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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Neurosci.</journal-id>
<journal-title-group>
<journal-title>Frontiers in Neuroscience</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Neurosci.</abbrev-journal-title>
</journal-title-group>
<issn pub-type="epub">1662-453X</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fnins.2025.1629305</article-id>
<article-version article-version-type="Version of Record" vocab="NISO-RP-8-2008"/>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Systematic Review</subject>
</subj-group>
</article-categories>
<title-group>
<article-title>Neuroimaging evidence of acupuncture in cognitive impairment following ischemic stroke: a systematic review</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author" equal-contrib="yes">
<name><surname>Qin</surname> <given-names>Chenyang</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
<xref ref-type="author-notes" rid="fn001"><sup>&#x02020;</sup></xref>
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<contrib contrib-type="author" corresp="yes" equal-contrib="yes">
<name><surname>Li</surname> <given-names>Bo</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x0002A;</sup></xref>
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<contrib contrib-type="author" equal-contrib="yes">
<name><surname>Zhuo</surname> <given-names>Bifang</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
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<contrib contrib-type="author" equal-contrib="yes">
<name><surname>Yang</surname> <given-names>Xinming</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
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<name><surname>Cui</surname> <given-names>Ying</given-names></name>
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<contrib contrib-type="author">
<name><surname>Meng</surname> <given-names>Zhihong</given-names></name>
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<aff id="aff1"><label>1</label><institution>First Teaching Hospital of Tianjin University of Traditional Chinese Medicine</institution>, <city>Tianjin</city>, <country country="cn">China</country></aff>
<aff id="aff2"><label>2</label><institution>National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion</institution>, <city>Tianjin</city>, <country country="cn">China</country></aff>
<aff id="aff3"><label>3</label><institution>Tianjin University of Traditional Chinese Medicine</institution>, <city>Tianjin</city>, <country country="cn">China</country></aff>
<author-notes>
<corresp id="c001"><label>&#x0002A;</label>Correspondence: Bo Li, <email xlink:href="mailto:ibou119@163.com">ibou119@163.com</email></corresp>
<fn fn-type="equal" id="fn001"><label>&#x02020;</label><p>These authors have contributed equally to this work</p></fn></author-notes>
<pub-date publication-format="electronic" date-type="pub" iso-8601-date="2026-01-12">
<day>12</day>
<month>01</month>
<year>2026</year>
</pub-date>
<pub-date publication-format="electronic" date-type="collection">
<year>2025</year>
</pub-date>
<volume>19</volume>
<elocation-id>1629305</elocation-id>
<history>
<date date-type="received">
<day>22</day>
<month>07</month>
<year>2025</year>
</date>
<date date-type="rev-recd">
<day>06</day>
<month>11</month>
<year>2025</year>
</date>
<date date-type="accepted">
<day>05</day>
<month>12</month>
<year>2025</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2026 Qin, Li, Zhuo, Yang, Cui and Meng.</copyright-statement>
<copyright-year>2026</copyright-year>
<copyright-holder>Qin, Li, Zhuo, Yang, Cui and Meng</copyright-holder>
<license>
<ali:license_ref start_date="2026-01-12">https://creativecommons.org/licenses/by/4.0/</ali:license_ref>
<license-p>This is an open-access article distributed under the terms of the <ext-link ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by/4.0/">Creative Commons Attribution License (CC BY)</ext-link>. 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.</license-p>
