            <given-names>Li-Ang</given-names>
          </name>
          <degrees>MD, MSc</degrees>
          <xref rid="aff04" ref-type="aff">4</xref>
          <xref rid="aff05" ref-type="aff">5</xref>
          <address>
            <institution>Department of Otorhinolaryngology-Head and Neck Surgery</institution>
            <institution>Chang Gung Memorial Hospital</institution>
            <institution>Linkou Main Branch</institution>
            <addr-line>No 5, Fu-Hsing Street</addr-line>
            <addr-line>Guishan District</addr-line>
            <addr-line>Taoyuan, 33305</addr-line>
            <country>Taiwan</country>
            <fax>886 3 397 9361</fax>
            <phone>886 3 328 1200 ext 3972</phone>
            <email>5738@cgmh.org.tw</email>
          </address>
          <xref rid="aff08" ref-type="aff">8</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-8414-595X</ext-link>
        </contrib>
      </contrib-group>
      <aff id="aff01">
        <label>1</label>
        <institution>Department of Computer Science and Information Engineering</institution>
        <institution>Graduate Institute of Biomedical Engineering</institution>
        <institution>Chang Gung University</institution>
        <addr-line>Taoyuan</addr-line>
        <country>Taiwan</country>
      </aff>
      <aff id="aff02">
        <label>2</label>
        <institution>Department of Neurology</institution>
        <institution>Chang Gung Memorial Hospital</institution>
        <institution>Linkou Main Branch</institution>
        <addr-line>Taoyuan</addr-line>
        <country>Taiwan</country>
      </aff>
      <aff id="aff03">
        <label>3</label>
        <institution>Department of Family Medicine</institution>
        <institution>Chang Gung Memorial Hospital</institution>
        <institution>Taipei Branch &#38; Linkou Main Branch</institution>
        <addr-line>Taoyuan</addr-line>
        <country>Taiwan</country>
      </aff>
      <aff id="aff04">
        <label>4</label>
        <institution>College of Medicine</institution>
        <institution>Chang Gung University</institution>
        <addr-line>Taoyuan</addr-line>
        <country>Taiwan</country>
      </aff>
      <aff id="aff05">
        <label>5</label>
        <institution>Department of Otorhinolaryngology-Head and Neck Surgery</institution>
        <institution>Chang Gung Memorial Hospital</institution>
        <institution>Linkou Main Branch</institution>
        <addr-line>Taoyuan</addr-line>
        <country>Taiwan</country>
      </aff>
      <aff id="aff06">
        <label>6</label>
        <institution>Department of Laboratory Medicine</institution>
        <institution>Chang Gung Memorial Hospital, Linkou Main Branch</institution>
        <addr-line>Taoyuan</addr-line>
        <country>Taiwan</country>
      </aff>
      <aff id="aff07">
        <label>7</label>
        <institution>Department of Medical Biotechnology and Laboratory Science</institution>
        <institution>Graduate Institute of Biomedical Sciences</institution>
        <institution>Chang Gung University</institution>
        <addr-line>Taoyuan</addr-line>
        <country>Taiwan</country>
      </aff>
      <aff id="aff08">
        <label>8</label>
        <institution>Institute of Brain Science</institution>
        <institution>National Yang Ming Chiao Tung University</institution>
        <addr-line>Taipei</addr-line>
        <country>Taiwan</country>
      </aff>
      <aff id="aff09">
        <label>9</label>
        <institution>Department of Educational Technology</institution>
        <institution>Tamkang University</institution>
        <addr-line>New Taipei</addr-line>
        <country>Taiwan</country>
      </aff>
      <aff id="aff10">
        <label>10</label>
        <institution>Center of Teacher Education</institution>
        <institution>National Taiwan University of Science and Technology</institution>
        <addr-line>Taipei</addr-line>
        <country>Taiwan</country>
      </aff>
      <aff id="aff11">
        <label>11</label>
        <institution>Department of Biomedical Engineering</institution>
        <institution>Chung Yuan Christian University</institution>
        <addr-line>Taoyuan</addr-line>
        <country>Taiwan</country>
      </aff>
      <author-notes>
        <corresp>Corresponding Author: Li-Ang Lee <email>5738@cgmh.org.tw</email></corresp>
      </author-notes>
      <pub-date pub-type="collection">
        <season>Oct-Dec</season>
        <year>2021</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>22</day>
        <month>11</month>
        <year>2021</year>
      </pub-date>
      <volume>9</volume>
      <issue>4</issue>
      <elocation-id>e13124</elocation-id>
      <history>
        <date date-type="received">
          <day>12</day>
          <month>12</month>
          <year>2018</year>
        </date>
        <date date-type="rev-request">
          <day>29</day>
          <month>4</month>
          <year>2019</year>
        </date>
        <date date-type="rev-recd">
          <day>2</day>
          <month>4</month>
          <year>2020</year>
        </date>
        <date date-type="accepted">
          <day>10</day>
          <month>9</month>
          <year>2021</year>
        </date>
      </history>
      <copyright-statement>©Yi-Ping Chao, Hai-Hua Chuang, Li-Jen Hsin, Chung-Jan Kang, Tuan-Jen Fang, Hsueh-Yu Li, Chung-Guei Huang, Terry B J Kuo, Cheryl C H Yang, Hsin-Yih Shyu, Shu-Ling Wang, Liang-Yu Shyu, Li-Ang Lee. Originally published in JMIR Serious Games (https://games.jmir.org), 22.11.2021.</copyright-statement>
      <copyright-year>2021</copyright-year>
      <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
        <p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Serious Games, is properly cited. The complete bibliographic information, a link to the original publication on https://games.jmir.org, as well as this copyright and license information must be included.</p>
      </license>
      <self-uri xlink:href="https://games.jmir.org/2021/4/e13124" xlink:type="simple"/>
      <abstract>
        <sec sec-type="background">
          <title>Background</title>
          <p>Learning through a 360° virtual reality (VR) or 2D video represents an alternative way to learn a complex medical education task. However, there is currently no consensus on how best to assess the effects of different learning materials on cognitive load estimates, heart rate variability (HRV), outcomes, and experience in learning history taking and physical examination (H&#38;P) skills.</p>
        </sec>
        <sec sec-type="objective">
          <title>Objective</title>
          <p>The aim of this study was to investigate how learning materials (ie, VR or 2D video) impact learning outcomes and experience through changes in cognitive load estimates and HRV for learning H&#38;P skills.</p>
        </sec>
        <sec sec-type="methods">
          <title>Methods</title>
          <p>This pilot system–design study included 32 undergraduate medical students at an academic teaching hospital. The students were randomly assigned, with a 1:1 allocation, to a 360° VR video group or a 2D video group, matched by age, sex, and cognitive style. The contents of both videos were different with regard to visual angle and self-determination. Learning outcomes were evaluated using the Milestone reporting form. Subjective and objective cognitive loads were estimated using the Paas Cognitive Load Scale, the National Aeronautics and Space Administration Task Load Index, and secondary-task reaction time. Cardiac autonomic function was assessed using HRV measurements. Learning experience was assessed using the AttrakDiff2 questionnaire and qualitative feedback. Statistical significance was accepted at a two-sided <italic>P</italic> value of &#60;.01.</p>
        </sec>
        <sec sec-type="results">
          <title>Results</title>
          <p>All 32 participants received the intended intervention. The sample consisted of 20 (63%) males and 12 (38%) females, with a median age of 24 (IQR 23-25) years. The 360° VR video group seemed to have a higher Milestone level than the 2D video group (<italic>P</italic>=.04). The reaction time at the 10th minute in the 360° VR video group was significantly higher than that in the 2D video group (<italic>P</italic>&#60;.001). Multiple logistic regression models of the overall cohort showed that the 360° VR video module was independently and positively associated with a reaction time at the 10th minute of ≥3.6 seconds (exp B=18.8, 95% CI 3.2-110.8; <italic>P</italic>=.001) and a Milestone level of ≥3 (exp B=15.0, 95% CI 2.3-99.6; <italic>P</italic>=.005). However, a reaction time at the 10th minute of ≥3.6 seconds was not related to a Milestone level of ≥3. A low-frequency to high-frequency ratio between the 5th and 10th minute of ≥1.43 seemed to be inversely associated with a hedonic stimulation score of ≥2.0 (exp B=0.14, 95% CI 0.03-0.68; <italic>P</italic>=.015) after adjusting for video module. The main qualitative feedback indicated that the 360° VR video module was fun but caused mild dizziness, whereas the 2D video module was easy to follow but tedious.</p>
        </sec>
        <sec sec-type="conclusions">
          <title>Conclusions</title>
          <p>Our preliminary results showed that 360° VR video learning may be associated with a better Milestone level than 2D video learning, and that this did not seem to be related to cognitive load estimates or HRV indexes in the novice learners. Of note, an increase in sympathovagal balance may have been associated with a lower hedonic stimulation score, which may have met the learners’ needs and prompted learning through the different video modules.</p>
        </sec>
        <sec sec-type="trial registration">
          <title>Trial Registration</title>
          <p>ClinicalTrials.gov NCT03501641; https://clinicaltrials.gov/ct2/show/NCT03501641</p>
        </sec>
      </abstract>
      <kwd-group>
        <kwd>cognitive load</kwd>
        <kwd>heart rate variability</kwd>
        <kwd>video learning</kwd>
        <kwd>learning outcome</kwd>
        <kwd>secondary-task reaction time</kwd>
        <kwd>virtual reality</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="introduction">
      <title>Introduction</title>
      <sec>
