<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE article PUBLIC "-//NLM//DTD Journal Publishing DTD v2.0 20040830//EN" "http://dtd.nlm.nih.gov/publishing/2.0/journalpublishing.dtd">
<article xmlns:xlink="http://www.w3.org/1999/xlink" article-type="research-article" dtd-version="2.0">
  <front>
    <journal-meta>
      <journal-id journal-id-type="publisher-id">JSG</journal-id>
      <journal-id journal-id-type="nlm-ta">JMIR Serious Games</journal-id>
      <journal-title>JMIR Serious Games</journal-title>
      <issn pub-type="epub">2291-9279</issn>
      <publisher>
        <publisher-name>JMIR Publications</publisher-name>
        <publisher-loc>Toronto, Canada</publisher-loc>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id">v9i3e25793</article-id>
      <article-id pub-id-type="pmid">34255648</article-id>
      <article-id pub-id-type="doi">10.2196/25793</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Review</subject>
        </subj-group>
        <subj-group subj-group-type="article-type">
          <subject>Review</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Association of Extensive Video Gaming and Cognitive Function Changes in Brain-Imaging Studies of Pro Gamers and Individuals With Gaming Disorder: Systematic Literature Review</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="editor">
          <name>
            <surname>Zary</surname>
            <given-names>Nabil</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Imani</surname>
            <given-names>Asad</given-names>
          </name>
        </contrib>
        <contrib contrib-type="reviewer">
          <name>
            <surname>Aksoy</surname>
            <given-names>Mehmet</given-names>
          </name>
        </contrib>
      </contrib-group>
      <contrib-group>
        <contrib id="contrib1" contrib-type="author">
          <name name-style="western">
            <surname>Choi</surname>
            <given-names>Eunhye</given-names>
          </name>
          <degrees>BSc, MSc</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-1116-2219</ext-link>
        </contrib>
        <contrib id="contrib2" contrib-type="author">
          <name name-style="western">
            <surname>Shin</surname>
            <given-names>Suk-Ho</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff2" ref-type="aff">2</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-1611-098X</ext-link>
        </contrib>
        <contrib id="contrib3" contrib-type="author">
          <name name-style="western">
            <surname>Ryu</surname>
            <given-names>Jeh-Kwang</given-names>
          </name>
          <degrees>PhD</degrees>
          <xref rid="aff3" ref-type="aff">3</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0001-6942-9399</ext-link>
        </contrib>
        <contrib id="contrib4" contrib-type="author">
          <name name-style="western">
            <surname>Jung</surname>
            <given-names>Kyu-In</given-names>
          </name>
          <degrees>MD, PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-2509-8377</ext-link>
        </contrib>
        <contrib id="contrib5" contrib-type="author">
          <name name-style="western">
            <surname>Hyun</surname>
            <given-names>Yerin</given-names>
          </name>
          <degrees>MA</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-1515-3352</ext-link>
        </contrib>
        <contrib id="contrib6" contrib-type="author">
          <name name-style="western">
            <surname>Kim</surname>
            <given-names>Jiyea</given-names>
          </name>
          <degrees>MA</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0003-1463-762X</ext-link>
        </contrib>
        <contrib id="contrib7" contrib-type="author" corresp="yes">
          <name name-style="western">
            <surname>Park</surname>
            <given-names>Min-Hyeon</given-names>
          </name>
          <degrees>MD, PhD</degrees>
          <xref rid="aff1" ref-type="aff">1</xref>
          <address>
            <institution>Department of Psychiatry</institution>
            <institution>Eunpyeong St. Mary’s Hospital, College of Medicine</institution>
            <institution>The Catholic University of Korea</institution>
            <addr-line>1021, Tongil-ro, Eunpyeong-gu</addr-line>
            <addr-line>Seoul, 03312</addr-line>
            <country>Republic of Korea</country>
            <phone>82 2 2030 2720</phone>
            <email>neominnie00@daum.net</email>
          </address>
          <ext-link ext-link-type="orcid">https://orcid.org/0000-0002-1731-1388</ext-link>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution>Department of Psychiatry</institution>
        <institution>Eunpyeong St. Mary’s Hospital, College of Medicine</institution>
        <institution>The Catholic University of Korea</institution>
        <addr-line>Seoul</addr-line>
        <country>Republic of Korea</country>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution>Dr. Shin’s Child and Adolescent Psychiatry Clinic</institution>
        <addr-line>Seoul</addr-line>
        <country>Republic of Korea</country>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution>Department of Physical Education</institution>
        <institution>College of Education</institution>
        <institution>Dongguk University</institution>
        <addr-line>Seoul</addr-line>
        <country>Republic of Korea</country>
      </aff>
      <author-notes>
        <corresp>Corresponding Author: Min-Hyeon Park <email>neominnie00@daum.net</email></corresp>
      </author-notes>
      <pub-date pub-type="collection">
        <season>Jul-Sep</season>
        <year>2021</year>
      </pub-date>
      <pub-date pub-type="epub">
        <day>9</day>
        <month>7</month>
        <year>2021</year>
      </pub-date>
      <volume>9</volume>
      <issue>3</issue>
      <elocation-id>e25793</elocation-id>
      <history>
        <date date-type="received">
          <day>17</day>
          <month>11</month>
          <year>2020</year>
        </date>
        <date date-type="rev-request">
          <day>8</day>
          <month>1</month>
          <year>2021</year>
        </date>
        <date date-type="rev-recd">
          <day>25</day>
          <month>3</month>
          <year>2021</year>
        </date>
        <date date-type="accepted">
          <day>2</day>
          <month>4</month>
          <year>2021</year>
        </date>
      </history>
      <copyright-statement>©Eunhye Choi, Suk-Ho Shin, Jeh-Kwang Ryu, Kyu-In Jung, Yerin Hyun, Jiyea Kim, Min-Hyeon Park. Originally published in JMIR Serious Games (https://games.jmir.org), 09.07.2021.</copyright-statement>
      <copyright-year>2021</copyright-year>
      <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/">
        <p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work, first published in JMIR Serious Games, is properly cited. The complete bibliographic information, a link to the original publication on https://games.jmir.org, as well as this copyright and license information must be included.</p>
      </license>
      <self-uri xlink:href="https://games.jmir.org/2021/3/e25793" xlink:type="simple"/>
      <abstract>
        <sec sec-type="background">
          <title>Background</title>
          <p>The World Health Organization announced the inclusion of gaming disorder (GD) in the International Classification of Diseases, 11th Revision, despite some concerns. However, video gaming has been associated with the enhancement of cognitive function. Moreover, despite comparable extensive video gaming, pro gamers have not shown any of the negative symptoms that individuals with GD have reported. It is important to understand the association between extensive video gaming and alterations in brain regions more objectively.</p>
        </sec>
        <sec sec-type="objective">
          <title>Objective</title>
          <p>This study aimed to systematically explore the association between extensive video gaming and changes in cognitive function by focusing on pro gamers and individuals with GD.</p>
        </sec>
        <sec sec-type="methods">
          <title>Methods</title>
          <p>Studies about pro gamers and individuals with GD were searched for in the PubMed and Web of Science databases using relevant search terms, for example, “pro-gamers” and “(Internet) gaming disorder.” While studies for pro gamers were searched for without date restrictions, only studies published since 2013 about individuals with GD were included in search results. Article selection was conducted by following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.</p>
        </sec>
        <sec sec-type="results">
          <title>Results</title>
          <p>By following the PRISMA guidelines, 1903 records with unique titles were identified. Through the screening process of titles and abstracts, 86 full-text articles were accessed to determine their eligibility. A total of 18 studies were included in this systematic review. Among the included 18 studies, six studies included pro gamers as participants, one study included both pro gamers and individuals with GD, and 11 studies included individuals with GD. Pro gamers showed structural and functional alterations in brain regions (eg, the left cingulate cortex, the insula subregions, and the prefrontal regions). Cognitive function (eg, attention and sensorimotor function) and cognitive control improved in pro gamers. Individuals with GD showed structural and functional alterations in brain regions (eg, the striatum, the orbitofrontal cortex, and the amygdala) that were associated with impaired cognitive control and higher levels of craving video game playing. They also showed increased cortical thickness in the middle temporal cortex, which indicated the acquisition of better skills. Moreover, it was suggested that various factors (eg, gaming expertise, duration or severity of GD, and level of self-control) seemed to modulate the association of extensive video game playing with changes in cognitive function.</p>
        </sec>
        <sec sec-type="conclusions">
          <title>Conclusions</title>
          <p>Although a limited number of studies were identified that included pro gamers and/or individuals who reported showing symptoms of GD for more than 1 year, this review contributed to the objective understanding of the association between extensive video game playing and changes in cognitive function. Conducting studies with a longitudinal design or with various comparison groups in the future would be helpful in deepening the understanding of this association.</p>
        </sec>
      </abstract>
      <kwd-group>
        <kwd>brain imaging</kwd>
        <kwd>cognitive function</kwd>
        <kwd>gaming disorder</kwd>
        <kwd>pro gamers</kwd>
        <kwd>video games</kwd>
        <kwd>cognition</kwd>
        <kwd>brain</kwd>
        <kwd>games</kwd>
        <kwd>gaming</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="introduction">
      <title>Introduction</title>
      <sec>
        <title>Background</title>
        <p>Video game playing has become one of the most popular leisure activities [<xref ref-type="bibr" rid="ref1">1</xref>]. With the growing popularity of video game playing, a minority of individuals have been reported to play video games in problematic ways, resulting in negative consequences (eg, withdrawal from socializing and death) [<xref ref-type="bibr" rid="ref2">2</xref>-<xref ref-type="bibr" rid="ref4">4</xref>]. By focusing on problematic video gaming in a minority of individuals, the World Health Organization (WHO) recently announced that the International Classification of Diseases, 11th Revision (ICD-11) included <italic>gaming disorder</italic> (GD) as a syndrome [<xref ref-type="bibr" rid="ref5">5</xref>,<xref ref-type="bibr" rid="ref6">6</xref>]. GD refers to the persistent engagement on the internet in playing games despite the psychological distress and the interference with daily activities for more than 12 months [<xref ref-type="bibr" rid="ref7">7</xref>]. However, there are concerns about the inclusion of GD as one of diseases in the ICD-11 [<xref ref-type="bibr" rid="ref6">6</xref>,<xref ref-type="bibr" rid="ref8">8</xref>], in that the objective evidence that showed there were harmful effects of GD was not sufficient (ie, little research examined causality and the persistence of symptoms) [<xref ref-type="bibr" rid="ref9">9</xref>].</p>
        <p>After the announcement by the WHO, GD was reported in the media to result in structural alterations in brain regions based on the results of a cross-sectional study that compared the brain structures of individuals with GD to those of healthy controls; this emphasized the necessity of treatment for GD [<xref ref-type="bibr" rid="ref10">10</xref>]. Although the tendency of GD was found to be negatively associated with the volume of gray matter (GM) in the prefrontal brain regions that are involved in cognitive control and sensorimotor functioning [<xref ref-type="bibr" rid="ref11">11</xref>], it is difficult to confirm the causality of the association in the cross-sectional studies. Moreover, unlike the focus on GD, playing video games was positively associated with cognitive function [<xref ref-type="bibr" rid="ref12">12</xref>-<xref ref-type="bibr" rid="ref15">15</xref>]. Video game players, compared to non–video game players, showed more integrated white matter (WM) in motor and visual pathways [<xref ref-type="bibr" rid="ref14">14</xref>] and higher levels of activation in the frontoparietal brain regions to detect visual stimulus despite the comparable cognitive performance [<xref ref-type="bibr" rid="ref15">15</xref>]. Playing video games for a longer duration was also associated with thicker cortices in the brain regions for attention, navigation, visuomotor function, and the resolution of ambiguity (eg, the left frontal eye field, the left dorsolateral prefrontal cortex [DLPFC], and the bilateral entorhinal cortex) [<xref ref-type="bibr" rid="ref12">12</xref>,<xref ref-type="bibr" rid="ref13">13</xref>]. That is, while the association of GD with alterations in brain regions was more focused, playing video games was also associated with cognitive enhancement.</p>
        <p>Furthermore, there are individuals who play video games extensively for more than 10 hours a day without reporting disrupted lifestyles (eg, a disrupted sleep-wake cycle) [<xref ref-type="bibr" rid="ref16">16</xref>]; these individuals are called pro gamers. They refer to a group of people who belong to a team through a contract and who make economic profits by taking part in e-sports competitions [<xref ref-type="bibr" rid="ref17">17</xref>]. The mean age of pro gamers in major leagues was reported to be 22 years [<xref ref-type="bibr" rid="ref18">18</xref>]. Although statistics for their mean age of retirement were not available, more than half of pro gamers reported that their retirement was dependent on their judgment of their performances in competitions [<xref ref-type="bibr" rid="ref17">17</xref>]. Since cognitive-motor speed (ie, the speed at which the cognitive process initiates actions) was found to start to decline at 24 years in a sample of StarCraft II players who were aged between 16 and 44 years old, regardless of their expertise level [<xref ref-type="bibr" rid="ref19">19</xref>], pro gamers were assumed to retire at 25 to 27 years of age.</p>
