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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Neurol.</journal-id>
<journal-title>Frontiers in Neurology</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Neurol.</abbrev-journal-title>
<issn pub-type="epub">1664-2295</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fneur.2025.1614586</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Neurology</subject>
<subj-group>
<subject>Systematic Review</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Efficacy and safety of repetitive transcranial magnetic therapy for post-stroke aphasia: a systematic review and meta-analysis of randomized controlled trials</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Xie</surname><given-names>Lin</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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</contrib>
<contrib contrib-type="author">
<name><surname>Diao</surname><given-names>Yingxiu</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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</contrib>
<contrib contrib-type="author">
<name><surname>Gong</surname><given-names>Cheng</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/2056368/overview"/>
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</contrib>
<contrib contrib-type="author">
<name><surname>Huang</surname><given-names>Jiahao</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<contrib contrib-type="author">
<name><surname>Huang</surname><given-names>Miao</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<uri xlink:href="https://loop.frontiersin.org/people/2543922/overview"/>
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<contrib contrib-type="author" corresp="yes">
<name><surname>Dong</surname><given-names>Zhenying</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x002A;</sup></xref>
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<aff id="aff1"><sup>1</sup><institution>Department of Rehabilitation Medicine, Ganzhou People&#x2019;s Hospital</institution>, <addr-line>Ganzhou, Jiangxi</addr-line>, <country>China</country></aff>
<aff id="aff2"><sup>2</sup><institution>Department of Rehabilitation Medicine, Gannan Medical University</institution>, <addr-line>Ganzhou, Jiangxi</addr-line>, <country>China</country></aff>
<aff id="aff3"><sup>3</sup><institution>Department of Rehabilitation Medicine, Xiangya Hospital, Central South University</institution>, <addr-line>Jiangxi</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by" id="fn0001"><p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1420557/overview">Nicholas Aderinto</ext-link>, Ladoke Akintola University of Technology, Nigeria</p></fn>
<fn fn-type="edited-by" id="fn0002"><p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1336469/overview">Georgios Mikellides</ext-link>, University of Nicosia, Cyprus</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/1994759/overview">Mark H. Myers</ext-link>, University of Tennessee Health Science Center (UTHSC), United States</p></fn>
<corresp id="c001">&#x002A;Correspondence: Zhenying Dong, <email>x7u03k@163.com</email></corresp>
</author-notes>
<pub-date pub-type="epub">
<day>20</day>
<month>10</month>
<year>2025</year>
</pub-date>
<pub-date pub-type="collection">
<year>2025</year>
</pub-date>
<volume>16</volume>
<elocation-id>1614586</elocation-id>
<history>
<date date-type="received">
<day>19</day>
<month>04</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>15</day>
<month>09</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x00A9; 2025 Xie, Diao, Gong, Huang, Huang and Dong.</copyright-statement>
<copyright-year>2025</copyright-year>
<copyright-holder>Xie, Diao, Gong, Huang, Huang and Dong</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/">
<p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p>
</license>
</permissions>
<abstract>
<sec id="sec1">
<title>Objective</title>
<p>The purpose of this meta-analysis was to investigate the effectiveness and safety of repetitive transcranial magnetic stimulation (rTMS) in the treatment of patients with post-stroke aphasia (PSA).</p>
</sec>
<sec id="sec2">
<title>Methods</title>
<p>The PubMed, PEDro, Embase, Cochrane Library, CNKI, Wanfang Data and Web of Science databases were systematically searched from inception until January 30, 2024. Eligible randomized controlled trials (RCTs) contained information on the population (PSA), intervention (rTMS), and outcomes (Western Aphasia Battery, Aphasia Quotient, Aphasia Battery in Chinese, Boston Diagnostic Aphasia Examination, Aachener Aphasie Test, Concise Chinese Aphasia Test and Computerized Picture Naming Test). Participants in the rTMS intervention group were compared with those in sham or other control groups. Two independent researchers searched for, screened, and qualified the articles. Two independent researchers extracted key information from each eligible study. The authors&#x2019; names, year of publication, setting, total sample size, rTMS parameters, baseline/mean difference (MD), and 95% confidence interval (CI) were extracted using a standardized form, and the methodological quality was assessed using the Cochrane Risk of Bias tool (Revman 5.40, Nordic Cochrane Center) and GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system.</p>
</sec>
<sec id="sec3">
<title>Results</title>
<p>Thirty relevant RCTs were included, involving a total of 1,597 patients. The analysis turned out that rTMS combined with speech and language therapy (SLT) resulted in significant improvements in auditory comprehension, naming, repetition, and spontaneous speech in patients with PSA compared with sham stimulation combined with SLT or SLT alone in the control group. (auditory comprehension, MD&#x202F;=&#x202F;1.94, 95%CI&#x202F;=&#x202F;[1.16, 2.17], <italic>p</italic>&#x202F;&#x003C;&#x202F;0.001; naming, MD&#x202F;=&#x202F;1.53, 95%CI&#x202F;=&#x202F;[0.82, 2.24], <italic>p</italic>&#x202F;&#x003C;&#x202F;0.001; repetition, MD&#x202F;=&#x202F;1.79, 95%CI&#x202F;=&#x202F;[1.20, 2.38], <italic>p</italic>&#x202F;&#x003C;&#x202F;0.001; spontaneous speech, MD&#x202F;=&#x202F;1.97, 95%CI&#x202F;=&#x202F;[1.65, 2.29], <italic>p</italic>&#x202F;&#x003C;&#x202F;0.001).</p>
</sec>
<sec id="sec4">
<title>Conclusion</title>
<p>This meta-analysis showed that rTMS can safely and effectively promote the recovery of speech function in patients with PSA.</p>
</sec>
<sec id="sec401">
<title>Clinical trial registration</title>
<p>The study has been registered with Prospero <uri xlink:href="https://www.crd.york.ac.uk/PROSPERO/search">https://www.crd.york.ac.uk/PROSPERO/search</uri>, (CRD42022363899).</p>
</sec>
</abstract>
<kwd-group>
<kwd>repetitive transcranial magnetic stimulation</kwd>
<kwd>post-stroke aphasia</kwd>
<kwd>systematic review</kwd>
<kwd>noninvasive brain stimulation</kwd>
<kwd>meta-analysis</kwd>
</kwd-group>
<counts>
<fig-count count="13"/>
<table-count count="4"/>
<equation-count count="0"/>
<ref-count count="74"/>
<page-count count="17"/>
<word-count count="11164"/>
</counts>
<custom-meta-wrap>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Stroke</meta-value>
</custom-meta>
</custom-meta-wrap>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="sec5">
<label>1</label>
<title>Introduction</title>
<p>Post-stroke aphasia (PSA) refers to impaired or permanent loss of the ability to express and understand speech symbols caused by cerebrovascular disease, which results in a variety of language dysfunction, including listening, speaking, reading, and writing (<xref ref-type="bibr" rid="ref1">1</xref>, <xref ref-type="bibr" rid="ref2">2</xref>). The incidence of PSA is high, with more than a third of stroke patients suffering from aphasia (<xref ref-type="bibr" rid="ref3">3</xref>, <xref ref-type="bibr" rid="ref4">4</xref>). Due to the inability to communicate correctly, PSA patients are more prone to be depressed and anxious, which can seriously affect their quality of rehabilitation and life (<xref ref-type="bibr" rid="ref5 ref6 ref7">5&#x2013;7</xref>). Recent data show that stroke patients with aphasia incur significantly higher hospitalization costs for medical treatment, nursing, and related medical services than those without, which puts a huge burden on patients, their families, and society (<xref ref-type="bibr" rid="ref8">8</xref>). The pathogenesis of PSA is not fully understood. However, some researchers have proposed the hypothesis that aphasia is related to the degree of lesions in the left hemisphere. When the lesions in the left hemisphere are small, the cortical area around the lesions in the ipsilateral hemisphere can play a role in compensating for ischemia. The right hemisphere&#x2019;s corresponding speech-motor and language areas can functionally compensate for ischemia when the left hemisphere is extensively diseased (<xref ref-type="bibr" rid="ref9">9</xref>, <xref ref-type="bibr" rid="ref10">10</xref>). Recently, researchers have also analyzed the mechanism of PSA from the perspective of neuroplasticity and explored possible intervention directions (<xref ref-type="bibr" rid="ref11">11</xref>).</p>
<p>Common clinical treatment modalities for PSA include medication and speech training. Commonly used pharmacological treatments include dopaminergic, acetylcholinesterase inhibitors, and amino acid neurotransmitters (<xref ref-type="bibr" rid="ref12">12</xref>). But of note, medication can only be used to improve some of the clinical symptoms of PSA patients. Due to the lack of uniform clinical standards for therapy, the effectiveness of speech and language training also varies from person to person (<xref ref-type="bibr" rid="ref13 ref14 ref15">13&#x2013;15</xref>). Early rehabilitation interventions include promoting communication outcome, functional restructuring, and blockade removal. Speech and language training (SLT) is highly recommended by the United State Stroke Foundation and the Australian Stroke Foundation as a significant treatment throughout aphasia (level 1A evidence) (<xref ref-type="bibr" rid="ref15">15</xref>). In addition, the effectiveness of traditional SLT varies from person to person and may be due to a variety of factors, such as the patient&#x2019;s level of aphasia, the technician&#x2019;s individual nursing skills, communication strategies, and many other factors. Exploring novel, easy-to-implement, and efficient rehabilitation methods is still urgently needed to improve the clinical outcome of PSA further.</p>
<p>In recent years, with the development of non-invasive brain stimulation techniques, neuromodulation techniques such as transcranial direct current stimulation(tDCS) and repetitive transcranial magnetic stimulation (rTMS) have been widely used in the treatment of various clinical disorders, including depression (<xref ref-type="bibr" rid="ref16">16</xref>), cognitive disorders (<xref ref-type="bibr" rid="ref17">17</xref>), motor dysfunction (<xref ref-type="bibr" rid="ref18">18</xref>), post-stroke dysphagia (<xref ref-type="bibr" rid="ref19">19</xref>), PSA (<xref ref-type="bibr" rid="ref20">20</xref>) and so on. Therefore, neuromodulation techniques are being used as novel therapeutic modalities that can complement the treatment of PSA. In addition, a recent net meta-analysis (<xref ref-type="bibr" rid="ref21">21</xref>) showed that rTMS, a commonly used clinical neuromodulation technique, has better efficacy than tDCS in treating people with PSA. In most clinical settings, rTMS is rarely used as a stand-alone treatment for post-stroke aphasia. Instead, rTMS is typically administered in combination with speech and language therapy (SLT), which remains the gold standard rehabilitation approach. Some trials also paired rTMS with pharmacological treatments or cognitive training interventions. This concurrent use is based on the rationale that neuromodulation may enhance neuroplasticity, thereby amplifying the effects of behavioral therapies. Understanding these treatment pairings is essential for interpreting differences in efficacy across studies. This net meta-analysis demonstrated that therapeutic effects in the naming domain were moderated by the mean period of each therapy condition and the first language, while significant associations with age, therapy period, and number of sessions were observed for spontaneous speech. Overall, LF-rTMS is the most prioritized NIBS mode to alleviate global severity.</p>