        <title>Competence-Based Medical Education Needs a Multifaceted Assessment System</title>
        <p>From premedical students to practicing physicians, competency-based medical education (CBME) has been applied in the design, implementation, and evaluation of medical education programs according to competency-based outcomes [<xref ref-type="bibr" rid="ref1">1</xref>]. CBME for undergraduate medical students can help to improve task-specific confidence and test performance after the course has been completed, resulting in better performance and patient care before residency training [<xref ref-type="bibr" rid="ref2">2</xref>]. CBME has been widely employed to promote greater learner-centeredness and curricular outcomes since 2010 [<xref ref-type="bibr" rid="ref3">3</xref>]. Furthermore, CBME must use multiple assessment tools that meet minimum requirements for quality. Therefore, a robust and multifaceted assessment system, including quantitative and qualitative methods, is essential for evaluating the progress of learners [<xref ref-type="bibr" rid="ref4">4</xref>].</p>
      </sec>
      <sec>
        <title>Simulation Provides Situated Learning and Assessment in a Safe Environment</title>
        <p>CBME is used to improve graduates’ competency levels, ensuring they are skillful and qualified in all critical areas of their occupation. To this end, CBME emphasizes the use and importance of simulation-based training, which considers patient safety and for which real-life opportunities are limited [<xref ref-type="bibr" rid="ref5">5</xref>]. This consideration is crucial for medical learners and teachers during the COVID-19 pandemic. History taking and physical examination (H&#38;P) is a principal competency, incorporating knowledge, skills, and behavior to initially approach a patient. Therefore, H&#38;P is a key performance level of otorhinolaryngology–head and neck surgery (ORL-HNS) [<xref ref-type="bibr" rid="ref6">6</xref>]. To enhance the development of H&#38;P skills, commonly used methods to assess this competency include in-training examinations such as the Milestone [<xref ref-type="bibr" rid="ref7">7</xref>], Mini Clinical Evaluation Exercise [<xref ref-type="bibr" rid="ref8">8</xref>], and oral examinations of clinical practice [<xref ref-type="bibr" rid="ref9">9</xref>]. Recently, simulations such as part-time trainers, integrated simulators, virtual reality (VR), and wearable devices have become increasingly popular for CBME [<xref ref-type="bibr" rid="ref10">10</xref>]. Simulation-based training, such as VR, has been shown to improve health professionals’ knowledge and skills outcomes and be an integrative step toward supervised clinical practice [<xref ref-type="bibr" rid="ref11">11</xref>]. In particular, VR allowed students to practice rounding skills, facilitate their education during the COVID-19 pandemic, and supplement their in-person clerkship education [<xref ref-type="bibr" rid="ref12">12</xref>].</p>
      </sec>
      <sec>
        <title>360° VR Video Can Provide High Authenticity and Fidelity to Encourage Learners</title>
        <p>VR consists of a computer-generated 3D simulation in which the user both explores and manipulates the contents of the environment to learn and assess clinical knowledge and skills [<xref ref-type="bibr" rid="ref13">13</xref>]. VR provides experiential learning and provides standardized, controlled exposure to situated events, patient-caregiver communication, and teamwork. The use of VR has been shown to be highly acceptable by learners in a wide range of health care settings [<xref ref-type="bibr" rid="ref14">14</xref>] and to play an essential role in improving performance [<xref ref-type="bibr" rid="ref15">15</xref>]. As a subtype of image-based VR, 360° VR video represents an immersive 3D medium featuring authenticity and fidelity using a VR head-mounted display. The use of 360° VR video opens up many possibilities in many domains of medical education [<xref ref-type="bibr" rid="ref16">16</xref>], such as an independent teaching aid or an adjunct to traditional face-to-face teaching [<xref ref-type="bibr" rid="ref17">17</xref>]. The application of 360° VR video has enhanced the effectiveness of medical education and training, raised the level of diagnosis and treatment, improved the doctor-patient relationship, and boosted medical execution efficiency [<xref ref-type="bibr" rid="ref18">18</xref>]. Using 360° VR videos to facilitate the acquisition of new clinical skills has been suggested to be a valuable step in developing a clinical teaching curriculum [<xref ref-type="bibr" rid="ref19">19</xref>].</p>
      </sec>
      <sec>
        <title>Incorporating Instructional Design Practices That Address the Elements of Cognitive Load Theory Is Important to Improve Learning Outcomes</title>
        <p>However, transferring practical skills to a clinical setting using a criterion-based training program with VR simulators is difficult [<xref ref-type="bibr" rid="ref20">20</xref>]. In addition to the poor mechanical performance of the simulated haptic feedback, complex tasks such as H&#38;P and surgical procedures can induce excessive cognitive load during simulation training, which can harm learning, especially for novices [<xref ref-type="bibr" rid="ref21">21</xref>]. Since the learner’s cognitive capacity during learning is limited, improper instructional design may waste precious cognitive resources, impair the essential processing, and cause generative underutilization during learning [<xref ref-type="bibr" rid="ref22">22</xref>]. Therefore, cognitive overload negatively impacts learning outcomes in simulation training [<xref ref-type="bibr" rid="ref23">23</xref>,<xref ref-type="bibr" rid="ref24">24</xref>]. For example, the increased cognitive load was significantly associated with the declined correct identification of a trained murmur during simulation training [<xref ref-type="bibr" rid="ref23">23</xref>]. A study of laparoscopic training [<xref ref-type="bibr" rid="ref24">24</xref>] reported that immersive VR simulation training resulted in the cognitive overload that impeded actual learning and skills acquisition compared with conventional VR simulation training. However, structured and distributed VR simulation practices may induce a lower cognitive load when the learning situation is increased in complexity [<xref ref-type="bibr" rid="ref21">21</xref>]. Recently, VR-based simulation training under cognitive load control has improved performance under similar conditions to an actual surgical task [<xref ref-type="bibr" rid="ref25">25</xref>]. Therefore, estimating cognitive load during 360° VR and 2D video learning is essential for practical instruction and reform.</p>
      </sec>
      <sec>
        <title>Estimating Cognitive Load During 360° VR Video Learning Is a Challenge</title>
        <p>Estimations of cognitive load and specific load types are still challenging based on current cognitive load theory [<xref ref-type="bibr" rid="ref26">26</xref>,<xref ref-type="bibr" rid="ref27">27</xref>]. For example, subjective cognitive load questionnaires, such as the Paas Cognitive Load Scale (Paas-CLS) [<xref ref-type="bibr" rid="ref28">28</xref>] and the National Aeronautics and Space Administration Task Load Index (NASA-TLX) [<xref ref-type="bibr" rid="ref29">29</xref>] have been shown to be good tools to measure intrinsic load, but not extraneous and germane loads [<xref ref-type="bibr" rid="ref30">30</xref>]. However, a lowering of intrinsic cognitive load can reduce total cognitive load, thus releasing working memory capacity [<xref ref-type="bibr" rid="ref31">31</xref>]. Furthermore, instructional techniques for reducing cognitive load have been shown to improve learning [<xref ref-type="bibr" rid="ref32">32</xref>]. In addition to estimating cognitive load, the NASA-TLX has been successfully applied to determine user acceptance when evaluating innovative applications [<xref ref-type="bibr" rid="ref33">33</xref>]. Nevertheless, a negative carryover effect due to failure in a VR simulation training program could affect the subjective cognitive load estimations [<xref ref-type="bibr" rid="ref34">34</xref>]. Therefore, objective estimates of cognitive load, including secondary-task performance [<xref ref-type="bibr" rid="ref35">35</xref>], during the training program have been applied in many medical education studies [<xref ref-type="bibr" rid="ref34">34</xref>-<xref ref-type="bibr" rid="ref36">36</xref>]. Secondary-task performance is a task that assesses participants’ attention and is limited by the storage capacity of visual short-term memory [<xref ref-type="bibr" rid="ref37">37</xref>]. Although secondary-task performance is a cognitive function test, it frequently deteriorates from baseline to dual-task among novices and is particularly useful for tracking changes in cognitive load in the early phases of simulation-based skills [<xref ref-type="bibr" rid="ref35">35</xref>].</p>
      </sec>
      <sec>
        <title>Autonomic Function Can Be Altered During VR Immersion</title>
        <p>VR immersion, especially containing stressful content, can evoke acute stress reactions accompanied by autonomic dysfunction [<xref ref-type="bibr" rid="ref38">38</xref>]. Heart rate variability (HRV) is a sensitive indicator of cardiac autonomic modulation [<xref ref-type="bibr" rid="ref39">39</xref>] and responds to any psychophysical changes immediately. Several physiological or psychological changes, such as stress [<xref ref-type="bibr" rid="ref40">40</xref>] and anxiety [<xref ref-type="bibr" rid="ref41">41</xref>], can change HRV. Reduced HRV indexes might reflect loss of cognitive efficiency [<xref ref-type="bibr" rid="ref36">36</xref>] and might predict increased cognitive load [<xref ref-type="bibr" rid="ref42">42</xref>] and poor cognitive performance [<xref ref-type="bibr" rid="ref43">43</xref>]. Nevertheless, immersive VR using the first-person perspective can induce body ownership illusion in an uncomfortable posture, reduced HRV indexes, and more mistakes in a cognitive task [<xref ref-type="bibr" rid="ref44">44</xref>]. Despite it being challenging to assess associations between HRV and subjective cognitive load due to sizeable interindividual variability [<xref ref-type="bibr" rid="ref45">45</xref>], measuring HRV during a learning task may help evaluate whether learning materials impact learning outcomes through cardiac changes autonomic function.</p>
