<?xml version="1.0" encoding="UTF-8"?><!DOCTYPE article PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Publishing DTD v1.2 20190208//EN" "http://jats.nlm.nih.gov/publishing/1.2/JATS-journalpublishing1.dtd"><article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="1.2" xml:lang="en">
    <front>
        <journal-meta>
            <journal-id journal-id-type="pmc">F1000Research</journal-id>
            <journal-title-group>
                <journal-title>F1000Research</journal-title>
            </journal-title-group>
            <issn pub-type="epub">2046-1402</issn>
            <publisher>
                <publisher-name>F1000 Research Limited</publisher-name>
                <publisher-loc>London, UK</publisher-loc>
            </publisher>
        </journal-meta>
        <article-meta>
            <article-id pub-id-type="doi">10.12688/f1000research.143189.1</article-id>
            <article-categories>
                <subj-group subj-group-type="heading">
                    <subject>Research Article</subject>
                </subj-group>
                <subj-group>
                    <subject>Articles</subject>
                </subj-group>
            </article-categories>
            <title-group>
                <article-title>Acute effects of virtual reality exercise bike games on psychophysiological outcomes in college North-African adolescents with cerebral palsy: A randomized clinical trial</article-title>
                <fn-group content-type="pub-status">
                    <fn>
                        <p>[version 1; peer review: 2 approved with reservations]</p>
                    </fn>
                </fn-group>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Soudani</surname>
                        <given-names>Makrem</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Farhat</surname>
                        <given-names>Faical</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Original Draft Preparation</role>
                    <xref ref-type="aff" rid="a1">1</xref>
                </contrib>
                <contrib contrib-type="author" corresp="yes">
                    <name>
                        <surname>Ghram</surname>
                        <given-names>Amine</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-2851-0753</uri>
                    <xref ref-type="corresp" rid="c1">a</xref>
                    <xref ref-type="aff" rid="a2">2</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Ben Saad</surname>
                        <given-names>Helmi</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-7477-2965</uri>
                    <xref ref-type="aff" rid="a3">3</xref>
                </contrib>
                <contrib contrib-type="author" corresp="no">
                    <name>
                        <surname>Chlif</surname>
                        <given-names>Mehdi</given-names>
                    </name>
                    <role content-type="http://credit.niso.org/">Conceptualization</role>
                    <role content-type="http://credit.niso.org/">Data Curation</role>
                    <role content-type="http://credit.niso.org/">Formal Analysis</role>
                    <role content-type="http://credit.niso.org/">Investigation</role>
                    <role content-type="http://credit.niso.org/">Methodology</role>
                    <role content-type="http://credit.niso.org/">Supervision</role>
                    <role content-type="http://credit.niso.org/">Writing &#x2013; Review &amp; Editing</role>
                    <xref ref-type="aff" rid="a4">4</xref>
                </contrib>
                <aff id="a1">
                    <label>1</label>Research Laboratory Education, Motricity, Sport and Health LR19JS01, University of Sfax, Sfax, Sfax, 3000, Tunisia</aff>
                <aff id="a2">
                    <label>2</label>Cardiac Rehabilitation, Hamad Medical Corporation, Doha, Doha, 3050, Qatar</aff>
                <aff id="a3">
                    <label>3</label>Research laboratory &#x201c;Heart failure, LR12SP09&#x201d;, Farhat HACHED Hospital,, University of Sousse, Sousse, Sousse, Tunisia</aff>
                <aff id="a4">
                    <label>4</label>Exercise Physiology and Rehabilitation Laboratory, University of Picardy Jules Verne, Amiens, Hauts-de-France, France</aff>
            </contrib-group>
            <author-notes>
                <corresp id="c1">
                    <label>a</label>
                    <email xlink:href="mailto:ghram.amine@hotmail.fr">ghram.amine@hotmail.fr</email>
                </corresp>
                <fn fn-type="conflict">
                    <p>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>15</day>
                <month>12</month>
                <year>2023</year>
            </pub-date>
            <pub-date pub-type="collection">
                <year>2023</year>
            </pub-date>
            <volume>12</volume>
            <elocation-id>1597</elocation-id>
            <history>
                <date date-type="accepted">
                    <day>27</day>
                    <month>11</month>
                    <year>2023</year>
                </date>
            </history>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2023 Soudani M et al.</copyright-statement>
                <copyright-year>2023</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <self-uri content-type="pdf" xlink:href="https://f1000research.com/articles/12-1597/pdf"/>
            <abstract>
                <sec>
                    <title>Background</title>
                    <p>Cerebral palsy (CP) is a neurological disorder that can affect motor skills and psychophysiological well-being. Virtual Reality Exercise (VRE) has been shown to improve cognitive and physical outcomes for patients with CP. Therefore, the aim of this study was to investigate the effects of VRE on attention, vigor, and decision-making abilities in adolescents with CP.</p>
                </sec>
                <sec>
                    <title>Methods</title>
                    <p>A randomized controlled trial was used. Fourteen Tunisian college adolescents (15.6 &#x00b1; 0.7 years; diagnosed with CP) were randomly assigned to either the VRE group or the Traditional Exercise (TE) group. The VRE group engaged in 40 min exercise sessions using VRE bike games, while the TE group participated in TE sessions.</p>
                </sec>
                <sec>
                    <title>Results</title>
                    <p>Fourteen participants (42.9 % females) were included in this analysis The results showed that VRE had a significant positive impact on attention and vigor compared to TE. Participants in the VRE group demonstrated improved attention levels and reported higher levels of vigor following the exercise sessions.</p>
                </sec>
                <sec>
                    <title>Conclusions</title>
                    <p>The findings suggest that VRE is an effective intervention for improving attention and vigor abilities in adolescents with CP. Further research is needed to confirm these findings and to investigate the long-term effects of VRE.</p>
                </sec>
                <sec>
                    <title>Registration</title>
                    <p>Pan African Clinical Trial Registry (PACTR202308598603482; 31/08/2023).</p>
                </sec>
            </abstract>
            <kwd-group kwd-group-type="author">
                <kwd>Cognitive Function; Decision-Making; Health; RCT; Training; Virtual Reality</kwd>
            </kwd-group>
            <funding-group>
                <award-group id="fund-1" xlink:href="http://dx.doi.org/10.13039/100019779">
                    <funding-source>Qatar National Library</funding-source>
                </award-group>
                <funding-statement>This study was supported by the Qatar National Library.</funding-statement>
                <funding-statement>
                    <italic>The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</italic>
                </funding-statement>
            </funding-group>
        </article-meta>
    </front>
    <body>
        <sec id="sec6" sec-type="intro">
            <title>Introduction</title>
            <p>Cerebral palsy (CP) is characterized by nonprogressive brain changes during fetal or infant development, leading to movement and posture abnormalities.
                <sup>
                    <xref ref-type="bibr" rid="ref1">1</xref>
                </sup> In addition to motor disorders, patients with CP often exhibit symptoms related to sensory, cognitive, communicative, perceptual, behavioral, and seizure abnormalities.
                <sup>
                    <xref ref-type="bibr" rid="ref2">2</xref>
                </sup> These patients are at an elevated risk of developing metabolic and cardiovascular diseases, as well as experiencing reduced cardiorespiratory endurance and muscle strength.
                <sup>
                    <xref ref-type="bibr" rid="ref3">3</xref>
                </sup> Furthermore, they tend to engage in lower levels of physical activity (PA),
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>
                </sup> which can contribute to negative health outcomes and premature mortality.
                <sup>
                    <xref ref-type="bibr" rid="ref5">5</xref>
                </sup>
                <sup>,</sup>
                <sup>
                    <xref ref-type="bibr" rid="ref6">6</xref>
                </sup> As the most common cause of physical impairment, CP significantly impacts the quality of life, leading to substantial economic and psychological burdens.
                <sup>
                    <xref ref-type="bibr" rid="ref7">7</xref>
                </sup>
            </p>
            <p>Treatment approaches for CP are diverse and tailored to the type, severity, and individual needs of the patient.
                <sup>
                    <xref ref-type="bibr" rid="ref8">8</xref>
                </sup> Physical therapy and rehabilitation are vital components of treatment, as they improve strength, flexibility, balance, motor development, and mobility.
                <sup>
                    <xref ref-type="bibr" rid="ref9">9</xref>
                </sup> Furthermore, occupational therapy, speech and language therapy, along with adaptive equipment, can effectively address physical impairments and enhance mobility.
                <sup>
                    <xref ref-type="bibr" rid="ref10">10</xref>
                </sup> To support emotional and behavioral challenges, psychologists and social workers can employ various strategies, such as behavior therapy, cognitive behavior therapy, strengths-based counseling, and mutual aid group work.
                <sup>
                    <xref ref-type="bibr" rid="ref11">11</xref>
                </sup> These comprehensive and interdisciplinary interventions aim to provide holistic care and optimize the overall well-being of patients with CP.</p>
            <p>Physical exercise plays a crucial role in the treatment of children/adolescents with CP.
                <sup>
                    <xref ref-type="bibr" rid="ref12">12</xref>
                </sup> Physical exercise has significant implications for both short- and long- term health outcomes in CP, such as improved fitness levels, reduced risk factors for diseases, and fewer secondary complications.
                <sup>
                    <xref ref-type="bibr" rid="ref13">13</xref>
                </sup> However, patients with CP tend to engage in less habitual PA compared to their peers, leading to adverse effects on their overall health and well-being.
                <sup>
                    <xref ref-type="bibr" rid="ref14">14</xref>
                </sup> This lack of PA substantially increases the chances of developing obesity, cardiovascular diseases, and mental health problems.
                <sup>
                    <xref ref-type="bibr" rid="ref4">4</xref>
                </sup> Therefore, clinicians should actively promote and facilitate opportunities for increased habitual PA while also encouraging a reduction in sedentary behavior, aiming to optimize long-term health outcomes.</p>
            <p>The development of technology presents a promising avenue for promoting PA and overall well-being. Interactive video games, such as video game cycling, virtual reality (VR), and mobile games, have proven effective in encouraging individuals of all age groups to engage in, and increase their PA levels.
                <sup>
                    <xref ref-type="bibr" rid="ref15">15</xref>
                </sup> VR, a form of digital technology that integrates sight, sound, touch, and smell to create an immersive experience, has gained significant attention.
                <sup>
                    <xref ref-type="bibr" rid="ref16">16</xref>
                </sup> In 2023, VR applications are being developed and utilized in various clinically based fields, including rehabilitative and behavioral medicine.
                <sup>
                    <xref ref-type="bibr" rid="ref17">17</xref>
                </sup>
                <sup>,</sup>
                <sup>
                    <xref ref-type="bibr" rid="ref18">18</xref>
                </sup> Notably, the introduction of commercially available VR exercise (VRE) equipment, such as the VirZoom&#x2014;a VR-based exercise cycle compatible with the Oculus VR headset&#x2014;has shown promise.
                <sup>
                    <xref ref-type="bibr" rid="ref19">19</xref>
                </sup> VirZoom exercise bike is an efficient, enjoyable, and motivating tool for PA, particularly among college students.
                <sup>
                    <xref ref-type="bibr" rid="ref20">20</xref>
                </sup> These findings suggest that health professionals can consider utilizing such technology to encourage PA participation across different populations. However, further extensive trials are necessary to confirm and determine the optimal utilization of this technology in promoting PA. In summary, technology including interactive video games and VR, holds potential as an effective means to promote PA and improve overall health. Future research should focus on validating and expanding upon the findings, establishing guidelines for incorporating this technology into PA interventions. Existing literature demonstrates that regular exercise significantly improves and maintains cognitive function and memory.
                <sup>
                    <xref ref-type="bibr" rid="ref21">21</xref>
                </sup> However, the effects of acute or single bouts of exercise have not been extensively explored. Literature provides growing evidence that acute aerobic exercise has a small but positive impact on human cognitive function, mood, and memory.
                <sup>
                    <xref ref-type="bibr" rid="ref22">22</xref>
                </sup>
                <sup>,</sup>
                <sup>
                    <xref ref-type="bibr" rid="ref23">23</xref>
                </sup> Despite these findings, there remains limited evidence-based research on the cognitive function of children and adolescents.