        <p>Taken together, playing video games for a longer duration did not result in the development of GD, and only a minority of people reported the development of GD [<xref ref-type="bibr" rid="ref6">6</xref>,<xref ref-type="bibr" rid="ref7">7</xref>]. Unlike negative opinions in the media toward video games and playing video games, playing them was associated with cognitive enhancement (eg, Zhang et al [<xref ref-type="bibr" rid="ref14">14</xref>] and Richlan et al [<xref ref-type="bibr" rid="ref15">15</xref>]). Video games were also suggested as a potential tool for clinical intervention for individuals with mental disorders (eg, Alzheimer disease) [<xref ref-type="bibr" rid="ref20">20</xref>]. Thus, it is necessary to explore the association between video game playing and alterations in brain regions in a more objective manner. Moreover, despite the comparable amount of video game experience between individuals with GD and pro gamers who play video games extensively without any symptoms of GD (eg, higher impulsivity for gaming) [<xref ref-type="bibr" rid="ref16">16</xref>], more studies have been conducted that focused on individuals with GD, and more review studies about GD have been conducted (eg, Leeman and Potenza [<xref ref-type="bibr" rid="ref21">21</xref>] and Wei et al [<xref ref-type="bibr" rid="ref22">22</xref>]). Since pro gamers, in addition to individuals with GD, are a population of interest for investigating the association between extensive video gaming and changes in cognitive function, reviewing studies that recruited pro gamers would deepen the understanding and effects of playing video games extensively.</p>
      </sec>
      <sec>
        <title>Objective</title>
        <p>This systematic review aimed to explore the association between extensive video game playing and changes in cognitive function. That is, this study reviewed brain-imaging studies that included pro gamers and/or individuals with GD.</p>
      </sec>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Search Strategy</title>
        <p>Literature searches were conducted in two databases: PubMed and Web of Science. Studies about pro gamers were searched for with the following search terms, without a restriction on the date: “pro-gamers,” “pro video game players,” “action video game experts,” “video gaming experts,” and “long-term video game players.” Studies about individuals with GD were searched for with the following search terms, with date restrictions: “(Internet) gaming disorder,” “(Internet) gaming addiction,” and “(online) video game addiction.” As many studies about GD have been conducted, only studies that were published since 2013 were included in the results of the literature search.</p>
      </sec>
      <sec>
        <title>Study Selection</title>
        <sec>
          <title>Overview</title>
          <p>The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines [<xref ref-type="bibr" rid="ref23">23</xref>] were followed in this study. Firstly, duplicates from the search results from the two databases were removed using EndNote X9 (Clarivate Analytics). After the removal of duplicates, the titles and abstracts of the remaining articles were screened to determine if they were eligible for full-text assessment. Secondly, full-text articles were carefully reviewed to determine their eligibility for this review based on selection criteria.</p>
        </sec>
        <sec>
          <title>Inclusion Criteria</title>
          <p>Inclusion criteria for articles in this review were as follows: (1) original research articles published in English, (2) the use of brain-imaging techniques, and (3) the recruitment of pro gamers and/or individuals with GD. Definitions of pro gamers and GD in this study are as follows:</p>
          <list list-type="bullet">
            <list-item>
              <p>Pro gamers are defined as individuals who (1) belong to e-sports teams, (2) are highly experienced video game players without reporting any problematic daily lifestyle behaviors, and/or (3) have won video game playing competitions.</p>
            </list-item>
            <list-item>
              <p>GD refers to persistent engagement in video game playing despite psychological distress and interference with daily activities [<xref ref-type="bibr" rid="ref24">24</xref>] for more than 1 year [<xref ref-type="bibr" rid="ref7">7</xref>].</p>
            </list-item>
          </list>
          <p>That is, articles about pro gamers were selected for inclusion when recruited participants met at least one description of pro gamers above. For example, a study that recruited video game experts, who were recognized as top-ranking players [<xref ref-type="bibr" rid="ref25">25</xref>], was included because the second description of pro gamers was met. The types of video games (eg, StarCraft and League of Legends) were not restricted for the selection. Articles were also selected for the review when recruited participants were confirmed to be diagnosed with GD for more than 12 months or when the stated mean duration of GD symptoms in participants was more than 1 year. In the process of the selection of articles about individuals with GD, the age of the individuals with GD was not restricted. This was because adults, in addition to adolescents, have also shown GD symptoms, despite the report that the prevalence of GD has increased especially in adolescents [<xref ref-type="bibr" rid="ref26">26</xref>] whose cognitive control is developing [<xref ref-type="bibr" rid="ref27">27</xref>] with different developmental trajectories of the limbic system and prefrontal cortex (PFC) regions [<xref ref-type="bibr" rid="ref28">28</xref>].</p>
        </sec>
        <sec>
          <title>Exclusion Criteria</title>
          <p>Articles were excluded when full texts were not available and when participants in studies did not meet any of the descriptions of pro gamers defined above. Articles were also excluded when they did not confirm that individuals with GD showed GD symptoms for more than 1 year or when they did not present the information of the mean duration of GD.</p>
        </sec>
      </sec>
      <sec>
        <title>Data Extraction</title>
        <p>The following data were extracted from the selected articles: information about the study (ie, study design, participants, duration of GD, and brain-imaging techniques used) and the brain regions that were associated with extensive video game playing.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <sec>
        <title>Literature Overview</title>
        <p>The searches of PubMed and Web of Science resulted in the identification of 2571 records. After the removal of duplicates, 1903 studies with unique titles were obtained for the screening of titles and abstracts. A total of 1761 studies were removed after the screening of titles, and another 56 studies were removed after the screening of abstracts. After excluding 1817 records, 86 full-text articles were comprehensively reviewed in order to assess their eligibility for inclusion in this review. After conducting assessments based on the inclusion criteria, 68 articles that did not meet the inclusion criteria or did not have full-text access were excluded (<xref rid="figure1" ref-type="fig">Figure 1</xref>). Thus, this review included 18 articles. The results of the extracted data from the selected articles are presented in three subsections: (1) information about the study, (2) alterations in brain regions in pro gamers, and (3) alterations in brain regions in individuals with GD.</p>
        <fig id="figure1" position="float">
          <label>Figure 1</label>
          <caption>
            <p>PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) flow diagram for the systematic literature review.</p>
          </caption>
          <graphic xlink:href="games_v9i3e25793_fig1.png" alt-version="no" mimetype="image" position="float" xlink:type="simple"/>
        </fig>
      </sec>
      <sec>
        <title>Information About the Study</title>
        <sec>
          <title>Study Design</title>
          <p>As seen in <xref ref-type="table" rid="table1">Table 1</xref> [<xref ref-type="bibr" rid="ref16">16</xref>,<xref ref-type="bibr" rid="ref20">20</xref>,<xref ref-type="bibr" rid="ref25">25</xref>,<xref ref-type="bibr" rid="ref29">29</xref>-<xref ref-type="bibr" rid="ref43">43</xref>], 16 studies had a cross-sectional design. One study [<xref ref-type="bibr" rid="ref16">16</xref>] had a correlational design and one study [<xref ref-type="bibr" rid="ref25">25</xref>] had a longitudinal design.</p>
          <table-wrap position="float" id="table1">
            <label>Table 1</label>
            <caption>
              <p>Summary of 18 studies included in this review.</p>
            </caption>
            <table width="1000" cellpadding="5" cellspacing="0" border="1" rules="groups" frame="hsides">
              <col width="170"/>
              <col width="360"/>
              <col width="170"/>
              <col width="300"/>
              <thead>
                <tr valign="top">
                  <td>Authors; study design</td>
                  <td>Participant information</td>
                  <td>Brain-imaging technique</td>
                  <td>Alterations in brain regions associated with extensive video gaming</td>
                </tr>
              </thead>
              <tbody>
                <tr valign="top">
                  <td>Hyun et al [<xref ref-type="bibr" rid="ref16">16</xref>]; correlational</td>
                  <td>Pro gamers: N=23; all males; mean age 19.8 (SD 1.7) years</td>
                  <td>Magnetic resonance imaging (MRI)</td>
                  <td>Cortical thickness in the right superior frontal gyrus, the right superior parietal gyrus, and the right precentral gyrus</td>
                </tr>
                <tr valign="top">
                  <td>Tanaka et al [<xref ref-type="bibr" rid="ref29">29</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Pro gamers: N=17; all males; mean age 24.1 (SD 2.9) years</p>
                      </list-item>
                      <list-item>
                        <p>Age- and educational level–matched control group: N=33; all males; weekly gaming duration was less than 2 hours</p>
                      </list-item>
                    </list>
                  </td>
                  <td>Structural MRI</td>
                  <td>Gray matter (GM) volume in the right posterior parietal cortex</td>
                </tr>
                <tr valign="top">
                  <td>Gong et al [<xref ref-type="bibr" rid="ref30">30</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Pro gamers: N=27; mean age 23.26 (SD 0.4) years</p>
                      </list-item>
                      <list-item>
                        <p>Amateur players: N=30; mean age 22.3 (SD 0.38) years; did not habitually engage in video game playing, and video gaming experience was less than 1 year</p>
                      </list-item>
                    </list>
                  </td>
                  <td>MRI</td>
                  <td>Functional connectivity (FC) and GM volume in the insular subregions</td>
                </tr>
                <tr valign="top">
                  <td>Gong et al [<xref ref-type="bibr" rid="ref31">31</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Pro gamers: N=23; all males; mean age 23.3 (SD 4.3) years</p>
                      </list-item>
                      <list-item>
                        <p>Amateur players: N=22; all males; mean age 22.3 (SD 3.46) years; video gaming experience was less than 1 year</p>
                      </list-item>
                    </list>
                  </td>
                  <td>Resting-state functional MRI (fMRI)</td>
                  <td>FC within and between the salience network (SN) and the central executive network (CEN)</td>
                </tr>
                <tr valign="top">
                  <td>Gong et al [<xref ref-type="bibr" rid="ref20">20</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Pro gamers: N=28; all males; mean age 24.6 (SD 1.4) years</p>
                      </list-item>
                      <list-item>
                        <p>Amateurs players: N=30; all males; mean age 24.3 (SD 1.8) years</p>
                      </list-item>
                    </list>
                  </td>
                  <td>Diffusion tensor imaging (DTI)</td>
                  <td>White matter (WM) networks in the prefrontal network, the limbic system, and the sensorimotor network</td>
                </tr>
                <tr valign="top">
                  <td>Gong et al [<xref ref-type="bibr" rid="ref25">25</xref>]; longitudinal</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Pro gamers: N=20; all males; mean age 21.42 (SD 1.64) years</p>
                      </list-item>
                      <list-item>
                        <p>Amateur players: N=20; all males; mean age 22.25 (SD 1.65) years; gaming experience was less than 1.5 years</p>
                      </list-item>
                    </list>
                  </td>
                  <td>Resting-state fMRI at the beginning and end of the study</td>
                  <td>Amplitude of low-frequency fluctuation (ALFF) in the brain regions of the default mode network (DMN), the CEN, and the SN</td>
                </tr>
                <tr valign="top">
                  <td>Han et al [<xref ref-type="bibr" rid="ref32">32</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Individuals with gaming disorder (GD): N=20; all males; mean age 20.9 (SD 2) years; mean duration of gaming disorder 4.9 (SD 0.9) years</p>
                      </list-item>
                      <list-item>
                        <p>Pro gamers: N=17; all males; mean age 20.8 (SD 1.5) years</p>
                      </list-item>
                      <list-item>
                        <p>Age- and educational level–matched healthy controls (HCs): N=18; all males; mean age 20.9 (SD 2.1) years</p>
                      </list-item>
                    </list>
                  </td>
                  <td>MRI</td>
                  <td>GM volume in cingulate gyrus, thalamus, and occipitotemporal areas</td>
                </tr>
                <tr valign="top">
                  <td>Ko et al [<xref ref-type="bibr" rid="ref33">33</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Participants with GD: N=15; mean age 24.67 (SD 3.11) years; mean education duration 15.47 (SD 1.56) years</p>
                      </list-item>
                      <list-item>
                        <p>Remission subjects from GD: N=15; mean age 24.8 (SD 2.68) years; mean education duration 15.87 (SD 1.41) years</p>
                      </list-item>
                      <list-item>
                        <p>HCs: N=15; mean age 24.47 (SD 2.83) years; mean education duration 16 (SD 1.13) years</p>
                      </list-item>
                    </list>
                  </td>
                  <td>Task-based fMRI (the presentation of neutral vs online game-related screenshots)</td>
                  <td>The bilateral dorsolateral prefrontal cortex (DLPFC), the precuneus, the left parahippocampus, the posterior cingulate, the right anterior cingulate, and the left superior parietal lobe</td>
                </tr>
                <tr valign="top">