      </sec>
      <sec>
        <title>Aims and Hypotheses of the Study</title>
        <p>This study aimed (1) to evaluate differences between two learning materials (ie, 360° VR video and 2D video) in the subjective and objective cognitive loads, autonomic function, outcome, and learning experience while students were learning H&#38;P skills and (2) to study how learning materials (ie, 360° VR or 2D video) impact learning outcomes through the changes in cognitive load and HRV. The initial hypotheses were that (1) subjective and objective cognitive loads and autonomic function would be changed while using different learning materials and (2) learners with higher learning outcomes and experience would have different cognitive load and autonomic function during the learning tasks than those with lower learning outcomes and experience.</p>
        <p>Therefore, we used cognitive questionnaires immediately after completing a video learning module to assess subjective cognitive load. We also used secondary-task reaction time and HRV to objectively estimate the dynamic changes of cognitive load and cardiac autonomic function during a video module for providing ongoing feedback to improve video learning. Subsequently, we used the Milestone report form to evaluate the real-patient H&#38;P. The Milestones have been designed according to the grounding principles of CBME and have become a significant formative component of the current accreditation model of graduate medical education [<xref ref-type="bibr" rid="ref46">46</xref>]. Although the Milestones were not designed to assess undergraduate medical students, we considered that some descriptors and targets of the Milestones were suitable for evaluating learner performance of H&#38;P as an undergraduate medical student moves from entry into clerkship through graduation. Furthermore, we applied the AttrakDiff2 questionnaire to assess the acceptance of technical innovations [<xref ref-type="bibr" rid="ref47">47</xref>]. The AttrakDiff2 questionnaire has been used to investigate learners’ experience of many educational innovations, such as mobile e-learning [<xref ref-type="bibr" rid="ref48">48</xref>] and augmented reality [<xref ref-type="bibr" rid="ref49">49</xref>]. Finally, we used anonymous qualitative feedback to determine the learning experience. We considered that the learning outcomes and the learning experience could meet learners’ needs and prompt their use of learning through different video modules.</p>
      </sec>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Study Design</title>
        <p>We conducted a prospective, randomized controlled, pilot system–design study from June 1 to October 30, 2018, at an academic teaching hospital (Department of ORL-HNS, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan). The Institutional Review Board of the Chang Gung Medical Foundation approved this study (No. 201601821B0), and we conducted all procedures in compliance with the Declaration of Helsinki 1975. We informed the participants about the aims of the study and then obtained written informed consent from them. We registered the entire study proposal at ClinicalTrials.gov (NCT03501641). <xref rid="figure1" ref-type="fig">Figure 1</xref> shows the study flowchart following the CONSORT 2010 guidelines [<xref ref-type="bibr" rid="ref50">50</xref>].</p>
        <fig id="figure1" position="float">
          <label>Figure 1</label>
          <caption>
            <p>The CONSORT flow diagram. NASA: National Aeronautics and Space Administration.</p>
          </caption>
          <graphic xlink:href="games_v9i4e13124_fig1.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
      </sec>
      <sec>
        <title>Setting</title>
        <sec>
          <title>Overview</title>
          <p>We used analysis, design, development, implementation, and evaluation models [<xref ref-type="bibr" rid="ref51">51</xref>] to design an effective instruction module for H&#38;P, including essential knowledge and competence according to the guidelines of the American Board of Otolaryngology [<xref ref-type="bibr" rid="ref7">7</xref>]. We used different working samples [<xref ref-type="bibr" rid="ref52">52</xref>], including instructions for how to formulate problems, solution steps, and final solutions, to demonstrate, step by step, how to perform an H&#38;P task in an outpatient setting. We also used self-explanation prompts [<xref ref-type="bibr" rid="ref53">53</xref>] to encourage the learner to recognize links between the knowledge and skills they learned. We recorded a 10-minute 360° video (4K resolution, 30 frames/s) with in-camera stitching, capturing 360° audio, and spherical stabilization using a 360° camera (Garmin VIRB 360; Garmin Ltd). We constructed the contents and scenario of this video according to a real clinical setting. The first portion of the video demonstrated skills of history taking under normal conditions, and the second portion demonstrated skills of how to quickly perform a physical examination (<xref ref-type="table" rid="table1">Table 1</xref>). Subsequently, we produced two videos with different visual angles (ie, 360° and 120°) using PowerDirector software (version 16; CyberLink Corp). Two senior investigators evaluated the videos and validated the learning materials. We then developed courseware with the same user interface for the 360° VR and 2D videos using Unity Editor (version 2017.3.1; Unity Technologies).</p>
        </sec>
        <sec>
          <title>The 360° VR Video Module</title>
          <p>This module was developed to arbitrarily review the immersive 3D 360° VR video through a head-mounted display (<xref rid="figure2" ref-type="fig">Figure 2</xref>). The users were immersed in the 360° experience to learn the H&#38;P skills.</p>
          <fig id="figure2" position="float">
            <label>Figure 2</label>
            <caption>
              <p>Example of 360° virtual reality video learning. Screenshot of the 360° virtual reality video (upper) demonstrating the learners watching a highly immersive 360° video. They arbitrarily changed their field of view to watch the skills of history taking and physical examination from a first-person perspective (lower).</p>
            </caption>
            <graphic xlink:href="games_v9i4e13124_fig2.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
          </fig>
        </sec>
        <sec>
          <title>The 2D Video Module</title>
          <p>The 2D video was played in a fixed 120° focused field of view through the same head-mounted display (<xref rid="figure3" ref-type="fig">Figure 3</xref>). The users reviewed the instructional video as in a theater environment.</p>
          <fig id="figure3" position="float">
            <label>Figure 3</label>
            <caption>
              <p>Example of 2D video learning. Screenshot of the 2D video (upper) showing the learners watching a 2D video in a theater environment. They watched the skills of history taking and physical examination in a fixed focus of view from a third-person perspective (lower).</p>
            </caption>
            <graphic xlink:href="games_v9i4e13124_fig3.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
          </fig>
          <table-wrap position="float" id="table1">
            <label>Table 1</label>
            <caption>
              <p>Summary of the models of 360° virtual reality video and 2D video.</p>
            </caption>
            <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
              <col width="330"/>
              <col width="340"/>
              <col width="330"/>
              <thead>
                <tr valign="top">
                  <td>Feature</td>
                  <td>360° virtual reality video module</td>
                  <td>2D video module</td>
                </tr>
              </thead>
              <tbody>
                <tr valign="top">
                  <td>Head-mounted display</td>
                  <td>Yes</td>
                  <td>Yes</td>
                </tr>
                <tr valign="top">
                  <td>Part I: history taking</td>
                  <td>Statically filmed</td>
                  <td>Statically filmed</td>
                </tr>
                <tr valign="top">
                  <td>Part II: physical examination</td>
                  <td>Dynamically filmed</td>
                  <td>Dynamically filmed</td>
                </tr>
                <tr valign="top">
                  <td>Visual angle</td>
                  <td>360°</td>
                  <td>120°</td>
                </tr>
                <tr valign="top">
                  <td>Immersion</td>
                  <td>Yes</td>
                  <td>No</td>
                </tr>
                <tr valign="top">
                  <td>Perspective</td>
                  <td>First person</td>
                  <td>Third person</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </sec>
      </sec>
      <sec>
        <title>Selection of Participants</title>
        <p>A convenience sampling approach was used, and 32 consecutive volunteers were recruited during the study period. The inclusion criteria were as follows: (1) aged &#62;20 years and (2) novices in ORL-HNS (ie, undergraduate medical students). The exclusion criteria were as follows: (1) contraindications for using VR, such as pregnancy, hypertension, motion sickness, inner ear infections, claustrophobia, recent surgery, pre-existing binocular vision abnormalities, heart disorders, or epilepsy, and (2) declining to participate. All of the volunteers had at least a basic level of computer literacy and could use VR headsets and controllers after instruction. We used the 25-item Group Embedded Figures Test (GEFT) (score range 0-18) to assess the participants’ cognitive style [<xref ref-type="bibr" rid="ref54">54</xref>]. The GEFT has been shown to have high reliability in medical education [<xref ref-type="bibr" rid="ref55">55</xref>], and we have previously validated its effectiveness of classifying learning preference in millennial undergraduate medical students [<xref ref-type="bibr" rid="ref56">56</xref>]. Field-independent learners prefer and have better performance in computer-assisted learning. We stratified the students into two subgroups: “field-dependent” (GEFT score ≤12) and “field-independent” (GEFT score &#62;12) [<xref ref-type="bibr" rid="ref57">57</xref>].</p>