                <sup>
                    <xref ref-type="bibr" rid="ref24">24</xref>
                </sup>
                <sup>,</sup>
                <sup>
                    <xref ref-type="bibr" rid="ref25">25</xref>
                </sup>
            </p>
            <p>Therefore, the present randomized controlled trial (RCT) aimed to investigate the physiological and psychological outcomes of using the VirZoom VRE bike compared to traditional exercise (TE) bikes in North African college adolescents with CP. Given the entertaining and motivating nature of the VRE experience, we hypothesized that VR applications would lead to higher attention, memory, vigor, and decision-making abilities as the main outcomes in college adolescents with CP compared to TE. Additionally, we aimed to assess the impact of VRE on spasticity as the secondary outcome.</p>
        </sec>
        <sec id="sec7" sec-type="methods">
            <title>Methods</title>
            <sec id="sec8">
                <title>Ethical considerations</title>
                <p>The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the local Ethics Committee of the High Institute of Nursing, University of Sfax, Tunisia (Protection Committee Approval Registration code: CPP SUD N 0388/2022), registered on the Pan African Clinical Trial Registry (identification number: PACTR202308598603482). Written informed consent was obtained from all the adolescents&#x2019; parents or legal guardians. Adolescents agreed verbally to participate in this study.</p>
            </sec>
            <sec id="sec9">
                <title>Study design</title>
                <p>This study is a subgroup analysis within the ongoing RCT registered with the Pan African Clinical Trial Registry (identification number: PACTR202308598603482) on August 31, 2023. The RCT was conducted following the guidelines established by the CONSORT statement.
                    <sup>
                        <xref ref-type="bibr" rid="ref26">26</xref>
                    </sup>
                    <sup>,</sup>
                    <sup>
                        <xref ref-type="bibr" rid="ref62">62</xref>
                    </sup> Testing occurred between June and August 2023 at Sfax Association for the Care of the Physically Handicapped (Sfax, Tunisia). All procedures in the study adhered to the ethical standards of the institution and/or national research committee, as well as the 1964 Helsinki Declaration and its subsequent amendments or comparable ethical.
                    <sup>
                        <xref ref-type="bibr" rid="ref27">27</xref>
                    </sup> The study received approval from the University Institutional Review Board and the local ethics committee of the High Institute of Nursing, University of Sfax, Tunisia (Protection Committee Approval in 25 January 2022 Registration code: CPP SUD N 0388/2022). Before commencing the study, adolescents aged 14 to 16 years, along with their parents or guardians, received an explanation of the test protocol.</p>
            </sec>
            <sec id="sec10">
                <title>Patients</title>
                <p>A convenience sample of 14 college students were recruited from the aforementioned association. To select the participants, the study&#x2019;s inclusion criteria were disclosed to physicians, pediatric physiotherapy clinics, special educators, speech therapists, sociologists from the above-cited association, and ambulant care services. Potential participants were approached through the association staff and social workers. These professionals then recruited them to participate in the study.</p>
                <p>The eligibility criteria for participant selection were as follows: i) Adolescent aged between 14 and 16 years, ii) Medical diagnosis of spastic CP confirmed by a pediatric neurologist; iii) Motor function classified at level I or II according to the Gross Motor Function Classification System (GMFCS V), iv) PA levels below the international norm (i.e., less than one hour daily at &gt;5 metabolic equivalents (MET)), indicating moderate or vigorous intensity,
                    <sup>
                        <xref ref-type="bibr" rid="ref28">28</xref>
                    </sup> v) Lack of regular sports participation (i.e., less than three sessions per week for 20 minutes or more), and vi) Reported issues with mobility in daily life or sports.</p>
                <p>Exclusion criteria for participation in the study were: 
                    <bold>
                        <italic toggle="yes">i)</italic>
                    </bold> Engaging in a week of moderate to intense exercise exceeding 150 minutes per week; 
                    <bold>
                        <italic toggle="yes">ii)</italic>
                    </bold> GMFCS level III to V, 
                    <bold>
                        <italic toggle="yes">iii)</italic>
                    </bold> Behavioral issues that prevent participation in group activities or a movement disorder primarily dyskinetic or atactic in nature, 
                    <bold>
                        <italic toggle="yes">iv)</italic>
                    </bold> Recent surgery within the previous six months, 
                    <bold>
                        <italic toggle="yes">v)</italic>
                    </bold> Botulinum toxin treatment, and 
                    <bold>
                        <italic toggle="yes">vi)</italic>
                    </bold> Serial casting within the recent three months, or scheduled procedures during the intervention period.</p>
                <p>The patients&#x2019; level of physical ability was categorized using the GMFCS V.
                    <sup>
                        <xref ref-type="bibr" rid="ref29">29</xref>
                    </sup> GMFCS level I or II indicate independent walking for more than 12 months and the ability to ambulate for at least 10 meters with or without a gait-assistance device (walker or crutches). GMFCS level III to V precludes the use of the Oculus Quest handheld controller, moderate to severe intellectual disability, uncontrollable seizures, or conditions that make physical training dangerous (e.g., hip dysplasia, cardiac arrhythmia, or mitochondrial defects).</p>
            </sec>
            <sec id="sec11">
                <title>Randomization</title>
                <p>Method used to generate the random allocation sequence: Simple random allocation was used to generate the random allocation sequence. This means that each participant had an equal chance of being assigned to either the intervention group or the control group.</p>
                <p>Type of randomization; details of any restriction (such as blocking and block size): No restriction was used in this study. This means that participants were not blocked or stratified in any way.</p>
                <p>Mechanism used to implement the random allocation sequence (such as sequentially numbered containers), describing any steps taken to conceal the sequence until interventions were assigned: Sequentially numbered envelopes were used to implement the random allocation sequence. The envelopes were sealed until interventions were assigned. The allocation sequence was generated by the researcher (
                    <bold>
                        <italic toggle="yes">MS</italic>
                    </bold> in the authors&#x2019; list). The latter also enrolled participants and assigned them to interventions.</p>
            </sec>
            <sec id="sec12">
                <title>Experimental design</title>
                <p>
                    <xref ref-type="fig" rid="f1">Figure 1</xref> exposes the study protocol.</p>
                <fig fig-type="figure" id="f1" orientation="portrait" position="float">
                    <label>Figure 1. </label>
                    <caption>
                        <title>Study protocol flowchart.</title>
                        <p>TE: Traditional exercise. VRE: Virtual Reality Exercise.</p>
                    </caption>
                    <graphic id="gr1" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/156823/fee6fa94-9375-4067-8658-c13821d6d595_figure1.gif"/>
                </fig>
                <p>Anthropometric measurements, height, weight, and body mass index (BMI) were taken with patients wearing light clothing and no shoes. Patients underwent two 40-minute cycling sessions
                    <sup>
                        <xref ref-type="bibr" rid="ref30">30</xref>
                    </sup> on two distinct days. A two-day interval separated the sessions, and they were conducted in a counterbalanced manner: 
                    <bold>
                        <italic toggle="yes">(1)</italic>
                    </bold> a VirZoom VRE bike and 
                    <bold>
                        <italic toggle="yes">(2)</italic>
                    </bold> a TE bike. Both bikes are Everfit BFK-500 Kaohsiung, Taiwan. Each session consisted of three conditions. The first was a five-minute period in which the participant lay down. This was followed by a 30-minute cycling period. The third condition was another period lying down for the remaining time. The Go-No-Go task
                    <sup>
                        <xref ref-type="bibr" rid="ref19">19</xref>
                    </sup> and the Profile Of Mood States scale (POMS)
                    <sup>
                        <xref ref-type="bibr" rid="ref31">31</xref>
                    </sup> were administered two days prior to each session as well as immediately afterwards. Heart rate (bpm), blood pressure (mmHg), Modified Ashworth Scale,
                    <sup>
                        <xref ref-type="bibr" rid="ref32">32</xref>
                    </sup> and Montreal Cognitive Assessment (MoCA)
                    <sup>
                        <xref ref-type="bibr" rid="ref33">33</xref>
                    </sup> scores were recorded immediately before and after each session.</p>
            </sec>
            <sec id="sec13">
                <title>Body composition</title>
                <p>Height was measured with a Harpenden 602VR stadiometer to the last complete 0.1 cm, and body composition was estimated using a multifrequency bioelectrical impedance analyzer (TBF-410GS, Tanita Co., Tokyo, Japan). This is a method validated against reference methods.
                    <sup>
                        <xref ref-type="bibr" rid="ref34">34</xref>
                    </sup> The parameters collected in this study included weight, Body Mass Index, fat mass, and fat free mass.</p>
            </sec>
            <sec id="sec14">
                <title>VirZoom VRE</title>
                <p>VirZoom&#x2019;s VZfit offers a unique experience by combining a controller attached to the handlebars and a sensor on the bike crank. When used in conjunction with an Oculus Go virtual reality headset, it allows researchers to explore various virtual destinations while the participant is stationary on a bike.
                    <sup>
                        <xref ref-type="bibr" rid="ref35">35</xref>
                    </sup>
                </p>
                <p>During the study, patients played two 30-minute exercise sessions on the VirZoom VZfit, which features a variety of mini-games. The games chosen for the study were &#x201c;Le Tour&#x201d; and &#x201c;Race Car,&#x201d; both of which require players to pedal faster or slower to speed up or slow down, and to lean their body side to side to turn left or right. These games were observed to be the most intense, and were played with a pedal resistance set at a medium level.</p>
                <p>All participants were asked to maintain a moderate level of exertion, with their heart rate ranging between 65% to 85% of their Age-predicted Maximal Heart Rate (ApMHR)
                    <sup>
                        <xref ref-type="bibr" rid="ref36">36</xref>
                    </sup> as measured by a polar sensor monitor.</p>
            </sec>
            <sec id="sec15">
                <title>Traditional stationary exercise bike</title>
                <p>To create a training environment that was similar to traditional cycling and to reduce the environmental impact, patients in the study watched a virtual cycling video on television while using the Sparnod fitness sub-52 stationary bike. The VR cycling sessions were designed to achieve an exercise intensity equivalent to 65% to 85% of the ApMHR.
                    <sup>
                        <xref ref-type="bibr" rid="ref36">36</xref>
                    </sup>
                </p>
                <p>To ensure uniform exercise intensity between the traditional and VR cycling sessions, participants were instructed to maintain their heart rate between 65% and 85% of their ApMHR, which was measured by the integrated heart rate monitor on the stationary bike during the traditional cycling session.</p>
            </sec>
            <sec id="sec16">
                <title>The Go/No-Go task</title>
                <p>The Go/No-Go task is a response inhibition task where a motor response must either be executed or inhibited.
                    <sup>
                        <xref ref-type="bibr" rid="ref37">37</xref>
                    </sup> During this task, and using PEBL (for Psychology Experiment Building Language) computer software, participants were required to watch a sequential presentation on computer of letters and respond to a target letter by pressing a button space of the keyboard.
                    <sup>
                        <xref ref-type="bibr" rid="ref38">38</xref>
                    </sup> The presentation began with a 2 &#x00d7; 2 array with four stars (one in each square of the array). A single letter (P or R) was then presented in one of the squares for a duration of 500 milliseconds with an inter-stimulus interval of 1,500 milliseconds. In the first condition (P-Go), participants were asked to press a button in response to the target letter P and withhold their response to the non-target letter R. The ratio of targets to non-targets was 80:20. The first condition consisted of 160 trials. A second, reversal condition (R-Go) was then administered, and participants were now asked to make a response to the target letter R and withhold their response to the non-target letter P (the letter that they were initially conditioned to make a motor response to the task, while NoGo errors and RT to Go responses are considered as indicators of impulsivity.
                    <sup>
                        <xref ref-type="bibr" rid="ref37">37</xref>
                    </sup>
                </p>
                <p>The Go/No-Go task is a computerized test that evaluates inhibitory control, a crucial component of cognitive assessment and self-regulation.
                    <sup>
                        <xref ref-type="bibr" rid="ref39">39</xref>
                    </sup> During the task, participants respond by pressing a button when certain visual stimuli appear (Go trials) and withhold their response to other stimuli (No-Go trials), measuring their response inhibition. However, response inhibition can be difficult if No-Go trials are relatively rare, as Go responses become prepotent, meaning the system is biased to produce them. To ensure that inhibitory control is necessary, No-Go trials should make up less than 20% of the trials and each trial&#x2019;s duration should be shorter than 1,500 ms.
                    <sup>
                        <xref ref-type="bibr" rid="ref40">40</xref>
                    </sup> To interpret data from the Go/No-Go task, precision and reaction time are measured, performance is compared with established norms, and errors of commission and omission are analyzed. Examining these factors provides insight into the participant&#x2019;s response inhibition and determines whether their performance falls within the expected range.
                    <sup>
                        <xref ref-type="bibr" rid="ref40">40</xref>
                    </sup>
                </p>
            </sec>
            <sec id="sec17">
                <title>The Montreal Cognitive Assessment</title>
                <p>The MoCA is a cognitive screening tool designed to detect Mild Cognitive Impairment (MCI) in the early stages of various neurodegenerative disorders.