                  <td>Yuan et al [<xref ref-type="bibr" rid="ref34">34</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Adolescents with GD: N=18; n=12 males; mean age 19.4 (SD 3.1) years</p>
                      </list-item>
                      <list-item>
                        <p>Age- and gender-matched HCs: N=18; daily gaming duration was less than 2 hours</p>
                      </list-item>
                    </list>
                  </td>
                  <td>MRI</td>
                  <td>Cortical thickness in the left lateral orbitofrontal cortex, the insula cortex, lingual gyrus, the right postcentral gyrus, the entorhinal cortex, the inferior parietal cortex, the left precentral cortex, the middle temporal cortices, the precuneus, the middle frontal cortex, and the inferior temporal cortices</td>
                </tr>
                <tr valign="top">
                  <td>Yuan et al [<xref ref-type="bibr" rid="ref35">35</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Participants with GD: N=18; n=12 males; mean age 19.4 (SD 3.1) years</p>
                      </list-item>
                      <list-item>
                        <p>Age- and gender-matched HCs: N=18; n=12 males; mean age 19.5 (SD 2.8) years; daily gaming duration was less than 2 hours</p>
                      </list-item>
                    </list>
                  </td>
                  <td>Resting-state fMRI</td>
                  <td>ALFF in brain regions, including major regions of the DMN</td>
                </tr>
                <tr valign="top">
                  <td>Ko et al [<xref ref-type="bibr" rid="ref36">36</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Male subjects with GD: N=26; mean age 24.58 (SD 3.23) years</p>
                      </list-item>
                      <list-item>
                        <p>Male HCs: N=23; mean age 24.35 (SD 2.12) years</p>
                      </list-item>
                    </list>
                  </td>
                  <td>Task-state fMRI (go/no-go task)</td>
                  <td>Activation in the frontostriatal network</td>
                </tr>
                <tr valign="top">
                  <td>Chen et al [<xref ref-type="bibr" rid="ref37">37</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Individuals with GD: N=15; all males; mean age 24.67 (SD 3.12) years</p>
                      </list-item>
                      <list-item>
                        <p>HCs: N=25; all males; mean age 24.47 (SD 2.83) years</p>
                      </list-item>
                    </list>
                  </td>
                  <td>Task-state fMRI (go/no-go task)</td>
                  <td>Activation in the right supplementary motor area (SMA) or pre-SMA</td>
                </tr>
                <tr valign="top">
                  <td>Ko et al [<xref ref-type="bibr" rid="ref38">38</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Male adults with GD: N=30; mean age 23.57 (SD 2.5) years</p>
                      </list-item>
                      <list-item>
                        <p>Age- and educational level–matched HCs: N=30; mean age 24.23 (SD 2.47) years</p>
                      </list-item>
                    </list>
                  </td>
                  <td>Resting-state fMRI</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>GM density in bilateral amygdala</p>
                      </list-item>
                      <list-item>
                        <p>FC of amygdala with the left DLPFC, the orbitofrontal lobe (OFL), and the contralateral insula</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Cai et al [<xref ref-type="bibr" rid="ref39">39</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Individuals with GD: N=27; n=23 males; mean age 17.9 (SD 0.9) years</p>
                      </list-item>
                      <list-item>
                        <p>Age-, gender-, and educational level–matched HCs: N=30; n=22 males; mean age 18.3 (SD 1.6) years</p>
                      </list-item>
                    </list>
                  </td>
                  <td>MRI</td>
                  <td>The volume in the striatum</td>
                </tr>
                <tr valign="top">
                  <td>Chen et al [<xref ref-type="bibr" rid="ref40">40</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Individuals with GD: N=28; all males; mean age 23.64 (SD 2.54) years</p>
                      </list-item>
                      <list-item>
                        <p>Age- and educational level–matched HCs: N=28; all males; mean age 24.14 (SD 2.53) years</p>
                      </list-item>
                    </list>
                  </td>
                  <td>Resting-state fMRI</td>
                  <td>FC between the left insula and the left DLPFC and OFL, and between interhemispheric insula</td>
                </tr>
                <tr valign="top">
                  <td>Jin et al [<xref ref-type="bibr" rid="ref41">41</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>College students with GD: N=25; n=16 males; mean age 19.12 (SD 1.05) years</p>
                      </list-item>
                      <list-item>
                        <p>Age- and gender-matched HCs: N=21; n=14 males; mean age 18.76 (SD 1.81) years</p>
                      </list-item>
                    </list>
                  </td>
                  <td>Resting-state fMRI</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>GM volume in the prefrontal regions and the right SMA</p>
                      </list-item>
                      <list-item>
                        <p>FC of prefrontal regions with temporal and occipital regions, and between several regions, including the bilateral caudate, the thalamus, the putamen, the insular cortex, and the right SMA</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Yuan et al [<xref ref-type="bibr" rid="ref42">42</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Individuals with GD: N=43; n=32 males; age range 16-22 years; primary internet activity was to play League of Legends</p>
                      </list-item>
                      <list-item>
                        <p>Age- and gender-matched HCs: N=44; n=34 males; age range 15-23 years</p>
                      </list-item>
                    </list>
                  </td>
                  <td>Resting-state fMRI</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Volume in the striatum</p>
                      </list-item>
                      <list-item>
                        <p>Resting-state FC within the dorsal and ventral striatum networks</p>
                      </list-item>
                    </list>
                  </td>
                </tr>
                <tr valign="top">
                  <td>Zhai et al [<xref ref-type="bibr" rid="ref43">43</xref>]; cross-sectional</td>
                  <td>
                    <list list-type="order">
                      <list-item>
                        <p>Subjects with GD: N=16; n=11 males; mean age 19.1 (SD 1.3) years; primary internet activity was to play League of Legends</p>
                      </list-item>
                      <list-item>
                        <p>Age- and gender-matched HCs: N=16; n=11 males; mean age 18.4 (SD 1.9) years</p>
                      </list-item>
                    </list>
                  </td>
                  <td>DTI</td>
                  <td>The global and local efficiency of WM networks</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </sec>
        <sec>
          <title>Participants</title>
          <p>Among the included 18 articles, six articles included pro gamers (<xref ref-type="table" rid="table1">Table 1</xref>). While pro gamers were compared with amateur video game players who had less gaming experience in five articles [<xref ref-type="bibr" rid="ref20">20</xref>,<xref ref-type="bibr" rid="ref25">25</xref>,<xref ref-type="bibr" rid="ref29">29</xref>-<xref ref-type="bibr" rid="ref31">31</xref>], one article [<xref ref-type="bibr" rid="ref16">16</xref>] included pro gamers with varied gaming expertise. One article [<xref ref-type="bibr" rid="ref32">32</xref>] included both pro gamers and individuals with GD. A total of 11 articles [<xref ref-type="bibr" rid="ref33">33</xref>-<xref ref-type="bibr" rid="ref43">43</xref>] included individuals with GD (<xref ref-type="table" rid="table1">Table 1</xref>). While one article [<xref ref-type="bibr" rid="ref33">33</xref>] recruited a remission group in addition to individuals with GD and healthy controls, 10 articles recruited individuals with GD and healthy controls. Moreover, six articles [<xref ref-type="bibr" rid="ref34">34</xref>,<xref ref-type="bibr" rid="ref35">35</xref>,<xref ref-type="bibr" rid="ref39">39</xref>,<xref ref-type="bibr" rid="ref41">41</xref>-<xref ref-type="bibr" rid="ref43">43</xref>] included female participants.</p>
        </sec>
        <sec>
          <title>Brain-Imaging Techniques</title>
          <p>Two studies used diffusion tensor imaging and six studies used magnetic resonance imaging to investigate the alterations in brain regions associated with extensive video game playing. Seven studies used resting-state functional magnetic resonance imaging (fMRI) and three studies used task-state fMRI. Tasks that were used in the studies included the presentation of gaming cues [<xref ref-type="bibr" rid="ref33">33</xref>] and tasks to measure cognitive control [<xref ref-type="bibr" rid="ref36">36</xref>,<xref ref-type="bibr" rid="ref37">37</xref>] (<xref ref-type="table" rid="table1">Table 1</xref>).</p>
        </sec>
      </sec>
      <sec>
        <title>Alterations in Brain Regions in Pro Gamers</title>
        <p>As seen in <xref ref-type="table" rid="table1">Table 1</xref>, pro gamers showed structural alterations in brain regions that were different from those in amateur players and individuals with GD. Pro gamers showed higher GM volume in the left cingulate gyrus [<xref ref-type="bibr" rid="ref32">32</xref>], the right posterior parietal cortex (PPC) [<xref ref-type="bibr" rid="ref29">29</xref>], and insula subregions, including the left long insular gyrus and central insular sulcus [<xref ref-type="bibr" rid="ref30">30</xref>], compared to amateur players. The GM volume in the left cingulate gyrus was also higher in pro gamers than in individuals with GD [<xref ref-type="bibr" rid="ref32">32</xref>]. Moreover, pro gamers showed decreased GM volume in some brain regions, including in the left middle occipital gyrus and the right inferior temporal gyrus, compared to healthy controls [<xref ref-type="bibr" rid="ref32">32</xref>]. The GM volume in the left thalamus was lower in pro gamers than in individuals with GD [<xref ref-type="bibr" rid="ref32">32</xref>]. Moreover, the pro gamers with longer career lengths were shown to have a thicker cortex in the right superior frontal gyrus, right superior parietal gyrus, and right precentral gyrus, and the pro gamers who won more in the competitions were shown to have a thicker PFC [<xref ref-type="bibr" rid="ref16">16</xref>].</p>
        <p>Pro gamers also showed functional alterations in brain regions. They showed increased amplitude of low-frequency fluctuation (ALFF) in brain regions of the default mode network (DMN), the central executive network (CEN), and the salience network (SN) compared to amateur players [<xref ref-type="bibr" rid="ref25">25</xref>]. That is, pro gamers showed increased ALFF in the posterior cingulate cortex (PCC), the right angular gyrus, the right DLPFC, the anterior cingulated cortex (ACC), and the right anterior insula [<xref ref-type="bibr" rid="ref25">25</xref>]. The WM network in the prefrontal regions, the limbic system, and the sensorimotor network was also more integrated in pro gamers compared to amateur players [<xref ref-type="bibr" rid="ref20">20</xref>]. Moreover, pro gamers, compared to amateur players, showed more functionally connected networks, not only between anterior and posterior insula subregions [<xref ref-type="bibr" rid="ref30">30</xref>] but also within and between the SN and CEN [<xref ref-type="bibr" rid="ref31">31</xref>].</p>
      </sec>
      <sec>
        <title>Alterations in Brain Regions in Individuals With GD</title>
        <p>Individuals with GD showed structural alterations compared to healthy controls and pro gamers (<xref ref-type="table" rid="table1">Table 1</xref>). Compared to both pro gamers and healthy controls, individuals with GD showed increased GM volume in the left thalamus [<xref ref-type="bibr" rid="ref32">32</xref>]. Compared to healthy controls, individuals with GD showed increased volume in the striatum (ie, right caudate and right nucleus accumbens [NAc]) [<xref ref-type="bibr" rid="ref39">39</xref>,<xref ref-type="bibr" rid="ref42">42</xref>]; they also had a thicker cortex in the left precentral cortex, the middle temporal cortices, the precuneus, the middle frontal cortex, and the inferior temporal cortices [<xref ref-type="bibr" rid="ref34">34</xref>]. Moreover, individuals with GD showed decreased GM volume in some brain regions compared to healthy controls. Individuals with GD were found to have decreased GM volume in the amygdala [<xref ref-type="bibr" rid="ref38">38</xref>], the temporal-occipital cortex (ie, the right middle occipital gyrus and the left inferior occipital gyrus) [<xref ref-type="bibr" rid="ref32">32</xref>], the prefrontal regions (ie, the bilateral DLPFC, the orbitofrontal cortex [OFC], and the ACC), and the right supplementary motor area (SMA) [<xref ref-type="bibr" rid="ref41">41</xref>]. The cortical thickness in the left lateral OFC, the insula cortex, the lingual gyrus, the right postcentral gyrus, the entorhinal cortex, and the inferior parietal cortex was also found to be decreased in individuals with GD compared to healthy controls [<xref ref-type="bibr" rid="ref34">34</xref>].</p>
        <p>Individuals with GD showed functional changes in brain regions in the resting state compared to healthy controls. The short path length in individuals with GD was found to be increased [<xref ref-type="bibr" rid="ref43">43</xref>]. Individuals with GD, compared to healthy controls, also showed increased ALFF in the left medial OFC, the left precuneus, the left SMA, the right parahippocampal gyrus, and the bilateral middle cingulate cortex [<xref ref-type="bibr" rid="ref35">35</xref>]. Moreover, individuals with GD showed increases in the resting-state functional connectivity (FC), not only between the bilateral amygdala and the contralateral insula [<xref ref-type="bibr" rid="ref38">38</xref>] but also between the bilateral insula [<xref ref-type="bibr" rid="ref40">40</xref>].</p>
        <p>Individuals with GD showed decreased resting-state activation or FC in some brain regions. The global and local efficiency of WM networks was found to be reduced in individuals with GD [<xref ref-type="bibr" rid="ref43">43</xref>]. The FC between prefrontal regions (ie, ACC, OFC, and DLPFC) and temporal and occipital regions (ie, pallidum, thalamus, caudate, and putamen) also decreased in individuals with GD compared to healthy controls [<xref ref-type="bibr" rid="ref41">41</xref>]. Moreover, individuals with GD, compared to healthy controls, showed both reduced FC in the dorsal and ventral striatum networks (ie, FC between the right caudate and the DLPFC, and FC between the right NAc and the OFC) [<xref ref-type="bibr" rid="ref42">42</xref>] and decreased FC of the left insula with the left DLPFC and the orbitofrontal lobe (OFL) [<xref ref-type="bibr" rid="ref40">40</xref>]. The FC of the bilateral amygdala with the left DLPFC and the FC of the right amygdala with the OFL were found to be decreased in individuals with GD [<xref ref-type="bibr" rid="ref38">38</xref>].</p>