<p>rTMS is a safe, painless, and easy-to-manipulate noninvasive neuromodulation technique that can modulate the excitability of cortical neurons on a temporal scale that exceeds the stimulation time course and on a spatial scale that exceeds the stimulation site (<xref ref-type="bibr" rid="ref22">22</xref>). rTMS works by generating an induced magnetic field in order to induce secondary electrical currents in the adjacent neural tissues, which activate the cerebral cortex and changes the brain tissue-related physiological processes to achieve localization of cortical functions; At the same time, it can also improve local blood rheology and cortical metabolism by regulating the excitability of local brain tissues, affecting the release and transmission of neurotransmitters within the brain, and promoting the repair of damaged brain cells (<xref ref-type="bibr" rid="ref22 ref23 ref24">22&#x2013;24</xref>), and thus has been widely used in clinical rehabilitation.</p>
<p>Although previous review (<xref ref-type="bibr" rid="ref20">20</xref>, <xref ref-type="bibr" rid="ref25">25</xref>) have discussed the therapeutic application of rTMS in patients with PSA, the clinical efficacy of rTMS in treating PSA patients, the optimal intervention parameters of rTMS and the safety of rTMS in the clinical treatment of PSA are still worthy of further analysis and exploration. And, recently, a number of new evidences of randomized controlled trials (RCTs) of rTMS for PSA have emerged. Thus, this meta-analysis aims to further explore the clinical efficacy and optimal intervention parameters of rTMS for PSA, and to provide a clinical evidence-based basis for the effective application of rTMS for PSA.</p>
</sec>
<sec sec-type="methods" id="sec6">
<label>2</label>
<title>Methods</title>
<sec id="sec7">
<label>2.1</label>
<title>Protocol and registration</title>
<p>Our systematic review was designed and implemented based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline (<xref ref-type="bibr" rid="ref26">26</xref>). The study has been registered with Prospero (CRD42022363899).</p>
</sec>
<sec id="sec8">
<label>2.2</label>
<title>Search strategy</title>
<p>In the initial screening, two researchers (CG and YXD) independently searched RCTs related to the topic in seven databases: Web of Science, PubMed, Embase, Cochrane Library, CNKI, Wanfang Data, and PEDro. Search for studies published between the date of database creation and September 28, 2022. We searched for standardized disease names in the International Classification of Diseases, 11th edition (ICD&#x202F;&#x2212;&#x202F;11). Ultimately, we identified the keywords for this study as &#x201C;Stroke,&#x201D; &#x201C;Aphasia,&#x201D; &#x201C;Language Expression Disorder,&#x201D; &#x201C;Listening Comprehension Disorder,&#x201D; and &#x201C;Repetitive Transcranial Magnetic Stimulation.&#x201D; In addition, we manually searched other relevant literature, such as studies included in some systematic reviews and meta-analyses, to broaden the search for eligible articles. As an example, the search strategy for the PubMed database is as follows (<xref ref-type="table" rid="tab1">Table 1</xref>).</p>
<table-wrap position="float" id="tab1">
<label>Table 1</label>
<caption>
<p>The specific search strategy of PubMed database.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" colspan="2">No. search items</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="middle">#1</td>
<td align="left" valign="top">Stroke [MESH]</td>
</tr>
<tr>
<td align="left" valign="middle">#2</td>
<td align="left" valign="top">(Cerebrovascular Accident) OR (Brain Vascular Accident) OR (Cerebrovascular Accidents) OR (Strokes) OR (CVA) OR (CVAs) OR (Cerebrovascular Apoplexy) OR (Apoplexy, Cerebrovascular) OR (Vascular Accident, Brain) OR (Brain Vascular Accident) OR (Vascular Accidents, Brain) OR (Brain Vascular Accidents) OR (Cerebrovascular Stroke) OR (Cerebrovascular Strokes) OR (Stroke, Cerebrovascular) OR (Strokes, Cerebrovascular) OR (Apoplexy) OR (Cerebral Stroke) OR (Cerebral Strokes)</td>
</tr>
<tr>
<td align="left" valign="middle">#3</td>
<td align="left" valign="top">#1 OR #2</td>
</tr>
<tr>
<td align="left" valign="middle">#4</td>
<td align="left" valign="top">Aphasia [MESH]</td>
</tr>
<tr>
<td align="left" valign="middle">#5</td>
<td align="left" valign="top">(Mixed Aphasia) OR (Global Aphasia) OR (Language Expression Disorder) OR (Listening Comprehension Disorder) OR (Motor Aphasia) OR (Broca Aphasia) OR (Wernicke Aphasia) OR (Alogia) OR (Alogia Acquired) OR (Aphasia) OR (Dysphasia)</td>
</tr>
<tr>
<td align="left" valign="middle">#6</td>
<td align="left" valign="top">#4 OR #5</td>
</tr>
<tr>
<td align="left" valign="middle">#7</td>
<td align="left" valign="top">Transcranial Magnetic Stimulation [MESH]</td>
</tr>
<tr>
<td align="left" valign="middle">#8</td>
<td align="left" valign="top">(Repetitive Transcranial Magnetic Stimulation) OR(Magnetic Stimulation, Transcranial) OR (Magnetic Stimulations, Transcranial) OR (Stimulation, Transcranial Magnetic) OR (Stimulations, Transcranial Magnetic) OR (Transcranial Magnetic Stimulations) OR (Transcranial Magnetic Stimulation, Single Pulse) OR (Transcranial Magnetic Stimulation, Paired Pulse) OR (Transcranial Magnetic Stimulation, Repetitive) OR (TMS) OR (rTMS) OR (iTBS)</td>
</tr>
<tr>
<td align="left" valign="middle">#9</td>
<td align="left" valign="top">#7 OR #8</td>
</tr>
<tr>
<td align="left" valign="middle">#10</td>
<td align="left" valign="top">#3 AND #6 AND #9</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="sec9">
<label>2.3</label>
<title>Inclusion and exclusion criteria of the study</title>
<p>Included studies were required to follow our pre-defined inclusion and exclusion criteria strictly. According to the PICOS principles, the inclusion criteria of our review were as follows: (1) participants: patients diagnosed with post-stroke aphasia; (2) interventions: rTMS; (3) comparison: experimental group (rTMS) versus control group (placebo or no treatment) condition; (4) outcomes: Western Aphasia Battery (WAB), Aphasia Quotient (AQ), Aphasia Battery in Chinese (ABC), Boston Diagnostic Aphasia Examination (BADE), Aachener Aphasie Test (AAT), Concise Chinese Aphasia Test (CCAT) and Computerized Picture Naming Test (CPNT); (5) type of studies: RCT; (6) studies published in English or Chinese. Exclusion criteria for the literature: (1) duplicate data; (2) full-text content not available; (3) data not extractable.</p>
</sec>
<sec id="sec10">
<label>2.4</label>
<title>Study selection</title>
<p>After completing the database search, we imported all retrieved studies into Endnote 20&#x2019;s document management system (Endnote 20, United States) and removed duplicate studies using the software management function. Two researchers (CG and LX) then read the title and abstract of each study simultaneously and screened studies based on the inclusion and exclusion criteria we had previously developed. For initially screened studies, the two researchers would downloaded and read through the full text, removing articles that do not meet the inclusion criteria and discussed them to confirm their eligibility. If the two researchers disagree on the screening process of a study, the principal investigator (ZYD) was asked to provide advice and reach an agreement.</p>
</sec>
<sec id="sec11">
<label>2.5</label>
<title>Data extraction</title>
<p>Two researchers (MH and LX) independently extracted the following data and items from the included literature: first author of the study, year of publication, the sample size of participating studies, age, gender, duration of disease, interventions tested, outcome indicators, and adverse effects. In addition, when the two researchers encountered difficulties in understanding or extracting the complete literature data during the data extraction process, the original authors of the literature would be contacted by sending an email to obtain the full trial data. When no response was received from the original author after three consecutive contacts, the study will be defined as missing data. Suppose two researchers disagree during the data extraction process. In that case, both would be placed in a research team with the Principal Investigator to discuss and resolve the issue. If the two researchers disagree on the screening process of a study, the principal investigator (ZYD) would be asked to provide advice and reach an agreement. The principal investigator will convene a meeting of the research team to discuss the reasons for any disagreements; once the sources of conflict are resolved, consensus will be reached.</p>
</sec>
<sec id="sec12">
<label>2.6</label>
<title>Quality assessment</title>
<p>The quality assessment of the literature studies was completed independently by two researchers (MH and JHH), then discussed to produce consistent results. Risk bias was assessed using the Cochrane Risk of Bias tool (Revman 5.40, Nordic Cochrane Center). A total of seven items were considered: random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other biases. The risk bias assessment was mapped, and different colors differentiated the results into three levels: high risk&#x2014;red, unknown risk&#x2014;yellow and low risk&#x2014;green. Heterogeneity between studies was statistically analyzed by Revman 5.40. The magnitude of heterogeneity was expressed as <italic>I</italic><sup>2</sup>, with heterogeneity judged as high risk when <italic>I</italic><sup>2</sup>&#x202F;&#x2265;&#x202F;75%, moderate risk when 75%&#x202F;&#x003E;&#x202F;<italic>I</italic><sup>2</sup>&#x202F;&#x2265;&#x202F;50%, low heterogeneity when 50%&#x202F;&#x003E;&#x202F;<italic>I</italic><sup>2</sup>&#x202F;&#x2265;&#x202F;25%, and no heterogeneity if <italic>I</italic><sup>2</sup>&#x202F;=&#x202F;0% (<xref ref-type="bibr" rid="ref27">27</xref>). I<sup>2</sup> quantifies the extent of heterogeneity between studies. On the one hand, we select the appropriate effect model for the forest plot according to the magnitude of I<sup>2</sup> to minimize the impact of high heterogeneity on the pooled results. On the other hand, during the assessment of evidence quality, we also use I<sup>2</sup> to grade the strength of the evidence. The quality of evidence for outcome indicators was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system, which examines study limitations, intermittency, inconsistency, and imprecision of results (<xref ref-type="bibr" rid="ref28">28</xref>). The results were assessed by grading the evidence for the outcome indicators as &#x201C;high,&#x201D; &#x201C;moderate,&#x201D; &#x201C;low,&#x201D; or &#x201C;very low,&#x201D; and the strength of the recommendations was divided into two levels: &#x201C;strong&#x201D; and &#x201C;weak&#x201D; (<xref ref-type="bibr" rid="ref29">29</xref>).</p>
</sec>
<sec id="sec13">
<label>2.7</label>
<title>Statistical analysis</title>
<p>The extracted study data were entered into Revman 5.40 software<sup>a</sup> for statistical and analytical purposes. The decision to use a fixed or a random effects model for the meta-analysis was based on the magnitude of heterogeneity. A random effects model was used when <italic>I</italic><sup>2</sup>&#x202F;&#x2265;&#x202F;50%, and a fixed effects model was used when <italic>I</italic><sup>2</sup>&#x202F;&#x003C;&#x202F;50%. Mean difference (MD) and 95% confidence interval (CI) were used to express the effect size for studies using the same measure. Vice versa, standardized mean difference (SMD) and 95%CI were used to express the effect size for studies using different measures. <italic>p</italic>&#x202F;&#x003C;&#x202F;0.05, statistically significant.</p>
</sec>
<sec id="sec14">
<label>2.8</label>
<title>Safety assessment</title>
<p>The number, type, and duration of adverse events that occurred during the rTMS intervention were counted in all the studies concerned. And statistically analyze the patients who experienced adverse events, as a percentage of the number of subjects. Record whether there were any intolerable or even life-threatening adverse reactions that caused the subjects to withdraw from the experiment. And, to track whether the adverse events in each study, still persisted during the follow-up time.</p>
</sec>
</sec>
<sec sec-type="results" id="sec15">
<label>3</label>
<title>Results</title>
<sec id="sec16">
<label>3.1</label>
<title>Literature search findings</title>