</license>
</permissions>
<abstract>
<sec>
<title>Objective</title>
<p>This review aimed to summarize neuroimaging evidence on the effects of acupuncture in post-ischemic stroke cognitive impairment (PISCI) and to explore its potential neural mechanisms.</p></sec>
<sec>
<title>Methods</title>
<p>A systematic search was conducted across multiple databases, including China National Knowledge Infrastructure (CNKI), SinoMed (China Biology Medicine Disc), the Chinese Scientific Journal Database (VIP), Wanfang Data, PubMed, the Cochrane Library, Embase, and Web of Science. Studies were selected according to inclusion and exclusion criteria. Risk of bias was assessed for all eligible studies.</p></sec>
<sec>
<title>Results</title>
<p>Eight studies met the inclusion criteria. These studies utilized resting-state functional magnetic resonance imaging (rs-fMRI) and magnetic resonance spectroscopy (MRS) to investigate the effects of acupuncture on brain activity and metabolic changes. The neuroimaging findings showed that all studies focused on the sustained effects of acupuncture on brain functional activity.</p></sec>
<sec>
<title>Conclusions</title>
<p>This review provides preliminary neuroimaging evidence supporting the potential benefits of acupuncture for PISCI. The findings suggest that the possible mechanisms of acupuncture for PISCI involve changes in the activity and enhanced functional connectivity of cognition-related brain regions. Additionally, acupuncture may influence brain networks and regulate neurochemical metabolites within cognition-related regions. However, as this field remains in its early stages, further validation is needed. Future studies should focus on well-designed, multicenter randomized controlled trials (RCTs) with large sample sizes and incorporate multiple neuroimaging techniques to better clarify and verify the neural mechanisms of acupuncture in PISCI.</p></sec>
<sec>
<title>Systematic review registration</title>
<p>PROSPERO, identifier: CRD420250652194.</p></sec></abstract>
<kwd-group>
<kwd>acupuncture</kwd>
<kwd>cognitive impairment</kwd>
<kwd>neuroimaging</kwd>
<kwd>ischemic stroke</kwd>
<kwd>MRI</kwd>
</kwd-group>
<funding-group>
  <funding-statement>The author(s) declared that financial support was received for this work and/or its publication. This work was supported by the project from the Open Project of National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion (Grant No. NCRCOP2023009) and the Innovation team for Research on Dominant Diseases of Acupuncture and Moxibustion (Grant No. 4042502034).</funding-statement>
</funding-group>
<counts>
<fig-count count="6"/>
<table-count count="6"/>
<equation-count count="0"/>
<ref-count count="127"/>
<page-count count="19"/>
<word-count count="13239"/>
</counts>
<custom-meta-group>
<custom-meta>
<meta-name>section-at-acceptance</meta-name>
<meta-value>Translational Neuroscience</meta-value>
</custom-meta>
</custom-meta-group>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="s1">
<label>1</label>
<title>Introduction</title>
<p>Each year, approximately 12.2 million people are newly diagnosed with stroke worldwide. Among adults, stroke is the leading cause of long-term disability and the second leading cause of death globally (<xref ref-type="bibr" rid="B31">Hilkens et al., 2024</xref>; <xref ref-type="bibr" rid="B50">Lekoubou et al., 2023</xref>). According to the 2021 Global Burden of Disease (GBD) study, stroke represents the most burdensome disease across all regions of East Asia (<xref ref-type="bibr" rid="B20">Ferrari et al., 2024</xref>). Ischemic stroke accounts for approximately 87% of all stroke cases (<xref ref-type="bibr" rid="B57">Li Y. et al., 2023</xref>) and is primarily caused by arterial occlusion leading to focal cerebral ischemia and hypoxia, which subsequently result in neuronal death and disruption of neural networks (<xref ref-type="bibr" rid="B26">Guo et al., 2021</xref>). Despite advances in acute treatments such as thrombolysis