      </sec>
      <sec>
        <title>Randomization and Blinding</title>
        <p>The participants were blinded to the purpose of the study during recruitment to minimize preparation bias. After the participants had provided consent and completed the GEFT, we randomly assigned them, with a 1:1 allocation, to the 360° VR video group and the 2D video group, matched by age, sex, and cognitive style (<xref rid="figure1" ref-type="fig">Figure 1</xref>). The Random Number Generators tool in SPSS software (version 24; IBM Corp) was used to create a list of random numbers for allocating the students, who were stratified by center with a 1:1 allocation using a fixed block size of 8 in both parallel subgroups. We concealed the allocation sequence before implementing the video module, and the module adhered to our computer-generated randomization protocol.</p>
      </sec>
      <sec>
        <title>Intervention</title>
        <p>After randomization, the participants reviewed their allocated video through a head-mounted display in the same space for 10 minutes. To reduce the effect of the head-mounted display on learning experience, both groups used the same VR device (VIVE VR headset; HTC Corp). We explained the functionality of the VR device to the participants before the intervention. In the 360° VR video group, the learners arbitrarily reviewed the instructor’s demonstrations and responses from standard patients and other medical staff from a first-person perspective in an immersive 360° environment (<xref rid="figure2" ref-type="fig">Figure 2</xref>). In the 2D video group, the learners simply watched the instructor’s demonstrations from a third-person perspective in a theater environment (<xref rid="figure3" ref-type="fig">Figure 3</xref>). During the learning course, the participants watched the movie by themselves at a time of their choosing.</p>
      </sec>
      <sec>
        <title>Methods of Measurement</title>
        <sec>
          <title>Overview</title>
          <p>We used five different face-to-face assessments, including the Paas-CLS and the NASA-TLX for subjectively estimating the cognitive load, the Milestone for assessing the learning outcomes, and the AttrakDiff2 questionnaire and anonymous qualitative feedback for determining the learning experience. There was one objective estimate of cognitive load using the secondary-task performance and one measurement of cardiac autonomic function using HRV monitoring.</p>
        </sec>
        <sec>
          <title>Paas Cognitive Load Scale</title>
          <p>We used the Paas-CLS [<xref ref-type="bibr" rid="ref28">28</xref>] to estimate the total cognitive load of the learning task immediately after the intervention. The Paas-CLS questionnaire is a single-item measure to rate the perceived intensity of mental effort along a 9-point scale, ranging from 1 (very, very low mental effort) to 9 (very, very high mental effort). The Paas-CLS questionnaire has good reliability (Cronbach α=.82-.90) in instructional research [<xref ref-type="bibr" rid="ref58">58</xref>].</p>
        </sec>
        <sec>
          <title>NASA Task Load Index</title>
          <p>The NASA-TLX questionnaire is a subjective assessment of cognitive load [<xref ref-type="bibr" rid="ref29">29</xref>]. This instrument consists of six subscales: mental demand, physical demand, temporal demand, performance, effort, and frustration. Participants rate the level of each dimension by making a mark on a visual analog scale (range 0-20) immediately after the intervention. The NASA-TLX questionnaire has good reliability (Cronbach α≥.80) to assess cognitive load [<xref ref-type="bibr" rid="ref59">59</xref>].</p>
        </sec>
        <sec>
          <title>Secondary-Task Performance</title>
          <p>Secondary-task performance has been shown to be sensitive in estimating intrinsic cognitive load among novices engaged in simulation-based learning [<xref ref-type="bibr" rid="ref35">35</xref>]. As the primary task in this study, the participants reviewed the video for 10 minutes. To ensure the use of similar perceptual-cognitive resources for the primary task [<xref ref-type="bibr" rid="ref60">60</xref>], the participants were asked to respond to a visual cue by pressing a button on a controller as soon as possible. The visual cue appeared in their field of view and lasted for 10 seconds. For exploring the importance of monitoring secondary-task reaction time, we measured the reaction time, deﬁned as the time from visual cue presentation to when the button was pressed, at 0 minutes, 5 minutes, and 10 minutes during the reviewing period. When the participants missed a response, we considered the reaction time to be “11 seconds” to avoid gaps in the performance results and inaccuracies in the estimates of the reaction time.</p>
        </sec>
        <sec>
          <title>Heart Rate Variability</title>
          <p>HRV has been shown to be an objective estimation of learners’ cognitive load in a learning environment [<xref ref-type="bibr" rid="ref61">61</xref>,<xref ref-type="bibr" rid="ref62">62</xref>]. For controlling preinterventional stress, the participants sat quietly for 20 minutes. We recorded 5-minute electrocardiogram signals of a single lead (lead I) using a Holter-like NeXus-4 amplifier and recording system (Mind Media BV) when the participant wore a head-mounted display and breathed normally as baseline data. During the 10-minute intervention, we recorded heart rates simultaneously and continuously. Electrocardiogram data were acquired with a sample rate of 1024 Hz, and the raw data were saved. The power spectrum was quantified by a fast Fourier transform [<xref ref-type="bibr" rid="ref39">39</xref>]. In our preliminary results, the energy-frequency-time distributions of the electrocardiogram data were nonlinear and nonstationary. Therefore, we used the empirical mode decomposition (EMD) method to decompose complicated data into a finite number of intrinsic mode functions that admitted well-behaved Hilbert transforms [<xref ref-type="bibr" rid="ref63">63</xref>]. The EMD method is an adaptive preprocessing technique for overcoming the limitations of HRV spectral analysis when assessing nonlinear and nonstationary system data [<xref ref-type="bibr" rid="ref64">64</xref>]. We performed HRV analysis using custom-developed MATLAB (version 7; The MathWorks, Inc) codes that allowed us to determine HRV parameters from sequences of 5-minute consecutive epochs of electrocardiogram signals. The requirements for the quality of HRV analysis were based on the European Society of Cardiology and the North American Society of Pacing and Electrophysiology guidelines [<xref ref-type="bibr" rid="ref65">65</xref>]. For the analysis, sequences of R wave to R wave (RR) intervals were selected without artifacts, ventricular excitations, or supraventricular excitations [<xref ref-type="bibr" rid="ref66">66</xref>]. We then calculated the RR interval, the SD of normal-to-normal RR intervals (SDNN), and the root mean square of successive heartbeat interval difference (RMSSD) using time-domain analysis. HRV in the frequency domain was described using spectral power values in the low-frequency (LF) band (0.04-0.15 Hz), the high-frequency (HF) band (0.15-0.40 Hz), and the LF/HF ratio. To reflect the different instructional content, we analyzed three time intervals: baseline, 0 to 5 minutes, and 5 to 10 minutes. These HRV indexes were chosen because low SDNN was associated with higher intrinsic and germane cognitive loads [<xref ref-type="bibr" rid="ref67">67</xref>] and poor performance [<xref ref-type="bibr" rid="ref68">68</xref>], low RMSSD was related to higher intrinsic cognitive load [<xref ref-type="bibr" rid="ref67">67</xref>] and worse performance on executive tasks [<xref ref-type="bibr" rid="ref69">69</xref>], and low LF/HF ratio was associated with high cognitive load [<xref ref-type="bibr" rid="ref70">70</xref>]. The HRV variables were measured before and after the intervention.</p>
        </sec>
        <sec>
          <title>Milestones</title>
          <p>The Milestones have been used to assess the development of resident physicians in key dimensions of the elements of physician competency in otolaryngology since 2004 [<xref ref-type="bibr" rid="ref7">7</xref>]. In this study, we prospectively recruited participants to perform H&#38;P in real patients with sleep-disordered breathing (SDB) at our teaching clinics. For evaluating learner performance of H&#38;P as an undergraduate medical student moves from entry into clerkship through graduation, we selected the level that best described that learner’s performance with the Milestone for care for patients with SDB [<xref ref-type="bibr" rid="ref6">6</xref>]. We used a brief 5-level Milestone report form to rate learner performance of H&#38;P, including (1) obtaining general H&#38;P, (2) recognizing signs and symptoms of SDB and the differences between children and adults, (3) performing detailed examinations with evaluations of upper airway anatomy, (4) interpreting the examinations and advanced diagnostic testing, and (5) teaching-focused H&#38;P.</p>
        </sec>
        <sec>
          <title>AttrakDiff2 Questionnaire</title>
          <p>The AttrakDiff2 questionnaire was developed to reliably evaluate the acceptance of technical innovations [<xref ref-type="bibr" rid="ref47">47</xref>]. It assesses qualities of pragmatism, hedonic stimulation, hedonic identification, and attractiveness using 28 questions. The participants were asked to respond to each question by making a mark on a 7-point Likert-like scale, ranging from –3 to 3, with a semantic differential design. Subsequently, the mean value of each quality created a scale value for pragmatism, hedonic stimulation, hedonic identification, and attractiveness. The AttrakDiff2 questionnaire has been applied to evaluate learners’ experience [<xref ref-type="bibr" rid="ref48">48</xref>,<xref ref-type="bibr" rid="ref71">71</xref>].</p>
        </sec>
      </sec>
      <sec>
        <title>Anonymous Qualitative Feedback</title>
        <p>Each participant in this study provided anonymous feedback about their experience of the module used.</p>
      </sec>
      <sec>
        <title>Outcome Measures</title>