<p>A total of seven databases were searched for literature, and the initial search resulted in 994 studies. Duplicate studies were screened out and removed by software, leaving 628 studies. Two researchers (YZL and CG) read the titles and abstracts of these studies and screened out 574 that were irrelevant to the topic. The remaining 54 studies were downloaded in full and read through, and 24 studies were still excluded (8 studies were screened for not using the internationally accepted aphasia ratings listed in the inclusion criteria or data on outcome indicators were not fully available; 12 studies were screened for not strictly using a randomized controlled trial design; four studies were screened for not using rTMS as the primary intervention in an experimental comparison study). Finally, 30 eligible studies were included (<xref ref-type="bibr" rid="ref30 ref31 ref32 ref33 ref34 ref35 ref36 ref37 ref38 ref39 ref40 ref41 ref42 ref43 ref44 ref45 ref46 ref47 ref48 ref49 ref50 ref51 ref52 ref53 ref54 ref55 ref56 ref57 ref58 ref59">30&#x2013;59</xref>) (<xref ref-type="fig" rid="fig1">Figure 1</xref>).</p>
<fig position="float" id="fig1">
<label>Figure 1</label>
<caption>
<p>Flow graph of selection and exclusion.</p>
</caption>
<graphic xlink:href="fneur-16-1614586-g001.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Flowchart illustrating the identification process for studies via databases and registers. Out of 994 records identified, 366 duplicates were removed, resulting in 628 screened records. From these, 574 records were excluded. Out of 54 sought reports, 30 were included in the review, after excluding reports for unsuitable outcomes, designs, or interventions.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec17">
<label>3.2</label>
<title>Characteristics of included studies</title>
<p>Across the included randomized controlled trials, rTMS was most commonly applied in conjunction with SLT, whereas a smaller number of trials compared rTMS plus SLT with SLT alone or with sham stimulation plus SLT. Only a few studies combined rTMS with pharmacological agents. This variability in study design illustrates that rTMS is more appropriately viewed as an adjunctive rather than independent therapy for PSA. To improve clarity, we have minimized use of acronyms in the Results section, spelling out the assessment tools (e.g., Western Aphasia Battery instead of WAB on first mention). <xref ref-type="table" rid="tab2">Table 2</xref> summarizes the basic data of the 30 RCTs. A total of 1,597 patients with PSA were included, with sample sizes ranging from 12 to 120, of which 819 patients with PSA were treated with rTMS. Subjects&#x2019; aphasia types had non-fluent aphasia, Broca aphasia, Motor aphasia, Global aphasia, and Various aphasia. Among the included RCTs, the outcome indicators for rating aphasia in post-stroke patients included Western Aphasia Battery (WAB), Aachener Aphasia Test (AAT), Aphasia Battery in Chinese (ABC), Aphasia Quotient (AQ); Concise Chinese Aphasia Test (CCAT); Computerized Picture Naming Test (CPNT) and Boston Diagnostic Aphasia Examination (BDAE).</p>
<table-wrap position="float" id="tab2">
<label>Table 2</label>
<caption>
<p>The characteristic of the included studies.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top">Study</th>
<th align="center" valign="top">Gender<break/>(M/F)</th>
<th align="center" valign="top">Age (years)</th>
<th align="center" valign="top">Stroke duration</th>
<th align="center" valign="top">Aphasia type</th>
<th align="center" valign="top">Interventions</th>
<th align="center" valign="top">Outcome measures</th>
<th align="center" valign="top">Total time</th>
<th align="center" valign="top">Follow-up</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">1. Barwood et al. (<xref ref-type="bibr" rid="ref59">59</xref>)</td>
<td align="center" valign="top">G1:2/4<break/>G2: 1/5</td>
<td align="center" valign="top">G1: 60.8&#x202F;&#x00B1;&#x202F;5.98<break/>G2: 67&#x202F;&#x00B1;&#x202F;13.11</td>
<td align="center" valign="top">3.49&#x202F;&#x00B1;&#x202F;1.27&#x202F;years<break/>3.46&#x202F;&#x00B1;&#x202F;1.53&#x202F;years</td>
<td align="center" valign="top">Non-fluent aphasia</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">BDAE</td>
<td align="center" valign="top">10&#x202F;days</td>
<td align="center" valign="top">2&#x202F;months</td>
</tr>
<tr>
<td align="left" valign="top">2. Chang (<xref ref-type="bibr" rid="ref46">46</xref>)</td>
<td align="center" valign="top">G1;35/28<break/>G2:33/30</td>
<td align="center" valign="top">67.3&#x202F;&#x00B1;&#x202F;19.9<break/>G2:66.4&#x202F;&#x00B1;&#x202F;15.8</td>
<td align="center" valign="top">6.9&#x202F;&#x00B1;&#x202F;3.1&#x202F;days<break/>7.3&#x202F;&#x00B1;&#x202F;3.5&#x202F;days</td>
<td align="center" valign="top">Broca aphasia</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">WAB</td>
<td align="center" valign="top">15&#x202F;days</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">3. Chen et al. (<xref ref-type="bibr" rid="ref58">58</xref>)</td>
<td align="center" valign="top">G1;3/5<break/>G2:3/4</td>
<td align="center" valign="top">65.7<break/>66.5</td>
<td align="center" valign="top">&#x003C;7&#x202F;days</td>
<td align="center" valign="top">Broca aphasia</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">ABC</td>
<td align="center" valign="top">10&#x202F;days</td>
<td align="center" valign="top">2&#x202F;weeks</td>
</tr>
<tr>
<td align="left" valign="top">4. Fan (<xref ref-type="bibr" rid="ref48">48</xref>)</td>
<td align="center" valign="top">G1;25<break/>G2:25</td>
<td align="center" valign="top">&#x2265;18</td>
<td align="center" valign="top">NR</td>
<td align="center" valign="top">NR</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">ABC; AQ</td>
<td align="center" valign="top">20&#x202F;days</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">5. Guo et al. (<xref ref-type="bibr" rid="ref49">49</xref>)</td>
<td align="center" valign="top">G1:11/9<break/>G2:12/8</td>
<td align="center" valign="top">62.1&#x202F;&#x00B1;&#x202F;10.6<break/>64.4&#x202F;&#x00B1;&#x202F;8.5</td>
<td align="center" valign="top">33.1&#x202F;&#x00B1;&#x202F;8.6&#x202F;days<break/>30.6&#x202F;&#x00B1;&#x202F;9.4&#x202F;days</td>
<td align="center" valign="top">Broca aphasia</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">WAB; AQ</td>
<td align="center" valign="top">24&#x202F;days</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">6. Haghighi et al. (<xref ref-type="bibr" rid="ref47">47</xref>)</td>
<td align="center" valign="top">G1:3/3<break/>G2:2/4</td>
<td align="center" valign="top">61.67&#x202F;&#x00B1;&#x202F;7.06<break/>60.50&#x202F;&#x00B1;&#x202F;11.85</td>
<td align="center" valign="top">4&#x2013;8&#x202F;weeks</td>
<td align="center" valign="top">Broca aphasia</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">WAB</td>
<td align="center" valign="top">10&#x202F;days</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">7. Heiss et al. (<xref ref-type="bibr" rid="ref55">55</xref>)</td>
<td align="center" valign="top">G1:15<break/>G2:14</td>
<td align="center" valign="top">68.5&#x202F;&#x00B1;&#x202F;8.19<break/>69.0&#x202F;&#x00B1;&#x202F;6.33</td>
<td align="center" valign="top">50.1&#x202F;&#x00B1;&#x202F;23.96&#x202F;days<break/>39.7&#x202F;&#x00B1;&#x202F;18.43&#x202F;days</td>
<td align="center" valign="top">NR</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">AAT</td>
<td align="center" valign="top">10&#x202F;days</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">8. Hu et al. (<xref ref-type="bibr" rid="ref4">4</xref>)</td>
<td align="center" valign="top">G1: 7/3<break/>G2: 6/4<break/>G3: 5/5<break/>G4: 6/4</td>
<td align="center" valign="top">46.5&#x202F;&#x00B1;&#x202F;12.1<break/>48.5&#x202F;&#x00B1;&#x202F;11.2<break/>50.7&#x202F;&#x00B1;&#x202F;10.4<break/>47.3&#x202F;&#x00B1;&#x202F;9.8</td>
<td align="center" valign="top">7.1&#x202F;&#x00B1;&#x202F;2.7&#x202F;months<break/>7.5&#x202F;&#x00B1;&#x202F;3.2&#x202F;months<break/>6.8&#x202F;&#x00B1;&#x202F;2.3&#x202F;months<break/>7.7&#x202F;&#x00B1;&#x202F;3.4&#x202F;months</td>
<td align="center" valign="top">Non-fluent aphasic</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G1: SLT&#x202F;+&#x202F;rTMS<break/>G3: SLT&#x202F;+&#x202F;sham rTMS<break/>G4: SLT</td>
<td align="center" valign="top">WAB</td>
<td align="center" valign="top">2&#x202F;weeks</td>
<td align="center" valign="top">2&#x202F;months</td>
</tr>
<tr>
<td align="left" valign="top">9. Lai et al. (<xref ref-type="bibr" rid="ref30">30</xref>)</td>
<td align="center" valign="top">G1:21/16<break/>G2:20/17</td>
<td align="center" valign="top">62.01&#x202F;&#x00B1;&#x202F;6.29<break/>61.49&#x202F;&#x00B1;&#x202F;6.36</td>
<td align="center" valign="top">1&#x202F;~&#x202F;3&#x202F;months</td>
<td align="center" valign="top">Various</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">AQ</td>
<td align="center" valign="top">8&#x202F;months</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">10. Li et al. (<xref ref-type="bibr" rid="ref43">43</xref>)</td>
<td align="center" valign="top">G1:9/6<break/>G2:7/8</td>
<td align="center" valign="top">65.3&#x202F;&#x00B1;&#x202F;5.6<break/>68.3&#x202F;&#x00B1;&#x202F;5.8</td>
<td align="center" valign="top">47.5&#x202F;&#x00B1;&#x202F;7.4&#x202F;days<break/>51.0&#x202F;&#x00B1;&#x202F;9.6&#x202F;days</td>
<td align="center" valign="top">Motor aphasia</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">AQ; WAB</td>
<td align="center" valign="top">3&#x202F;weeks</td>
<td align="center" valign="top">3&#x202F;weeks</td>
</tr>
<tr>
<td align="left" valign="top">11. Liu et al. (<xref ref-type="bibr" rid="ref31">31</xref>)</td>
<td align="center" valign="top">G1:24/16<break/>G2:26/14</td>
<td align="center" valign="top">54.1&#x202F;&#x00B1;&#x202F;6.2<break/>53.3&#x202F;&#x00B1;&#x202F;5.4</td>
<td align="center" valign="top">58.4&#x202F;&#x00B1;&#x202F;15.6&#x202F;days<break/>60.2&#x202F;&#x00B1;&#x202F;14.3&#x202F;days</td>
<td align="center" valign="top">NR</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">AQ; WAB</td>
<td align="center" valign="top">4&#x202F;weeks</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">12. Peng and Zhou (<xref ref-type="bibr" rid="ref37">37</xref>)</td>
<td align="center" valign="top">G1:26/14<break/>G2:27/13<break/>G3:24/16</td>
<td align="center" valign="top">59.79&#x202F;&#x00B1;&#x202F;5.58<break/>59.80&#x202F;&#x00B1;&#x202F;5.91<break/>59.73&#x202F;&#x00B1;&#x202F;5.82</td>
<td align="center" valign="top">10.4&#x202F;&#x00B1;&#x202F;2.83&#x202F;days<break/>10.4&#x202F;&#x00B1;&#x202F;2.76&#x202F;days<break/>10.37&#x202F;&#x00B1;&#x202F;2.8&#x202F;days</td>
<td align="center" valign="top">NR</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS<break/>G3: SLT</td>
<td align="center" valign="top">AQ; WAB</td>
<td align="center" valign="top">4&#x202F;weeks</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">13. Qiu et al. (<xref ref-type="bibr" rid="ref36">36</xref>)</td>
<td align="center" valign="top">G1:19/1<break/>G2:18/2</td>
<td align="center" valign="top">55.00&#x202F;&#x00B1;&#x202F;10.72<break/>52.25&#x202F;&#x00B1;&#x202F;15.00</td>
<td align="center" valign="top">2.12&#x202F;&#x00B1;&#x202F;1.8&#x202F;months<break/>1.56&#x202F;&#x00B1;&#x202F;1.6&#x202F;months</td>
<td align="center" valign="top">Non-fluent aphasia</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">WAB</td>
<td align="center" valign="top">4&#x202F;weeks</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">14. Qu et al. (<xref ref-type="bibr" rid="ref35">35</xref>)</td>
<td align="center" valign="top">G1:13/7<break/>G2:14/6</td>
<td align="center" valign="top">68.60&#x202F;&#x00B1;&#x202F;7.78<break/>67.80&#x202F;&#x00B1;&#x202F;7.32</td>
<td align="center" valign="top">26.5&#x202F;&#x00B1;&#x202F;12.5&#x202F;days<break/>25.8&#x202F;&#x00B1;&#x202F;11.8&#x202F;days</td>
<td align="center" valign="top">Non-fluent aphasia</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">AQ; WAB</td>
<td align="center" valign="top">2&#x202F;weeks</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">15. Ren et al. (<xref ref-type="bibr" rid="ref38">38</xref>)</td>
<td align="center" valign="top">G1:12/6<break/>G2: 7/6<break/>G3:9/6</td>
<td align="center" valign="top">65.95&#x202F;&#x00B1;&#x202F;8.53<break/>62.46&#x202F;&#x00B1;&#x202F;10.95<break/>63.60&#x202F;&#x00B1;&#x202F;16.71</td>
<td align="center" valign="top">55.9&#x202F;&#x00B1;&#x202F;19.4&#x202F;days<break/>50.6&#x202F;&#x00B1;&#x202F;23.8&#x202F;days<break/>61.2&#x202F;&#x00B1;&#x202F;22.7&#x202F;days</td>