        <p>Additionally, studies that used task-based fMRI showed that individuals with GD showed increased activation in the frontostriatal network (ie, bilateral OFL, ACC, left putamen, right DLPFC, and middle temporal lobe) [<xref ref-type="bibr" rid="ref36">36</xref>] but decreased activation in the right SMA or pre-SMA [<xref ref-type="bibr" rid="ref37">37</xref>] compared to healthy controls in the task that required inhibition. Furthermore, when gaming cues were presented, individuals with GD showed higher activation in the bilateral DLPFC, the precuneus, the left parahippocampus, the posterior cingulate, the right anterior cingulate, and the left superior parietal lobe compared to healthy controls [<xref ref-type="bibr" rid="ref33">33</xref>]. Individuals with GD also showed higher activation in the right DLPFC, the left parahippocampus, and the left middle temporal gyrus in response to gaming cues compared to the remission group of participants [<xref ref-type="bibr" rid="ref33">33</xref>].</p>
      </sec>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <sec>
        <title>Overview</title>
        <p>This review aimed to explore the association between extensive video game playing and changes in cognitive functions by focusing on pro gamers and individuals with GD. That is, this study systematically reviewed the brain-imaging studies that included pro gamers and/or individuals with GD. By following PRISMA guidelines, 18 studies were included in this review. Based on selected studies, it was found that pro gamers and individuals with GD showed different structural and functional alterations in brain regions, despite the comparable level of gaming engagement.</p>
      </sec>
      <sec>
        <title>Primary Results of the Studies Including Pro Gamers</title>
        <p>Results showed both increased and decreased GM volume in brain regions of pro gamers. Pro gamers, compared to both healthy controls and individuals with GD, showed a thicker cortex in the left cingulate cortex, which is involved in the maintenance of attention and control over executive functioning [<xref ref-type="bibr" rid="ref32">32</xref>]. Pro gamers also showed structural enhancement in brain regions that are involved in visual working memory, attention, and sensorimotor function (eg, the right PPC and insular subregions) compared to amateur video game players [<xref ref-type="bibr" rid="ref29">29</xref>,<xref ref-type="bibr" rid="ref30">30</xref>]. The increased GM volume in the right PPC was positively associated with better visual working memory performance in pro gamers [<xref ref-type="bibr" rid="ref29">29</xref>], and the increased GM volume in insular subregions was suggested to contribute to functional integration within insular regions [<xref ref-type="bibr" rid="ref30">30</xref>]. However, pro gamers showed decreased GM volume in occipitotemporal regions for visual processing (eg, the left middle occipital gyrus) compared to amateur players, and they showed decreased GM volume in the left thalamus, which is involved in reward processing, compared to individuals with GD [<xref ref-type="bibr" rid="ref32">32</xref>]. These structural alterations in pro gamers suggested that pro gamers did not show impaired reward processing but showed enhanced cognitive function (eg, cognitive control and visual working memory), along with reduced cortical thickness in brain regions that are involved in the processing of visual stimuli. Moreover, since pro gamers—who reported longer video game experience or higher rates of winning in competitions—were found to show a thicker cortex in frontal regions for cognitive flexibility (eg, the right superior frontal gyrus) [<xref ref-type="bibr" rid="ref16">16</xref>], it was suggested that gaming expertise seemed to modulate the association between extensive video game experience and cognitive enhancement in pro gamers.</p>
        <p>Results also showed functional enhancement in brain regions of pro gamers. Pro gamers showed more functional integration between anterior and posterior insular subregions [<xref ref-type="bibr" rid="ref30">30</xref>] and within and between the SN and the CEN [<xref ref-type="bibr" rid="ref31">31</xref>]. That is, the attention and sensorimotor functions were more coordinated in pro gamers [<xref ref-type="bibr" rid="ref30">30</xref>], and they showed improvement in the ability to process information [<xref ref-type="bibr" rid="ref31">31</xref>]. The plasticity of WM networks in brain regions for sensorimotor function and cognitive control (eg, the sensorimotor network and the prefrontal network) was also more enhanced in pro gamers compared to amateur players [<xref ref-type="bibr" rid="ref20">20</xref>]. Pro gamers were found to integrate information more efficiently by showing nodal and global enhancement in WM networks [<xref ref-type="bibr" rid="ref20">20</xref>]. Moreover, it was found that activation in the DMN (eg, PCC), the CEN (eg, the right DLPFC), and the SN (eg, the ACC), which was higher in pro gamers than in amateur players at the beginning of the study, decreased after the pro gamers were asked not to play video games for 1 year [<xref ref-type="bibr" rid="ref25">25</xref>]. The results of that longitudinal study suggested that extensive video game playing seemed to enhance the development of brain regions [<xref ref-type="bibr" rid="ref25">25</xref>]. Consistent with structural alterations in pro gamers, when compared to amateur players, pro gamers showed functional enhancements within and between the brain regions that are involved in attention, visual processing, sensorimotor function, and cognitive control.</p>
      </sec>
      <sec>
        <title>Primary Results of the Studies Including Individuals With GD</title>
        <p>Individuals with GD were found to show structural alterations in frontostriatal regions. While the cortical thickness of the brain regions that were associated with executive function and decision making (eg, the DLPFC, the OFC, and the amygdala) decreased in those with GD [<xref ref-type="bibr" rid="ref34">34</xref>,<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref41">41</xref>], the volumes of the brain regions for reward processing (eg, the striatum) increased in individuals with GD as compared to healthy controls [<xref ref-type="bibr" rid="ref39">39</xref>,<xref ref-type="bibr" rid="ref42">42</xref>]. Individuals with GD also showed increased volumes in the brain region that is involved in the expectation of rewards (ie, the left thalamus) compared to pro gamers [<xref ref-type="bibr" rid="ref32">32</xref>]. The structural alterations in brain regions of individuals with GD suggested that they showed impairment in executive functioning and higher levels of craving to play video games [<xref ref-type="bibr" rid="ref34">34</xref>]. In particular, the increased volume in the striatum was found to be associated with impairment of cognitive control [<xref ref-type="bibr" rid="ref39">39</xref>]. However, individuals with GD showed increased volume in the middle temporal cortex, which is involved in the acquisition of skills, compared to healthy controls [<xref ref-type="bibr" rid="ref34">34</xref>]. That is, despite impaired cognitive control in individuals with GD, their higher level of video game playing experience, compared to that of healthy controls, was associated with improved skills.</p>
        <p>Individuals with GD were found to show not only structural alterations but also functional alterations compared to healthy controls. Individuals with GD showed reduced levels of integration within WM networks [<xref ref-type="bibr" rid="ref43">43</xref>]. The increased short path length [<xref ref-type="bibr" rid="ref43">43</xref>] and increased resting-state FC within and between the bilateral insula and the amygdala [<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref40">40</xref>] in individuals with GD were found to be associated with a higher level of impulsivity. An increased resting-state activation in certain brain regions (eg, the left medial OFC) [<xref ref-type="bibr" rid="ref35">35</xref>] was also associated with impairment of cognitive control in individuals with GD. Moreover, the CEN (eg, DLPFC) and the reward circuits (eg, amygdala) in individuals with GD, compared to healthy controls, were found to be less functionally integrated in the resting state [<xref ref-type="bibr" rid="ref38">38</xref>,<xref ref-type="bibr" rid="ref40">40</xref>]. That is, the FC within the frontostriatal networks, which are involved in the processing of motivation and cognitive control, was found to decrease in individuals with GD during the resting state [<xref ref-type="bibr" rid="ref41">41</xref>,<xref ref-type="bibr" rid="ref42">42</xref>]. It was suggested that they showed both higher levels of impulsivity and impaired cognitive control.</p>
        <p>Consistent with the resting-state functional alterations in individuals with GD, the task-state fMRI studies showed impairment of cognitive control in individuals with GD. When the execution of cognitive control was required, individuals with GD showed increased activation in the frontostriatal networks, unlike healthy controls who showed increased activation only in the DLPFC [<xref ref-type="bibr" rid="ref36">36</xref>]. That is, not only frontal regions but also striatal regions were activated in individuals with GD for response inhibition. However, activation in the brain region that is involved in executing proper behavior (eg, pre-SMA) decreased in individuals with GD in the cognitive control task [<xref ref-type="bibr" rid="ref37">37</xref>]. Moreover, when the gaming cue was presented, individuals with GD showed increased activation in brain regions that are involved in the processing of affective or salient stimuli and craving (eg, the bilateral DLPFC, the posterior cingulate, and the anterior cingulate) compared to healthy controls [<xref ref-type="bibr" rid="ref33">33</xref>]. The remission group, who showed lower levels of craving video game playing than individuals with GD, also showed higher activation in the brain region for visual attention (ie, the superior parietal lobe), though the difference in activation between the remission group and healthy controls was not significant [<xref ref-type="bibr" rid="ref33">33</xref>].</p>
        <p>Furthermore, there was a difference in structural and functional alterations in brain regions among individuals with GD. Individuals who reported more severe levels of GD showed an increased volume in the NAc, which is involved in the processing of rewards [<xref ref-type="bibr" rid="ref39">39</xref>]. Individuals who reported having GD for a longer duration showed not only an increased volume in the left precentral gyrus and precuneus but also a decreased volume in the lingual gyrus [<xref ref-type="bibr" rid="ref34">34</xref>]. They also showed more abnormal resting-state activation in the left medial OFC and the left precuneus [<xref ref-type="bibr" rid="ref35">35</xref>]. Moreover, the level of self-control in individuals with GD was negatively associated with activation of the bilateral caudate nucleus [<xref ref-type="bibr" rid="ref36">36</xref>]. These findings suggest that it was plausible that the severity or duration of GD and impaired self-control mediated the association between extensive video game playing and changes in cognitive function.</p>
        <p>Taken together, pro gamers and individuals with GD showed different structural and functional alterations in brain regions despite comparable extensive engagement in video game playing. Pro gamers showed enhancement in cognitive function (eg, attention and visuomotor function) and better cognitive control. Unlike pro gamers, individuals with GD showed impairment in cognitive control and higher levels of craving video game playing. They also showed improvement in the acquisition of skills. Moreover, factors that seemed to modulate the association of extensive video game playing with changes in cognitive function (ie, gaming expertise, duration or severity of GD, and level of self-control) were identified. That is, although individuals with GD showed impaired executive functioning, extensive video game playing was associated with enhancement in cognitive function in not only pro gamers but also in those with GD.</p>
      </sec>
      <sec>
        <title>Limitations</title>
        <p>There were three limitations in this review. The first limitation was the limited number of studies. Only a few studies were identified that included pro gamers. Most studies that included individuals with GD did not consider or state the duration of GD despite its importance. According to the WHO’s announcement, the diagnosis of GD should be based on the report of symptoms for more than 12 months [<xref ref-type="bibr" rid="ref7">7</xref>]; only a subgroup of individuals were found to show persistent symptoms of GD over 12 months [<xref ref-type="bibr" rid="ref44">44</xref>]. That is, more studies should be conducted that include pro gamers and individuals who had reported GD for more than 1 year. The second limitation was the design of the studies. Although one study had a longitudinal design, most included studies had cross-sectional designs. More brain-imaging studies with longitudinal designs should be conducted, as these would be helpful in tracking alterations in brain regions and in understanding causality in the association between extensive video game playing and changes in cognitive function. The last limitation was the comparison group. Most included studies recruited participants who did not habitually play video games as the comparison group. There was a group of highly engaged video game players who were not pro gamers and did not show any symptoms of GD [<xref ref-type="bibr" rid="ref45">45</xref>]; therefore, comparing alterations in brain regions between individuals with GD and highly engaged video game players or pro gamers would be helpful to deepen the understanding of the effect of video game playing on structural and functional alterations in brain regions and to identify the mediating factors of their association. Further studies should be conducted while considering these limitations.</p>
      </sec>
      <sec>
        <title>Conclusions</title>
        <p>Pro gamers and individuals with GD showed differences in structural and functional alterations in certain brain regions. While pro gamers showed enhancement in cognitive functions (eg, cognitive control), individuals with GD showed impaired cognitive control despite the acquisition of better skills compared to non–video game players. Mediating factors (eg, the duration of GD) were found to be associated with different alterations of brain regions in pro gamers and individuals with GD. That is, it was suggested that various factors seemed to modulate the association of extensive video game playing with changes in cognitive function. However, a limited number of brain-imaging studies included pro gamers and/or individuals who reported symptoms of GD for more than 1 year. Thus, more studies that include pro gamers and/or individuals with GD, as well as more diverse comparison groups, and ones that longitudinally track alterations in brain regions should be conducted in the future.</p>