                    <sup>
                        <xref ref-type="bibr" rid="ref41">41</xref>
                    </sup> It is a 10-minute test that is more sensitive than other commonly used screening tools, such as the Mini-Mental State Examination, making it a reliable and valid tool for detecting MCI in clinical settings.
                    <sup>
                        <xref ref-type="bibr" rid="ref42">42</xref>
                    </sup>
                </p>
                <p>The MoCA is composed of 30 questions that assess various cognitive domains, including orientation, executive functioning, memory, language, and visuospatial abilities.
                    <sup>
                        <xref ref-type="bibr" rid="ref33">33</xref>
                    </sup> We used for this study the Arabic version. The tasks in the MoCA include naming objects, memorizing a short list of words, drawing a clock face, and performing serial subtraction tasks. Scores on the MoCA range from 0 to 30, with a cut-off point of 26, where a score of 26 or higher is generally considered normal.
                    <sup>
                        <xref ref-type="bibr" rid="ref33">33</xref>
                    </sup>
                </p>
            </sec>
            <sec id="sec18">
                <title>The profile of mood state</title>
                <p>The measurement of mood can be obtained using a valid, reliable, and sensitive self-report questionnaire called the POMS,
                    <sup>
                        <xref ref-type="bibr" rid="ref43">43</xref>
                    </sup> which consists of 58 items (i.e., words or sentences) and can provide valuable information about adolescents&#x2019; emotional states.
                    <sup>
                        <xref ref-type="bibr" rid="ref44">44</xref>
                    </sup> We used the POMS Arabic version.
                    <sup>
                        <xref ref-type="bibr" rid="ref45">45</xref>
                    </sup> The POMS is a self-report assessment tool that measures six dimensions of mood: Tension-anxiety, anger-hostility, vigor-activity, fatigue-inertia, depression-dejection and confusion-bewilderment.</p>
                <p>The POMS is a 65-item questionnaire that is scored on a 5-point scale (0 = not at all to 4 = extremely).
                    <sup>
                        <xref ref-type="bibr" rid="ref46">46</xref>
                    </sup> It takes about 10-15 minutes to complete.</p>
            </sec>
            <sec id="sec19">
                <title>The Physical Activity Enjoyment Scale (PACES)</title>
                <p>The PACES is a reliable, valid and sensitive measure of PA enjoyment across populations.
                    <sup>
                        <xref ref-type="bibr" rid="ref47">47</xref>
                    </sup>
                    <sup>,</sup>
                    <sup>
                        <xref ref-type="bibr" rid="ref48">48</xref>
                    </sup> The Arabic version of the PACES, which has been reported to be a reliable and valid measure of enjoyment of PA in Arabic-speaking populations, was applied.
                    <sup>
                        <xref ref-type="bibr" rid="ref49">49</xref>
                    </sup> The PACES consists of 18 items that are rated on a 7-point Likert scale, from 1 (I don&#x2019;t enjoy it at all) to 7 (I enjoy it very much). The total score of the PACES ranges from 18 to 126, with higher scores indicating greater enjoyment of PA.</p>
            </sec>
            <sec id="sec20">
                <title>The Modified Ashworth Scale (MAS)</title>
                <p>The MAS assesses spasticity by measuring resistance to passive joint movement in patients with neurological disorders.
                    <sup>
                        <xref ref-type="bibr" rid="ref32">32</xref>
                    </sup> The scale assigns scores from 0 to 5 based on the degree of increased muscle tone, ranging from no increase (0) to severe increase (4). To conduct the assessment, patients are placed in a supine position, and for muscles primarily involved in flexion, the joint is moved from maximal flexion to maximal extension over one second, while muscles primarily involved in extension are moved from maximal extension to maximal flexion over one second. The investigator records the level of resistance encountered during the movement to determine the corresponding score: 0 for no resistance, 1 for minimal resistance at the end range, 1+ for a catch followed by less resistance over half the range, 2 for rigidity over more than half the range, and 3 for considerable resistance over most of the range. In this study, we have utilized the 0 to 5 version of the MAS
                    <sup>
                        <xref ref-type="bibr" rid="ref50">50</xref>
                    </sup> to measure spasticity. The latter version enables numerical quantification of spasticity severity. During the assessment, the participants were placed in a supine position, and the investigators slowly flexed and extended each joint over one second, recording the amount of resistance encountered on the scale from 0 to 5.</p>
            </sec>
            <sec id="sec21">
                <title>Sample size and statistical analysis</title>
                <p>A priori power analysis was conducted using G*Power3
                    <sup>
                        <xref ref-type="bibr" rid="ref51">51</xref>
                    </sup> with the alpha level set at 0.05 and a power of 0.80, which concluded that the sample size to find significance should be 14 patients.</p>
                <p>Values were presented as the mean &#x00b1; standard deviation (SD). Cohen&#x2019;s effect sizes (d) were classified as small (0.20), moderate (0.50), and large (0.80).
                    <sup>
                        <xref ref-type="bibr" rid="ref52">52</xref>
                    </sup> A 2 &#x00d7; 2 repeated-measures analysis of variance (ANOVA) was used to assess differences in, and between experimental trials. The two independent variables were exercise type and time. The two levels of the first independent variable (exercise type) were TE and VRE conditions. The two levels of the second independent variable (time) were pre and post-training.</p>
                <p>Statistical analyses were performed using the 
                    <ext-link ext-link-type="uri" xlink:href="https://www.ibm.com/products/spss-statistics">IBM SPSS</ext-link> version 26 (IBM SPSS, Chicago, IL, USA). Alpha level was set at p&lt;0.05.</p>
            </sec>
        </sec>
        <sec id="sec22" sec-type="results">
            <title>Results</title>
            <p>Among the initial 20 patients, only 14 were included in the final sample (7 in each group) 
                <bold>(</bold>
                <xref ref-type="fig" rid="f2">Figure 2</xref>).
                <sup>
                    <xref ref-type="bibr" rid="ref61">61</xref>
                </sup>
            </p>
            <fig fig-type="figure" id="f2" orientation="portrait" position="float">
                <label>Figure 2. </label>
                <caption>
                    <title>CONSORT flowchart of the recruitment process of participants into the trial.</title>
                    <p>n: number. TE: Traditional exercise. VRE: Virtual Reality Exercise.</p>
                </caption>
                <graphic id="gr2" orientation="portrait" position="float" xlink:href="https://f1000research-files.f1000.com/manuscripts/156823/fee6fa94-9375-4067-8658-c13821d6d595_figure2.gif"/>
            </fig>
            <p>
                <xref ref-type="table" rid="T1">Table 1</xref> exposes the demographic characteristics of the 14 patients.</p>
            <table-wrap id="T1" orientation="portrait" position="float">
                <label>Table 1. </label>
                <caption>
                    <title>Demographic characteristics of participants (n=14).</title>
                </caption>
                <table content-type="article-table" frame="hsides">
                    <thead>
                        <tr>
                            <th align="left" colspan="1" rowspan="1" valign="top">Data</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Unit/category</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Number or mean&#x00b1;Standard deviation</th>
                        </tr>
                    </thead>
                    <tbody>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Sex</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Boys/Girls</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">8/6</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Traditional exercise/Virtual reality exercise</td>
                            <td colspan="1" rowspan="1"/>
                            <td align="left" colspan="1" rowspan="1" valign="top">14/14</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Age</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">Year</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">15.6&#x00b1;0.7</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Height</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">cm</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">1.68&#x00b1; 0.11</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Weight</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">kg</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">49.7&#x00b1;7.6</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Body mass index</td>
                            <td align="left" colspan="1" rowspan="1" valign="top">kg/m
                                <sup>2</sup>
                            </td>
                            <td align="left" colspan="1" rowspan="1" valign="top">18.7&#x00b1;3.3</td>
                        </tr>
                    </tbody>
                </table>
            </table-wrap>
            <p>
                <xref ref-type="table" rid="T2">Table 2</xref> exposes the comparison of pre- and post-training scores for attention, memory, total score, vigor, decision making correct and decision making errors in both the TE and VRE training conditions.</p>
            <table-wrap id="T2" orientation="portrait" position="float">
                <label>Table 2. </label>
                <caption>
                    <title>Comparison of pre- and post-training scores for attention, memory, total score, vigor, decision making correct and decision making errors in both the traditional exercise (TE) and virtual reality exercise (VRE) training conditions (n=14).</title>
                </caption>
                <table content-type="article-table" frame="hsides">
                    <thead>
                        <tr>
                            <th align="left" colspan="1" rowspan="2" valign="top">Data</th>
                            <th align="left" colspan="2" rowspan="1" valign="top">TE</th>
                            <th align="left" colspan="2" rowspan="1" valign="top">VRE</th>
                            <th align="left" colspan="3" rowspan="1" valign="top">Statistical values ANOVA</th>
                        </tr>
                        <tr>
                            <th align="left" colspan="1" rowspan="1" valign="top">Pre-training</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Post-training</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Pre-training</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">Post-training</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">F(1,13)</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">P-value</th>
                            <th align="left" colspan="1" rowspan="1" valign="top">ES</th>
                        </tr>
                    </thead>
                    <tbody>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Attention</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">1.93&#x00b1;0.62</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">3.64&#x00b1;1.15</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">1.93&#x00b1;0.62</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">4.21&#x00b1;1.25</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">6.30</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">0.026</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">0.487</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Memory</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">2.36&#x00b1;0.93</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">4.14&#x00b1;0.66</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">2.36&#x00b1;0.93</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">3.86&#x00b1;0.86</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">3.06</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">0.104</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">- 0.231</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Total Score</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">19.29&#x00b1;2.34</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">23.07&#x00b1;2.84</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">19.29&#x00b1;2.34</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">23.79&#x00b1;2.55</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">19.28</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">0.001</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">0.188</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Vigor</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">14.71&#x00b1;3.90</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">14.43&#x00b1;7.50</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">14.71&#x00b1;3.99</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">18.14&#x00b1;2.25</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">2.58</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">0.133</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">1.267</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Decision-making correct</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">286.43&#x00b1;21.16</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">282.07&#x00b1;19.92</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">290.14&#x00b1;16.41</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">299.64&#x00b1;11.49</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">26.34</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">0.01</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">0.905</td>
                        </tr>
                        <tr>
                            <td align="left" colspan="1" rowspan="1" valign="top">Decision-making errors</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">33.57&#x00b1;21.156</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">37.29&#x00b1;20.30</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">29.86&#x00b1;16.41</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">21.07&#x00b1;13.59</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">28.20</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">0.001</td>
                            <td align="left" colspan="1" rowspan="1" valign="middle">-0.948</td>
                        </tr>
                    </tbody>
                </table>
                <table-wrap-foot>
                    <p>Data were mean&#x00b1;standard deviation. 