        <p>The primary outcome measure of this study was the Milestone level after completing the video learning module. The secondary outcomes were the AttrakDiff2 questionnaire scales.</p>
      </sec>
      <sec>
        <title>Sample Size</title>
        <p>The sample size was estimated using primary outcome effects (the Milestone) based on a priori study (360° VR video: mean 3.1, SD 0.7; 2D video: mean 2.3, SD 0.6). A two-tailed Wilcoxon-Mann-Whitney <italic>U</italic> test was used to calculate a sample size of 16 in each group (normal parent distribution; calculated effect size, 1.23; type I error, 0.01; power, 70%). For a block size of 8, we decided to enroll a total of 32 students to show the difference in the Milestone level.</p>
      </sec>
      <sec>
        <title>Statistical Analysis</title>
        <p>The D’Agostino-Pearson omnibus normality test showed that most of the continuous variables were nonnormally distributed, and they were presented as median and IQR. Differences between groups were analyzed using the Wilcoxon signed-rank test, the Mann-Whitney <italic>U</italic> test, or the Fisher exact test as appropriate. Effect sizes were calculated using the Hodges-Lehmann method for the Mann-Whiney <italic>U</italic> test and the Wilcoxon signed-rank test, or odds ratios for the Fisher exact test. The Spearman correlation test was used to analyze relationships between variables of interest. The Bonferroni correction was used to adjust <italic>P</italic> values because of the increased risk of a type I error when conducting multiple statistical tests at the same time [<xref ref-type="bibr" rid="ref72">72</xref>]. Continuous variables were dichotomized using the median split. Variables of interest were analyzed for multivariate logistic regression models. All <italic>P</italic> values were two‐sided, and statistical significance was accepted at <italic>P</italic>&#60;.01. Statistical analyses were performed using G*Power software (version 3.1.9.2; Heinrich-Heine-Universität Düsseldorf), Prism for Windows (version 7.0; GraphPad Software Inc), and SPSS Statistics for Windows (version 25; IBM Corp).</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Study Participants</title>
        <p>A total of 32 volunteers were recruited, of which 20 (63%) were males and 12 (38%) were females. The median age was 24 (IQR 23-25) years. There were 3 (9%) field-dependent and 29 (91%) field-independent participants. <xref ref-type="table" rid="table2">Table 2</xref> summarizes the variables of interest for the overall study cohort. As expected, there were no significant differences in age, sex, or cognitive style between the 360° VR video and 2D video groups at baseline. After randomization, all participants received the intended intervention. There were no protocol deviations in this study.</p>
        <table-wrap position="float" id="table2">
          <label>Table 2</label>
          <caption>
            <p>Demographics and cognitive style.</p>
          </caption>
          <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
            <col width="30"/>
            <col width="260"/>
            <col width="100"/>
            <col width="200"/>
            <col width="140"/>
            <col width="180"/>
            <col width="90"/>
            <thead>
              <tr valign="top">
                <td colspan="2">Variables</td>
                <td>Overall (N=32)</td>
                <td>360° virtual reality video group (n=16)</td>
                <td>2D video group (n=16)</td>
                <td>Effect size<sup>a</sup> (95% CI)</td>
                <td><italic>P</italic> value<sup>b</sup></td>
              </tr>
            </thead>
            <tbody>
              <tr valign="top">
                <td colspan="7">
                  <bold>Demographics</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Age (years), median (IQR)</td>
                <td>24 (23-25)</td>
                <td>24 (23-25)</td>
                <td>24 (23-25)</td>
                <td>0 (–1 to 0)</td>
                <td>.29</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Sex (male), n (%)</td>
                <td>20 (63)</td>
                <td>10 (63)</td>
                <td>10 (63)</td>
                <td>1.0 (0.2 to 4.2)</td>
                <td>&#62;.99</td>
              </tr>
              <tr valign="top">
                <td colspan="2">Cognitive style: field-dependent, n (%)</td>
                <td>3 (9)</td>
                <td>1 (6)</td>
                <td>2 (13)</td>
                <td>2.1 (0.2 to 26.3)</td>
                <td>&#62;.99</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="table2fn1">
              <p><sup>a</sup>Effect sizes were calculated using the Hodges-Lehmann method for the Mann-Whiney <italic>U</italic> test and Wilcoxon signed-rank test, or odds ratios for the Fisher exact test.</p>
            </fn>
            <fn id="table2fn2">
              <p><sup>b</sup><italic>P</italic> values were calculated based on the Mann-Whiney <italic>U</italic> test for continuous variables (two-tailed) or the Fisher exact test for categorical variables (two-tailed).</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Estimates of Subjective and Objective Cognitive Load</title>
        <sec>
          <title>Paas Cognitive Load Scale</title>
          <p>The Paas-CLS showed that the participants had a significantly higher total cognitive load than the reference value of “5” in the overall cohort (<italic>P</italic>=.001) after 10 minutes of video instruction (<xref ref-type="table" rid="table3">Table 3</xref>). Furthermore, the Paas-CLS score of the 360° VR video group was comparable to that of the 2D video group.</p>
        </sec>
        <sec>
          <title>NASA Task Load Index</title>
          <p>The overall cohort had a significantly higher score for mental demand (corrected <italic>P</italic>&#60;.001) than the reference value of “10” before and after the Bonferroni correction (<xref ref-type="table" rid="table3">Table 3</xref>). The physical demand score of the 360° VR video group was higher than that of the 2D video group; however, this difference did not reach statistical significance after the Bonferroni correction (<xref rid="figure4" ref-type="fig">Figure 4</xref>, upper).</p>
          <table-wrap position="float" id="table3">
            <label>Table 3</label>
            <caption>
              <p>Subjective measures of cognitive load.</p>
            </caption>
            <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
              <col width="30"/>
              <col width="250"/>
              <col width="170"/>
              <col width="200"/>
              <col width="170"/>
              <col width="100"/>
              <col width="80"/>
              <thead>
                <tr valign="top">
                  <td colspan="2">Variables</td>
                  <td>Overall (N=32), median (IQR)</td>
                  <td>360° virtual reality video group (n=16), median (IQR)</td>
                  <td>2D video group (n=16), median (IQR)</td>
                  <td>Effect size<sup>a</sup> (95% CI)</td>
                  <td><italic>P</italic> value<sup>b</sup></td>
                </tr>
              </thead>
              <tbody>
                <tr valign="top">
                  <td colspan="2">Subjective measurement: Paas Cognitive Load Scale</td>
                  <td>6 (5-7)<sup>c</sup></td>
                  <td>6 (5-7)</td>
                  <td>5 (5-7)</td>
                  <td>0 (–1 to 1)</td>
                  <td>.78</td>
                </tr>
                <tr valign="top">
                  <td colspan="7">
                    <bold>National Aeronautics and Space Administration Task Load Index</bold>
                  </td>
                </tr>
                <tr valign="top">
                  <td>
                    <break/>
                  </td>
                  <td>Mental demand</td>
                  <td>14 (11-15)<sup>c</sup></td>
                  <td>14 (12-15)</td>
                  <td>12 (10-16)</td>
                  <td>1 (–2 to 3)</td>
                  <td>.45</td>
                </tr>
                <tr valign="top">
                  <td>
                    <break/>
                  </td>
                  <td>Physical demand</td>
                  <td>10 (7-14)</td>
                  <td>12 (9-14)</td>
                  <td>9 (4-12)</td>
                  <td>4 (0 to 7)</td>
                  <td>.047</td>
                </tr>
                <tr valign="top">
                  <td>
                    <break/>
                  </td>
                  <td>Temporal demand</td>
                  <td>10 (7-11)</td>
                  <td>10 (8-13)</td>
                  <td>9 (6-10)</td>
                  <td>1 (–1 to 4)</td>
                  <td>.18</td>
                </tr>
                <tr valign="top">
                  <td>
                    <break/>
                  </td>
                  <td>Performance</td>
                  <td>12 (6-15)</td>
                  <td>11 (6-15)</td>
                  <td>13 (6-15)</td>
                  <td>0 (–4 to 4)</td>
                  <td>.93</td>
                </tr>
                <tr valign="top">
                  <td>
                    <break/>
                  </td>
                  <td>Effort</td>
                  <td>12 (10-15)</td>
                  <td>13 (11-15)</td>
                  <td>12 (7-15)</td>
                  <td>1 (–2 to 5)</td>
                  <td>.45</td>
                </tr>
                <tr valign="top">
                  <td>
                    <break/>
                  </td>
                  <td>Frustration</td>
                  <td>8 (4-13)</td>
                  <td>10 (5-13)</td>
                  <td>7 (3-13)</td>
                  <td>2 (–2 to 6)</td>
                  <td>.29</td>
                </tr>
              </tbody>
            </table>
            <table-wrap-foot>
              <fn id="table3fn1">
                <p><sup>a</sup>Effect sizes were calculated using the Hodges-Lehmann method for the Mann-Whiney <italic>U</italic> test and the Wilcoxon signed-rank test, or odds ratios for the Fisher exact test.</p>
              </fn>
              <fn id="table3fn2">
                <p><sup>b</sup><italic>P</italic> values were calculated based on the Mann-Whiney <italic>U</italic> test (two-tailed).</p>