and mechanical thrombectomy, a significant proportion of stroke survivors experience varying degrees of cognitive impairment during recovery (<xref ref-type="bibr" rid="B35">Huang et al., 2022</xref>; <xref ref-type="bibr" rid="B39">Kalaria et al., 2016</xref>; <xref ref-type="bibr" rid="B59">Li et al., 2022</xref>). Post-stroke cognitive impairment (PSCI) is a common complication characterized by memory decline, reduced attention, and executive dysfunction, which significantly affect patients&#x00027; quality of life and life expectancy (<xref ref-type="bibr" rid="B82">Stinear et al., 2020</xref>). The prevalence and incidence of PSCI vary depending on the outcome definition and the timing of assessment (<xref ref-type="bibr" rid="B74">Pendlebury and Rothwell, 2009</xref>). A large review of almost 300,000 individuals in 12 countries indicated that the prevalence of PSCI ranges from 20% to 80% (<xref ref-type="bibr" rid="B85">Sun et al., 2014</xref>). Among its subtypes, post-ischemic stroke cognitive impairment (PISCI) is a major form of PSCI and has been associated with adverse outcomes, including severe disability, depression, increased mortality, and recurrent strokes (<xref ref-type="bibr" rid="B45">Korostynski et al., 2021</xref>; <xref ref-type="bibr" rid="B48">Kwon et al., 2020</xref>; <xref ref-type="bibr" rid="B71">Mijajlovi&#x00107; et al., 2017</xref>; <xref ref-type="bibr" rid="B86">Swartz et al., 2016</xref>). However, effective treatment options for PISCI remain limited.</p>
<p>Current therapeutic strategies for PISCI primarily include cholinesterase inhibitors, cognitive training, and non-invasive brain stimulation techniques (<xref ref-type="bibr" rid="B11">Cicerone et al., 2011</xref>; <xref ref-type="bibr" rid="B101">Wang et al., 2022c</xref>; <xref ref-type="bibr" rid="B105">Whyte et al., 2008</xref>; <xref ref-type="bibr" rid="B106">Winstein et al., 2016</xref>). However, pharmacological treatments often provide only temporary symptomatic relief, do not substantially delay disease progression, and are frequently associated with gastrointestinal side effects (<xref ref-type="bibr" rid="B5">Beristain and Golombievski, 2015</xref>; <xref ref-type="bibr" rid="B19">Eshaghi Ghalibaf et al., 2023</xref>; <xref ref-type="bibr" rid="B68">Malik et al., 2022</xref>). The long term effectiveness of cognitive training is constrained by patient adherence and the need for individualized interventions (<xref ref-type="bibr" rid="B5">Beristain and Golombievski, 2015</xref>; <xref ref-type="bibr" rid="B36">Irazoki et al., 2020</xref>). Additionally, the clinical efficacy of non-invasive brain stimulation remains inconclusive (<xref ref-type="bibr" rid="B81">Snowball et al., 2013</xref>; <xref ref-type="bibr" rid="B112">Yang et al., 2024</xref>). Therefore, there is an urgent need to explore safe and effective alternative or adjunctive therapies. Acupuncture, a core treatment modality in Traditional Chinese Medicine (TCM), is widely applied in stroke rehabilitation (<xref ref-type="bibr" rid="B61">Liu et al., 2021</xref>; <xref ref-type="bibr" rid="B76">Qiu et al., 2021</xref>; <xref ref-type="bibr" rid="B98">Wang et al., 2022a</xref>; <xref ref-type="bibr" rid="B114">Yang et al., 2022</xref>) and has shown promising effects in improving post-stroke cognitive function (<xref ref-type="bibr" rid="B9">Chavez et al., 2017</xref>). Several meta-analyses suggest potential benefits of acupuncture for PISCI (<xref ref-type="bibr" rid="B29">Han et al., 2024</xref>; <xref ref-type="bibr" rid="B46">Kuang et al., 2021</xref>; <xref ref-type="bibr" rid="B62">Liu et al., 2023</xref>; <xref ref-type="bibr" rid="B102">Wang et al., 2022d</xref>; <xref ref-type="bibr" rid="B107">Wu et al., 2024</xref>). For example, <xref ref-type="bibr" rid="B83">Su et al. (2024)</xref> reported that acupuncture combined with repetitive transcranial magnetic stimulation (rTMS) was more effective than rTMS alone, while <xref ref-type="bibr" rid="B62">Liu et al. (2023)</xref> found that acupuncture was more effective than conventional rehabilitation training in improving cognitive function. In addition, a multicenter RCT (<xref ref-type="bibr" rid="B123">Zhang et al., 2022</xref>) indicated that acupuncture significantly improved post-stroke cognitive function.</p>