<td align="center" valign="top">Global aphasia</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">WAB</td>
<td align="center" valign="top">3&#x202F;weeks</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">16. Rubi-fessen et al. (<xref ref-type="bibr" rid="ref50">50</xref>)</td>
<td align="center" valign="top">G1:5/10<break/>G2:9/6</td>
<td align="center" valign="top">67.9&#x202F;&#x00B1;&#x202F;8.12<break/>69.6&#x202F;&#x00B1;&#x202F;6.67</td>
<td align="center" valign="top">41.5&#x202F;&#x00B1;&#x202F;21.5&#x202F;days<break/>48.7&#x202F;&#x00B1;&#x202F;21.6&#x202F;days</td>
<td align="center" valign="top">NR</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">AAT</td>
<td align="center" valign="top">10&#x202F;days</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">17. Seni&#x00F3;w et al. (<xref ref-type="bibr" rid="ref54">54</xref>)</td>
<td align="center" valign="top">G1:8/12<break/>G2:10/10</td>
<td align="center" valign="top">61.8&#x202F;&#x00B1;&#x202F;11.8<break/>59.7&#x202F;&#x00B1;&#x202F;10.7</td>
<td align="center" valign="top">33.5&#x202F;&#x00B1;&#x202F;24.1&#x202F;days<break/>39.9&#x202F;&#x00B1;&#x202F;28.9&#x202F;days</td>
<td align="center" valign="top">Various</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">BDAE</td>
<td align="center" valign="top">3&#x202F;weeks</td>
<td align="center" valign="top">15&#x202F;weeks</td>
</tr>
<tr>
<td align="left" valign="top">18. Shen (<xref ref-type="bibr" rid="ref41">41</xref>)</td>
<td align="center" valign="top">G1:16/14<break/>G2:17/13</td>
<td align="center" valign="top">57.31&#x202F;&#x00B1;&#x202F;2.51<break/>57.28&#x202F;&#x00B1;&#x202F;2.35</td>
<td align="center" valign="top">3.75&#x202F;&#x00B1;&#x202F;1.32&#x202F;days<break/>3.25&#x202F;&#x00B1;&#x202F;1.25&#x202F;days</td>
<td align="center" valign="top">NR</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT</td>
<td align="center" valign="top">ABC</td>
<td align="center" valign="top">4&#x202F;weeks</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">19. Tao (<xref ref-type="bibr" rid="ref40">40</xref>)</td>
<td align="center" valign="top">G1:20/11<break/>G2:18/13</td>
<td align="center" valign="top">60.2&#x202F;&#x00B1;&#x202F;5.1<break/>59.3&#x202F;&#x00B1;&#x202F;4.5</td>
<td align="center" valign="top">NR</td>
<td align="center" valign="top">NR</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT</td>
<td align="center" valign="top">AQ; ABC</td>
<td align="center" valign="top">4&#x202F;weeks</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">20. Thiel et al. (<xref ref-type="bibr" rid="ref53">53</xref>)</td>
<td align="center" valign="top">G1:13<break/>G2:11</td>
<td align="center" valign="top">69.8&#x202F;&#x00B1;&#x202F;7.96<break/>71.2&#x202F;&#x00B1;&#x202F;7.78</td>
<td align="center" valign="top">37.5&#x202F;&#x00B1;&#x202F;18.5&#x202F;days<break/>50.6&#x202F;&#x00B1;&#x202F;22.6&#x202F;days</td>
<td align="center" valign="top">Various</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">AAT</td>
<td align="center" valign="top">10&#x202F;days</td>
<td align="center" valign="top">3&#x202F;weeks</td>
</tr>
<tr>
<td align="left" valign="top">21. Tsai et al. (<xref ref-type="bibr" rid="ref52">52</xref>)</td>
<td align="center" valign="top">G1:24/9<break/>G2:17/6</td>
<td align="center" valign="top">62.3&#x202F;&#x00B1;&#x202F;12.1<break/>11.6&#x202F;&#x00B1;&#x202F;4.3</td>
<td align="center" valign="top">17.8&#x202F;&#x00B1;&#x202F;7.2&#x202F;months<break/>18.3&#x202F;&#x00B1;&#x202F;8.2&#x202F;months</td>
<td align="center" valign="top">Non-fluent aphasia</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">CCAT</td>
<td align="center" valign="top">10&#x202F;days</td>
<td align="center" valign="top">3&#x202F;months</td>
</tr>
<tr>
<td align="left" valign="top">22. Waldowski et al. (<xref ref-type="bibr" rid="ref56">56</xref>)</td>
<td align="center" valign="top">G1:6/7<break/>G2:7/6</td>
<td align="center" valign="top">62.31&#x202F;&#x00B1;&#x202F;11.03<break/>60.15&#x202F;&#x00B1;&#x202F;10.58</td>
<td align="center" valign="top">28.9&#x202F;&#x00B1;&#x202F;19.4&#x202F;days<break/>48.5&#x202F;&#x00B1;&#x202F;32.33&#x202F;days</td>
<td align="center" valign="top">Various</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">CPNT; BDAE</td>
<td align="center" valign="top">3&#x202F;weeks</td>
<td align="center" valign="top">15&#x202F;weeks</td>
</tr>
<tr>
<td align="left" valign="top">23. Wang et al. (<xref ref-type="bibr" rid="ref51">51</xref>)</td>
<td align="center" valign="top">G1:14/1<break/>G2:13/2</td>
<td align="center" valign="top">61.3&#x202F;&#x00B1;&#x202F;13.2<break/>60.4&#x202F;&#x00B1;&#x202F;11.9</td>
<td align="center" valign="top">16.8&#x202F;&#x00B1;&#x202F;6.4&#x202F;months<break/>16.1&#x202F;&#x00B1;&#x202F;7.3&#x202F;months</td>
<td align="center" valign="top">Non-fluent aphasia</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">CCAT</td>
<td align="center" valign="top">2&#x202F;weeks</td>
<td align="center" valign="top">3&#x202F;months</td>
</tr>
<tr>
<td align="left" valign="top">24. Wang et al. (<xref ref-type="bibr" rid="ref39">39</xref>)</td>
<td align="center" valign="top">G1:23/3<break/>G2:11/4<break/>G3:9/6</td>
<td align="center" valign="top">59.53&#x202F;&#x00B1;&#x202F;1.37<break/>57.00&#x202F;&#x00B1;&#x202F;1.24<break/>47.07&#x202F;&#x00B1;&#x202F;1.37</td>
<td align="center" valign="top">&#x003C; 3&#x202F;months</td>
<td align="center" valign="top">NR</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">WAB</td>
<td align="center" valign="top">2&#x202F;weeks</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">25. Weiduschat et al. (<xref ref-type="bibr" rid="ref57">57</xref>)</td>
<td align="center" valign="top">G1:1/5<break/>G2:4/0</td>
<td align="center" valign="top">66.67&#x202F;&#x00B1;&#x202F;8.26<break/>63.75&#x202F;&#x00B1;&#x202F;3.83</td>
<td align="center" valign="top">45.2&#x202F;&#x00B1;&#x202F;21.0&#x202F;days<break/>57.5&#x202F;&#x00B1;&#x202F;23.3&#x202F;days</td>
<td align="center" valign="top">Various</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT&#x202F;+&#x202F;sham rTMS</td>
<td align="center" valign="top">AAT</td>
<td align="center" valign="top">2&#x202F;weeks</td>
<td align="center" valign="top">7&#x202F;weeks</td>
</tr>
<tr>
<td align="left" valign="top">26. Fang et al. (<xref ref-type="bibr" rid="ref45">45</xref>)</td>
<td align="center" valign="top">G1:28/20<break/>G2:30/22</td>
<td align="center" valign="top">64.3&#x202F;&#x00B1;&#x202F;15.7<break/>63.5&#x202F;&#x00B1;&#x202F;16.5</td>
<td align="center" valign="top">10.7&#x202F;&#x00B1;&#x202F;3.5&#x202F;days<break/>10.7&#x202F;&#x00B1;&#x202F;3.7&#x202F;days</td>
<td align="center" valign="top">NR</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G2: SLT</td>
<td align="center" valign="top">AQ; WAB</td>
<td align="center" valign="top">4&#x202F;weeks</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">27. Yang et al. (<xref ref-type="bibr" rid="ref42">42</xref>)</td>
<td align="center" valign="top">G1:11/9<break/>G2:10/10</td>
<td align="center" valign="top">46.34&#x202F;&#x00B1;&#x202F;11.5<break/>47.64&#x202F;&#x00B1;&#x202F;13.6</td>
<td align="center" valign="top">6&#x202F;months</td>
<td align="center" valign="top">NR</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G3: SLT</td>
<td align="center" valign="top">WAB</td>
<td align="center" valign="top">4&#x202F;weeks</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">28. Yin et al. (<xref ref-type="bibr" rid="ref33">33</xref>)</td>
<td align="center" valign="top">G1:24/26<break/>G2:25/25</td>
<td align="center" valign="top">58.45&#x202F;&#x00B1;&#x202F;3.50<break/>57.35&#x202F;&#x00B1;&#x202F;4.20</td>
<td align="center" valign="top">&#x2264;7&#x202F;days</td>
<td align="center" valign="top">Various</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G3: SLT</td>
<td align="center" valign="top">AQ; ABC</td>
<td align="center" valign="top">4&#x202F;weeks</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">29. Zhang et al. (<xref ref-type="bibr" rid="ref34">34</xref>)</td>
<td align="center" valign="top">G1:30<break/>G2:30</td>
<td align="center" valign="top">63.2&#x202F;&#x00B1;&#x202F;10.3</td>
<td align="center" valign="top">NR</td>
<td align="center" valign="top">Motor aphasia</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G3: SLT</td>
<td align="center" valign="top">ABC</td>
<td align="center" valign="top">10&#x202F;days</td>
<td align="center" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">30. Zhou et al. (<xref ref-type="bibr" rid="ref32">32</xref>)</td>
<td align="center" valign="top">G1:30/23<break/>G2:28/25</td>
<td align="center" valign="top">61.25&#x202F;&#x00B1;&#x202F;8.41<break/>59.87&#x202F;&#x00B1;&#x202F;7.64</td>
<td align="center" valign="top">9.35&#x202F;&#x00B1;&#x202F;3.27&#x202F;weeks<break/>8.91&#x202F;&#x00B1;&#x202F;2.36&#x202F;weeks</td>
<td align="center" valign="top">Motor aphasia</td>
<td align="center" valign="top">G1: SLT&#x202F;+&#x202F;rTMS<break/>G3: SLT</td>
<td align="center" valign="top">AQ; WAB</td>
<td align="center" valign="top">4&#x202F;weeks</td>
<td align="center" valign="top">No</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>M, male; F, Female; G1, group 1; G2, group 2; G3, group 3; G3, group4; SLT, speech and language training; rTMS, repetitive transcranial magnetic stimulation; NR, not report; AAT, Aachener Aphasie Test; CCAT, Concise Chinese Aphasia Test; CPNT, Computerized Picture Naming Test; AQ, Aphasia Quotient; ABC, Aphasia Battery in Chinese; WAB, Western Aphasia Battery; BADE, Boston Diagnostic Aphasia Examination.</p>
</table-wrap-foot>
</table-wrap>
<p>In addition, <xref ref-type="table" rid="tab3">Table 3</xref> summarizes the intervention parameters of rTMS for post-stroke patients in each study, such as stimulation site, intensity, frequency, number of pulses, and stimulation time. Among the studies we included, 2 studies used rTMS at 0.5&#x202F;Hz to treat PSA patients, 28 studies used rTMS at 1&#x202F;Hz to treat PSA patients, and 3 studies used rTMS at 10&#x202F;Hz to treat PSA patients. Overall, there are more clinical studies using low-frequency rTMS to treat PSA than high-frequency rTMS. And low-frequency rTMS treatment is mainly 1&#x202F;Hz rTMS.</p>
<table-wrap position="float" id="tab3">
<label>Table 3</label>
<caption>
<p>Main parameters of rTMS.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th align="left" valign="top" rowspan="2">Study</th>
<th align="center" valign="top" colspan="5">Parameters</th>
<th align="left" valign="top" rowspan="2">Adverse events and rates</th>
</tr>
<tr>
<th align="center" valign="top">Frequency</th>
<th align="left" valign="top">Stimulation location</th>
<th align="center" valign="top">Intensity</th>
<th align="center" valign="top">Number of pulses a day</th>
<th align="center" valign="top">Stimulation time</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">1. Barwood et al. (<xref ref-type="bibr" rid="ref59">59</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">The anterior portion of homolog to right pars triangularis in Broca&#x2019;s area</td>
<td align="center" valign="top">90% RTM</td>
<td align="center" valign="top">1,200 pulses</td>
<td align="center" valign="top">20&#x202F;min a day, 10&#x202F;days</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">2. Chang (<xref ref-type="bibr" rid="ref46">46</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">Broca&#x2019;s area in the right hemisphere</td>
<td align="center" valign="top">80% RTM</td>
<td align="center" valign="top">500 pulses</td>
<td align="center" valign="top">20&#x202F;min a day, 15&#x202F;days</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">3. Chen et al. (<xref ref-type="bibr" rid="ref58">58</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">Broca&#x2019;s area in the right hemisphere</td>
<td align="center" valign="top">80% RTM</td>
<td align="center" valign="top">500 pulses</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week, 2&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">4. Fan (<xref ref-type="bibr" rid="ref48">48</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">No report</td>
<td align="center" valign="top">90% RTM</td>
<td align="center" valign="top">1,200 pulses</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week, 4&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">5. Guo et al. (<xref ref-type="bibr" rid="ref49">49</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">Right side hemispheric language mirror area</td>