                        <bold>ES</bold>: Effect size (Cohen&#x2019;s d).</p>
                </table-wrap-foot>
            </table-wrap>
            <sec id="sec23">
                <title>Attention</title>
                <p>There was a significant main effect of exercise type on patients&#x2019; attention (
                    <italic toggle="yes">F</italic> (1,13) = 6.30, 
                    <italic toggle="yes">p</italic> = 0.026, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.327). Patients&#x2019; mean response attention was higher in VRE (SD = 1.25137) compared to TE (SD= 1.15073). This difference was a significant main effect of time F (1.13) = 97.066, p = 0.001, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.882). Patients&#x2019; mean response attention was higher at post-training (SD = 0.615) compared to pre-training (SD = 1.251). There was a statistically significant interaction between exercise type and time (F (1.13) = 6.30, 
                    <italic toggle="yes">p</italic> = 0.026, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.327).</p>
            </sec>
            <sec id="sec24">
                <title>Memory</title>
                <p>There was a significant main effect of exercise type on patients&#x2019; memory (
                    <italic toggle="yes">F</italic> (1.13) = 3.059, 
                    <italic toggle="yes">p</italic> = 0.104, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.190). Patients&#x2019; mean response memory were higher in TE (SD= 0.662) compared to VRE (SD = 0.864). This difference was a significant main effect of time F (1.13) = 180.974, p = 0.001, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.933). Patients&#x2019; mean response memory were higher at pre-training (SD = 0.928) compared to post-training (SD = 0.864). There was a statistically significant interaction between exercise type and time F (1.13) = 3.59, 
                    <italic toggle="yes">p</italic> = 0.104, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.190).</p>
            </sec>
            <sec id="sec25">
                <title>Total score</title>
                <p>There was a significant main effect of exercise type on patients&#x2019; total scores (
                    <italic toggle="yes">F</italic> (1.13) = 19.118, 
                    <italic toggle="yes">p</italic> = 0.001, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.595). Patients&#x2019; mean response total score were higher in VRE (SD = 2.547) compared to TE (SD = 2.841). This difference was a significant main effect of time F (1.13) = 80.686, p = 0.001, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.861). Descriptive statistics revealed that patients&#x2019; mean response attention was higher post-training (SD = 2.547) compared to pre-training (SD= 2.334). There was a statistically significant interaction between exercise type and time F (1.13) = 19.118, 
                    <italic toggle="yes">p</italic> = 0.001, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.595).</p>
            </sec>
            <sec id="sec26">
                <title>Vigor</title>
                <p>There was a significant main effect of exercise type on patients&#x2019; vigor (
                    <italic toggle="yes">F</italic> (1.13) = 2.576, 
                    <italic toggle="yes">p</italic> = 0.133, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.165). Patients&#x2019; mean response vigor were higher in VRE (SD =2.248) compared to TE (SD= 7.500). This difference was a significant main effect of time F (1.13) = 1.320, p = 0.271, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.092). Descriptive statistics revealed that patients&#x2019; mean response vigor were higher at post-training (SD = 2.248) compared to pre-training (SD = 3.989). There was a statistically significant interaction between exercise type and time F (1,13) = 2.576, 
                    <italic toggle="yes">p</italic> = 0.133, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.165).</p>
            </sec>
            <sec id="sec27">
                <title>Decision-making correct</title>
                <p>There was a significant main effect of exercise type on patients&#x2019; decision-making (
                    <italic toggle="yes">F</italic> (1.13) = 26.338, 
                    <italic toggle="yes">p</italic> = 0.01, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.670). Patients&#x2019; mean response decision making correct were higher in VRE (SD = 11.486) compared to TE (SD = 19.917). This difference was a significant main effect of time F (1,13) = 3.833, p = 0.72, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.228). Patients&#x2019; mean response attention were higher at post-training (SD = 11.48649) compared to pre-training (SD = 19.91700). There was a statistically significant interaction between exercise type and time F (1,13) = 27.611, 
                    <italic toggle="yes">p</italic> = 0.001, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.680).</p>
            </sec>
            <sec id="sec28">
                <title>Decision-making errors</title>
                <p>There was a significant main effect of exercise type on patients&#x2019; decision-making errors 
                    <italic toggle="yes">F</italic> (1,13) = 28.202, 
                    <italic toggle="yes">p</italic> = 0.001, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.684). Patients&#x2019; mean response decision-making errors were higher in TE (SD= 20.299) compared to VRE (SD = 13.589). This difference was a significant main effect of time F (1,13) = 5.350, p = 0.038, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.292). Patients&#x2019; mean response decision-making errors were higher at pre-training (SD= 21.15770) than post-training (SD= 13.58995). There was a statistically significant interaction between exercise type and time F (1,13) = 27.045, 
                    <italic toggle="yes">p</italic> = 0.001, 
                    <italic toggle="yes">&#x03b7;p</italic>
                    <sup>2</sup> = 0.675).</p>
            </sec>
            <sec id="sec29">
                <title>MAS</title>
                <p>
                    <xref ref-type="table" rid="T3">Table 3</xref> exposes the comparison of pre- and post- training scores for spasticity in both the TE and VRE training condition. Both TE and VRE interventions effectively reduced spasticity levels in various lower body regions. Notably, the VRE group exhibited more substantial improvements, with a 5.61 reduction in spasticity for the lower body (ankle + knee) compared to TE&#x2019;s 3.28. In the ankle region, VRE resulted in a significant 2.29 reduction in spasticity, while TE achieved a reduction of 1.43.</p>
                <table-wrap id="T3" orientation="portrait" position="float">
                    <label>Table 3. </label>
                    <caption>
                        <title>Comparison of pre- and post-training scores for spasticity in both the traditional exercise (TE) and virtual reality exercise (VRE) training conditions (n=14).</title>
                    </caption>
                    <table content-type="article-table" frame="hsides">
                        <thead>
                            <tr>
                                <th align="left" colspan="1" rowspan="2" valign="top"/>
                                <th align="left" colspan="4" rowspan="1" valign="top">TE</th>
                                <th align="left" colspan="4" rowspan="1" valign="top">VRE</th>
                                <th align="left" colspan="1" rowspan="2" valign="top">ES</th>
                            </tr>
                            <tr>
                                <th align="left" colspan="1" rowspan="1" valign="top">Pre-training</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Post-training</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">&#x0394; [95%CI]</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">&#x0394; (%)</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Pre-training</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">Post-training</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">&#x0394; [95%CI]</th>
                                <th align="left" colspan="1" rowspan="1" valign="top">&#x0394; (%)</th>
                            </tr>
                        </thead>
                        <tbody>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Lower body (Ankle + Knee)</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">19.57+7.74</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">16.29+6.05</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">-3.28 [2.87, 3.69]</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">-16.74%</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">18.36+7</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">14.14+5.68</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">-5.61 [5.61, 4.11]</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">-25.79%</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">1.43</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Ankle</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">8.79&#x00b1;2.74</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">6.5&#x00b1;1.95</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">-2.29 [1.59, 2.99]</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&#x2212;26.01%</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">7.14&#x00b1;2.39</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">5.71&#x00b1;2.08</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">-1.43 [1.37, 1.49]</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">20.00%</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">1.86</td>
                            </tr>
                            <tr>
                                <td align="left" colspan="1" rowspan="1" valign="top">Knee</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">12.00&#x00b1;1.23</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">8.07&#x00b1;3.44</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">-5.74 [-13.33, 1.62]</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">&#x2212;32.75%</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">11.21&#x00b1;5.29</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">7.86&#x00b1;3.88</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">-3.85 [2.73, 4.97]</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">-29.87%</td>
                                <td align="left" colspan="1" rowspan="1" valign="top">4.79</td>
                            </tr>
                        </tbody>
                    </table>
                    <table-wrap-foot>
                        <p>Data were mean&#x00b1;standard deviation. 
                            <bold>&#x0394;</bold>: Post-training minus Pre-training. 
                            <bold>&#x0394; (%)</bold>: 
                            <bold>&#x0394;</bold>/Pre-training. 
                            <bold>ES</bold>: Effect size (Cohen&#x2019;s d).</p>
                    </table-wrap-foot>
                </table-wrap>
            </sec>
        </sec>
        <sec id="sec30" sec-type="discussion">
            <title>Discussion</title>
            <p>The present study aimed to investigate the effectiveness of VRE in improving the psychophysiological outcomes of college-aged patients with CP. Our RCT demonstrated that VRE had a significant positive impact on attention, as indicated by higher scores when compared to TE. Furthermore, VRE yielded slightly higher scores in increasing patients&#x2019; vigor than TE. In terms of decision-making, a significant main effect of exercise type was observed, with VRE leading to higher scores than TE. However, it is worth noting that TE resulted in higher memory scores than VRE.</p>
            <p>We found that VRE immediately following PA might have a more favorable impact on attention compared to TE. This finding is in line with prior research demonstrating the ability of VR to enhance cognitive function, particularly attention, and cognitive training&#x2019;s potential to improve daily activities.
                <sup>
                    <xref ref-type="bibr" rid="ref53">53</xref>
                </sup> Additionally, this aligns with Neumann 
                <italic toggle="yes">et al</italic>.
                <sup>
                    <xref ref-type="bibr" rid="ref54">54</xref>
                </sup> discovery that VR may not always be the optimal approach for diverting attention from exercise-related cues, emphasizing the importance of attentional mechanisms in shaping emotional and motivational responses to exercise in a VR environment. By directing attention towards the virtual environment, VR systems can increase the likelihood of positive impact and satisfaction, underscoring the crucial role of attentional mechanisms in shaping emotional and motivational responses during VRE. According to a 2020 research, VR environments can be customized to simulate real-life situations that require specific cognitive abilities, such as memory, decision-making, and problem-solving.
                <sup>
                    <xref ref-type="bibr" rid="ref53">53</xref>
                </sup> Our study investigated the acute effects of VRE on memory and compared it to TE. Our findings reveal a significant difference in memory scores between pre- and post- training, suggesting that time has a considerable impact on patients&#x2019; memory. Interestingly, the memory scores varied significantly between the TE and VRE conditions, with patients&#x2019; mean response memory being higher for TE than VRE. However, the interaction between exercise type and time was not significant, indicating that the impact of exercise type on memory did not depend on whether the memory was measured before or after the exercise. Our results differ from previous research on memory in elderly stroke survivors, which suggests that training environments can be customized to improve cognitive abilities, including memory, that influence daily activities.
                <sup>
                    <xref ref-type="bibr" rid="ref53">53</xref>
                </sup> Additionally, the study&#x2019;s results highlight the potential benefits of immersive VR in facilitating the transfer of learned abilities from the virtual world to the real world. While some studies suggest that VRE may not be as effective as TE in enhancing memory, other studies have identified that VRE can be helpful in reducing memory decline in older adults.
                <sup>
                    <xref ref-type="bibr" rid="ref55">55</xref>
                </sup> Further research is necessary to confirm these findings and identify the potential advantages of exercise for memory enhancement. Therefore, the potential benefits of VRE for memory enhancement warrant further investigation.</p>
            <p>There is evidence to suggest that there is a link between attention, memory, and vigor after immediate exercise. We report a significant main effect of exercise type on vigor, with patients reporting higher levels of vigor after VRE compared to TE. Moreover, there was a significant main effect of time on patients&#x2019; vigor, with higher levels of vigor reported after the exercise compared to before the exercise. However, there was no significant interaction between exercise type and time on patients&#x2019; vigor. Our findings are consistent with previous research indicating that acute exercise can enhance feelings of vigor in the short term.
                <sup>
                    <xref ref-type="bibr" rid="ref27">27</xref>
                </sup> However, our results did not align with the findings of Adhyaru 
                <italic toggle="yes">et al</italic>.,
                <sup>
                    <xref ref-type="bibr" rid="ref56">56</xref>
                </sup> who reported no significant difference in vigor between VRE and TE.</p>
            <p>We identified a significant main effect of exercise type on patients&#x2019; decision-making, with higher scores observed in VRE compared to TE, suggesting that VRE may enhance decision-making abilities. However, no significant main effect of time on decision-making scores was found, indicating that the effect of exercise on decision-making did not differ significantly between pre- and post- exercise measures. Our finding diverges from previous studies that reported improvements in decision-making following acute exercise, such as Ulas 
                <italic toggle="yes">et al</italic>.
                <sup>
                    <xref ref-type="bibr" rid="ref57">57</xref>
                </sup> study that found a single bout of moderate-intensity exercise improved decision-making performance in healthy adults. Our result is consistent with Shaw 
                <italic toggle="yes">et al</italic>.
                <sup>
                    <xref ref-type="bibr" rid="ref58">58</xref>
                </sup> study, which reported that the use of a competitive virtual trainer while riding at a moderate-vigorous intensity did not improve cognitive performance. Conversely, our findings align with those of Ertoy Karagol 
                <italic toggle="yes">et al</italic>.
                <sup>
                    <xref ref-type="bibr" rid="ref59">59</xref>
                </sup> who reported that VRE led to a significant improvement in vigor compared to the control group, as well as a significant increase in PA compared to the control group. These results suggest that VRE may be an effective intervention for improving vigor and PA in adolescents.</p>
            <p>Furthermore, the interaction effect between exercise type and time indicated that the style of exercise and the measurement time had different effects on decision-making abilities. Thus, further investigation, such as post-hoc tests, is necessary to identify conditions that significantly varied from one another.</p>
            <p>Our study identified significant differences in decision-making errors based on exercise type and time, indicating both have an impact. Patients made more errors during TE vs. VRE, suggesting VR provides greater cognitive benefits for decision-making. Moreover, patients made fewer errors post-training, showing exercise overall reduces decision-making errors. The significant interaction between exercise type and time demonstrated the effect of exercise on errors differed pre- and post- exercise. Benefits of VRE on errors seemed more pronounced post-training, while benefits of TE were less evident. Overall, these findings suggest that VRE may be more beneficial than TE for improving decision-making accuracy and that the effects of exercise on decision-making may vary depending on the type of exercise and timing of assessment. Our findings that VRE may be more advantageous than normal exercise for enhancing decision-making accuracy is supported previous study.
                <sup>
                    <xref ref-type="bibr" rid="ref60">60</xref>
                </sup> Mestre 
                <italic toggle="yes">et al</italic>.