<p>Nevertheless, the mechanisms by which acupuncture promotes cognitive recovery remain unclear. Several studies have provided insights into the potential mechanisms by which acupuncture ameliorates PISCI. A review suggested that acupuncture may enhance synaptic plasticity by regulating long-term potentiation (LTP) and long-term depression (LTD), thereby facilitating cognitive recovery (<xref ref-type="bibr" rid="B75">Qin et al., 2022</xref>). Other studies have shown that acupuncture can inhibit neuronal apoptosis (<xref ref-type="bibr" rid="B55">Li N. et al., 2023</xref>), a pathological process considered to be a key contributor to cognitive decline after stroke (<xref ref-type="bibr" rid="B69">Mattson, 2000</xref>). In addition, electro acupuncture stimulation has been reported to suppress the expression of inflammatory cytokines in the hippocampus and plasma, leading to improved cognitive function in rats (<xref ref-type="bibr" rid="B94">Wang et al., 2020</xref>). Studies have also demonstrated that acupuncture may alleviate cognitive impairment by enhancing cerebral blood flow (<xref ref-type="bibr" rid="B66">Ma et al., 2020</xref>) and reducing oxidative stress (<xref ref-type="bibr" rid="B18">Du et al., 2018</xref>). Collectively, these findings suggest that acupuncture exerts regulatory effects through multiple neurobiological mechanisms, although the specific processes remain to be fully elucidated.</p>
<p>PISCI has been linked to both functional and structural alterations in multiple brain regions, including disrupted functional connectivity (<xref ref-type="bibr" rid="B6">Bournonville et al., 2018</xref>), structural changes (<xref ref-type="bibr" rid="B4">Benedict et al., 2020</xref>), abnormal neural network activity (<xref ref-type="bibr" rid="B90">Wahl, 2018</xref>), and neuro inflammatory responses (<xref ref-type="bibr" rid="B79">Shishkina et al., 2021</xref>), all of which contribute to cognitive decline. Neuroimaging techniques, such as functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), functional near-infrared spectroscopy (fNIRS), and magnetic resonance spectroscopy (MRS), provide crucial tools for investigating the neural mechanisms underlying PISCI (<xref ref-type="bibr" rid="B117">Yu et al., 2024</xref>) and offer novel perspectives for exploring the effects of acupuncture. To date, however, no systematic review has comprehensively synthesized neuroimaging evidence on the effects of acupuncture in PISCI. Accordingly, the present review summarizes current neuroimaging findings on acupuncture in PISCI and explores potential neural mechanisms. Through this synthesis, the review seeks to deepen understanding of how acupuncture may improve cognitive outcomes in PISCI and to provide a theoretical foundation for its clinical application.</p></sec>
<sec id="s2">
<label>2</label>
<title>Methods</title>
<sec>
<label>2.1</label>
<title>Protocol and registration</title>
<p>The protocol for this systematic review (SR) was registered in PROSPERO (registration number CRD420250652194). The review was conducted in accordance with the PRISMA statement (<xref ref-type="bibr" rid="B72">Moher et al., 2009</xref>).</p>
</sec>
<sec>
<label>2.2</label>
<title>Eligibility criteria</title>
<sec>
<label>2.2.1</label>
<title>Inclusion criteria</title>
<p>The inclusion criteria are shown in <xref ref-type="table" rid="T1">Table 1</xref>.</p>
<table-wrap position="float" id="T1">
<label>Table 1</label>
<caption><p>Inclusion criteria of this study.</p></caption>
<table frame="box" rules="all">
<tbody>
<tr>
<td valign="top" align="left">Study type</td>
<td valign="top" align="left">Published randomized and non-randomized controlled studies (RCTs and non-RCTs) in English and Chinese on acupuncture for PISCI.</td>