<td align="center" valign="top">70%RTM</td>
<td align="center" valign="top">1,800 pulses</td>
<td align="center" valign="top">30&#x202F;min a day, 6&#x202F;days a week, 4&#x202F;weeks</td>
<td align="left" valign="top">Headache; nausea &#x003C;24&#x202F;h (<italic>n</italic> =&#x202F;2/40)</td>
</tr>
<tr>
<td align="left" valign="top">6. Haghighi et al. (<xref ref-type="bibr" rid="ref47">47</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">The inferior posterior frontal gyrus</td>
<td align="center" valign="top">100%RTM</td>
<td align="center" valign="top">No report</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week, 2&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">7. Heiss et al. (<xref ref-type="bibr" rid="ref55">55</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">Contralesional inferior frontal gyrus</td>
<td align="center" valign="top">90%RTM</td>
<td align="center" valign="top">No report</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week, 2&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">8. Hu et al. (<xref ref-type="bibr" rid="ref44">44</xref>)</td>
<td align="center" valign="top">G1: 1&#x202F;Hz<break/>G2: 10&#x202F;Hz</td>
<td align="left" valign="top">Mirror area within Broca&#x2019;s area</td>
<td align="center" valign="top">80%RTM</td>
<td align="center" valign="top">600 pulses</td>
<td align="center" valign="top">10&#x202F;min a day, 5&#x202F;days a week, 2&#x202F;weeks</td>
<td align="left" valign="top">Dizziness &#x003C;24&#x202F;h<break/>(<italic>n</italic> =&#x202F;1/20)</td>
</tr>
<tr>
<td align="left" valign="top">9. Lai et al. (<xref ref-type="bibr" rid="ref30">30</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">Broca or Wernicke area in the right hemisphere</td>
<td align="center" valign="top">90%RTM</td>
<td align="center" valign="top">1,200 pulses</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week, 8&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">10. Li et al. (<xref ref-type="bibr" rid="ref43">43</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">Broca&#x2019;s mirror area in the right hemisphere</td>
<td align="center" valign="top">80%RTM</td>
<td align="center" valign="top">1,200 pulses</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week, 3&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">11. Liu et al. (<xref ref-type="bibr" rid="ref31">31</xref>)</td>
<td align="center" valign="top">10&#x202F;Hz</td>
<td align="left" valign="top">Broca&#x2019;s and Wernicke&#x2019;s zones in the left hemisphere</td>
<td align="center" valign="top">90%RTM</td>
<td align="center" valign="top">1,200 pulses</td>
<td align="center" valign="top">10&#x202F;min a day, 5&#x202F;days a week, 4&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">12. Peng and Zhou (<xref ref-type="bibr" rid="ref37">37</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">Broca&#x2019;s area in the right hemisphere</td>
<td align="center" valign="top">80%RTM</td>
<td align="center" valign="top">960 pulses</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week, 4&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">13. Qiu et al. (<xref ref-type="bibr" rid="ref36">36</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">Broca&#x2019;s mirror area in the right hemisphere</td>
<td align="center" valign="top">80%RTM</td>
<td align="center" valign="top">1,200 pulses</td>
<td align="center" valign="top">once a day, 5&#x202F;days a week, 4&#x202F;weeks</td>
<td align="left" valign="top">Dizziness &#x003C;24&#x202F;h (<italic>n</italic> =&#x202F;1/20)</td>
</tr>
<tr>
<td align="left" valign="top">14. Qu et al. (<xref ref-type="bibr" rid="ref35">35</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">Broca&#x2019;s area in the right hemisphere</td>
<td align="center" valign="top">100%<break/>RTM</td>
<td align="center" valign="top">1,200 pulses</td>
<td align="center" valign="top">once a day, 5&#x202F;days a week, 2&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">15. Ren et al. (<xref ref-type="bibr" rid="ref38">38</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">G1: The homolog of the left Broca&#x2019;s area; G2: The homolog of the left Wernicke&#x2019;s area</td>
<td align="center" valign="top">80%RTM</td>
<td align="center" valign="top">1,200 pulses</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week, 3&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">16. Rubi-fessen et al. (<xref ref-type="bibr" rid="ref50">50</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">The right triangular part of the inferior frontal gyrus</td>
<td align="center" valign="top">90%RTM</td>
<td align="center" valign="top">No report</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week, 2&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">17. Seni&#x00F3;w et al. (<xref ref-type="bibr" rid="ref54">54</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">The right-hemisphere homolog of Broca&#x2019;s area</td>
<td align="center" valign="top">90%RTM</td>
<td align="center" valign="top">1800 pulses</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week, 3&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">18. Shen (<xref ref-type="bibr" rid="ref41">41</xref>)</td>
<td align="center" valign="top">0.5&#x202F;Hz</td>
<td align="left" valign="top">Language mirror area of the cerebral hemisphere</td>
<td align="center" valign="top">80%RTM</td>
<td align="center" valign="top">600 pulses</td>
<td align="center" valign="top">22&#x202F;min a day, 5&#x202F;days a week, 4&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">19. Tao (<xref ref-type="bibr" rid="ref40">40</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">No report</td>
<td align="center" valign="top">No report</td>
<td align="center" valign="top">1,200 pulses</td>
<td align="center" valign="top">23&#x202F;min a day, 7&#x202F;days a week, 4&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">20. Thiel et al. (<xref ref-type="bibr" rid="ref53">53</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">The right triangular part of the posterior inferior frontal gyrus</td>
<td align="center" valign="top">90%RTM</td>
<td align="center" valign="top">No report</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week, 2&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">21. Tsai et al. (<xref ref-type="bibr" rid="ref52">52</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">The contralesional pars triangularis</td>
<td align="center" valign="top">90%RTM</td>
<td align="center" valign="top">600 pulses</td>
<td align="center" valign="top">10&#x202F;min a day, 5&#x202F;days a week, 2&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">22. Waldowski et al. (<xref ref-type="bibr" rid="ref56">56</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">Two parts of Broca&#x2019;s area homologs: the anterior part and posterior part</td>
<td align="center" valign="top">90%RTM</td>
<td align="center" valign="top">No report</td>
<td align="center" valign="top">30&#x202F;min a day, 5&#x202F;days a week, 3&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">23. Wang et al. (<xref ref-type="bibr" rid="ref51">51</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">The contralesional target area</td>
<td align="center" valign="top">90%RTM</td>
<td align="center" valign="top">1,200 pulses</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week, 2&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">24. Wang et al. (<xref ref-type="bibr" rid="ref39">39</xref>)</td>
<td align="center" valign="top">G1: 1&#x202F;Hz<break/>G2: 0.5&#x202F;Hz</td>
<td align="left" valign="top">Broca&#x2019;s area of the left cerebral hemisphere</td>
<td align="center" valign="top">90%RTM</td>
<td align="center" valign="top">1,200 pulses</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week, 2&#x202F;weeks<break/>40&#x202F;min a day, 5&#x202F;days a week, 2&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">25. Weiduschat et al. (<xref ref-type="bibr" rid="ref57">57</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">The right triangular part of the inferior frontal gyrus</td>
<td align="center" valign="top">90%RTM</td>
<td align="center" valign="top">No report</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week, 2&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">26. Fang et al. (<xref ref-type="bibr" rid="ref45">45</xref>)</td>
<td align="center" valign="top">G1: 10&#x202F;Hz<break/>G2:1&#x202F;Hz</td>
<td align="left" valign="top">G1: Broca&#x2019;s area of the left cerebral hemisphere<break/>G2: Broca&#x2019;s area of the right cerebral hemisphere</td>
<td align="center" valign="top">80%RTM</td>
<td align="center" valign="top">1,000 pulses</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week,4&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">27. Yang et al. (<xref ref-type="bibr" rid="ref42">42</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">Right inferior frontal gyrus triangle</td>
<td align="center" valign="top">80%RTM</td>
<td align="center" valign="top">480 pulses</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week,4&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">28. Yin et al. (<xref ref-type="bibr" rid="ref33">33</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">Broca&#x2019;s and Wernicke&#x2019;s zones in the right hemisphere</td>
<td align="center" valign="top">40%&#x202F;~&#x202F;90%RTM</td>
<td align="center" valign="top">800 pulses</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week,2&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">29. Zhang et al. (<xref ref-type="bibr" rid="ref34">34</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">Broca&#x2019;s area of the right cerebral hemisphere</td>
<td align="center" valign="top">80%RTM</td>
<td align="center" valign="top">500 pulses</td>
<td align="center" valign="top">30&#x202F;min a day, 10 consecutive days</td>
<td align="left" valign="top">No</td>
</tr>
<tr>
<td align="left" valign="top">30. Zhou et al. (<xref ref-type="bibr" rid="ref32">32</xref>)</td>
<td align="center" valign="top">1&#x202F;Hz</td>
<td align="left" valign="top">Broca&#x2019;s area of the right cerebral hemisphere</td>
<td align="center" valign="top">90%RTM</td>
<td align="center" valign="top">1,200 pulses</td>
<td align="center" valign="top">20&#x202F;min a day, 5&#x202F;days a week, 4&#x202F;weeks</td>
<td align="left" valign="top">No</td>
</tr>
</tbody>
</table>
</table-wrap>
</sec>
<sec id="sec18">
<label>3.3</label>
<title>Quality assessment result</title>
<p>The risk of bias assessment showed that in all included RCTs, four RCTs (<xref ref-type="bibr" rid="ref31">31</xref>, <xref ref-type="bibr" rid="ref40">40</xref>, <xref ref-type="bibr" rid="ref49">49</xref>, <xref ref-type="bibr" rid="ref55">55</xref>) did not use blinding for the assessment of outcome indicators and had a high risk of detection bias. And nine studies (<xref ref-type="bibr" rid="ref31">31</xref>, <xref ref-type="bibr" rid="ref33">33</xref>, <xref ref-type="bibr" rid="ref34">34</xref>, <xref ref-type="bibr" rid="ref37">37</xref>, <xref ref-type="bibr" rid="ref41">41</xref>, <xref ref-type="bibr" rid="ref45">45</xref>, <xref ref-type="bibr" rid="ref50">50</xref>, <xref ref-type="bibr" rid="ref52">52</xref>, <xref ref-type="bibr" rid="ref58">58</xref>) did not explicitly report blinding for assessing outcome indicators, and the risk of detection bias was unclear. The risk of bias was low for all RCTs in the other items evaluated for risk of bias. Overall, the risk of bias was low in our included studies (<xref ref-type="fig" rid="fig2">Figures 2</xref>, <xref ref-type="fig" rid="fig3">3</xref>).</p>
<fig position="float" id="fig2">
<label>Figure 2</label>
<caption>
<p>Risk of bias summary of included studies.</p>
</caption>
<graphic xlink:href="fneur-16-1614586-g002.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">An illustration of a risk of bias summary table for various studies, displaying colored circles: green with a plus symbol indicating low risk, yellow with a question mark indicating unclear risk, and red with a minus symbol indicating high risk. The studies are labeled along the top, with types of biases listed on the side, including selection, performance, detection, attrition, reporting, and other biases.</alt-text>
</graphic>