              </fn>
              <fn id="table3fn3">
                <p><sup>c</sup><italic>P</italic>&#60;.01, compared with a reference value (score of “5” for the Paas Cognitive Load Scale or score of “10” for the National Aeronautics and Space Administration Task Load Index subscale) and based on the Wilcoxon signed-rank test (two-tailed). <italic>P</italic> values were significant after the Bonferroni correction.</p>
              </fn>
            </table-wrap-foot>
          </table-wrap>
          <fig id="figure4" position="float">
            <label>Figure 4</label>
            <caption>
              <p>Comparisons of the physical demands and Milestone levels between the 360° virtual reality video group and the 2D video group. The 360° virtual reality video group had a higher physical demand score (upper) and Milestone level (lower) than the 2D video group. However, these differences did not reach statistical significance. <italic>P</italic> values were calculated using the Mann-Whiney <italic>U</italic> test (two-tailed).</p>
            </caption>
            <graphic xlink:href="games_v9i4e13124_fig4.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
          </fig>
        </sec>
        <sec>
          <title>Secondary-Task Performance</title>
          <p>In the overall cohort (<xref ref-type="table" rid="table4">Table 4</xref>), the reaction time at the 10th minute was significantly higher than the reaction time at the 5th minute (corrected <italic>P</italic>=.003) but comparable to the reaction time at baseline. In contrast, the reaction time at the 5th minute was equal to the reaction time at baseline after the Bonferroni correction. In the 360° VR video group, the reaction time at the 10th minute was significantly higher than the reaction time at the 5th minute (corrected <italic>P</italic>=.003) and the reaction time at baseline (corrected <italic>P</italic>=.006). Still, the reaction time at the 5th minute and the reaction time at baseline were comparable (<xref rid="figure5" ref-type="fig">Figure 5</xref>, upper). In the 2D video group, differences in the reaction time across various time points were not statistically significant. Furthermore, the reaction time at the 10th minute of the 360° VR video group was significantly higher than that of the 2D video group (corrected <italic>P</italic>&#60;.001), even though differences in the reaction time at the 5th minute and reaction time at baseline were not statistically significant.</p>
          <fig id="figure5" position="float">
            <label>Figure 5</label>
            <caption>
              <p>Comparisons of the secondary-task reaction time and SD of normal-to-normal RR intervals (SDNN) between the 360° virtual reality video group and the 2D video group. Notably, the reaction time in the 360° virtual reality video group was significantly higher at the 10th minute compared to the reaction times at baseline and at the 5th minute, whereas the reaction time in the 2D video group was lower at the 10th minute compared to that at baseline. The 360° virtual reality video group had a significantly higher reaction time at the 10th minute (upper) than the 2D video group (upper). The SDNN at 5 to 10 minutes in the 360° virtual reality video group was lower than the SDNN at baseline (lower). <italic>P</italic> values were calculated using the Wilcoxon signed-rank test or Mann-Whitney <italic>U</italic> test as appropriate after the Bonferroni correction.</p>
            </caption>
            <graphic xlink:href="games_v9i4e13124_fig5.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
          </fig>
        </sec>
      </sec>
      <sec>
        <title>Heart Rate Variability</title>
        <p>Differences across the RR at 5 to 10 minutes, RR at 0 to 5 minutes, and RR at baseline were not statistically significant in the overall cohort, the 360° VR video group, and the 2D video group, respectively. Furthermore, the RR at 5 to 10 minutes, RR at 0 to 5 minutes, and RR at baseline were comparable between both groups (<xref ref-type="table" rid="table4">Table 4</xref>). Differences in the SDNN index were not statistically significant for either intragroup comparisons or intergroup comparisons. Differences in the RMSSD index were not statistically significant for either intragroup comparisons or intergroup comparisons. Differences in the LF/HF index were not statistically significant for either intragroup comparisons or intergroup comparisons.</p>
        <table-wrap position="float" id="table4">
          <label>Table 4</label>
          <caption>
            <p>Objective estimates of cognitive load.</p>
          </caption>
          <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
            <col width="30"/>
            <col width="230"/>
            <col width="160"/>
            <col width="170"/>
            <col width="150"/>
            <col width="180"/>
            <col width="80"/>
            <thead>
              <tr valign="top">
                <td colspan="2">Variables</td>
                <td>Overall (N=32), median (IQR)</td>
                <td>360° virtual reality video group (n=16), median (IQR)</td>
                <td>2D video group (n=16), median (IQR)</td>
                <td>Effect size<sup>a</sup> (95% CI)</td>
                <td><italic>P</italic> value<sup>b</sup></td>
              </tr>
            </thead>
            <tbody>
              <tr valign="top">
                <td colspan="7">
                  <bold>Secondary-task performance</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Reaction time–baseline (s)</td>
                <td>2.6 (1.4-7.4)</td>
                <td>2.5 (1.3-3.4)<sup>c,d</sup></td>
                <td>3.4 (1.6-10.2)</td>
                <td>–0.6 (–5.0 to 0.7)</td>
                <td>.34</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Reaction time–5th min (s)</td>
                <td>1.6 (0.9-3.6)<sup>d,</sup><sup>e</sup></td>
                <td>1.3 (0.9-1.6)<sup>d,e</sup></td>
                <td>1.8 (1.0-8.2)</td>
                <td>–0.4 (–2.0 to 0.13)</td>
                <td>.18</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>Reaction time–10th min (s)</td>
                <td>3.6 (1.3-11.0)<sup>d,e</sup></td>
                <td>11.0 (7.5-11.0)<sup>c</sup><sup>,</sup><sup>d,</sup><sup>e</sup></td>
                <td>1.3 (1.0-3.1)<sup>d</sup></td>
                <td>8.3 (3.6 to 9.8)<sup>d</sup></td>
                <td>&#60;.001</td>
              </tr>
              <tr valign="top">
                <td colspan="7">
                  <bold>Heart rate variability</bold>
                </td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>RR–baseline (ms)</td>
                <td>810 (741-918)</td>
                <td>825 (742-937)</td>
                <td>802 (721-891)</td>
                <td>25 (–75 to 122)</td>
                <td>.62</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>RR–0 to 5 min (ms)</td>
                <td>810 (730-908)</td>
                <td>833 (762-925)</td>
                <td>772 (724-884)</td>
                <td>45 (–42 to 143)</td>
                <td>.31</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>RR–5 to 10 min (ms)</td>
                <td>779 (722-889)</td>
                <td>794 (736-911)</td>
                <td>779 (709-866)</td>
                <td>20 (–64 to 117)</td>
                <td>.75</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>SDNN–baseline (ms)</td>
                <td>69.9 (48.7-135.1)</td>
                <td>88.3 (65.7-139.0)</td>
                <td>57.3 (42.7-135.6)</td>
                <td>25.3 (–6.1 to 65.6)</td>
                <td>.10</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>SDNN–0 to 5 min (ms)</td>
                <td>59.8 (45.5-151.3)</td>
                <td>72.0 (58.6-184.4)</td>
                <td>51.7 (39.2-107.7)</td>
                <td>20.1 (–6.4 to 95.3)</td>
                <td>.11</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>SDNN–5 to 10 min (ms)</td>
                <td>69.8 (42.3-121.9)</td>
                <td>71.2 (51.7-128.2)</td>
                <td>58.9 (35.8-91.7)</td>
                <td>16.3 (–20.9 to 52.2)</td>
                <td>.27</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>RMSSD–baseline (ms)</td>
                <td>60.7 (31.7-179.4)</td>
                <td>106.3 (39.7-189.1)</td>
                <td>34.3 (28.6-175.1)</td>
                <td>29.8 (–6.7 to 107.2)</td>
                <td>.13</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>RMSSD–0 to 5 min (ms)</td>
                <td>63.0 (30.4-203.8)</td>
                <td>78.0 (34.5-252.4)</td>
                <td>37.4 (23.8-133.7)</td>
                <td>24.8 (–12.9 to 129.0)</td>
                <td>.29</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>RMSSD–5 to 10 min (ms)</td>
                <td>54.9 (27.8-145.0)</td>
                <td>72.1 (31.9-158.5)</td>
                <td>39.4 (27.5-96.8)</td>
                <td>8.7 (–17.9 to 71.5)</td>
                <td>.51</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>LF/HF ratio–baseline</td>
                <td>1.02 (0.78-1.96)</td>
                <td>0.86 (0.77-1.96)</td>
                <td>1.21 (0.79-1.96)</td>
                <td>–0.13 (–0.63 to 0.39)</td>
                <td>.59</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>LF/HF ratio–0 to 5 min</td>
                <td>1.19 (0.72-2.83)</td>
                <td>0.93 (0.67-3.35)</td>
                <td>1.59 (0.77-2.34)</td>
                <td>–0.11 (–1.09 to 1.11)</td>
                <td>.91</td>
              </tr>
              <tr valign="top">
                <td>
                  <break/>
                </td>
                <td>LF/HF ratio–5 to 10 min</td>
                <td>1.43 (0.86-2.80)</td>
                <td>1.43 (0.74-2.89)</td>
                <td>1.43 (0.89-2.86)</td>
                <td>–0.04 (–0.84 to 0.79)</td>
                <td>.81</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="table4fn1">
              <p><sup>a</sup>Effect sizes were calculated using the Hodges-Lehmann method for the Mann-Whiney <italic>U</italic> test.</p>
            </fn>
            <fn id="table4fn2">