      </sec>
    </sec>
  </body>
  <back>
    <app-group/>
    <glossary>
      <title>Abbreviations</title>
      <def-list>
        <def-item>
          <term id="abb1">ACC</term>
          <def>
            <p>anterior cingulate cortex</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb2">AI</term>
          <def>
            <p>artificial intelligence</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb3">ALFF</term>
          <def>
            <p>amplitude of low-frequency fluctuation</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb4">CEN</term>
          <def>
            <p>central executive network</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb5">DLPFC</term>
          <def>
            <p>dorsolateral prefrontal cortex</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb6">DMN</term>
          <def>
            <p>default mode network</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb7">FC</term>
          <def>
            <p>functional connectivity</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb8">fMRI</term>
          <def>
            <p>functional magnetic resonance imaging</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb9">GD</term>
          <def>
            <p>gaming disorder</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb10">GM</term>
          <def>
            <p>gray matter</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb11">ICD-11</term>
          <def>
            <p>International Classification of Diseases, 11th Revision</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb12">NAc</term>
          <def>
            <p>nucleus accumbens</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb13">OFC</term>
          <def>
            <p>orbitofrontal cortex</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb14">OFL</term>
          <def>
            <p>orbitofrontal lobe</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb15">PCC</term>
          <def>
            <p>posterior cingulate cortex</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb16">PFC</term>
          <def>
            <p>prefrontal cortex</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb17">PHR</term>
          <def>
            <p>personal health record</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb18">PPC</term>
          <def>
            <p>posterior parietal cortex</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb19">PRISMA</term>
          <def>
            <p>Preferred Reporting Items for Systematic Reviews and Meta-Analyses</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb20">SMA</term>
          <def>
            <p>supplementary motor area</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb21">SN</term>
          <def>
            <p>salience network</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb22">WHO</term>
          <def>
            <p>World Health Organization</p>
          </def>
        </def-item>
        <def-item>
          <term id="abb23">WM</term>
          <def>
            <p>white matter</p>
          </def>
        </def-item>
      </def-list>
    </glossary>
    <ack>
      <p>This study was supported by a grant from Game Science Forum in South Korea and by the Technology Innovation Program (grant PC20ONDI0074; AI [artificial intelligence]-Driven Global PHR [personal health record] Pediatric Developmental Disability Management/Treatment Platform) that was funded by the Ministry of Trade, Industry and Energy, Korea. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.</p>
    </ack>
    <fn-group>
      <fn fn-type="con">
        <p>MHP was the principal investigator and was involved in study conception, study design, data capture, data analysis, and interpretation of the results. EC was the primary writer of the manuscript and was involved in study conception, data capture, data analysis, and interpretation of the results. SHS was involved in study conception, data analysis, and editing of the manuscript. JKR, KIJ, YH, and JK were involved in data capture, data analysis, and editing of the manuscript.</p>
      </fn>
      <fn fn-type="conflict">
        <p>None declared.</p>
      </fn>
    </fn-group>
    <ref-list>
      <ref id="ref1">
        <label>1</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Lee</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Schoenstedt</surname>
              <given-names>LJ</given-names>
            </name>
          </person-group>
          <article-title>Comparison of eSports and traditional sports consumption motives</article-title>
          <source>J Res</source>
          <year>2011</year>
          <volume>6</volume>
          <issue>2</issue>
          <fpage>39</fpage>
          <lpage>44</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://files.eric.ed.gov/fulltext/EJ954495.pdf"/>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref2">
        <label>2</label>
        <nlm-citation citation-type="web">
          <article-title>S Korean dies after gaming session</article-title>
          <source>BBC News</source>
          <year>2005</year>
          <month>08</month>
          <day>10</day>
          <access-date>2019-09-09</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://news.bbc.co.uk/2/hi/technology/4137782.stm">http://news.bbc.co.uk/2/hi/technology/4137782.stm</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref3">
        <label>3</label>
        <nlm-citation citation-type="web">
          <article-title>Chinese online gamer dies after three-day session</article-title>
          <source>BBC News</source>
          <year>2011</year>
          <month>02</month>
          <day>22</day>
          <access-date>2019-09-09</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.bbc.com/news/world-asia-pacific-12541769">https://www.bbc.com/news/world-asia-pacific-12541769</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref4">
        <label>4</label>
        <nlm-citation citation-type="web">
          <article-title>My gaming addiction stops me from having relationships</article-title>
          <source>BBC News</source>
          <year>2019</year>
          <month>10</month>
          <day>09</day>
          <access-date>2019-10-12</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.bbc.com/news/newsbeat-49978427">https://www.bbc.com/news/newsbeat-49978427</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref5">
        <label>5</label>
        <nlm-citation citation-type="web">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Good</surname>
              <given-names>OS</given-names>
            </name>
          </person-group>
          <article-title>'Gaming disorder' officially on World Health Organization's list of diseases</article-title>
          <source>Polygon</source>
          <year>2019</year>
          <month>05</month>
          <day>25</day>
          <access-date>2019-05-25</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.polygon.com/2019/5/25/18639893/gaming-disorder-addiction-world-health-organization-who-icd-11">https://www.polygon.com/2019/5/25/18639893/gaming-disorder-addiction-world-health-organization-who-icd-11</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref6">
        <label>6</label>
        <nlm-citation citation-type="web">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Rettner</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
          <article-title>Video game addiction becomes official mental disorder in controversial decision by WHO</article-title>
          <source>Live Science</source>
          <year>2019</year>
          <month>05</month>
          <day>28</day>
          <access-date>2019-09-09</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.livescience.com/65580-video-game-addiction-mental-health-disorder.html">https://www.livescience.com/65580-video-game-addiction-mental-health-disorder.html</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref7">
        <label>7</label>
        <nlm-citation citation-type="web">
          <article-title>Addictive behaviors: Gaming disorder</article-title>
          <source>World Health Organization</source>
          <year>2018</year>
          <month>09</month>
          <day>14</day>
          <access-date>2019-09-09</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.who.int/news-room/q-a-detail/addictive-behaviours-gaming-disorder">https://www.who.int/news-room/q-a-detail/addictive-behaviours-gaming-disorder</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref8">
        <label>8</label>
        <nlm-citation citation-type="web">
          <article-title>Video game addiction is a mental health disorder, World Health Organization says</article-title>
          <source>NBC News</source>
          <year>2019</year>
          <month>05</month>
          <day>26</day>
          <access-date>2019-09-09</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.nbcnews.com/tech/video-games/video-game-addiction-mental-health-disorder-world-health-organization-says-n1010441">https://www.nbcnews.com/tech/video-games/video-game-addiction-mental-health-disorder-world-health-organization-says-n1010441</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref9">
        <label>9</label>
        <nlm-citation citation-type="web">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Kim</surname>
              <given-names>HJ</given-names>
            </name>
          </person-group>
          <article-title>Psychologists express concern over registration of game disorder disease code</article-title>
          <source>ZDNet Korea</source>
          <year>2019</year>
          <month>07</month>
          <day>04</day>
          <access-date>2019-09-09</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://www.zdnet.co.kr/view/?no=20190704142700">http://www.zdnet.co.kr/view/?no=20190704142700</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref10">
        <label>10</label>
        <nlm-citation citation-type="web">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Park</surname>
              <given-names>G</given-names>
            </name>
          </person-group>
          <article-title>'Game addiction' altering the structure of the brain, the importance of early treatment</article-title>
          <source>KBS News</source>
          <year>2019</year>
          <month>03</month>
          <day>11</day>
          <access-date>2019-09-10</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://news.kbs.co.kr/news/view.do?ncd=4154955&#38;ref=A">http://news.kbs.co.kr/news/view.do?ncd=4154955&#38;ref=A</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref11">
        <label>11</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Pan</surname>
              <given-names>N</given-names>
            </name>
            <name name-style="western">
              <surname>Yang</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Du</surname>
              <given-names>X</given-names>
            </name>
            <name name-style="western">
              <surname>Qi</surname>
              <given-names>X</given-names>
            </name>
            <name name-style="western">
              <surname>Du</surname>
              <given-names>G</given-names>
            </name>
            <name name-style="western">
              <surname>Zhang</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Li</surname>
              <given-names>X</given-names>
            </name>
            <name name-style="western">
              <surname>Zhang</surname>
              <given-names>Q</given-names>
            </name>
          </person-group>
          <article-title>Brain structures associated with internet addiction tendency in adolescent online game players</article-title>
          <source>Front Psychiatry</source>
          <year>2018</year>
          <volume>9</volume>
          <fpage>67</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://doi.org/10.3389/fpsyt.2018.00067"/>
          </comment>
          <pub-id pub-id-type="doi">10.3389/fpsyt.2018.00067</pub-id>
          <pub-id pub-id-type="medline">29559931</pub-id>
          <pub-id pub-id-type="pmcid">PMC5845632</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref12">
        <label>12</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Kühn</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Lorenz</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Banaschewski</surname>
              <given-names>T</given-names>
            </name>
            <name name-style="western">
              <surname>Barker</surname>
              <given-names>GJ</given-names>
            </name>
            <name name-style="western">
              <surname>Büchel</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Conrod</surname>
              <given-names>PJ</given-names>
            </name>
            <name name-style="western">
              <surname>Flor</surname>
              <given-names>H</given-names>
            </name>
            <name name-style="western">
              <surname>Garavan</surname>
              <given-names>H</given-names>
            </name>
            <name name-style="western">
              <surname>Ittermann</surname>
              <given-names>B</given-names>
            </name>
            <name name-style="western">
              <surname>Loth</surname>
              <given-names>E</given-names>
            </name>
            <name name-style="western">
              <surname>Mann</surname>
              <given-names>K</given-names>
            </name>
            <name name-style="western">
              <surname>Nees</surname>
              <given-names>F</given-names>
            </name>
            <name name-style="western">
              <surname>Artiges</surname>
              <given-names>E</given-names>
            </name>
            <name name-style="western">
              <surname>Paus</surname>
              <given-names>T</given-names>
            </name>
            <name name-style="western">
              <surname>Rietschel</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Smolka</surname>
              <given-names>MN</given-names>
            </name>
            <name name-style="western">
              <surname>Ströhle</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>Walaszek</surname>
              <given-names>B</given-names>
            </name>
            <name name-style="western">
              <surname>Schumann</surname>
              <given-names>G</given-names>
            </name>
            <name name-style="western">
              <surname>Heinz</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>Gallinat</surname>
              <given-names>J</given-names>
            </name>
            <collab>IMAGEN Consortium</collab>
          </person-group>
          <article-title>Positive association of video game playing with left frontal cortical thickness in adolescents</article-title>
          <source>PLoS One</source>
          <year>2014</year>
          <volume>9</volume>
          <issue>3</issue>
          <fpage>e91506</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://dx.plos.org/10.1371/journal.pone.0091506"/>
          </comment>