</fig>
<fig position="float" id="fig3">
<label>Figure 3</label>
<caption>
<p>Risk of bias graph of included studies.</p>
</caption>
<graphic xlink:href="fneur-16-1614586-g003.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Bar chart showing bias risks across seven categories: Random sequence generation (100% low risk), Allocation concealment (85% low, 15% unclear risk), Blinding of participants (60% low, 30% unclear, 10% high risk), Blinding of outcome (100% low risk), Incomplete outcome data (100% low risk), Selective reporting (80% low, 20% unclear risk), Other bias (100% low risk). Green indicates low risk, yellow unclear, and red high risk.</alt-text>
</graphic>
</fig>
<p>We evaluated the level of evidence for the outcome indicators of the included studies by GRADE. Three outcome indicators were rated as intermediate, (AQ, ABC and WAB) due to high heterogeneity between studies (<italic>I</italic> <sup>2</sup>&#x202F;&#x003E;&#x202F;80%) and were therefore downgraded in the inconsistency assessment. Four outcome indicators (AAT, BADE, CCAT and CPNT) were rated as intermediate because the sample sizes were too small (<italic>n</italic>&#x202F;&#x003C;&#x202F;100), which tended to influence the imprecision of the study results, and were downgraded in the imprecision assessment. The remaining outcome indicators were not found to be downgraded factors in each of the GRADE assessments. Overall, the GRADE recommended evidence level for the outcome indicator was &#x201C;strong&#x201D; (<xref ref-type="table" rid="tab4">Table 4</xref>).</p>
<table-wrap position="float" id="tab4">
<label>Table 4</label>
<caption>
<p>Grading of recommendations assessment, development, and evaluation (GRADE) quality of evidence.</p>
</caption>
<table frame="hsides" rules="groups">
<thead>
<tr>
<th rowspan="2">Assessment content</th>
<th align="center" valign="top" colspan="7">Outcomes</th>
</tr>
<tr>
<th align="center" valign="top">AAT</th>
<th align="center" valign="top">ABC</th>
<th align="center" valign="top">AQ</th>
<th align="center" valign="top">BADE</th>
<th align="center" valign="top">CCAT</th>
<th align="center" valign="top">CPNT</th>
<th align="center" valign="top">WAB</th>
</tr>
</thead>
<tbody>
<tr>
<td align="left" valign="top">Number of studies</td>
<td align="center" valign="top">4</td>
<td align="center" valign="top">7</td>
<td align="center" valign="top">16</td>
<td align="center" valign="top">2</td>
<td align="center" valign="top">2</td>
<td align="center" valign="top">3</td>
<td align="center" valign="top">12</td>
</tr>
<tr>
<td align="left" valign="top">Design</td>
<td align="center" valign="top">RCT</td>
<td align="center" valign="top">RCT</td>
<td align="center" valign="top">RCT</td>
<td align="center" valign="top">RCT</td>
<td align="center" valign="top">RCT</td>
<td align="center" valign="top">RCT</td>
<td align="center" valign="top">RCT</td>
</tr>
<tr>
<td align="left" valign="top">Study limitations</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
</tr>
<tr>
<td align="left" valign="top">Inconsistency</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">&#x2212;1&#x002A;</td>
<td align="center" valign="top">&#x2212;1&#x002A;</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">&#x2212;1&#x002A;</td>
</tr>
<tr>
<td align="left" valign="top">Indirectness</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
</tr>
<tr>
<td align="left" valign="top">Imprecision</td>
<td align="center" valign="top">&#x2212;1<sup>#</sup></td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">&#x2212;1<sup>#</sup></td>
<td align="center" valign="top">&#x2212;1<sup>#</sup></td>
<td align="center" valign="top">&#x2212;1<sup>#</sup></td>
<td align="center" valign="top">0</td>
</tr>
<tr>
<td align="left" valign="top">Publication bias</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
<td align="center" valign="middle">0</td>
</tr>
<tr>
<td align="left" valign="top">Effect size</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
<td align="center" valign="top">0</td>
</tr>
<tr>
<td align="left" valign="top">GRADE quality</td>
<td align="center" valign="middle">Moderate</td>
<td align="center" valign="middle">Moderate</td>
<td align="center" valign="middle">Moderate</td>
<td align="center" valign="middle">Moderate</td>
<td align="center" valign="middle">Moderate</td>
<td align="center" valign="middle">Moderate</td>
<td align="center" valign="middle">Moderate</td>
</tr>
<tr>
<td align="left" valign="top">Symbolic expression</td>
<td align="center" valign="middle">&#x2295;&#x202F;&#x2295;&#x202F;&#x2295;&#x2296;</td>
<td align="center" valign="middle">&#x2295;&#x202F;&#x2295;&#x202F;&#x2295;&#x2296;</td>
<td align="center" valign="middle">&#x2295;&#x202F;&#x2295;&#x202F;&#x2295;&#x2296;</td>
<td align="center" valign="middle">&#x2295;&#x202F;&#x2295;&#x202F;&#x2295;&#x2296;</td>
<td align="center" valign="middle">&#x2295;&#x202F;&#x2295;&#x202F;&#x2295;&#x2296;</td>
<td align="center" valign="middle">&#x2295;&#x202F;&#x2295;&#x202F;&#x2295;&#x2296;</td>
<td align="center" valign="middle">&#x2295;&#x202F;&#x2295;&#x202F;&#x2295;&#x2296;</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p>AAT, Aachener Aphasie Test; ABC, Aphasia Battery in Chinese; AQ, Aphasia Quotient; BADE, Boston Diagnostic Aphasia Examination. CCAT, Concise Chinese Aphasia Test; CPNT, Computerized Picture Naming Test; WAB, Western Aphasia Battery. &#x002A;High heterogeneity (I<sup>2</sup> &#x003E;&#x202F;80%); <sup>#</sup>the sample size was too small (<italic>n</italic>&#x202F;&#x003C;&#x202F;100).</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec id="sec19">
<label>3.4</label>
<title>Results of statistical analysis</title>
<p>There are 12 studies (<xref ref-type="bibr" rid="ref31">31</xref>, <xref ref-type="bibr" rid="ref32">32</xref>, <xref ref-type="bibr" rid="ref35">35</xref>, <xref ref-type="bibr" rid="ref36">36</xref>, <xref ref-type="bibr" rid="ref38">38</xref>, <xref ref-type="bibr" rid="ref39">39</xref>, <xref ref-type="bibr" rid="ref43 ref44 ref45 ref46 ref47">43&#x2013;47</xref>, <xref ref-type="bibr" rid="ref49">49</xref>) rated the speech function of PSA patients by WAB with <italic>I</italic><sup>2</sup>&#x202F;&#x003E;&#x202F;50% between studies and therefore used a random-effects model for data analysis. The results of the forest plot analysis showed that patients treated with rTMS had greater improvements in areas of verbal comprehension and expression. The specific improvement results were as follows: rTMS was more effective in improving auditory comprehension in PSA patients compared to control group (MD&#x202F;=&#x202F;1.94, 95% CI&#x202F;=&#x202F;[1.16, 2.17], <italic>I</italic><sup>2</sup>&#x202F;=&#x202F;79%, <italic>p</italic>&#x202F;&#x003C;&#x202F;0. 001, <xref ref-type="fig" rid="fig4">Figure 4</xref>); rTMS was more effective in improving naming ability in PSA patients compared to control group (MD&#x202F;=&#x202F;1.53, 95% CI&#x202F;=&#x202F;[0.82, 2.24], <italic>I</italic><sup>2</sup>&#x202F;=&#x202F;77%, <italic>p</italic>&#x202F;&#x003C;&#x202F;0. 001, <xref ref-type="fig" rid="fig5">Figure 5</xref>); rTMS was more effective in improving verbal repetition in PSA patients compared with the control group (MD&#x202F;=&#x202F;1.79, 95% CI&#x202F;=&#x202F;[1.20, 2.38], <italic>I</italic><sup>2</sup>&#x202F;=&#x202F;50%, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.001, <xref ref-type="fig" rid="fig6">Figure 6</xref>); and rTMS was more effective in improving PSA patients&#x2019; spontaneous speech (MD&#x202F;=&#x202F;1.97, 95% CI&#x202F;=&#x202F;[1.65, 2.29], <italic>I</italic><sup>2</sup>&#x202F;=&#x202F;0%, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.001, <xref ref-type="fig" rid="fig7">Figure 7</xref>).</p>
<fig position="float" id="fig4">
<label>Figure 4</label>
<caption>
<p>Forest plot for auditory comprehension (Western Aphasia Battery).</p>
</caption>
<graphic xlink:href="fneur-16-1614586-g004.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot displaying the comparison between experimental and control groups for two subgroups: rTMS plus SLT versus SLT and rTMS plus SLT versus sham rTMS plus SLT. Mean differences with confidence intervals and weight percentages are shown for each study. Combined results indicate a significant overall effect favoring the experimental groups with heterogeneity statistics provided. Black diamonds represent summary estimates, and horizontal lines indicate confidence intervals, with arrows marking extended ranges.</alt-text>
</graphic>
</fig>
<fig position="float" id="fig5">
<label>Figure 5</label>
<caption>
<p>Forest plot for naming (Western Aphasia Battery).</p>
</caption>
<graphic xlink:href="fneur-16-1614586-g005.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot comparing experimental groups (rTMS+SLT) to control groups. Studies are listed with individual mean differences plotted as black squares, and confidence intervals as horizontal lines. Larger diamonds represent subgroup totals, showing the overall effect favoring the experimental group with significant heterogeneity indicated.</alt-text>
</graphic>
</fig>
<fig position="float" id="fig6">
<label>Figure 6</label>
<caption>
<p>Forest plot for repetition (Western Aphasia Battery).</p>
</caption>
<graphic xlink:href="fneur-16-1614586-g006.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot comparing experimental and control groups on the mean difference in two subgroups: rTMS vs SLT and rTMS+SLT vs Sham rTMS+SLT. Data include study names, mean, standard deviation, and sample size for each group. Each study's confidence interval is shown. Pooled results indicate overall effectiveness, with diamonds representing summary statistics.</alt-text>
</graphic>
</fig>
<fig position="float" id="fig7">
<label>Figure 7</label>
<caption>
<p>Forest plot for spontaneous speech (Western Aphasia Battery).</p>
</caption>
<graphic xlink:href="fneur-16-1614586-g007.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot showing meta-analysis results of various studies comparing rTMS+SLT to SLT alone and rTMS+SLT to Sham rTMS+SLT. Each study lists the mean difference (IV, Fixed, 95% CI), with favorability indicated towards either control or experimental groups. Subtotals and overall totals are shown with their respective confidence intervals, illustrating heterogeneity and overall effect significance.</alt-text>
</graphic>
</fig>
<p>The degree of impairment in PSA patients was assessed in 16 studies (<xref ref-type="bibr" rid="ref30">30</xref>, <xref ref-type="bibr" rid="ref32">32</xref>, <xref ref-type="bibr" rid="ref33">33</xref>, <xref ref-type="bibr" rid="ref35 ref36 ref37 ref38 ref39 ref40">35&#x2013;40</xref>, <xref ref-type="bibr" rid="ref43 ref44 ref45 ref46 ref47 ref48 ref49">43&#x2013;49</xref>) using AQ scores with an <italic>I</italic><sup>2</sup> &#x003E;&#x202F;50% between studies, so the data were analyzed using a random effects model. The results of data analysis showed that compared to the control group, the experimental group showed better improvement in AQ scores than the control group (MD&#x202F;=&#x202F;13.82, 95% CI&#x202F;=&#x202F;[11.68, 15.97], <italic>I</italic><sup>2</sup>&#x202F;=&#x202F;52%, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.001; <xref ref-type="fig" rid="fig8">Figure 8</xref>).</p>
<fig position="float" id="fig8">
<label>Figure 8</label>
<caption>
<p>Forest plot for Aphasia Quotient (AQ).</p>
</caption>
<graphic xlink:href="fneur-16-1614586-g008.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot showing the mean differences in studies comparing rTMS plus SLT with SLT or Sham rTMS plus SLT. The diagram includes individual study results with mean differences, confidence intervals, and weights. Combined results for each subgroup and the overall effect are displayed with diamond symbols, indicating a positive effect favoring the experimental group. Heterogeneity statistics are provided at the bottom of the plot.</alt-text>
</graphic>
</fig>
<p>The degree of language loss in PSA patients was assessed by ABC in 7 studies (<xref ref-type="bibr" rid="ref33">33</xref>, <xref ref-type="bibr" rid="ref34">34</xref>, <xref ref-type="bibr" rid="ref40 ref41 ref42">40&#x2013;42</xref>, <xref ref-type="bibr" rid="ref48">48</xref>, <xref ref-type="bibr" rid="ref58">58</xref>) with <italic>I</italic><sup>2</sup>&#x202F;&#x003E;&#x202F;50% between studies, and we analyzed the data using a random-effects model. The results of the forest plot analysis showed that compared to the control group, the experimental group had better outcomes in ABC scores (MD&#x202F;=&#x202F;24.79, 95% CI&#x202F;=&#x202F;[17.80, 31.77], <italic>I</italic><sup>2</sup>&#x202F;=&#x202F;95%, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.001; <xref ref-type="fig" rid="fig9">Figure 9</xref>).</p>