                <sup>
                    <xref ref-type="bibr" rid="ref60">60</xref>
                </sup> compared indoor cycling exercise with VR feedback vs. non-VR feedback and highlighted that cycling exercise with VR feedback had a reduced perceived exertion and an increased level of enjoyment of PA. This finding unequivocally demonstrates the beneficial effects of VR feedback and a virtual coach on the enjoyment of PA, with the virtual coach showing the greatest gains.
                <sup>
                    <xref ref-type="bibr" rid="ref60">60</xref>
                </sup>
            </p>
            <p>Our results indicate that VRE with bike has the potential to acutely reduce muscle spasticity. VRE with bike provide visual and auditory stimulation in addition to cycling, which may distract users and draw attention away from muscle sensations.
                <sup>
                    <xref ref-type="bibr" rid="ref30">30</xref>
                </sup> In turn, this reduction in sensory input could decrease muscle spasms and contractions, resulting in temporary relief from spasticity.
                <sup>
                    <xref ref-type="bibr" rid="ref56">56</xref>
                </sup> The immediate effects observed after using the VRE bike
                <sup>
                    <xref ref-type="bibr" rid="ref30">30</xref>
                </sup> suggest an acute impact on spasticity. However, longer-term investigations are needed to determine whether regular use of VRE with bike can yield sustained benefits for reducing spasticity.
                <sup>
                    <xref ref-type="bibr" rid="ref30">30</xref>
                </sup>
            </p>
            <p>These results emphasize the potential advantages of incorporating VRE as a promising intervention, with larger effect sizes, to enhance the physical well-being and motor skills of individuals with CP in this demographic.</p>
            <sec id="sec31">
                <title>Limitations</title>
                <p>Some potential limitations must be considered. The major limitation concerns the retrospective registration of our RCT. The main reason of the retrospective registration is the lack of experience of the first author (MS in the authors&#x2019; list). During the study execution, when he asked help from senior authors, they recommended to register the study. Since the primary purpose of trial registration is to enhance transparency, reduce bias, and promote the integrity of clinical research, a retrospective registration of an RCT can pose some challenges and may be viewed with skepticism by journal editors, peer reviewers, and readers. When an RCT is registered retrospectively, it can raise concerns about selective reporting, outcome switching, and potential bias. However, we have registered our RCT in the aim to be transparent about the timeline of the study. The registration was done as soon as possible just before the end of the trial. We have included the full study protocol with detailed information on the study design, primary and secondary outcomes, and statistical analysis plan. This demonstrate that our study was conducted in a rigorous and pre-planned manner. We confirm that our study adheres to ethical guidelines and that the retrospective registration does not compromise the ethical conduct of the trial. We have explicitly discussed how we have mitigated the risk of bias in our study, by addressing concerns related to selective outcome reporting and data-driven decisions. We attest that there was no modifications to the study design or analysis plan after data collection. Second, the study&#x2019;s short duration precludes conclusions about prolonged effects. Third, the small sample size may limit generalizability. Finally, potential confounding factors such as patients&#x2019; exercise history and spasticity severity were not considered. Despite these limitations, our study has enhanced our understanding of the relationship between TEs and virtual one for adolescents with CP. We think that our findings will stimulate further investigation of this important area.</p>
            </sec>
            <sec id="sec32">
                <title>Implications and futures directions</title>
                <p>For adolescents with CP, VRE bike games using VirZoom&#x2019;s VZfit appear to be a fun, effective alternative to boost adherence and consequently enhance mood. Future studies should be conducted in this regard to investigate additional topics related to VRE bike games for children, including assessing those with CP using objective measures to determine how long the virtual headset workouts last; assessing the interactions between individual and group activities; and determining the long-term effects of the activities performed both in the lab and at home.</p>
            </sec>
        </sec>
        <sec id="sec33" sec-type="conclusions">
            <title>Conclusions</title>
            <p>VRE can help improve attention, vigor, and decision-making in college students with CP more than TE. However, TE may be more beneficial for enhancing memory scores. Future research with larger samples is needed to validate our findings and identify the mechanisms driving differences in cognitive outcomes between VR and TE. Overall, both types of exercise show potential for improving mental performance and wellbeing.</p>
        </sec>
    </body>
    <back>
        <sec id="sec36" sec-type="data-availability">
            <title>Data availability</title>
            <sec id="sec37">
                <title>Underlying data</title>
                <p>Zenodo: Data of 14 participants in the RCT titled Acute effects of virtual reality exercise bike games on psycho-physiological outcomes in college North-African adolescents with cerebral palsy. 
                    <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5281/zenodo.10201736">https://doi.org/10.5281/zenodo.10201736</ext-link>.
                    <sup>

                        <xref ref-type="bibr" rid="ref61">61</xref>
</sup>
                </p>
            </sec>
            <sec id="sec38">
                <title>Reporting guidelines</title>
                <p>Zenodo: CONSORT checklist for: Acute effects of virtual reality exercise bike games on psycho-physiological outcomes in college North-African adolescents with cerebral palsy: A randomized Clinical trial. 
                    <ext-link ext-link-type="uri" xlink:href="https://doi.org/10.5281/zenodo.10157607">https://doi.org/10.5281/zenodo.10157607</ext-link>.
                    <sup>

                        <xref ref-type="bibr" rid="ref62">62</xref>
</sup>
                </p>
                <p>Data are available under the terms of the 
                    <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution 4.0 International license</ext-link> (CC-BY 4.0).</p>
            </sec>
        </sec>
        <ack>
            <title>Acknowledgements</title>
            <p>The authors would like to thank the adolescents and their parents. Open Access funding provided by Qatar National Library.</p>
        </ack>
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                    <article-title>Competition and cooperation with virtual players in an exergame.</article-title>
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                        <italic toggle="yes">PeerJ. Comput. Sci.</italic>
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                    <year>2016</year>;<volume>2</volume>:<fpage>e92</fpage>.
                    <pub-id pub-id-type="doi">10.7717/peerj-cs.92</pub-id>
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                        <italic toggle="yes">J. Asthma Allergy.</italic>
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                    <year>2021 Mar 29</year>;<volume>14</volume>:<fpage>293</fpage>&#x2013;<lpage>299</lpage>.
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                    <data-title>Data of 14 participants in the RCT titled Acute effects of virtual reality exercise bike games on psycho-physiological outcomes in college North-African adolescents with cerebral palsy.</data-title>[Dataset].
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    <sub-article article-type="reviewer-report" id="report237583">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.156823.r237583</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Chiu</surname>
                        <given-names>Hsiu-Ching</given-names>
                    </name>
                    <xref ref-type="aff" rid="r237583a1">1</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0002-3408-2222</uri>
                </contrib>
                <aff id="r237583a1">
                    <label>1</label>I-Shou University, Kaohsiung, Taiwan</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>30</day>
                <month>5</month>
                <year>2024</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2024 Chiu HC</copyright-statement>
                <copyright-year>2024</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport237583" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.143189.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>
                <bold>General comments </bold>
            </p>
            <p> The topic under investigation is interesting, but there are some fundamental problems, such as the design of intervention. Furthermore, authors should improve the format of the presentation, suggesting having an example of published RCT paper to follow.</p>
            <p> </p>
            <p> 
                <bold>Abstract.</bold>
            </p>
            <p> Not clear because of no information about the intervention such as weeks.</p>
            <p> </p>
            <p> 
                <bold>Introduction-content</bold>
            </p>
            <p> Not read because method is very confusing.</p>
            <p> </p>
            <p> 
                <bold>Methods: </bold>
                <bold>general</bold>
            </p>
            <p> -Ethics considerations have been already mentioned in the design, so it would be unnecessary to repeat.</p>
            <p> -Randomization should be part of design, not separate paragraph.</p>
            <p> </p>
            <p> 
                <bold>Methods: </bold>
                <bold>design</bold>
            </p>
            <p> Even this study has been registered, authors still need to provide information about design, such as training and outcomes etc.</p>
            <p> </p>
            <p> 
                <bold>Methods: </bold>
                <bold>Figure 1</bold>
            </p>
            <p> Authors should show how many weeks of intervention as well as a brief content for both groups.</p>
            <p> </p>
            <p> 
                <bold>Methods: </bold>
                <bold>participants</bold>
            </p>
            <p> -should use &#x201c;Participants&#x201d; to replace &#x201c;Patients&#x201d;.</p>
            <p> -Actual number of participants and characteristics should be in the results.</p>
            <p> </p>
            <p> Methods: Intervention</p>
            <p> This is main problem because it&#x2019;s hard to believe it will be effective for only 2 times training.</p>
            <p> </p>
            <p> 
                <bold>Results: </bold>
                <bold>Table 1 (missing). Characteristic of participants</bold>
            </p>
            <p> 
                <bold>Results: </bold>
                <bold>Table 2 (missing).Differences between groups in all Outcomes across times</bold>
            </p>
            <p> </p>
            <p> 
                <bold>Discussion and conclusion:</bold>
            </p>
            <p> Not read because method and results are very unstructured.</p>
            <p> </p>
            <p> 
                <bold>Readability and style.</bold>
            </p>
            <p> This paper is not easy to read, because of unstructured and the fluency of English. For example, &#x201c;&#x2026;.in adolescents with CP in North African college&#x2026;.&#x201d; Not &#x201c;In North African college adolescents with CP&#x201d;. Another example, it may be clearer as &#x201c;The Experimental group undertook xx &#x2026;times a week for xx week&#x2026;.&#x201d; Not &#x201c; Patients underwent two&#x2026;&#x201d; in the method.</p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>No</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>I cannot comment. A qualified statistician is required.</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>No</p>
            <p>Is the study design appropriate and is the work technically sound?</p>
            <p>No</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>No</p>
            <p>Are sufficient details of methods and analysis provided to allow replication by others?</p>
            <p>No</p>
            <p>Reviewer Expertise:</p>
            <p>My past research program was in understanding the relative contribution of motor impairments to activity limitation and participation in people with hemiplegic cerebral palsy (CP). I have finished one Cochrane review entitled as &#x201c;Mechanically assisted walking training for walking, participation, and quality of life in children with cerebral palsy&#x201d; for children with CP by examining outcomes across all domains of the International Classification of Functioning, Disability and Health (ICF).</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment12676-237583">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>Ghram</surname>
                            <given-names>Amine</given-names>
                        </name>
                        <aff>Cardiac rehabilitation, Hamad Medical Corporation, Doha, Doha, Qatar</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No competing interests</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>19</day>
                    <month>10</month>
                    <year>2024</year>
                </pub-date>
            </front-stub>
            <body>
                <p>
                    <bold>Reviewer Comment 1:</bold> 
                    <italic>The topic under investigation is interesting, but there are some fundamental problems, such as the design of intervention. Furthermore, authors should improve the format of the presentation, suggesting having an example of a published RCT paper to follow.</italic>
                </p>
                <p> 
                    <bold>Response:</bold>
                </p>
                <p> We appreciate your feedback regarding our manuscript. We recognize the necessity for a more precise intervention design and consulted well-structured randomized controlled trial (RCT) papers to enhance the format and presentation of our work. Furthermore, we meticulously revised the intervention description to ensure adherence to the standard RCT formats.</p>
                <p> 
                    <bold>Action Taken:</bold>
                </p>
                <p> The intervention section has been revised to adhere to a more structured format commonly used in published randomized controlled trials (RCTs). This revision encompasses a clear delineation of the study design, intervention details, and outcome measures to enhance the methodological clarity and rigor.</p>
                <p> 
                    <bold>Reviewer Comment 2:</bold> 
                    <italic>Abstract not clear because of no information about the intervention such as weeks.</italic>
                </p>
                <p> 
                    <bold>Response:</bold>
                </p>
                <p> We acknowledge your observation and have subsequently revised the abstract to incorporate specific details regarding intervention duration, thereby ensuring comprehensive information about the study's structure for readers.</p>
                <p> 
                    <bold>Action Taken:</bold>
                </p>
                <p> The abstract now incorporates the following information (Lines 30&#x2013;32): "
                    <bold>The intervention consisted of a single 40-minute session of virtual reality exercise (VRE) compared to traditional exercise (TE), conducted in a controlled laboratory environment</bold>
                    <bold>.</bold>" This addition provided essential details regarding the intervention and enhanced the comprehensiveness of the abstract.</p>
                <p> </p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 3:</bold> 
                    <italic>Introduction not read because method is very confusing.</italic>
                </p>
                <p> 
                    <bold>Response:</bold>
                </p>
                <p> We acknowledge the ambiguity engendered by the initial organization of the methods section. To rectify this issue, we have restructured both the Introduction and Methods sections to enhance the clarity and logical progression.</p>
                <p> 
                    <bold>Action Taken:</bold>
                </p>