          <pub-id pub-id-type="doi">10.1371/journal.pone.0091506</pub-id>
          <pub-id pub-id-type="medline">24633348</pub-id>
          <pub-id pub-id-type="pii">PONE-D-13-50589</pub-id>
          <pub-id pub-id-type="pmcid">PMC3954649</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref13">
        <label>13</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Kühn</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Gallinat</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Amount of lifetime video gaming is positively associated with entorhinal, hippocampal and occipital volume</article-title>
          <source>Mol Psychiatry</source>
          <year>2014</year>
          <month>07</month>
          <volume>19</volume>
          <issue>7</issue>
          <fpage>842</fpage>
          <lpage>847</lpage>
          <pub-id pub-id-type="doi">10.1038/mp.2013.100</pub-id>
          <pub-id pub-id-type="medline">23958958</pub-id>
          <pub-id pub-id-type="pii">mp2013100</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref14">
        <label>14</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Zhang</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Du</surname>
              <given-names>G</given-names>
            </name>
            <name name-style="western">
              <surname>Yang</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Qin</surname>
              <given-names>W</given-names>
            </name>
            <name name-style="western">
              <surname>Li</surname>
              <given-names>X</given-names>
            </name>
            <name name-style="western">
              <surname>Zhang</surname>
              <given-names>Q</given-names>
            </name>
          </person-group>
          <article-title>Higher integrity of the motor and visual pathways in long-term video game players</article-title>
          <source>Front Hum Neurosci</source>
          <year>2015</year>
          <month>3</month>
          <day>10</day>
          <volume>9</volume>
          <fpage>1</fpage>
          <lpage>7</lpage>
          <pub-id pub-id-type="doi">10.3389/fnhum.2015.00098</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref15">
        <label>15</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Richlan</surname>
              <given-names>F</given-names>
            </name>
            <name name-style="western">
              <surname>Schubert</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Mayer</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Hutzler</surname>
              <given-names>F</given-names>
            </name>
            <name name-style="western">
              <surname>Kronbichler</surname>
              <given-names>M</given-names>
            </name>
          </person-group>
          <article-title>Action video gaming and the brain: fMRI effects without behavioral effects in visual and verbal cognitive tasks</article-title>
          <source>Brain Behav</source>
          <year>2018</year>
          <month>01</month>
          <volume>8</volume>
          <issue>1</issue>
          <fpage>e00877</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://doi.org/10.1002/brb3.877"/>
          </comment>
          <pub-id pub-id-type="doi">10.1002/brb3.877</pub-id>
          <pub-id pub-id-type="medline">29568680</pub-id>
          <pub-id pub-id-type="pii">BRB3877</pub-id>
          <pub-id pub-id-type="pmcid">PMC5853626</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref16">
        <label>16</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Hyun</surname>
              <given-names>GJ</given-names>
            </name>
            <name name-style="western">
              <surname>Shin</surname>
              <given-names>YW</given-names>
            </name>
            <name name-style="western">
              <surname>Kim</surname>
              <given-names>B</given-names>
            </name>
            <name name-style="western">
              <surname>Cheong</surname>
              <given-names>JH</given-names>
            </name>
            <name name-style="western">
              <surname>Jin</surname>
              <given-names>SN</given-names>
            </name>
            <name name-style="western">
              <surname>Han</surname>
              <given-names>DH</given-names>
            </name>
          </person-group>
          <article-title>Increased cortical thickness in professional on-line gamers</article-title>
          <source>Psychiatry Investig</source>
          <year>2013</year>
          <month>12</month>
          <volume>10</volume>
          <issue>4</issue>
          <fpage>388</fpage>
          <lpage>392</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://psychiatryinvestigation.org/journal/view.php?doi=10.4306/pi.2013.10.4.388"/>
          </comment>
          <pub-id pub-id-type="doi">10.4306/pi.2013.10.4.388</pub-id>
          <pub-id pub-id-type="medline">24474988</pub-id>
          <pub-id pub-id-type="pmcid">PMC3902157</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref17">
        <label>17</label>
        <nlm-citation citation-type="web">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Lee</surname>
              <given-names>YH</given-names>
            </name>
            <name name-style="western">
              <surname>Jung</surname>
              <given-names>MG</given-names>
            </name>
            <name name-style="western">
              <surname>Jang</surname>
              <given-names>MJ</given-names>
            </name>
            <name name-style="western">
              <surname>Lee</surname>
              <given-names>JJ</given-names>
            </name>
            <name name-style="western">
              <surname>Nam</surname>
              <given-names>GD</given-names>
            </name>
            <name name-style="western">
              <surname>Han</surname>
              <given-names>JO</given-names>
            </name>
            <name name-style="western">
              <surname>Lim</surname>
              <given-names>TJ</given-names>
            </name>
            <name name-style="western">
              <surname>Yun</surname>
              <given-names>DJ</given-names>
            </name>
            <name name-style="western">
              <surname>Yoo</surname>
              <given-names>HG</given-names>
            </name>
            <name name-style="western">
              <surname>Kim</surname>
              <given-names>SP</given-names>
            </name>
          </person-group>
          <source>The 2018 Survey on the Korean E-sports Industry</source>
          <year>2018</year>
          <month>12</month>
          <day>31</day>
          <access-date>2019-05-29</access-date>
          <publisher-loc>Jeollanam-do Province, South Korea</publisher-loc>
          <publisher-name>Korea Creative Content Agency</publisher-name>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://www.kocca.kr/cop/bbs/view/B0000147/1837423.do?searchCnd=1&#38;searchWrd=2018+%EC%9D%B4%EC%8A%A4%ED%8F%AC%EC%B8%A0&#38;cateTp1=&#38;cateTp2=&#38;useAt=&#38;menuNo=201825&#38;categorys=0&#38;subcate=0&#38;cateCode=&#38;type=&#38;instNo=0&#38;questionTp=&#38;uf_Setting=&#38;recovery=&#38;option1=&#38;option2=&#38;year=&#38;categoryCOM062=&#38;categoryCOM063=&#38;categoryCOM208=&#38;categoryInst=&#38;morePage=&#38;delCode=0&#38;qtp=&#38;pageIndex=1">https://tinyurl.com/fa8fev96</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref18">
        <label>18</label>
        <nlm-citation citation-type="web">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Chapman</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <article-title>Salaries of pro gamers</article-title>
          <source>CHRON</source>
          <year>2018</year>
          <month>06</month>
          <day>27</day>
          <access-date>2019-10-21</access-date>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://work.chron.com/salaries-pro-gamers-26166.html">https://work.chron.com/salaries-pro-gamers-26166.html</ext-link>
          </comment>
        </nlm-citation>
      </ref>
      <ref id="ref19">
        <label>19</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Thompson</surname>
              <given-names>JJ</given-names>
            </name>
            <name name-style="western">
              <surname>Blair</surname>
              <given-names>MR</given-names>
            </name>
            <name name-style="western">
              <surname>Henrey</surname>
              <given-names>AJ</given-names>
            </name>
          </person-group>
          <article-title>Over the hill at 24: Persistent age-related cognitive-motor decline in reaction times in an ecologically valid video game task begins in early adulthood</article-title>
          <source>PLoS One</source>
          <year>2014</year>
          <volume>9</volume>
          <issue>4</issue>
          <fpage>e94215</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://dx.plos.org/10.1371/journal.pone.0094215"/>
          </comment>
          <pub-id pub-id-type="doi">10.1371/journal.pone.0094215</pub-id>
          <pub-id pub-id-type="medline">24718593</pub-id>
          <pub-id pub-id-type="pii">PONE-D-13-36153</pub-id>
          <pub-id pub-id-type="pmcid">PMC3981764</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref20">
        <label>20</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Gong</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Ma</surname>
              <given-names>W</given-names>
            </name>
            <name name-style="western">
              <surname>Gong</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>He</surname>
              <given-names>H</given-names>
            </name>
            <name name-style="western">
              <surname>Dong</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Zhang</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Li</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Luo</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Yao</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
          <article-title>Action video game experience related to altered large-scale white matter networks</article-title>
          <source>Neural Plast</source>
          <year>2017</year>
          <volume>2017</volume>
          <fpage>7543686</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://doi.org/10.1155/2017/7543686"/>
          </comment>
          <pub-id pub-id-type="doi">10.1155/2017/7543686</pub-id>
          <pub-id pub-id-type="medline">28706740</pub-id>
          <pub-id pub-id-type="pmcid">PMC5494573</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref21">
        <label>21</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Leeman</surname>
              <given-names>RF</given-names>
            </name>
            <name name-style="western">
              <surname>Potenza</surname>
              <given-names>MN</given-names>
            </name>
          </person-group>
          <article-title>A targeted review of the neurobiology and genetics of behavioural addictions: An emerging area of research</article-title>
          <source>Can J Psychiatry</source>
          <year>2013</year>
          <month>05</month>
          <volume>58</volume>
          <issue>5</issue>
          <fpage>260</fpage>
          <lpage>273</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/23756286"/>
          </comment>
          <pub-id pub-id-type="doi">10.1177/070674371305800503</pub-id>
          <pub-id pub-id-type="medline">23756286</pub-id>
          <pub-id pub-id-type="pmcid">PMC3762982</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref22">
        <label>22</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Wei</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Zhang</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Turel</surname>
              <given-names>O</given-names>
            </name>
            <name name-style="western">
              <surname>Bechara</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>He</surname>
              <given-names>Q</given-names>
            </name>
          </person-group>
          <article-title>A tripartite neurocognitive model of internet gaming disorder</article-title>
          <source>Front Psychiatry</source>
          <year>2017</year>
          <volume>8</volume>
          <fpage>285</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://dx.doi.org/10.3389/fpsyt.2017.00285"/>
          </comment>
          <pub-id pub-id-type="doi">10.3389/fpsyt.2017.00285</pub-id>
          <pub-id pub-id-type="medline">29312016</pub-id>
          <pub-id pub-id-type="pmcid">PMC5735083</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref23">
        <label>23</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Moher</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Liberati</surname>
              <given-names>A</given-names>
            </name>
            <name name-style="western">
              <surname>Tetzlaff</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Altman</surname>
              <given-names>DG</given-names>
            </name>
          </person-group>
          <article-title>Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement</article-title>
          <source>PLoS Med</source>
          <year>2009</year>
          <month>07</month>
          <day>21</day>
          <volume>6</volume>
          <issue>7</issue>
          <fpage>e1000097</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://dx.plos.org/10.1371/journal.pmed.1000097"/>
          </comment>
          <pub-id pub-id-type="doi">10.1371/journal.pmed.1000097</pub-id>
          <pub-id pub-id-type="medline">19621072</pub-id>
          <pub-id pub-id-type="pmcid">PMC2707599</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref24">
        <label>24</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Wang</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Yin</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Sun</surname>
              <given-names>YW</given-names>
            </name>
            <name name-style="western">
              <surname>Zhou</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Chen</surname>
              <given-names>X</given-names>
            </name>
            <name name-style="western">
              <surname>Ding</surname>
              <given-names>WN</given-names>
            </name>
            <name name-style="western">
              <surname>Wang</surname>
              <given-names>W</given-names>
            </name>
            <name name-style="western">
              <surname>Li</surname>
              <given-names>W</given-names>
            </name>
            <name name-style="western">
              <surname>Xu</surname>
              <given-names>JR</given-names>
            </name>
            <name name-style="western">
              <surname>Du</surname>
              <given-names>YS</given-names>
            </name>
          </person-group>
          <article-title>Decreased prefrontal lobe interhemispheric functional connectivity in adolescents with internet gaming disorder: A primary study using resting-state FMRI</article-title>
          <source>PLoS One</source>
          <year>2015</year>
          <volume>10</volume>
          <issue>3</issue>