<fig position="float" id="fig9">
<label>Figure 9</label>
<caption>
<p>Forest plot for Aphasia Battery in Chinese (ABC).</p>
</caption>
<graphic xlink:href="fneur-16-1614586-g009.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot showing the mean differences and confidence intervals for studies comparing rTMS+SLT versus SLT, and rTMS+SLT versus sham rTMS+SLT. Each study is represented by a green square, with the size indicating study weight. Results show overall favor for the experimental groups, highlighted by two diamond shapes representing combined effects. Heterogeneity statistics are provided, and the total combined effect size shows significant benefit for experimental conditions.</alt-text>
</graphic>
</fig>
<p>In 4 studies (<xref ref-type="bibr" rid="ref50">50</xref>, <xref ref-type="bibr" rid="ref53">53</xref>, <xref ref-type="bibr" rid="ref55">55</xref>, <xref ref-type="bibr" rid="ref56">56</xref>), the verbal function of PSA patients was assessed using the AAT scale, with an <italic>I</italic><sup>2</sup>&#x202F;&#x003C;&#x202F;50% between studies, and we analyzed the data using a fixed effects model. The results of the forest plot analysis showed that compared to the control group, the experimental group showed a significant improvement in AAT scores compared with the control group (MD&#x202F;=&#x202F;13.74, 95% CI&#x202F;=&#x202F;[9.43, 18.06], <italic>I</italic><sup>2</sup>&#x202F;=&#x202F;0%, <italic>p</italic>&#x202F;&#x003C;&#x202F;0.001; <xref ref-type="fig" rid="fig10">Figure 10</xref>).</p>
<fig position="float" id="fig10">
<label>Figure 10</label>
<caption>
<p>Forest plot for Aachener Aphasie Test (AAT).</p>
</caption>
<graphic xlink:href="fneur-16-1614586-g010.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot showing a meta-analysis of four studies comparing experimental and control groups. The studies are by Heiss et al. 2013, Rubi-fessen et al. 2015, Thiel et al. 2013, and Waldowski et al. 2012. Each study displays mean differences with 95% confidence intervals. The combined mean difference is 13.74 with a 95% confidence interval of 9.43 to 18.06. Heterogeneity is indicated as Chi&#x00B2; = 0.41 and I&#x00B2; = 0 percent. A diamond symbol at the combined mean shows overall effect, favoring the experimental group.</alt-text>
</graphic>
</fig>
<p>The severity of aphasia in PSA patients was assessed in two studies (<xref ref-type="bibr" rid="ref54">54</xref>, <xref ref-type="bibr" rid="ref59">59</xref>) using the BADE scale, with an <italic>I</italic><sup>2</sup>&#x202F;&#x003C;&#x202F;50% between studies, and we analyzed the data using a fixed effects model. The results of the analysis of the forest plot showed that the experimental group had a better improvement than the control group in terms of BADE scores in patients with PSA (MD&#x202F;=&#x202F;38.37, 95% CI&#x202F;=&#x202F;[6.32, 70.42], <italic>I</italic><sup>2</sup>&#x202F;=&#x202F;22%, <italic>p</italic>&#x202F;=&#x202F;0.02; <xref ref-type="fig" rid="fig11">Figure 11</xref>).</p>
<fig position="float" id="fig11">
<label>Figure 11</label>
<caption>
<p>Forest plot for Boston Diagnostic Aphasia Examination (BADE).</p>
</caption>
<graphic xlink:href="fneur-16-1614586-g011.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot comparing experimental and control groups across two studies. Barwood et al. 2011 shows a mean difference of 10.16 with a confidence interval from -48.30 to 68.62. Seniow et al. 2013 shows a mean difference of 50.50 with a confidence interval from 12.18 to 88.82. The overall effect is 38.37 with a confidence interval from 6.32 to 70.42. Total heterogeneity is Chi-squared equals 1.28, I-squared equals 22 percent. The test for overall effect shows Z equals 2.35 with a P-value of 0.02.</alt-text>
</graphic>
</fig>
<p>Two studies (<xref ref-type="bibr" rid="ref51">51</xref>, <xref ref-type="bibr" rid="ref52">52</xref>) used the CCAT scale to assess language function in PSA patients, and the <italic>I</italic><sup>2</sup>&#x202F;value between studies was 0%, thus the data were analyzed using a fixed effects model. The results of the analysis of the forest plot showed that the experimental group had a more positive contribution in improving the CCAT scores of PSA patients compared to the control group (MD&#x202F;=&#x202F;1.39, 95% CI&#x202F;=&#x202F;[0.25, 2.53], <italic>I</italic><sup>2</sup>&#x202F;=&#x202F;0%, <italic>p</italic>&#x202F;=&#x202F;0.02; <xref ref-type="fig" rid="fig12">Figure 12</xref>).</p>
<fig position="float" id="fig12">
<label>Figure 12</label>
<caption>
<p>Forest plot for Concise Chinese Aphasia Test (CCAT).</p>
</caption>
<graphic xlink:href="fneur-16-1614586-g012.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot comparing two studies' mean differences between experimental and control groups, showing green squares representing mean differences with confidence intervals. Tsai et al. 2014 has a mean difference of 1.00, while Wang et al. 2014 has 2.00. The overall effect is 1.39 with statistical significance (P = 0.02). Heterogeneity is low (I&#x00B2; = 0%).</alt-text>
</graphic>
</fig>
<p>In addition, 3 studies (<xref ref-type="bibr" rid="ref51">51</xref>, <xref ref-type="bibr" rid="ref52">52</xref>, <xref ref-type="bibr" rid="ref56">56</xref>) tested the naming function of PSA patients by CPNT alone, with an <italic>I</italic><sup>2</sup>&#x202F;&#x003C;&#x202F;50% between studies, so the data were analyzed using a fixed effects model. The results of the forest plot analysis showed that the experimental group was more able to improve the naming ability of PSA patients and promote the recovery of verbal function compared to the control group (MD&#x202F;=&#x202F;3.95, 95% CI&#x202F;=&#x202F;[0.84, 7.06], <italic>I</italic><sup>2</sup>&#x202F;=&#x202F;8%, <italic>p</italic>&#x202F;=&#x202F;0.01; <xref ref-type="fig" rid="fig13">Figure 13</xref>).</p>
<fig position="float" id="fig13">
<label>Figure 13</label>
<caption>
<p>Forest plot for Computerized Picture Naming Test (CPNT).</p>
</caption>
<graphic xlink:href="fneur-16-1614586-g013.tif" mimetype="image" mime-subtype="tiff">
<alt-text content-type="machine-generated">Forest plot comparing experimental and control groups across three studies. Mean differences with 95% confidence intervals are shown: Tsai et al. (8.90), Waldowski et al. (2.58), and Wang et al. (14.60). A fixed-effects model indicates an overall mean difference of 3.95. Heterogeneity statistics: Chi-square equals 4.80, degrees of freedom is 2, P equals 0.09, and I-squared is 58%. The overall effect test shows Z equals 2.49, P equals 0.01, favoring the experimental group.</alt-text>
</graphic>
</fig>
</sec>
<sec id="sec20">
<label>3.5</label>
<title>Adverse event reporting results</title>
<p>Of the 30 studies we included, only three studies reported the occurrence of adverse events. One of these studies (<xref ref-type="bibr" rid="ref49">49</xref>) reported that two participants treated with rTMS experienced transient headache and nausea with a duration of &#x003C;24&#x202F;h, which accounted for 2/819 of the total number of participants in the experimental group of our study. Two other studies (<xref ref-type="bibr" rid="ref36">36</xref>, <xref ref-type="bibr" rid="ref44">44</xref>) reported transient dizziness in two subjects treated with rTMS for &#x003C;24&#x202F;h, which accounted for 2/819 of the total number of participants in the experimental group of our study. In summary the number of patients with PSA treated with rTMS who developed adverse events as a proportion of the total number of participants in the experimental group was 4/819. In addition, based on the results reported in all studies, no patients withdrew from the experimental studies due to exhibited excessive adverse reactions. Moreover, only three of the 30 included studies reported adverse events (reporting rate 10%), and all RCTs had small sample sizes (<italic>n</italic>&#x202F;&#x003C;&#x202F;100). Therefore, we must consider the possibility of publication bias arising from unrecorded or unreported adverse events, which could underestimate the true risks of rTMS and thereby overstate its safety. We recommend that future studies continue to adhere strictly to established rTMS safety guidelines to ensure rigorous practice.</p>
</sec>
</sec>
<sec sec-type="discussion" id="sec21">
<label>4</label>
<title>Discussion</title>
<p>The aim of this meta-analysis was to determine the efficacy of rTMS on the rehabilitation of speech function in patients with PSA. In the analysis obtained so far, we found that rTMS can effectively promote the recovery of speech function in PSA patients, which is consistent with the partial results of previous studies (<xref ref-type="bibr" rid="ref60 ref61 ref62">60&#x2013;62</xref>). Previous studies used rTMS as the intervention in PSA patients and employed speech-function scales (WAB, AQ, ABC, etc.) as outcome measures; they likewise demonstrated that rTMS can effectively improve language abilities in this population, but none assessed the safety of rTMS for PSA. The analysis with WAB as the assessment outcome showed that rTMS combined with SLT treatment was more effective than SLT alone in treating patients with PSA, as evidenced by the improvement in patients&#x2019; language abilities such as auditory comprehension, naming, repetition, and spontaneous speech. Compared with previous meta-analyses (<xref ref-type="bibr" rid="ref20">20</xref>, <xref ref-type="bibr" rid="ref25">25</xref>), we have not only added recently published RCTs but also widened the spectrum of stimulation frequencies employed across studies and incorporated a broader array of outcome measures to provide more comprehensive assessments. Meanwhile, the improvement of the results assessed by CCAT and AAT indicated that rTMS could effectively enhance the speech function of PSA patients. In addition, the improvement of the assessment results by AQ, ABC and BADE showed that rTMS could effectively reduce the degree of aphasia impairment in PSA patients. In addition, to provide a higher level of evidence support, we conducted a more in-depth analysis and discussion of the mechanism of action of rTMS in treating PSA patients and the treatment effects of different intervention parameters.</p>
<p>Currently, more researchers prefer the &#x201C;hemispheric balance theory&#x201D; for the treatment rationale of rTMS in stroke patients (<xref ref-type="bibr" rid="ref63">63</xref>, <xref ref-type="bibr" rid="ref64">64</xref>). An important factor influencing treatment efficacy is the site of stimulation. In the majority of trials, rTMS was delivered to the contralesional hemisphere, most often the right inferior frontal gyrus or its homolog of Broca&#x2019;s area. Several studies, however, applied stimulation to lesioned hemisphere regions or adopted bilateral protocols. While our data were not sufficient to conduct subgroup meta-analysis of stimulation site, existing evidence suggests that site-specific modulation may differentially affect language outcomes in patients with Broca-type, global, or motor aphasia. Likewise, pairing rTMS with behavioral interventions such as SLT appears to maximize recovery potential compared to rTMS alone. Future large-scale trials should stratify patients according to stimulation target and aphasia profile to clarify whether specific protocols yield superior outcomes. In our brain, the bilateral hemispheres are in a state of equilibrium of mutual inhibition under normal physiological conditions, usually called &#x201C;transcallosal mutual inhibition.&#x201D; However, the hemispheric equilibrium of mutual inhibition can be disrupted in stroke patients with brain damage. For example, motor aphasia occurs in patients with damage to the Broca&#x2019;s area in the left hemisphere, resulting in a decrease in the inhibitory capacity of the right hemisphere, which in turn leads to an activation of the right hemisphere and an increase in the inhibitory effect of the right hemisphere on the left hemisphere, thus breaking the balance of bilateral hemispheric inhibition and affecting the recovery of speech function in patients with post-stroke aphasia (<xref ref-type="bibr" rid="ref63">63</xref>, <xref ref-type="bibr" rid="ref64">64</xref>). In order to correct the imbalance between the two hemispheres, we need to regulate the excitability of both cortices, and rTMS can do just this. It has been shown that rTMS can produce an electric field in the brain based on the principle of electromagnetic induction, which induces depolarized neurons to regulate cortical excitability (<xref ref-type="bibr" rid="ref65">65</xref>). It has been found that high-frequency (&#x003E;1&#x202F;Hz) rTMS increases cortical excitability and low-frequency (&#x2264;1&#x202F;Hz) rTMS decreases cortical excitability (<xref ref-type="bibr" rid="ref66 ref67 ref68">66&#x2013;68</xref>). and through this mechanism, rTMS can regulate the imbalance in both hemispheres (<xref ref-type="bibr" rid="ref69 ref70 ref71">69&#x2013;71</xref>) and cause plasticity changes in the cerebral cortex, thus promoting the recovery of speech function in post-stroke aphasic patients (<xref ref-type="bibr" rid="ref50">50</xref>, <xref ref-type="bibr" rid="ref72">72</xref>). Thiel et al. (<xref ref-type="bibr" rid="ref53">53</xref>) investigated the mechanism of rTMS using fMRI and found that rTMS could inhibit the hyperactivation of the healthy hemisphere, which led to a decrease in the inhibitory ability of the healthy hemisphere on the language control area of the affected hemisphere and promoted the rebalancing of the bilateral hemispheres, thus improving the language function of patients with post-stroke aphasia.</p>