</tr>
<tr>
<td valign="top" align="left">Patients</td>
<td valign="top" align="left">Meeting the diagnostic criteria for ischemic stroke, with cognitive impairment confirmed by neuropsychological assessments, and no restrictions on age, gender, race, or region.</td>
</tr>
<tr>
<td valign="top" align="left">Intervention</td>
<td valign="top" align="left">(1) studies in which acupuncture was the sole intervention in the treatment group, with the control group receiving either a placebo, drug, conventional therapy, or sham acupuncture; or <break/>(2) studies where acupuncture was administered alongside other therapies in the treatment group, provided that the control group received those same other therapies without the acupuncture.</td>
</tr>
<tr>
<td valign="top" align="left">Outcomes</td>
<td valign="top" align="left">At least one of the following neuroimaging tools was used: MRI, DTI, MRS, or fNIRS.</td>
</tr></tbody>
</table>
</table-wrap>
</sec>
<sec>
<label>2.2.2</label>
<title>Exclusion criteria</title>
<p>Studies were excluded if they met any of the following conditions:</p>
<list list-type="simple">
<list-item><p>(1) Reviews, comments, animal studies, letters, protocols, case reports, or duplicate studies;</p></list-item>
<list-item><p>(2) Studies involving non-ischemic stroke populations or without a clear assessment of cognitive impairment;</p></list-item>
<list-item><p>(3) Studies comparing two different acupuncture methods;</p></list-item>
<list-item><p>(4) Studies lacking available data on both neuroimaging outcomes and cognitive function outcomes;</p></list-item>
<list-item><p>(5) Studies not published in Chinese or English, or studies for which the full text was unavailable.</p></list-item>
</list>
</sec>
</sec>
<sec>
<label>2.3</label>
<title>Information sources and search strategy</title>
<p>A systematic search was conducted across multiple databases from their inception to February 28, 2025. The databases included China National Knowledge Infrastructure (CNKI), SinoMed (China Biology Medicine Disc), the Chinese Scientific Journal Database (VIP), Wanfang Data, PubMed, the Cochrane Library, Embase, and Web of Science. The main search terms are listed in <xref ref-type="table" rid="T2">Table 2</xref>.</p>
<table-wrap position="float" id="T2">
<label>Table 2</label>
<caption><p>The main terms of this study.</p></caption>
<table frame="box" rules="all">
<thead>
<tr>
<th valign="top" align="left"><bold>Number</bold></th>
<th valign="top" align="left"><bold>Terms</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">1</td>
<td valign="top" align="left">Cognitive dysfunction</td>
</tr>
<tr>
<td valign="top" align="left">2</td>
<td valign="top" align="left">Cognitive impairment</td>
</tr>
<tr>
<td valign="top" align="left">3</td>
<td valign="top" align="left">Cognitive decline</td>
</tr>
<tr>
<td valign="top" align="left">4</td>
<td valign="top" align="left">Acupuncture</td>
</tr>
<tr>
<td valign="top" align="left">5</td>
<td valign="top" align="left">Acupoint</td>
</tr>
<tr>
<td valign="top" align="left">6</td>
<td valign="top" align="left">Needle</td>
</tr>
<tr>
<td valign="top" align="left">7</td>
<td valign="top" align="left">Warm needling</td>
</tr>
<tr>
<td valign="top" align="left">8</td>
<td valign="top" align="left">Warm acupuncture</td>
</tr>
<tr>
<td valign="top" align="left">9</td>
<td valign="top" align="left">Electronic acupuncture</td>
</tr>
<tr>
<td valign="top" align="left">10</td>
<td valign="top" align="left">Electro acupuncture</td>
</tr>
<tr>
<td valign="top" align="left">11</td>
<td valign="top" align="left">Fire acupuncture</td>
</tr>
<tr>
<td valign="top" align="left">12</td>
<td valign="top" align="left">Auricular needle</td>
</tr>
<tr>
<td valign="top" align="left">13</td>
<td valign="top" align="left">Scalp needle</td>
</tr>
<tr>
<td valign="top" align="left">14</td>
<td valign="top" align="left">Abdominal needle</td>
</tr>
<tr>
<td valign="top" align="left">15</td>