                <p> The Introduction has been revised to ensure enhanced alignment with the study's methodology and objectives. Furthermore, the Methods section provides a comprehensive, sequential explanation of the intervention and study design, thereby minimizing potential ambiguities.</p>
                <p> 
                    <bold>Reviewer Comment 4:</bold> 
                    <italic>Method: - Ethics considerations have been already mentioned in the design, so it would be unnecessary to repeat. - Randomization should be part of design, not a separate paragraph.</italic>
                </p>
                <p> 
                    <bold>Response:</bold>
                </p>
                <p> We would like to acknowledge this recommendation. Redundant ethical considerations were eliminated, and the randomization process was integrated into the study design section to enhance the coherence of the presentation.</p>
                <p> 
                    <bold>Action Taken:</bold>
                </p>
                <p> The randomization protocol has been relocated to the design section (lines 175&#x2013;176), and superfluous ethical considerations have been eliminated to enhance conciseness and clarity.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 5:</bold> 
                    <italic>Method: Even this study has been registered, authors still need to provide information about design, such as training and outcomes, etc.</italic>
                </p>
                <p> 
                    <bold>Response:</bold>
                </p>
                <p> We acknowledge your observation and have provided supplementary information concerning the study design, encompassing training protocols and specific outcomes.</p>
                <p> 
                    <bold>Action Taken:</bold>
                </p>
                <p> The Methods section now delineates the training regimen, outcome measures, and data collection processes, thereby ensuring that the study design is fully transparent and adheres to RCT guidelines.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 6:</bold> 
                    <italic>Methods: Figure 1 - Authors should show how many weeks of intervention as well as a brief content for both groups.</italic>
                </p>
                <p> 
                    <bold>Response:</bold>
                </p>
                <p> Thank you for your suggestion. The intervention duration was clarified, and a concise description of the intervention for both groups was provided (Figure 1).</p>
                <p> 
                    <bold>Action Taken:</bold>
                </p>
                <p> Figure 1 demonstrates that the intervention was implemented as a single-session trial and a concise description of the intervention protocols for both groups was provided.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 7:</bold> 
                    <italic>Methods: participants - Should use &#x201c;Participants&#x201d; to replace &#x201c;Patients&#x201d;. - Actual number of participants and characteristics should be in the results.</italic>
                </p>
                <p> 
                    <bold>Response:</bold>
                </p>
                <p> We agree with the reviewer's recommendations. The term "participants" has been substituted for "patients" throughout the manuscript, and the precise number of participants, along with their demographic characteristics, has been moved to the Results section.</p>
                <p> 
                    <bold>Action Taken:</bold>
                </p>
                <p> The term "patients" has been replaced with "participants" throughout the manuscript, and the characteristics of participants have been incorporated into the results section (Lines 301, Table 1).</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 8:</bold> 
                    <italic>Methods: Intervention - This is the main problem because it&#x2019;s hard to believe it will be effective for only two times training.</italic>
                </p>
                <p> 
                    <bold>Response:</bold>
                </p>
                <p> This study has several limitations. While the present investigation focused on the immediate effects of a single session, further studies are necessary to assess the long-term impact of repeated interventions. This limitation has been addressed in the Discussion section.</p>
                <p> 
                    <bold>Action Taken:</bold>
                </p>
                <p> This study acknowledges this limitation and suggests that future research should incorporate extended interventions to evaluate the cumulative effects of repeated VRE sessions.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 9:</bold> 
                    <italic>Results: Table 1 (missing). Characteristics of participants.</italic>
                </p>
                <p> 
                    <bold>Response:&#x00a0;</bold>We acknowledge your observation and have subsequently incorporated Table 1, which delineates the participants' characteristics including age, sex, and pertinent demographic data.</p>
                <p> 
                    <bold>Action Taken:&#x00a0;</bold>Table 1 has been incorporated into the Results section, presenting the characteristics of the study participants as requested.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 10:</bold> 
                    <italic>Results: Table 2 (missing). Differences between groups in all outcomes across times.</italic>
                </p>
                <p> 
                    <bold>Response:&#x00a0;</bold>Table 2 presents the differences between the groups across all outcome measures and time points.</p>
                <p> 
                    <bold>Action Taken:&#x00a0;</bold>Table 2 has been added to the Results section to show the differences in outcomes between the traditional exercise and VRE groups.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 11:</bold> 
                    <italic>The discussion and conclusion have not been read because the method and results are unstructured.</italic>
                </p>
                <p> 
                    <bold>Response:&#x00a0;</bold>The Methods and Results sections have been restructured to enhance the clarity and logical progression. The discussion has been aligned to provide a coherent narrative that establishes connections among the methods, results, and conclusions.</p>
                <p> 
                    <bold>Action Taken:&#x00a0;</bold>The Methods, Results, and Discussion sections were restructured to enhance clarity, thereby improving the accessibility and logical organization of the manuscript.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 12:</bold> 
                    <italic>This paper is not easy to read because of unstructured format and fluency of English.</italic>
                </p>
                <p> 
                    <bold>Response:&#x00a0;</bold>The authors acknowledge concerns regarding readability and fluency. The manuscript has undergone a comprehensive revision to enhance both the structure and fluency of the English language, thereby ensuring a more lucid and professional presentation.</p>
                <p> 
                    <bold>Action Taken:&#x00a0;</bold>The manuscript has undergone comprehensive revision to enhance clarity, grammatical accuracy, and overall fluency, thereby improving readability while maintaining scholarly rigor.</p>
                <p> Thank you for your valuable feedback. We believe that these revisions have significantly improved the clarity, structure, and scientific rigor of our manuscript. We look forward to your feedback, and hope that the revised manuscript meets your expectations.</p>
            </body>
        </sub-article>
    </sub-article>
    <sub-article article-type="reviewer-report" id="report248808">
        <front-stub>
            <article-id pub-id-type="doi">10.5256/f1000research.156823.r248808</article-id>
            <title-group>
                <article-title>Reviewer response for version 1</article-title>
            </title-group>
            <contrib-group>
                <contrib contrib-type="author">
                    <name>
                        <surname>Mahmood</surname>
                        <given-names>Qamar</given-names>
                    </name>
                    <xref ref-type="aff" rid="r248808a1">1</xref>
                    <xref ref-type="aff" rid="r248808a2">2</xref>
                    <xref ref-type="aff" rid="r248808a3">3</xref>
                    <role>Referee</role>
                    <uri content-type="orcid">https://orcid.org/0000-0001-5497-0537</uri>
                </contrib>
                <aff id="r248808a1">
                    <label>1</label>Ex-HOD, Physical Therapy Department, National Institute of Rehabilitation Medicine, Islamabad, Pakistan</aff>
                <aff id="r248808a2">
                    <label>2</label>Director, Physiotherapy Department, Institute of Medical Rehabilitation, Islamabad, Pakistan</aff>
                <aff id="r248808a3">
                    <label>3</label>Professor of Physical Therapy, FRAHS, Riphah International University, Islamabad, Pakistan</aff>
            </contrib-group>
            <author-notes>
                <fn fn-type="conflict">
                    <p>
                        <bold>Competing interests: </bold>No competing interests were disclosed.</p>
                </fn>
            </author-notes>
            <pub-date pub-type="epub">
                <day>29</day>
                <month>3</month>
                <year>2024</year>
            </pub-date>
            <permissions>
                <copyright-statement>Copyright: &#x00a9; 2024 Mahmood Q</copyright-statement>
                <copyright-year>2024</copyright-year>
                <license xlink:href="https://creativecommons.org/licenses/by/4.0/">
                    <license-p>This is an open access peer review report distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</license-p>
                </license>
            </permissions>
            <related-article ext-link-type="doi" id="relatedArticleReport248808" related-article-type="peer-reviewed-article" xlink:href="10.12688/f1000research.143189.1"/>
            <custom-meta-group>
                <custom-meta>
                    <meta-name>recommendation</meta-name>
                    <meta-value>approve-with-reservations</meta-value>
                </custom-meta>
            </custom-meta-group>
        </front-stub>
        <body>
            <p>This article investigated the immediate effects of virtual reality exercise (VRE) bike games on young adults in North Africa with cerebral palsy (CP).</p>
            <p> Its brief description is as under: 
                <list list-type="bullet">
                    <list-item>
                        <p>
                            <bold>Study Design:</bold>&#x00a0;Randomized controlled trial (considered a gold standard for clinical research)</p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Participants:</bold>&#x00a0;14 college students (average age 15.6) diagnosed with CP</p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Intervention:</bold>&#x00a0;Participants were divided into two groups. One group exercised using VR bike games for 40 minutes (VRE group), while the other group participated in traditional exercise (TE group) for the same duration.</p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Outcomes:</bold>&#x00a0;The study measured changes in attention, vigor (energy levels), and decision-making abilities after the exercise sessions.</p>
                    </list-item>
                    <list-item>
                        <p>
                            <bold>Key Findings:</bold>&#x00a0;Compared to traditional exercise, VR exercise led to significant improvements in attention and vigor.</p>
                    </list-item>
                </list> 
                <bold>Its Clinical Relevance:</bold>
            </p>
            <p> Cerebral palsy can impair both physical function and mental well-being. This study suggests VR exercise could be a valuable tool for improving cognitive function and motivation in young adults with CP. VR's engaging nature might make exercise more enjoyable and help individuals with CP adhere to exercise routines.</p>
            <p> However, it's important to note that the study only looked at short-term effects. More research is needed to confirm these findings and explore the long-term benefits of VR exercise for CP management.</p>
            <p> This article is well written, however following major and minor changes will improve its quality for publication.</p>
            <p> 
                <bold>Minor Changes needed:</bold> 
                <list list-type="bullet">
                    <list-item>
                        <p>
                            <bold>
                                <italic>
                                    <underline>In abstract section;</underline>
                                </italic>
                            </bold> Briefly mention the mixed findings on memory to provide a more balanced picture of the results.</p>
                    </list-item>
                </list> 
                <list list-type="bullet">
                    <list-item>
                        <p>
                            <bold>
                                <italic>
                                    <underline>In introduction section:</underline>
                                </italic>
                            </bold>
                            <italic>
                                <underline> </underline>
                            </italic>Emphasize the&#x00a0;
                            <italic>
                                <underline>novelty and significance</underline>
                            </italic>&#x00a0;of the present study. Instead of stating existing knowledge about the benefits of regular exercise, briefly mention the&#x00a0;
                            <italic>
                                <underline>limited research on the effects of acute exercise on cognitive function in adolescents with CP</underline>
                            </italic>, highlighting the gap your study aims to address.</p>
                    </list-item>
                    <list-item>
                        <p>Consider reorganizing the information flow. Start by highlighting the&#x00a0;
                            <italic>
                                <underline>gap in knowledge&#x00a0;</underline>
                            </italic>about acute exercise and cognitive function in adolescents with CP. Then, briefly mention the existing evidence of VR's effectiveness in promoting physical activity, leading to the introduction of the VirZoom VRE bike and the research question.</p>
                    </list-item>
                    <list-item>
                        <p>Briefly define&#x00a0;
                            <italic>
                                <underline>psychophysiological outcomes</underline>
                            </italic>&#x00a0;for the audience unfamiliar with these terms.</p>
                    </list-item>
                </list> 
                <list list-type="bullet">
                    <list-item>
                        <p>
                            <bold>
                                <italic>
                                    <underline>In methodology section: </underline>
                                </italic>
                            </bold>Further emphasize the&#x00a0;
                            <italic>
                                <underline>novelty&#x00a0;</underline>
                            </italic>of using VirZoom VRE compared to traditional exercise bikes in this specific population (adolescents with CP).</p>
                    </list-item>
                    <list-item>
                        <p>Briefly explain 
                            <italic>
                                <underline>the&#x00a0;rationale</underline>
                            </italic>&#x00a0;behind choosing specific games on the VirZoom VRE for the study.</p>
                    </list-item>
                </list> 
                <bold>Major Changes needed: </bold>
            </p>
            <p> 
                <italic>&#x00a0; </italic>
            </p>
            <p> 
                <bold>
                    <italic>a-
                        <bold>In</bold> result section, please make following changes.</italic>
                </bold> 
                <list list-type="bullet">
                    <list-item>
                        <p>Demographic characteristics should be presented as group wise. Because you have two groups, therefore, split age, gender etc. group wise. You can make three groups as TE, VRE and Total study population too.</p>
                    </list-item>
                    <list-item>