          <fpage>e0118733</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://dx.plos.org/10.1371/journal.pone.0118733"/>
          </comment>
          <pub-id pub-id-type="doi">10.1371/journal.pone.0118733</pub-id>
          <pub-id pub-id-type="medline">25738502</pub-id>
          <pub-id pub-id-type="pii">PONE-D-14-37269</pub-id>
          <pub-id pub-id-type="pmcid">PMC4349655</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref25">
        <label>25</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Gong</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Yao</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Gan</surname>
              <given-names>X</given-names>
            </name>
            <name name-style="western">
              <surname>Peng</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Ma</surname>
              <given-names>W</given-names>
            </name>
            <name name-style="western">
              <surname>Yao</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
          <article-title>A reduction in video gaming time produced a decrease in brain activity</article-title>
          <source>Front Hum Neurosci</source>
          <year>2019</year>
          <volume>13</volume>
          <fpage>134</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://doi.org/10.3389/fnhum.2019.00134"/>
          </comment>
          <pub-id pub-id-type="doi">10.3389/fnhum.2019.00134</pub-id>
          <pub-id pub-id-type="medline">31057383</pub-id>
          <pub-id pub-id-type="pmcid">PMC6478706</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref26">
        <label>26</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Bremer</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>The internet and children: Advantages and disadvantages</article-title>
          <source>Child Adolesc Psychiatr Clin N Am</source>
          <year>2005</year>
          <month>07</month>
          <volume>14</volume>
          <issue>3</issue>
          <fpage>405</fpage>
          <lpage>428, viii</lpage>
          <pub-id pub-id-type="doi">10.1016/j.chc.2005.02.003</pub-id>
          <pub-id pub-id-type="medline">15936666</pub-id>
          <pub-id pub-id-type="pii">S1056-4993(05)00019-2</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref27">
        <label>27</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Steinberg</surname>
              <given-names>L</given-names>
            </name>
          </person-group>
          <article-title>Cognitive and affective development in adolescence</article-title>
          <source>Trends Cogn Sci</source>
          <year>2005</year>
          <month>02</month>
          <volume>9</volume>
          <issue>2</issue>
          <fpage>69</fpage>
          <lpage>74</lpage>
          <pub-id pub-id-type="doi">10.1016/j.tics.2004.12.005</pub-id>
          <pub-id pub-id-type="medline">15668099</pub-id>
          <pub-id pub-id-type="pii">S1364-6613(04)00317-1</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref28">
        <label>28</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Cho</surname>
              <given-names>YU</given-names>
            </name>
            <name name-style="western">
              <surname>Lee</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Lee</surname>
              <given-names>JE</given-names>
            </name>
            <name name-style="western">
              <surname>Kim</surname>
              <given-names>KH</given-names>
            </name>
            <name name-style="western">
              <surname>Lee</surname>
              <given-names>DY</given-names>
            </name>
            <name name-style="western">
              <surname>Jung</surname>
              <given-names>YC</given-names>
            </name>
          </person-group>
          <article-title>Exploratory metabolomics of biomarker identification for the internet gaming disorder in young Korean males</article-title>
          <source>J Chromatogr B Analyt Technol Biomed Life Sci</source>
          <year>2017</year>
          <month>07</month>
          <day>01</day>
          <volume>1057</volume>
          <fpage>24</fpage>
          <lpage>31</lpage>
          <pub-id pub-id-type="doi">10.1016/j.jchromb.2017.04.046</pub-id>
          <pub-id pub-id-type="medline">28482325</pub-id>
          <pub-id pub-id-type="pii">S1570-0232(17)30149-6</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref29">
        <label>29</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Tanaka</surname>
              <given-names>S</given-names>
            </name>
            <name name-style="western">
              <surname>Ikeda</surname>
              <given-names>H</given-names>
            </name>
            <name name-style="western">
              <surname>Kasahara</surname>
              <given-names>K</given-names>
            </name>
            <name name-style="western">
              <surname>Kato</surname>
              <given-names>R</given-names>
            </name>
            <name name-style="western">
              <surname>Tsubomi</surname>
              <given-names>H</given-names>
            </name>
            <name name-style="western">
              <surname>Sugawara</surname>
              <given-names>SK</given-names>
            </name>
            <name name-style="western">
              <surname>Mori</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Hanakawa</surname>
              <given-names>T</given-names>
            </name>
            <name name-style="western">
              <surname>Sadato</surname>
              <given-names>N</given-names>
            </name>
            <name name-style="western">
              <surname>Honda</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Watanabe</surname>
              <given-names>K</given-names>
            </name>
          </person-group>
          <article-title>Larger right posterior parietal volume in action video game experts: A behavioral and voxel-based morphometry (VBM) study</article-title>
          <source>PLoS One</source>
          <year>2013</year>
          <volume>8</volume>
          <issue>6</issue>
          <fpage>e66998</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://dx.plos.org/10.1371/journal.pone.0066998"/>
          </comment>
          <pub-id pub-id-type="doi">10.1371/journal.pone.0066998</pub-id>
          <pub-id pub-id-type="medline">23776706</pub-id>
          <pub-id pub-id-type="pii">PONE-D-12-12605</pub-id>
          <pub-id pub-id-type="pmcid">PMC3679077</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref30">
        <label>30</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Gong</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>He</surname>
              <given-names>H</given-names>
            </name>
            <name name-style="western">
              <surname>Liu</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Ma</surname>
              <given-names>W</given-names>
            </name>
            <name name-style="western">
              <surname>Dong</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Luo</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Yao</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
          <article-title>Enhanced functional connectivity and increased gray matter volume of insula related to action video game playing</article-title>
          <source>Sci Rep</source>
          <year>2015</year>
          <month>04</month>
          <day>16</day>
          <volume>5</volume>
          <fpage>9763</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://doi.org/10.1038/srep09763"/>
          </comment>
          <pub-id pub-id-type="doi">10.1038/srep09763</pub-id>
          <pub-id pub-id-type="medline">25880157</pub-id>
          <pub-id pub-id-type="pii">srep09763</pub-id>
          <pub-id pub-id-type="pmcid">PMC5381748</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref31">
        <label>31</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Gong</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>He</surname>
              <given-names>H</given-names>
            </name>
            <name name-style="western">
              <surname>Ma</surname>
              <given-names>W</given-names>
            </name>
            <name name-style="western">
              <surname>Liu</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Huang</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Dong</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Gong</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Li</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Luo</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Yao</surname>
              <given-names>D</given-names>
            </name>
          </person-group>
          <article-title>Functional integration between salience and central executive networks: A role for action video game experience</article-title>
          <source>Neural Plast</source>
          <year>2016</year>
          <volume>2016</volume>
          <fpage>9803165</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://doi.org/10.1155/2016/9803165"/>
          </comment>
          <pub-id pub-id-type="doi">10.1155/2016/9803165</pub-id>
          <pub-id pub-id-type="medline">26885408</pub-id>
          <pub-id pub-id-type="pmcid">PMC4739029</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref32">
        <label>32</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Han</surname>
              <given-names>DH</given-names>
            </name>
            <name name-style="western">
              <surname>Lyoo</surname>
              <given-names>IK</given-names>
            </name>
            <name name-style="western">
              <surname>Renshaw</surname>
              <given-names>PF</given-names>
            </name>
          </person-group>
          <article-title>Differential regional gray matter volumes in patients with on-line game addiction and professional gamers</article-title>
          <source>J Psychiatr Res</source>
          <year>2012</year>
          <month>04</month>
          <volume>46</volume>
          <issue>4</issue>
          <fpage>507</fpage>
          <lpage>515</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="http://europepmc.org/abstract/MED/22277302"/>
          </comment>
          <pub-id pub-id-type="doi">10.1016/j.jpsychires.2012.01.004</pub-id>
          <pub-id pub-id-type="medline">22277302</pub-id>
          <pub-id pub-id-type="pii">S0022-3956(12)00005-2</pub-id>
          <pub-id pub-id-type="pmcid">PMC4632992</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref33">
        <label>33</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Ko</surname>
              <given-names>CH</given-names>
            </name>
            <name name-style="western">
              <surname>Liu</surname>
              <given-names>GC</given-names>
            </name>
            <name name-style="western">
              <surname>Yen</surname>
              <given-names>JY</given-names>
            </name>
            <name name-style="western">
              <surname>Chen</surname>
              <given-names>CY</given-names>
            </name>
            <name name-style="western">
              <surname>Yen</surname>
              <given-names>CF</given-names>
            </name>
            <name name-style="western">
              <surname>Chen</surname>
              <given-names>CS</given-names>
            </name>
          </person-group>
          <article-title>Brain correlates of craving for online gaming under cue exposure in subjects with internet gaming addiction and in remitted subjects</article-title>
          <source>Addict Biol</source>
          <year>2013</year>
          <month>05</month>
          <volume>18</volume>
          <issue>3</issue>
          <fpage>559</fpage>
          <lpage>569</lpage>
          <pub-id pub-id-type="doi">10.1111/j.1369-1600.2011.00405.x</pub-id>
          <pub-id pub-id-type="medline">22026537</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref34">
        <label>34</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Yuan</surname>
              <given-names>K</given-names>
            </name>
            <name name-style="western">
              <surname>Cheng</surname>
              <given-names>P</given-names>
            </name>
            <name name-style="western">
              <surname>Dong</surname>
              <given-names>T</given-names>
            </name>
            <name name-style="western">
              <surname>Bi</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Xing</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Yu</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Zhao</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Dong</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>von Deneen</surname>
              <given-names>KM</given-names>
            </name>
            <name name-style="western">
              <surname>Liu</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Qin</surname>
              <given-names>W</given-names>
            </name>
            <name name-style="western">
              <surname>Tian</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Cortical thickness abnormalities in late adolescence with online gaming addiction</article-title>
          <source>PLoS One</source>
          <year>2013</year>
          <volume>8</volume>
          <issue>1</issue>
          <fpage>e53055</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://dx.plos.org/10.1371/journal.pone.0053055"/>
          </comment>
          <pub-id pub-id-type="doi">10.1371/journal.pone.0053055</pub-id>
          <pub-id pub-id-type="medline">23326379</pub-id>
          <pub-id pub-id-type="pii">PONE-D-12-17595</pub-id>
          <pub-id pub-id-type="pmcid">PMC3541375</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref35">
        <label>35</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Yuan</surname>
              <given-names>K</given-names>
            </name>
            <name name-style="western">
              <surname>Jin</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Cheng</surname>
              <given-names>P</given-names>
            </name>
            <name name-style="western">
              <surname>Yang</surname>
              <given-names>X</given-names>
            </name>
            <name name-style="western">
              <surname>Dong</surname>
              <given-names>T</given-names>
            </name>
            <name name-style="western">
              <surname>Bi</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Xing</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>von Deneen</surname>
              <given-names>KM</given-names>
            </name>
            <name name-style="western">
              <surname>Yu</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Liu</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Liang</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Cheng</surname>
              <given-names>T</given-names>
            </name>
            <name name-style="western">
              <surname>Qin</surname>
              <given-names>W</given-names>
            </name>
            <name name-style="western">
              <surname>Tian</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Amplitude of low frequency fluctuation abnormalities in adolescents with online gaming addiction</article-title>