              <p><sup>b</sup><italic>P</italic> values were calculated based on the Mann-Whiney <italic>U</italic> test (continuous variables).</p>
            </fn>
            <fn id="table4fn3">
              <p><sup>c</sup><italic>P</italic>&#60;.01, compared with the baseline value, using the Wilcoxon signed-rank test (two-tailed).</p>
            </fn>
            <fn id="table4fn4">
              <p><sup>d</sup><italic>P</italic> values were significant after the Bonferroni correction.</p>
            </fn>
            <fn id="table4fn5">
              <p><sup>e</sup><italic>P</italic>&#60;.01, compared with the 5th-minute value of reaction time or the 0-to-5–minute values of R wave to R wave (RR), standard deviation of normal-to-normal RR intervals (SDNN), root mean square of successive heartbeat interval difference (RMSSD), low frequency (LF), high frequency (HF), or LF/HF ratio, using the Wilcoxon signed-rank test (two-tailed).</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Primary Outcome: Milestone Level</title>
        <p>Overall, the participants had a significantly higher Milestone level (median 3, IQR 2-4) than the reference value of “1” (<italic>P</italic>&#60;.001) after 10 minutes of video instruction. Although the Milestone level of the 360° VR video group (median 3, IQR 3-4) was higher than that of the 2D video group (median 2, IQR 2-3), the difference did not reach statistical significance (effect size=1, 95% CI 0-1; <italic>P</italic>=.02) (<xref rid="figure4" ref-type="fig">Figure 4</xref>, lower).</p>
      </sec>
      <sec>
        <title>Secondary Outcomes: AttrakDiff2 Questionnaire Scales</title>
        <p>The overall cohort and the 360° VR and 2D video groups had significantly positive learning experiences in terms of pragmatic quality, hedonic stimulation, hedonic identification, and attractiveness, compared with the reference value of “0” with all corrected <italic>P</italic>&#60;.01, after 10 minutes of video instruction (<xref ref-type="table" rid="table5">Table 5</xref>). There were no statistically significant differences in pragmatic quality, hedonic stimulation, hedonic identification, or attractiveness between the two groups.</p>
        <table-wrap position="float" id="table5">
          <label>Table 5</label>
          <caption>
            <p>Acceptance of technical innovations assessed by the AttrakDiff2 questionnaire.</p>
          </caption>
          <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
            <col width="190"/>
            <col width="180"/>
            <col width="180"/>
            <col width="190"/>
            <col width="180"/>
            <col width="80"/>
            <thead>
              <tr valign="top">
                <td>Variables</td>
                <td>Overall (N=32), median (IQR)<sup>a</sup></td>
                <td>360° virtual reality video group (n=16), median (IQR)<sup>a</sup></td>
                <td>2D video group (n=16), median (IQR)<sup>a</sup></td>
                <td>Effect size<sup>b</sup> (95% CI)</td>
                <td><italic>P</italic> value<sup>c</sup></td>
              </tr>
            </thead>
            <tbody>
              <tr valign="top">
                <td>Pragmatic quality</td>
                <td>1.9 (1.2-2.3)</td>
                <td>2.0 (1.2-2.4)</td>
                <td>1.8 (1.2-2.3)</td>
                <td>0.1 (–0.4 to 0.7)</td>
                <td>.59</td>
              </tr>
              <tr valign="top">
                <td>Hedonic stimulation</td>
                <td>2.0 (1.0-2.5)</td>
                <td>2.1 (1.2-2.6)</td>
                <td>2.0 (0.9-2.4)</td>
                <td>0.1 (–0.4 to 0.7)</td>
                <td>.42</td>
              </tr>
              <tr valign="top">
                <td>Hedonic identification</td>
                <td>1.9 (1.2-2.4)</td>
                <td>1.8 (1.5-2.4)</td>
                <td>2.1 (1.5-2.9)</td>
                <td>0.1 (–0.6 to 0.9)</td>
                <td>.90</td>
              </tr>
              <tr valign="top">
                <td>Attractiveness</td>
                <td>1.3 (0.9-2.1)</td>
                <td>1.2 (1.1-1.9)</td>
                <td>1.6 (0.6-2.3)</td>
                <td>–0.1 (–0.9 to 0.7)</td>
                <td>.84</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="table5fn1">
              <p><sup>a</sup><italic>P</italic>&#60;.01 for all variables, compared with a reference value of “0” for the AttrakDiff2 questionnaire using the Wilcoxon signed-rank test (two-tailed). <italic>P</italic> values were significant after the Bonferroni correction.</p>
            </fn>
            <fn id="table5fn2">
              <p><sup>b</sup>Effect sizes were calculated using the Hodges-Lehmann method for the Mann-Whiney <italic>U</italic> test.</p>
            </fn>
            <fn id="table5fn3">
              <p><sup>c</sup><italic>P</italic> values were calculated based on the Mann-Whiney <italic>U</italic> test for continuous variables (two-tailed).</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
      </sec>
      <sec>
        <title>Correlations Between the Learning Modules, Cognitive Load Estimates, Learning Outcomes, and Technical Acceptance</title>
        <p>To investigate how learning materials impact learning outcomes through the changes in cognitive load and HRV, we dichotomized the Milestone level, AttrakDiff2 questionnaire scales, cognitive load variables, and HRV indexes. <xref rid="figure6" ref-type="fig">Figure 6</xref> demonstrates the associations between variables of interest.</p>
        <fig id="figure6" position="float">
          <label>Figure 6</label>
          <caption>
            <p>Associations between the video learning modules, cognitive load measures, heart rate variability, learning outcome, and learning experience. Solid blue lines indicate an independent positive association between two variables after adjustment for video module using multivariate logistic regression models. In contrast, dashed blue lines indicate a positive association, and a dashed red line shows an inverse association without statistical significance after adjustment for the video module. HF: high frequency; LF: low frequency; Paas-CLS: Paas Cognitive Load Scale; RMSSD: root mean square of successive heartbeat interval difference; RR: R wave to R wave; SDNN: SD of normal-to-normal RR intervals.</p>
          </caption>
          <graphic xlink:href="games_v9i4e13124_fig6.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
      </sec>
      <sec>
        <title>Qualitative Evaluation</title>
        <sec>
          <title>Benefits</title>
          <p>The 360° VR video group reported that the 360° VR video module was “fun to learn” (3/16, 19%) and “good for physical examinations” (1/16, 6%). Qualitative feedback from the 2D video group emphasized that they found the 2D video module “easy to follow” (2/16, 13%) and “highly efficient” (1/16, 6%).</p>
        </sec>
        <sec>
          <title>Faults</title>
          <p>Out of 16 participants in the 360° VR video group, 3 (19%) reported that it caused “mild VR dizziness.” Notably, the 2D video learners said that the module was “tedious” (3/16, 19%) and that there was “no interaction” (1/16, 6%).</p>
        </sec>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <sec>
        <title>Principal Findings</title>
        <p>This study’s main findings highlighted the complexities of cognitive load estimations and HRV indexes inherent in developing and evaluating 360° VR and 2D video learning. Our results showed that video learning resulted in a higher total cognitive load and mental demand and prolonged the reaction time at the 10th minute; however, video learning also enhanced a Milestone level of H&#38;P skills with positive learning experiences. Using the same head-mounted display, both the 360° VR and 2D videos were efficient learning methods with positive learning experiences for novice learners. Notably, the 360° VR video learners demonstrated a higher Milestone level of H&#38;P in actual patients with SDB than the 2D video learners. Although both video modules produced comparable total cognitive load and subscales, the 360° VR video learners had a more prolonged reaction time at the 10th minute than the 2D video learners.</p>
        <p>Interestingly, in the second portion of the video, the 360° VR video learners had a longer reaction time than the baseline data. These findings suggested that the immersive 360° VR video could reduce secondary-task performance without increasing subjective cognitive loads. Furthermore, the elevated LF/HF ratio at 0 to 5 minutes correlated with a reduced hedonic stimulation scale. Combined with qualitative feedback, we found that the students seemed to consume more cognitive resources to fit the immersive 360° VR video than the 2D video learning. This preliminary study suggests that the immersive 360° VR video might lead to a better Milestone level than the 2D video, which seemed to be unrelated to cognitive load estimates and HRV indexes in novice learners.</p>
      </sec>
      <sec>
        <title>Limitations</title>
        <p>This study used quantitative and qualitative measures and methods to evaluate different video learning materials and showed its potential clinical applicability for learning H&#38;P skills. However, several limitations should be addressed. First, this study needs external validation due to the small sample size. Although H&#38;P is one of the essential training topics for undergraduate medical students, our outcomes may not be generalizable to junior residents who already have basic knowledge, skills, and attitudes. Second, assessments of the learner’s performance in the workplace, such as the Mini Clinical Evaluation Exercise, were not included in this study. Third, there were several significant associations between variables of interest in this study. However, the potential relationships between video module, cognitive load, and HRV might be underestimated using such stringent criteria for multiple tests [<xref ref-type="bibr" rid="ref73">73</xref>]. Accordingly, further studies with a larger sample size with the extended competence spectrum and learning outcome assessments are warranted to confirm our results and inferences.</p>
      </sec>
      <sec>
        <title>Comparison With Prior Work</title>