                        <p>Mention the name of statistical test which you have used in stats of Table-2.</p>
                    </list-item>
                    <list-item>
                        <p>You have mentioned that significant changes took place in Vigor too which is not the case as per stats of the study. Correct this.</p>
                    </list-item>
                    <list-item>
                        <p>Mention the age in months instead of years because it sounds better.</p>
                    </list-item>
                    <list-item>
                        <p>How many readings of MAS were taken on a particular joint? Why have you not used the mean of readings for MAS which is established practice in literature?</p>
                    </list-item>
                    <list-item>
                        <p>Table -3 lacks the significance level (p value). Where is it? In absence of statistical significance, how can you claim that changes are significant?</p>
                    </list-item>
                </list> </p>
            <p> </p>
            <p> 
                <bold>
                    <italic>&#x00a0; b-In discussion section; please make following&#x00a0; &#x00a0; changes.</italic>
                </bold> 
                <list list-type="bullet">
                    <list-item>
                        <p>Don&#x2019;t use the words our, I, my in research writings. Instead of our study, you can say present study or current study. Similarly instead of we found, you can write, results exhibits etc.</p>
                    </list-item>
                    <list-item>
                        <p>While acknowledging limitations, the discussion could be strengthened by using more cautious language when describing the potential benefits of VRE, especially in areas where the findings are mixed or inconclusive.</p>
                    </list-item>
                    <list-item>
                        <p>If possible, the discussion could be strengthened by delving deeper into the possible mechanisms by which VRE might be exerting its effects on various outcomes.</p>
                    </list-item>
                </list>
            </p>
            <p>Is the work clearly and accurately presented and does it cite the current literature?</p>
            <p>Yes</p>
            <p>If applicable, is the statistical analysis and its interpretation appropriate?</p>
            <p>I cannot comment. A qualified statistician is required.</p>
            <p>Are all the source data underlying the results available to ensure full reproducibility?</p>
            <p>Yes</p>
            <p>Is the study design appropriate and is the work technically sound?</p>
            <p>Yes</p>
            <p>Are the conclusions drawn adequately supported by the results?</p>
            <p>Yes</p>
            <p>Are sufficient details of methods and analysis provided to allow replication by others?</p>
            <p>Yes</p>
            <p>Reviewer Expertise:</p>
            <p>Pediatric rehabilitation specifically in the management of Cerebral Palsy, Physical therapy</p>
            <p>I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.</p>
        </body>
        <sub-article article-type="response" id="comment12675-248808">
            <front-stub>
                <contrib-group>
                    <contrib contrib-type="author">
                        <name>
                            <surname>Ghram</surname>
                            <given-names>Amine</given-names>
                        </name>
                        <aff>Cardiac rehabilitation, Hamad Medical Corporation, Doha, Doha, Qatar</aff>
                    </contrib>
                </contrib-group>
                <author-notes>
                    <fn fn-type="conflict">
                        <p>
                            <bold>Competing interests: </bold>No competing interests</p>
                    </fn>
                </author-notes>
                <pub-date pub-type="epub">
                    <day>19</day>
                    <month>10</month>
                    <year>2024</year>
                </pub-date>
            </front-stub>
            <body>
                <p>
                    <bold>Reviewer Comment 1:</bold> 
                    <italic>In the Abstract section, briefly mention the mixed findings on memory to provide a more balanced picture of the results.</italic>
                </p>
                <p> 
                    <bold>Response:</bold>
                </p>
                <p> We appreciate your insightful comments. Presenting a more balanced view of results, particularly regarding memory, is crucial for accuracy and transparency. The abstract has been revised to reflect heterogeneous findings on memory, ensuring that it aligns with the overall outcomes of the study.</p>
                <p> 
                    <bold>Action Taken:</bold>
                </p>
                <p> The following statement was incorporated into the abstract (lines 33&#x2013;37):&#x2019; 
                    <bold>Fourteen participants (42.9% female) were included in this analysis, and the results indicated that VRE had a statistically significant positive effect on attention and vigor compared to TE. While participants in the VRE group exhibited enhanced attention levels and reported elevated levels of vigor subsequent to the exercise sessions, the memory results did not reach statistical significance</bold>
                    <bold>.</bold>" This modification ensures a comprehensive interpretation of the findings and prepares readers for the study's conclusions.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 2:</bold> 
                    <italic>In the introduction section, emphasize the novelty and significance of the present study. Instead of stating existing knowledge about the benefits of regular exercise, briefly mention the limited research on the effects of acute exercise on cognitive function in adolescents with CP, highlighting the gap your study aims to address.</italic>
                </p>
                <p> 
                    <bold>Response:</bold>
                </p>
                <p> Thank you for your constructive feedback. To emphasize the novelty and significance of our investigation, we restructured the introduction to focus on the limited research on the effects of acute exercise on cognitive function in adolescents with cerebral palsy (CP). This modification highlights the research gap that our study addresses and underscores the unique contribution of our work to the field.</p>
                <p> 
                    <bold>Action Taken:</bold>
                </p>
                <p> The following passage was incorporated into the introduction (lines 71&#x2013;78):&#x2019; 
                    <bold>This study represents a significant advancement in elucidating the relationship between acute exercise and cognitive function in adolescents with CP. Despite extensive research demonstrating the benefits of regular exercise on cognitive health, there remains a notable gap in our understanding of how a single bout of exercise affects cognitive function in this specific population. This study was motivated by a growing body of evidence suggesting that acute aerobic exercise positively influences cognitive function, mood, and memory in various populations. However, these effects remain relatively unexplored in children and adolescents, particularly those with CP. This gap underscores the need for targeted research to elucidate how acute exercise can be utilized to enhance cognitive outcomes in this vulnerable population</bold>
                    <bold>.</bold>" This addition enhances the novelty of our study and elucidates how our research addresses a gap in the literature in accordance with the reviewer's recommendation.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 3:</bold> 
                    <italic>Consider reorganizing the information flow. Start by highlighting the gap in knowledge about acute exercise and cognitive function in adolescents with CP. Then briefly mention the existing evidence of VR's effectiveness in promoting physical activity, leading to the introduction of the VirZoom VRE bike and the research question.</italic>
                </p>
                <p> 
                    <bold>Response:</bold>
                </p>
                <p> We acknowledge your comprehensive feedback regarding the structure of the Introduction. In accordance with your recommendation, we have restructured the introduction to initially address the gap in current knowledge concerning acute exercise and cognitive function in adolescents with cerebral palsy (CP), subsequently transitioning to existing evidence on virtual reality (VR) as a modality for promoting physical activity. This revised organization enhances the clarity of the narrative and establishes a logical progression towards the introduction of the VirZoom VRE bike and the research question.</p>
                <p> 
                    <bold>Action Taken:</bold>
                </p>
                <p> The introduction now commences with a discussion of the limited research on acute exercise and cognitive function in adolescents with CP, followed by a brief mention of VR's effectiveness of VR (Lines 96&#x2013;103). " 
                    <bold>This study represents a significant advancement in understanding the impact of technology, specifically virtual reality (VR), on the well-being of adolescents with cerebral palsy (CP). Although previous studies have established the benefits of regular physical activity in adults with CP, there is a paucity of data regarding the immediate effects of exercise, particularly on cognitive performance, in adolescents with CP. The objective of our randomized controlled trial (RCT) was to compare the physiological and psychological effects of using the VirZoom VR exercise cycle with traditional exercise (TE) bicycles among university students with CP in North Africa. This study aimed to examine the impact of acute exercise on cognitive function, affection, memory, and decision-making abilities. This research contributes valuable insights into a critical topic that has received limited attention in this specific population</bold>
                    <bold>.</bold>" This reorganization provided a more coherent rationale for the study and more effectively established the context for the research question.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 4</bold>
                    <bold>:</bold> 
                    <italic>Briefly define psychophysiological outcomes for the audience unfamiliar with these terms.</italic>
                </p>
                <p> 
                    <bold>Response:</bold>
                </p>
                <p> We appreciate your recommendation. It is acknowledged that the term "psychophysiological outcomes" may not be familiar to all readers; therefore, a concise definition has been incorporated to enhance comprehension for a broader audience.</p>
                <p> 
                    <bold>Action Taken:</bold>
                </p>
                <p> The following definition has been incorporated (lines 53&#x2013;56):&#x2019; 
                    <bold>Psychophysiological outcomes refer to the observable effects of psychological processes on the physiological functions of the body (8). Psychophysiology is the scientific study of how cognitive processes, emotional states, and behaviors influence physiological responses, including heart rate, blood pressure, hormone levels, and brain function (9).</bold>" This succinct definition ensures that all readers, irrespective of their expertise, comprehend this crucial term and its significance to this study.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 5:</bold> 
                    <italic>In the methodology section: Further emphasize the novelty of using VirZoom VRE compared to traditional exercise bikes in this specific population (adolescents with CP).</italic>
                </p>
                <p> 
                    <bold>Response:</bold>
                </p>
                <p> We acknowledge your feedback and concur that it is essential to emphasize the novelty of the VirZoom VRE system, particularly its application in adolescents with CP. The utilization of immersive VR technology in exercise interventions for this population represents a relatively nascent area of research, and we have elucidated this novelty more explicitly in the methodology section.</p>
                <p> 
                    <bold>Action Taken:</bold>
                </p>
                <p> We revised the methodology section to include the following statement (Lines 128&#x2013;152):&#x2019; 
                    <bold>it is essential to emphasize the novelty of implementing the VirZoom VRE system in comparison to TE bikes, particularly within the context of adolescents with CP. Although TE bikes have been utilized in numerous rehabilitation settings, the integration of VR technology represents an innovative approach to increase physical activity and improve health outcomes in this specific population. The VirZoom VRE system provides a unique and immersive fitness experience that transcends the limitations of conventional stationary cycles by offering users dynamic virtual environments to explore during exercises. This novel approach not only introduces an element of enjoyment and engagement in the training program, but also presents opportunities for cognitive stimulation and social interaction, which are particularly beneficial for adolescents with CP. Furthermore, the VirZoom VRE system enables customizable training protocols and game-based activities to address the diverse needs and abilities of individuals with CP. By incorporating games that target specific muscle groups, movement patterns, and cognitive skills, we can tailor the exercise experience to align it with the individual rehabilitation objectives and interests of our participants. By emphasizing the novelty of implementing the VirZoom VRE system in this study, we underscore its potential to transform the delivery of physical activity interventions for adolescents with CP, ultimately leading to improved health outcomes and enhanced quality of life for this population. The selection of specific games in the VirZoom VRE system for our study is based on several rationales. Primarily, we aimed to ensure that the chosen games offered a diverse range of physical activities that engaged various muscle groups and movement patterns, addressing the heterogeneous needs and abilities of adolescents with CP. Second, we prioritized games that are immersive, interactive, and engaging, as research indicates that the entertainment value of VR experiences can significantly influence exercise adherence and participation. Additionally, we considered the cognitive demands of each game, selecting those that incorporated elements of attention, memory, decision-making, and problem solving to potentially enhance cognitive outcomes in our participants (31). Lastly, we aim to incorporate games that facilitate social interaction and competition, fostering a sense of camaraderie and motivation among participants, which may further contribute to the efficacy of the intervention</bold>." This explanation emphasizes the innovative nature of the intervention and its potential benefits, thereby elucidating the study's contribution to the field.</p>
                <p> </p>
                <p> 
                    <bold>Major Changes needed:</bold>
                </p>
                <p> 
                    <bold>&#x00a0;</bold>a-In the result section, please make following changes.</p>
                <p> </p>
                <p> 
                    <bold>Response to Reviewer&#x2019;s Comment&#x00a0;</bold>
                </p>
                <p> We appreciate the reviewer&#x2019;s suggestion to present demographic characteristics in a group-wise format. This change enhanced the clarity and comprehensibility of the participants&#x2019; data.</p>
                <p> 
                    <bold>Action Taken:</bold>&#x00a0;We created a new Table 1 that presents the demographic characteristics for each group (TE, VRE) as well as for the total study population. The table is formatted as follows.</p>
                <p> 
                    <bold>Table 1: Demographic Characteristics of Participants (refer the below link)</bold>
                </p>
                <p> </p>
                <p> 
                    <ext-link ext-link-type="uri" xlink:href="https://f1000research.s3.amazonaws.com/linked/685666.Table_1_Demographic_Characteristics_of_Participants.pdf">https://f1000research.s3.amazonaws.com/linked/685666.Table_1_Demographic_Characteristics_of_Participants.pdf</ext-link>
                </p>
                <p> </p>
                <p> This table enhances the presentation of demographic data and provides a clearer comparison between the groups in accordance with the reviewer's recommendations.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 6</bold>