          <source>PLoS One</source>
          <year>2013</year>
          <volume>8</volume>
          <issue>11</issue>
          <fpage>e78708</fpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://dx.plos.org/10.1371/journal.pone.0078708"/>
          </comment>
          <pub-id pub-id-type="doi">10.1371/journal.pone.0078708</pub-id>
          <pub-id pub-id-type="medline">24223843</pub-id>
          <pub-id pub-id-type="pii">PONE-D-13-19594</pub-id>
          <pub-id pub-id-type="pmcid">PMC3817073</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref36">
        <label>36</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Ko</surname>
              <given-names>CH</given-names>
            </name>
            <name name-style="western">
              <surname>Hsieh</surname>
              <given-names>TJ</given-names>
            </name>
            <name name-style="western">
              <surname>Chen</surname>
              <given-names>CY</given-names>
            </name>
            <name name-style="western">
              <surname>Yen</surname>
              <given-names>CF</given-names>
            </name>
            <name name-style="western">
              <surname>Chen</surname>
              <given-names>CS</given-names>
            </name>
            <name name-style="western">
              <surname>Yen</surname>
              <given-names>JY</given-names>
            </name>
            <name name-style="western">
              <surname>Wang</surname>
              <given-names>PW</given-names>
            </name>
            <name name-style="western">
              <surname>Liu</surname>
              <given-names>GC</given-names>
            </name>
          </person-group>
          <article-title>Altered brain activation during response inhibition and error processing in subjects with internet gaming disorder: A functional magnetic imaging study</article-title>
          <source>Eur Arch Psychiatry Clin Neurosci</source>
          <year>2014</year>
          <month>12</month>
          <volume>264</volume>
          <issue>8</issue>
          <fpage>661</fpage>
          <lpage>672</lpage>
          <pub-id pub-id-type="doi">10.1007/s00406-013-0483-3</pub-id>
          <pub-id pub-id-type="medline">24469099</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref37">
        <label>37</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Chen</surname>
              <given-names>CY</given-names>
            </name>
            <name name-style="western">
              <surname>Huang</surname>
              <given-names>MF</given-names>
            </name>
            <name name-style="western">
              <surname>Yen</surname>
              <given-names>JY</given-names>
            </name>
            <name name-style="western">
              <surname>Chen</surname>
              <given-names>CS</given-names>
            </name>
            <name name-style="western">
              <surname>Liu</surname>
              <given-names>GC</given-names>
            </name>
            <name name-style="western">
              <surname>Yen</surname>
              <given-names>CF</given-names>
            </name>
            <name name-style="western">
              <surname>Ko</surname>
              <given-names>CH</given-names>
            </name>
          </person-group>
          <article-title>Brain correlates of response inhibition in internet gaming disorder</article-title>
          <source>Psychiatry Clin Neurosci</source>
          <year>2015</year>
          <month>04</month>
          <volume>69</volume>
          <issue>4</issue>
          <fpage>201</fpage>
          <lpage>209</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://doi.org/10.1111/pcn.12224"/>
          </comment>
          <pub-id pub-id-type="doi">10.1111/pcn.12224</pub-id>
          <pub-id pub-id-type="medline">25047685</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref38">
        <label>38</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Ko</surname>
              <given-names>CH</given-names>
            </name>
            <name name-style="western">
              <surname>Hsieh</surname>
              <given-names>TJ</given-names>
            </name>
            <name name-style="western">
              <surname>Wang</surname>
              <given-names>PW</given-names>
            </name>
            <name name-style="western">
              <surname>Lin</surname>
              <given-names>WC</given-names>
            </name>
            <name name-style="western">
              <surname>Yen</surname>
              <given-names>CF</given-names>
            </name>
            <name name-style="western">
              <surname>Chen</surname>
              <given-names>CS</given-names>
            </name>
            <name name-style="western">
              <surname>Yen</surname>
              <given-names>JY</given-names>
            </name>
          </person-group>
          <article-title>Altered gray matter density and disrupted functional connectivity of the amygdala in adults with internet gaming disorder</article-title>
          <source>Prog Neuropsychopharmacol Biol Psychiatry</source>
          <year>2015</year>
          <month>03</month>
          <day>03</day>
          <volume>57</volume>
          <fpage>185</fpage>
          <lpage>192</lpage>
          <pub-id pub-id-type="doi">10.1016/j.pnpbp.2014.11.003</pub-id>
          <pub-id pub-id-type="medline">25448779</pub-id>
          <pub-id pub-id-type="pii">S0278-5846(14)00219-X</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref39">
        <label>39</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Cai</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Yuan</surname>
              <given-names>K</given-names>
            </name>
            <name name-style="western">
              <surname>Yin</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Feng</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Bi</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Li</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Yu</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Jin</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Qin</surname>
              <given-names>W</given-names>
            </name>
            <name name-style="western">
              <surname>Tian</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Striatum morphometry is associated with cognitive control deficits and symptom severity in internet gaming disorder</article-title>
          <source>Brain Imaging Behav</source>
          <year>2016</year>
          <month>03</month>
          <volume>10</volume>
          <issue>1</issue>
          <fpage>12</fpage>
          <lpage>20</lpage>
          <pub-id pub-id-type="doi">10.1007/s11682-015-9358-8</pub-id>
          <pub-id pub-id-type="medline">25720356</pub-id>
          <pub-id pub-id-type="pii">10.1007/s11682-015-9358-8</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref40">
        <label>40</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Chen</surname>
              <given-names>CY</given-names>
            </name>
            <name name-style="western">
              <surname>Yen</surname>
              <given-names>JY</given-names>
            </name>
            <name name-style="western">
              <surname>Wang</surname>
              <given-names>PW</given-names>
            </name>
            <name name-style="western">
              <surname>Liu</surname>
              <given-names>GC</given-names>
            </name>
            <name name-style="western">
              <surname>Yen</surname>
              <given-names>CF</given-names>
            </name>
            <name name-style="western">
              <surname>Ko</surname>
              <given-names>CH</given-names>
            </name>
          </person-group>
          <article-title>Altered functional connectivity of the insula and nucleus accumbens in internet gaming disorder: A resting state fMRI study</article-title>
          <source>Eur Addict Res</source>
          <year>2016</year>
          <volume>22</volume>
          <issue>4</issue>
          <fpage>192</fpage>
          <lpage>200</lpage>
          <comment>
            <ext-link ext-link-type="uri" xlink:type="simple" xlink:href="https://www.karger.com?DOI=10.1159/000440716"/>
          </comment>
          <pub-id pub-id-type="doi">10.1159/000440716</pub-id>
          <pub-id pub-id-type="medline">26863028</pub-id>
          <pub-id pub-id-type="pii">000440716</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref41">
        <label>41</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Jin</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Zhang</surname>
              <given-names>T</given-names>
            </name>
            <name name-style="western">
              <surname>Cai</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Bi</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Li</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Yu</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Zhang</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Yuan</surname>
              <given-names>K</given-names>
            </name>
          </person-group>
          <article-title>Abnormal prefrontal cortex resting state functional connectivity and severity of internet gaming disorder</article-title>
          <source>Brain Imaging Behav</source>
          <year>2016</year>
          <month>09</month>
          <volume>10</volume>
          <issue>3</issue>
          <fpage>719</fpage>
          <lpage>729</lpage>
          <pub-id pub-id-type="doi">10.1007/s11682-015-9439-8</pub-id>
          <pub-id pub-id-type="medline">26311395</pub-id>
          <pub-id pub-id-type="pii">10.1007/s11682-015-9439-8</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref42">
        <label>42</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Yuan</surname>
              <given-names>K</given-names>
            </name>
            <name name-style="western">
              <surname>Yu</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Cai</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Feng</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Li</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Bi</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Liu</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Zhang</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Jin</surname>
              <given-names>C</given-names>
            </name>
            <name name-style="western">
              <surname>Li</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Qin</surname>
              <given-names>W</given-names>
            </name>
            <name name-style="western">
              <surname>Tian</surname>
              <given-names>J</given-names>
            </name>
          </person-group>
          <article-title>Frontostriatal circuits, resting state functional connectivity and cognitive control in internet gaming disorder</article-title>
          <source>Addict Biol</source>
          <year>2017</year>
          <month>05</month>
          <volume>22</volume>
          <issue>3</issue>
          <fpage>813</fpage>
          <lpage>822</lpage>
          <pub-id pub-id-type="doi">10.1111/adb.12348</pub-id>
          <pub-id pub-id-type="medline">26769234</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref43">
        <label>43</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Zhai</surname>
              <given-names>J</given-names>
            </name>
            <name name-style="western">
              <surname>Luo</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Qiu</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Kang</surname>
              <given-names>Y</given-names>
            </name>
            <name name-style="western">
              <surname>Liu</surname>
              <given-names>B</given-names>
            </name>
            <name name-style="western">
              <surname>Yu</surname>
              <given-names>D</given-names>
            </name>
            <name name-style="western">
              <surname>Lu</surname>
              <given-names>X</given-names>
            </name>
            <name name-style="western">
              <surname>Yuan</surname>
              <given-names>K</given-names>
            </name>
          </person-group>
          <article-title>The topological organization of white matter network in internet gaming disorder individuals</article-title>
          <source>Brain Imaging Behav</source>
          <year>2017</year>
          <month>12</month>
          <volume>11</volume>
          <issue>6</issue>
          <fpage>1769</fpage>
          <lpage>1778</lpage>
          <pub-id pub-id-type="doi">10.1007/s11682-016-9652-0</pub-id>
          <pub-id pub-id-type="medline">27815774</pub-id>
          <pub-id pub-id-type="pii">10.1007/s11682-016-9652-0</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref44">
        <label>44</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>Wartberg</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Kriston</surname>
              <given-names>L</given-names>
            </name>
            <name name-style="western">
              <surname>Zieglmeier</surname>
              <given-names>M</given-names>
            </name>
            <name name-style="western">
              <surname>Lincoln</surname>
              <given-names>T</given-names>
            </name>
            <name name-style="western">
              <surname>Kammerl</surname>
              <given-names>R</given-names>
            </name>
          </person-group>
          <article-title>A longitudinal study on psychosocial causes and consequences of internet gaming disorder in adolescence</article-title>
          <source>Psychol Med</source>
          <year>2019</year>
          <month>01</month>
          <volume>49</volume>
          <issue>2</issue>
          <fpage>287</fpage>
          <lpage>294</lpage>
          <pub-id pub-id-type="doi">10.1017/S003329171800082X</pub-id>
          <pub-id pub-id-type="medline">29622057</pub-id>
          <pub-id pub-id-type="pii">S003329171800082X</pub-id>
        </nlm-citation>
      </ref>
      <ref id="ref45">
        <label>45</label>
        <nlm-citation citation-type="journal">
          <person-group person-group-type="author">
            <name name-style="western">
              <surname>King</surname>
              <given-names>DL</given-names>
            </name>
            <name name-style="western">
              <surname>Delfabbro</surname>
              <given-names>PH</given-names>
            </name>
          </person-group>
          <article-title>The cognitive psychopathology of internet gaming disorder in adolescence</article-title>
          <source>J Abnorm Child Psychol</source>
          <year>2016</year>
          <month>2</month>
          <day>15</day>
          <volume>44</volume>
          <issue>8</issue>
          <fpage>1635</fpage>
          <lpage>1645</lpage>
          <pub-id pub-id-type="doi">10.1007/s10802-016-0135-y</pub-id>
          <pub-id pub-id-type="medline">26875565</pub-id>
        </nlm-citation>
      </ref>
    </ref-list>
  </back>
</article>