        <p>Our results indicate that both 360° VR and 2D video learning modules can increase H&#38;P competency. Traditionally, students learn clinical skills, such as H&#38;P, from clinical teachers. Instructional videos offer an excellent pedagogical approach to enhance medical students’ clinical competencies and self-confidence levels [<xref ref-type="bibr" rid="ref74">74</xref>,<xref ref-type="bibr" rid="ref75">75</xref>]. Moreover, using videos as a delivery format can improve the effects and attractiveness of text-based e-learning [<xref ref-type="bibr" rid="ref76">76</xref>]. Therefore, clinical teachers can use videos as learning resources for students’ independent learning [<xref ref-type="bibr" rid="ref77">77</xref>]. Recently, many universities and teaching institutes have promoted the use of instructional videos as a resource for self-directed education and student-centered programs, especially during the COVID-19 pandemic.</p>
        <p>Immersive 360° VR videos allow for a virtual experience where learners can improve their competencies by experiencing all of the sights and sounds of teaching clinics and responses from the patients, families, and medical staff from a first-person perspective. When working memory and information processing capacities are limited, 360° VR video learning can trigger a higher cognitive load or stress than conventional 2D video learning. In this study, 360° VR video learning might reduce participants’ attention toward the secondary task without changing subjective cognitive load estimates and HRV indexes regardless of the learning outcome. Therefore, the quality of 360° VR video learning modules still needs to be improved concerning reducing objective cognitive load.</p>
        <p>Approximately 25% of our volunteers reported high vibration, out-of-focus blur, eye fatigue, and motion sickness in the preparation phase of the 360° VR video production. A literature review revealed that immersive 360° VR video might induce 3D visual fatigue [<xref ref-type="bibr" rid="ref78">78</xref>] and visually induced motion sickness [<xref ref-type="bibr" rid="ref79">79</xref>,<xref ref-type="bibr" rid="ref80">80</xref>] and may interrupt autonomic balance [<xref ref-type="bibr" rid="ref81">81</xref>]. Therefore, we used spherical stabilization to smooth quick movements and vibrations and dynamic depth of field to reduce visual discomfort [<xref ref-type="bibr" rid="ref82">82</xref>]. In addition, we chose a 10-minute instructional course to reduce these known side effects. Although levels of cardiac autonomic balance, as reflected by the LF/HF ratio, were similar during the 360° VR video learning and equivalent to those of the 2D video learning, our 360° VR video learners still experienced a more prolonged secondary-task reaction time, mainly in the second portion of the video.</p>
        <p>In contrast, the 2D video learners did not report these problems while using the same head-mounted display. Although the participants might have an adequate cognitive function to overcome the impaired attention for obtaining the H&#38;P competence, the instructors need to design a 360° VR video with less distraction and lower cognitive load. A motion capture unit to synchronize vestibular response and visual information may reduce motion sickness [<xref ref-type="bibr" rid="ref83">83</xref>], and further studies are warranted to investigate this issue.</p>
        <p>Interestingly, the elevated LF/HF ratio at 5 to 10 minutes seemed to be associated with lower hedonic stimulation. Since these cognitive load estimates were not related to Milestone level, they could be used to improve the quality of video learning. For example, the virtual environment sustained the increased LF/HF ratio and acted as a stimulatory driver for cardiac autonomic activity after mental stress [<xref ref-type="bibr" rid="ref84">84</xref>]. Therefore, limited time to immerse into the virtual environment could improve the learners’ experience.</p>
        <p>This study applied the adaptive EMD method and the well-behaved Hilbert transform technique to process the nonstationary electrocardiogram signals [<xref ref-type="bibr" rid="ref63">63</xref>,<xref ref-type="bibr" rid="ref64">64</xref>]. Importantly, we found that all RR intervals at different time points significantly and positively correlated with the total cognitive load. Furthermore, the significant association between the RR at 5 to 10 minutes and the Paas-CLS score was independent of the video module. Using similar analytic technology, Ghaderyan and Abbasi also observed that an increased RR interval was associated with higher cognitive load estimations [<xref ref-type="bibr" rid="ref85">85</xref>]. Moreover, prolonged reaction time at the 5th minute seemed to be related to the RR at 5 to 10 minutes. These observations reflected that novice learners need to improve their cognitive efficiency when learning from dynamically filmed video from a first-person perspective for dealing with elevated cognitive load. These results also indicated that subjective and objective estimates of cognitive load and HRV monitoring have considerable potential to help us better understand a learner’s processing strategy to video learning modules, enhance our comprehension of contextual information, and improve video learning. Future studies are warranted to confirm the benefits of cognitive load and HRV measures in video learning.</p>
      </sec>
      <sec>
        <title>Conclusions</title>
        <p>Our preliminary results suggested that 360° VR video learning may result in a better H&#38;P performance despite causing a more prolonged secondary-task reaction time than 2D video learning. Furthermore, the increased LF/HF ratio was associated with lower acceptance of video learning. Qualitative evaluation reflected varying benefits and faults between the 360° VR and 2D videos. Consequently, the students seemed to consume more cognitive resources to fit the immersive 360° VR video than 2D video learning. Without cognitive overload, the undergraduate medical students could adjust their mental efficiency to handle the decreased cognitive reserve when learning through the 360° VR video module. This study indicates that the ubiquitous and diverse roles of multimodal cognitive load estimations and HRV measures in video learning may function as part of an integrated CBME curriculum. Further research is necessary to assess their effects on other performance outcomes.</p>
      </sec>
    </sec>
  </body>
  <back>
    <app-group>
      <supplementary-material id="app1">
        <label>Multimedia Appendix 1</label>
        <p>CONSORT-EHEALTH checklist V1.6.1.</p>
        <media xlink:href="games_v9i4e13124_app1.pdf" xlink:title="PDF File  (Adobe PDF File), 2510 KB"/>
      </supplementary-material>
    </app-group>
    <glossary>
      <title>Abbreviations</title>
      <def-list>
        <def-item>
          <term id="abb1">CBME</term>
          <def>
            <p>competency-based medical education</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb2">EMD</term>
          <def>
            <p>empirical mode decomposition</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb3">GEFT</term>
          <def>
            <p>Group Embedded Figures Test</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb4">H&#38;P</term>
          <def>
            <p>history taking and physical examination</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb5">HF</term>
          <def>
            <p>high frequency</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb6">HRV</term>
          <def>
            <p>heart rate variability</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb7">LF</term>
          <def>
            <p>low frequency</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb8">NASA-TLX</term>
          <def>
            <p>National Aeronautics and Space Administration Task Load Index</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb9">ORL-HNS</term>
          <def>
            <p>otorhinolaryngology–head and neck surgery</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb10">Paas-CLS</term>
          <def>
            <p>Paas Cognitive Load Scale</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb11">RMSSD</term>
          <def>
            <p>root mean square of successive heartbeat interval difference</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb12">RR</term>
          <def>
            <p>R wave to R wave</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb13">SDB</term>
          <def>
            <p>sleep-disordered breathing</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb14">SDNN</term>
          <def>
            <p>SD of normal-to-normal RR intervals</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb15">VR</term>
          <def>
            <p>virtual reality</p>
          </def>
        </def-item>
      </def-list>
    </glossary>
    <ack>
      <p>We are indebted to our trained study staff, especially Ping-Yun Lin, Yun-Kai Chang, Ming-Yen Chung, and Chung-Fang Hsiao. This work was financially supported by grants from the Ministry of Science and Technology, Taiwan, Republic of China (grants 106-2511-S-182A-003-MY2 and 108-2511-H-182A-001), and grants from the Chang Gung Medical Foundation, Taiwan, Republic of China (grants CMRPG3G1381–3 and CMRPG3G1931). The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and the decision to submit the manuscript for publication.</p>
    </ack>
    <fn-group>
      <fn fn-type="con">
        <p>YPC, HHC, HYS, SLW, and LAL participated in the conception and design of this work. YPC, LJH, LYS, and LAL collected the data. YPC, HHC, TBJK, CCHY, HYS, SLW, and LAL analyzed and interpreted the data. YPC, LJH, CJK, TJF, HYL, TBJK, CCHY, HYS, LYS, and LAL carried out the development of the project software. All authors participated in the writing of the manuscript and take public responsibility for it. YPC, HHC, LJH, CGH, TBJK, CCHY, HYS, SLW, and LAL critically revised the manuscript for important intellectual content. All authors reviewed the final version of the manuscript and approved it for publication. All authors attested to the validity and legitimacy of the data in the manuscript and agree to be named as author of the manuscript.</p>
      </fn>
      <fn fn-type="conflict">
        <p>None declared.</p>
      </fn>
    </fn-group>
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