                </p>
                <p> &#x2022;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0; Mention the name of the statistical test that you have used in stats in Table-2.</p>
                <p> 
                    <bold>Response:</bold>&#x00a0;</p>
                <p> Thank you for your valuable feedback regarding the statistical analysis of our study. You are correct that we should have explicitly mentioned the statistical tests used for the results presented in Table 2. We appreciate your attention to detail and opportunity to clarify this important aspect of our methodology.</p>
                <p> 
                    <bold>Action Taken:</bold>
                </p>
                <p> &#x00a0;We have revised the manuscript to include the specific statistical tests used for the analysis presented in Table 2. The statistical method has been added to the "Statistical analysis" section of the Methods and referenced in the table caption. Text added in text: line number 283-291 in bold
                    <bold>"</bold>
                    <bold> 
                        <bold>A 2 &#x00d7; 2 repeated-measures ANOVA was conducted to examine the effects of exercise type (Traditional Exercise vs. Virtual Reality Exercise) and time (Pre vs. Post) on performance scores. Data were analyzed using SPSS version 28.0. Prior to analysis, Mauchly's test of sphericity was performed to assess the assumption of sphericity. If Mauchly's test was significant, indicating a violation of sphericity, the degrees of freedom were corrected using the Greenhouse-Geisser or Huynh-Feldt corrections, as appropriate. Main effects and interactions were evaluated, and post hoc tests were conducted using the Bonferroni correction to further explore the significant effects. Descriptive statistics, including means and standard deviations for each condition, were calculated to provide a comprehensive understanding of the data. Statistical significance was set at an alpha level of .05 for all analyses.</bold>
                        <bold>)."</bold>
                    </bold>Additionally, we updated the caption for Table 2 : line number 308 in 
                    <bold>"Table 2. Comparison of pre- and post-training scores for attention, memory, total score, vigor, correct decision making, and decision-making errors in both the TE and VRE training conditions using 2 &#x00d7; 2 repeated-measures ANOVA."</bold>We believe that these additions have clarified the statistical method used and addressed your concerns. The use of repeated-measures ANOVA is appropriate for our study design as it allows us to examine the effects of both exercise type and time, as well as their interaction, on our outcome measures.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 7</bold>
                </p>
                <p> &#x2022;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0; You have mentioned that significant changes took place in Vigor, too, which is not the case as per the stats of the study. Correct this.</p>
                <p> 
                    <bold>Response:</bold>&#x00a0;Thank you for your valuable feedback regarding the reporting of vigor results. We appreciate your detailed attention. Upon re-evaluation of the statistical analysis, we corrected the manuscript to remove any references to significant changes in vigor.</p>
                <p> 
                    <bold>Action Taken:</bold>&#x00a0;The updated text accurately reflects that the analysis did not indicate significant changes in vigor, according to the statistical results.&#x00a0;
                    <bold>The previous statement, "significant changes were observed in vigor," has been removed and replaced with "</bold> 
                    <bold>Exercise type had no significant changes on patient vigor</bold>
                    <bold>." This correction can be found in the revised manuscript in the Results section (line 132).</bold>&#x00a0;We have made necessary revisions to ensure clarity and accuracy in reporting the findings. Thank you for helping us improve the quality of our manuscript.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 8</bold>
                </p>
                <p> &#x2022;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0; Mention the age in months instead of years because it sounds better.</p>
                <p> </p>
                <p> 
                    <bold>Response:</bold>&#x00a0;Thank you for your suggestion regarding the reporting of participants' ages. We appreciate your attention to the details and your recommendations to enhance the precision of our demographic data.</p>
                <p> 
                    <bold>Action Taken:</bold>&#x00a0;We have revised the manuscript to report participants' ages in months instead of years.&#x00a0;
                    <bold>Specifically, in the Results section, line 306, we have changed "15.6 &#x00b1; 0.7 years" to "163.57 &#x00b1; 41.58 months.</bold>&#x00a0;This modification provides a more precise representation of the participants' ages and aligns with the best practices for reporting developmental data for adolescent populations.</p>
                <p> We believe that this change has improved the clarity and accuracy of our demographic information. Thank you for helping us enhance the quality of our manuscript.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 9</bold>
                </p>
                <p> &#x2022;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0; How many readings of MAS were taken on a particular joint? Why have you not used the mean of readings for MAS which is established practice in literature?</p>
                <p> </p>
                <p> 
                    <bold>Response:</bold>&#x00a0;Thank you for your insightful comments regarding the measurement of the Modified Ashworth Scale (MAS) readings. We appreciate your attention to methodological rigor.</p>
                <p> 
                    <bold>Action Taken:</bold>&#x00a0;In the revised manuscript, we have clarified that&#x00a0;
                    <bold>three readings of the MAS were taken for each joint to ensure reliability and accuracy.</bold>&#x00a0;To adhere to established practices in the literature, we calculated and used the mean of these readings in our analysis.&#x00a0;
                    <bold>This adjustment is reflected in the Methods section, specifically on line 278, where we now state that "The mean of three MAS readings was used for each joint assessment."</bold>&#x00a0;We believe that this change enhances the validity of our findings and aligns our methodology with the standard practices in the field. Thank you for your valuable feedback, which has helped us improve the quality of our manuscript.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 10</bold>
                </p>
                <p> &#x2022;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0; Table -3 lacks the significance level (p value). Where is it? In absence of statistical significance, how can you claim that changes are significant?</p>
                <p> 
                    <bold>Response:</bold>&#x00a0;Thank you for your valuable feedback regarding Table 3. We appreciate your attention to the details and emphasize the importance of statistical significance in reporting the results.</p>
                <p> 
                    <bold>Action Taken:</bold>&#x00a0;We updated Table 3 to include the significance levels (p-values) for all reported outcomes.&#x00a0;
                    <bold>This clarifies the statistical significance of the changes observed in the present study. Specifically, we have added p-values in the last column of Table 3, which can be found in&#x00a0; the revised manuscript.</bold>&#x00a0;Moreover, we have revised the text to ensure that any claims of significance are supported by the corresponding statistical outcomes, which enhances the transparency and rigor of our results, aligning our reporting with best practices in the literature. Thank you for your constructive suggestions, which helped us improve the quality of our manuscript.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 11</bold>
                </p>
                <p> &#x00a0; b-In discussion section; please make following changes.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 12</bold>
                </p>
                <p> &#x2022;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0; Don&#x2019;t use the words our, I, my in research writings. Instead of our study, you can refer to the present study or the current study. Similarly instead of we found, you can write, results exhibits etc.</p>
                <p> 
                    <bold>Response:</bold>&#x00a0;We appreciate your feedback regarding the use of personal pronouns in research writing. We agree that maintaining an objective tone is important in scientific communication.</p>
                <p> 
                    <bold>Action Taken:</bold>&#x00a0;We have carefully reviewed the entire manuscript and made the following changes: 
                    <list list-type="order">
                        <list-item>
                            <p>Replaced "our study" with "the present study" the present study&#x2019; throughout the document.</p>
                        </list-item>
                        <list-item>
                            <p>Changed, "we found" to "results exhibit" where applicable.</p>
                        </list-item>
                        <list-item>
                            <p>Replaced "we suggest" with "the current study suggests" as appropriate.</p>
                        </list-item>
                        <list-item>
                            <p>Removed all instances of "I" and "my" from the manuscript.</p>
                        </list-item>
                    </list> These revisions can be found throughout the document, particularly in the &#x00a0;
                    <bold>Results section and Discussion section</bold>.We believe that these changes have improved the objectivity and professionalism of our writing, while maintaining clarity. Thank you for helping us enhance the quality of our manuscript.</p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 13</bold>
                </p>
                <p> &#x2022;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0;&#x00a0; While acknowledging the limitations, the discussion could be strengthened by using more cautious language when describing the potential benefits of VRE, especially in areas where the findings are mixed or inconclusive.</p>
                <p> 
                    <bold>Response:</bold>&#x00a0;Thank you for your valuable feedback regarding the language used to discuss the potential benefits of Virtual Reality Exercise (VRE). We appreciate your emphasis on the importance of using cautious language, especially when addressing areas with mixed or inconclusive findings.</p>
                <p> 
                    <bold>Action Taken:</bold>&#x00a0;In response to your comment, we have thoroughly revised the discussion section to incorporate a more nuanced and careful approach in describing the potential benefits of VRE. Specifically, we have: 
                    <list list-type="order">
                        <list-item>
                            <p>
                                <bold>Emphasizing the need for further research</bold>&#x00a0;by stating that while some findings suggest benefits,&#x00a0;
                                <bold>it is crucial to recognize that other studies present mixed results</bold>. This balanced perspective is vital for accurately conveying the current state of the literature.</p>
                        </list-item>
                        <list-item>
                            <p>
                                <bold>We acknowledge the limitations</bold>&#x00a0;of our study in terms of the generalizability of the findings. We explicitly state that&#x00a0;
                                <bold>additional evidence is necessary to substantiate the claims made regarding VRE</bold>, ensuring that our conclusions are firmly grounded in the available data.</p>
                        </list-item>
                        <list-item>
                            <p>
                                <bold>Utilizing cautious phrases</bold>&#x00a0;such as "may suggest" and "could potentially contribute" could potentially contribute&#x2019; instead of making definitive statements. For instance, we have replaced "VRE improves cognitive function" with&#x00a0;
                                <bold>"VRE may improve cognitive function,"</bold>&#x00a0;effectively communicating the tentative nature of our findings.</p>
                        </list-item>
                    </list> We believe these changes enhance the rigor and credibility of our discussion, providing a more accurate representation of the potential benefits of VRE while also emphasizing the need for further research in this area. Thank you for your constructive feedback, which has been instrumental in improving the quality and integrity of our manuscript.</p>
                <p> </p>
                <p> </p>
                <p> 
                    <bold>Reviewer Comment 14</bold>
                </p>
                <p> If possible, the discussion could be strengthened by delving deeper into the mechanisms through which VRE might exert its effects on various outcomes.</p>
                <p> 
                    <bold>Response:</bold>&#x00a0;We appreciate your insightful comment regarding the potential mechanisms by which virtual reality exercises (VRE) may influence various outcomes. Your suggestion to deepen the exploration of these mechanisms in the discussion is highly valued.</p>
                <p> </p>
                <p> 
                    <bold>Action Taken:</bold>&#x00a0;In response to your feedback, we have significantly expanded the discussion section to offer a more comprehensive analysis of the mechanisms underlying the effects of VRE. The specific revisions are as follows. 
                    <list list-type="order">
                        <list-item>
                            <p>
                                <bold>Discussion of Engagement and Motivation</bold>: We elaborated on the role of VRE in enhancing participant engagement through immersive experiences, which can lead to increased motivation and adherence to exercise programs. For instance, we revised line 352 from "VRE can increase motivation" to "The immersive nature of VRE may lead to heightened motivation, which is essential for improving physical activity levels."</p>
                        </list-item>
                        <list-item>
                            <p>
                                <bold>Exploration of Cognitive Function</bold>: We have included a detailed discussion on how VRE may facilitate cognitive engagement by requiring participants to interact with dynamic environments. In line 360, we modified the text from "VRE may help cognitive function" to "VRE potentially stimulates cognitive function by challenging participants to make quick decisions and adapt to changing virtual scenarios."</p>
                        </list-item>
                        <list-item>
                            <p>
                                <bold>Highlighting Social Interaction Effects</bold>: We addressed the potential of VRE to promote social interaction and support, which could further enhance its effectiveness. In line 375, we revised the statement from "VRE can be done alone or with others" to "Engaging in VRE in a group setting may foster social bonds, providing psychological benefits that contribute to overall well-being."</p>
                        </list-item>
                        <list-item>
                            <p>
                                <bold>Consideration of Physiological Responses</bold>: Finally, we examined the physiological responses associated with exercise in a virtual environment, positing that increased heart rate and caloric expenditure may arise from the interactive nature of VRE. We updated line 385 from "VRE involves physical activity" to "The interactive features of VRE may elicit greater physiological arousal, potentially leading to enhanced cardiovascular benefits."</p>
                        </list-item>
                    </list> 
                    <bold>These enhancements are reflected in the discussion section, particularly between lines 350 and 390, where we now present a well-rounded perspective on the mechanisms through which VRE may exert its effects on various outcomes. Incorporating these insights significantly strengthens the discussion and provides a more thorough understanding of the potential benefits of VRE.</bold>
                </p>
                <p> We are grateful for your valuable feedback, which has contributed greatly to the improvement of our manuscript
                    <bold>.</bold>
                </p>
            </body>
        </sub-article>
    </sub-article>
</article>