<p>Among the 30 RCTs included, only three employed high-frequency rTMS; the remainder used low-frequency stimulation, and no uniform outcome measures were adopted. Thus, the available data are insufficient for a subgroup analysis comparing the efficacy of high- versus low-frequency rTMS. And the results of forest plot data show that both high-frequency rTMS and low-frequency rTMS can have a positive therapeutic effect on aphasia in stroke patients. Combined with the balance theory of both human hemispheres (<xref ref-type="bibr" rid="ref73">73</xref>), there are good reasons to try the combination of high-frequency rTMS and low-frequency rTMS and to conduct a comparative efficacy study with low-frequency rTMS or high-frequency rTMS alone to explore the best treatment option of rTMS for post-stroke aphasia treatment. Yan et al. (<xref ref-type="bibr" rid="ref45">45</xref>) reported in the previous study that combining high-frequency rTMS with low-frequency rTMS can effectively promote the recovery of speech function in stroke patients. Moreover, Hu et al. (<xref ref-type="bibr" rid="ref44">44</xref>) also proven that low-frequency rTMS had superior and longer-lasting therapeutic effects than high-frequency rTMS on the recovery of speech function in patients with non-fluent aphasia, especially in the areas of spontaneous speech, aphasia quotient, and auditory comprehension function. However, a study by Wang et al. (<xref ref-type="bibr" rid="ref39">39</xref>) showed that there was no difference in the therapeutic effect of low-frequency rTMS of different frequencies on patients with PSA. It can be seen that more, multicenter, RCTs with large sample sizes of high-frequency rTMS in combination with low-frequency rTMS are still needed to further approach the optimal intervention parameters of rTMS for post-stroke aphasia in the future.</p>
<p>Wang et al. (<xref ref-type="bibr" rid="ref39">39</xref>) and Shen (<xref ref-type="bibr" rid="ref41">41</xref>) expanded the selection of parameters of the commonly used rTMS and conducted a comparative study of the efficacy of 0.5-Hz rTMS and 1-Hz rTMS on PSA patients. The results found that patients in the sham stimulation group, both 0.5&#x202F;Hz group, and 1&#x202F;Hz group all had better WAB scores after treatment. Moreover, there was no statistically significant difference in the efficacy between the 0.5&#x202F;Hz group and the 1&#x202F;Hz group in treating patients with PSA, nor was there a significant difference in the improvement of WAB scores in PSA patients. However, the two groups were not identical regarding improvement in speech function. With the extension of treatment time, the 0.5&#x202F;Hz group showed better progress than the 1&#x202F;Hz group in auditory comprehension indexes.</p>
<p>In comparison, the 1&#x202F;Hz group showed better improvement than the 0.5&#x202F;Hz group in spontaneous speech indexes. The results of Wang et al. suggest that 0.5&#x202F;Hz and 1&#x202F;Hz rTMS can produce respective more advantageous therapeutic effects on different aphasic symptoms, so should different frequencies of rTMS should be selected for targeted treatment to enhance the therapeutic effects of rTMS on PSA patients corresponding to various symptoms of aphasia. More RCTs with different stimulation frequencies of rTMS for PSA need to be conducted in the future to expand the selection of treatment parameters so that we can provide individualized treatment for PSA patients with different symptoms in the clinical treatment of PSA patients.</p>
<p>An expert guideline published in 2021 (<xref ref-type="bibr" rid="ref74">74</xref>) addresses the safety and recommendations for the use of rTMS in healthy subjects and patient populations. This guideline provides the most up-to-date information on the possible induction of seizures, which are theorized to be the most serious risk of rTMS. It has become apparent that such a risk is low, even in patients taking drugs acting on the central nervous system, at least with the use of traditional stimulation parameters and focal coils for which large data sets are available. However, in this study, we included a total of 819 subjects, but only 4 subjects experienced symptoms such as transient dizziness and nausea, and no patient experienced any seizure symptoms. First, we were not direct participants in this RCT and cannot be certain that these side effects necessarily came from the therapeutic effects of rTMS, and second, if these adverse effects did come as a result of the rTMS intervention, they did not result in any persistent, irreversible changes in the condition of the PSA patients. Finally, compared to the total number of participants in the trial, the number of patients experiencing adverse effects was only 0.5% of the total, making the probability of adverse events extremely low. Considering the clinical application of rTMS, the treatment of PSA patients with rTMS is indeed highly safe.</p>
<sec id="sec22">
<label>4.1</label>
<title>Study limitations</title>
<p>However, our meta-analysis also has several limitations that should be considered. First, the sample size of our included RCTs was small (<italic>n</italic>&#x202F;&#x003C;&#x202F;100), and too small a sample size tends to bias the assessment of treatment effects and overestimate the efficacy of rTMS. Second, although our studies all showed the positive impact of transcranial magnetic stimulation (TMS) in patients with post-stroke aphasia, most did not report patient follow-ups further to confirm the long-term effects of TMS. Third, the studies we included differed regarding the stimulation sites and the number of pulses. The number of available studies did not allow for more detailed subgroup analysis. Fourth, the absence of gray reports may lead to bias in comprehensive analysis results. Meaningful research is more likely to be accepted for publication, making us cautious about jumping to conclusions. Fifth, this study lack of patient-level data and possible cultural/geographical biases (majority of studies from China). Therefore, more multicenter follow-up, double-blind RCTs should be conducted to facilitate longitudinal and cross-sectional comparisons of different stimulation parameters of rTMS, to determine the optimal treatment protocol, and to improve the clinical efficacy of rTMS in patients with PSA. Moreover, heterogeneity in the site of stimulation across studies limits the generalizability of pooled results. Most studies targeted contralesional areas, but some used ipsilesional or bilateral protocols, which may lead to distinct therapeutic trajectories. The absence of detailed subgroup analyses also prevents us from assessing whether different aphasia phenotypes (e.g., Broca, global, motor) respond differently to rTMS. This remains an important future direction for tailoring interventions.</p>
</sec>
</sec>
<sec sec-type="conclusions" id="sec23">
<label>5</label>
<title>Conclusion</title>
<p>This study shows that rTMS can safely and effectively improve speech function in patients with post-stroke aphasia (PSA), particularly in auditory comprehension, naming, repetition, and spontaneous speech, which aligns with the findings of Gholami et al. (<xref ref-type="bibr" rid="ref20">20</xref>) Transient adverse events such as headache, nausea, and dizziness were observed during treatment, but the incidence was very low (0.49%) and the symptoms resolved within 24&#x202F;h. Furthermore, our systematic review and analysis indicate that different rTMS frequencies produce distinct therapeutic benefits for specific aphasic symptoms: 0.5&#x202F;Hz rTMS outperforms 1&#x202F;Hz rTMS in improving auditory comprehension, whereas 1&#x202F;Hz rTMS is more advantageous for enhancing spontaneous speech. Future multicenter, large-sample randomized controlled trials using different rTMS frequencies are needed to determine the optimal stimulation parameters for PSA.</p>
</sec>
</body>
<back>
<sec sec-type="data-availability" id="sec24">
<title>Data availability statement</title>
<p>The original contributions presented in the study are included in the article/<xref ref-type="supplementary-material" rid="SM1">Supplementary material</xref>, further inquiries can be directed to the corresponding author.</p>
</sec>
<sec sec-type="author-contributions" id="sec25">
<title>Author contributions</title>
<p>LX: Methodology, Conceptualization, Writing &#x2013; review &#x0026; editing. YD: Data curation, Conceptualization, Writing &#x2013; review &#x0026; editing, Project administration. CG: Formal analysis, Methodology, Project administration, Writing &#x2013; original draft. JH: Methodology, Conceptualization, Writing &#x2013; review &#x0026; editing, Project administration, Data curation. MH: Methodology, Project administration, Writing &#x2013; review &#x0026; editing, Investigation. ZD: Conceptualization, Writing &#x2013; original draft, Investigation.</p>
</sec>
<sec sec-type="funding-information" id="sec26">
<title>Funding</title>
<p>The author(s) declare that no financial support was received for the research and/or publication of this article.</p>
</sec>
<ack>
<p>The authors would like to express their sincere gratitude to Ganzhou People&#x2019;s Hospital, Gannan Medical University, and Jiangxi Provincial People&#x2019;s Hospital for their invaluable support and contributions to this research. Their resources and collaboration significantly enhanced the quality of our study. We also thank our colleagues for their insightful discussions and assistance throughout the research process, which greatly aided our efforts.</p>
</ack>
<sec sec-type="COI-statement" id="sec27">
<title>Conflict of interest</title>
<p>The authors declare that this research was conducted without any commercial or financial relationships that could be perceived as potential conflicts of interest.</p>
</sec>
<sec sec-type="ai-statement" id="sec28">
<title>Generative AI statement</title>
<p>The authors declare that no Gen AI was used in the creation of this manuscript.</p>
<p>Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.</p>
</sec>
<sec sec-type="disclaimer" id="sec29">
<title>Publisher&#x2019;s note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p>
</sec>
<sec sec-type="supplementary-material" id="sec30">
<title>Supplementary material</title>
<p>The Supplementary material for this article can be found online at: <ext-link xlink:href="https://www.frontiersin.org/articles/10.3389/fneur.2025.1614586/full#supplementary-material" ext-link-type="uri">https://www.frontiersin.org/articles/10.3389/fneur.2025.1614586/full#supplementary-material</ext-link></p>
<supplementary-material xlink:href="Image_1.TIF" id="SM1" mimetype="image/tiff" xmlns:xlink="http://www.w3.org/1999/xlink"/>
<supplementary-material xlink:href="Image_2.TIF" id="SM2" mimetype="image/tiff" xmlns:xlink="http://www.w3.org/1999/xlink"/>
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