<td valign="top" align="left">Wrist ankle needle</td>
</tr>
<tr>
<td valign="top" align="left">16</td>
<td valign="top" align="left">Body acupuncture</td>
</tr>
<tr>
<td valign="top" align="left">17</td>
<td valign="top" align="left">Ischemic stroke</td>
</tr>
<tr>
<td valign="top" align="left">18</td>
<td valign="top" align="left">Apoplexy</td>
</tr>
<tr>
<td valign="top" align="left">19</td>
<td valign="top" align="left">Brain infarction</td>
</tr>
<tr>
<td valign="top" align="left">20</td>
<td valign="top" align="left">Cerebral infarction</td>
</tr>
<tr>
<td valign="top" align="left">21</td>
<td valign="top" align="left">Cerebrovascular accident</td>
</tr>
<tr>
<td valign="top" align="left">22</td>
<td valign="top" align="left">Cerebrovascular apoplexy</td>
</tr>
<tr>
<td valign="top" align="left">23</td>
<td valign="top" align="left">Neuroimaging</td>
</tr>
<tr>
<td valign="top" align="left">24</td>
<td valign="top" align="left">MRI</td>
</tr>
<tr>
<td valign="top" align="left">25</td>
<td valign="top" align="left">Magnetic Resonance Imaging</td>
</tr>
<tr>
<td valign="top" align="left">26</td>
<td valign="top" align="left">PET</td>
</tr>
<tr>
<td valign="top" align="left">27</td>
<td valign="top" align="left">Positron-Emission Tomography</td>
</tr>
<tr>
<td valign="top" align="left">28</td>
<td valign="top" align="left">fMRI</td>
</tr>
<tr>
<td valign="top" align="left">29</td>
<td valign="top" align="left">Functional magnetic resonance imaging</td>
</tr>
<tr>
<td valign="top" align="left">30</td>
<td valign="top" align="left">DTI</td>
</tr>
<tr>
<td valign="top" align="left">31</td>
<td valign="top" align="left">Diffusion Tensor Imaging</td>
</tr>
<tr>
<td valign="top" align="left">32</td>
<td valign="top" align="left">sMRI</td>
</tr>
<tr>
<td valign="top" align="left">33</td>
<td valign="top" align="left">Structural magnetic resonance imaging</td>
</tr>
<tr>
<td valign="top" align="left">34</td>
<td valign="top" align="left">fNIRS</td>
</tr>
<tr>
<td valign="top" align="left">35</td>
<td valign="top" align="left">Functional near-infrared spectroscopy</td>
</tr>
<tr>
<td valign="top" align="left">36</td>
<td valign="top" align="left">MRS</td>
</tr>
<tr>
<td valign="top" align="left">37</td>
<td valign="top" align="left">Magnetic resonance spectroscopy</td>
</tr>
<tr>
<td valign="top" align="left">38</td>
<td valign="top" align="left">Cognitive impairment-related terms: 1 OR 2 OR 3</td>
</tr>
<tr>
<td valign="top" align="left">39</td>
<td valign="top" align="left">Acupuncture-related terms: 4 OR 5 OR 6 OR 7 OR 8 OR 9 OR 10 OR 11 OR 12 OR 13 OR 14 OR 15 OR 16</td>
</tr>
<tr>
<td valign="top" align="left">40</td>
<td valign="top" align="left">Stroke-related terms: 17 OR 18 OR 19 OR 20 OR 21 OR 22</td>
</tr>
<tr>
<td valign="top" align="left">41</td>
<td valign="top" align="left">Neuroimaging-related terms: 23 OR 24 OR 25 OR 26 OR 27 OR 28 OR 29 30 OR 31 OR 32 OR 33 OR 34 OR 35 OR 36 OR 37</td>
</tr>
<tr>
<td valign="top" align="left">42</td>
<td valign="top" align="left">Final searching terms: 38 AND 39 AND 40 AND 41</td>
</tr></tbody>
</table>
</table-wrap>
</sec>
<sec>
<label>2.4</label>
<title>Selection process</title>
<p>The retrieved articles were first imported into NoteExpress software (version 4.1.0) to remove duplicates. Two independent researchers (Qin and Zhuo) then screened titles and abstracts based on the eligibility criteria. Full texts of potentially eligible studies were subsequently reviewed to determine final inclusion. Any discrepancies were resolved through consensus.</p>
</sec>
<sec>
<label>2.5</label>
<title>Data collection process</title>
<p>Data extraction was carried out by Yang using a standardized template in Microsoft Excel 2019 to record the following information: general study characteristics (first author, year of publication, study design), participant details (sample size, sex, age, time since stroke, treatment duration), intervention information, control group details, and outcome measures. The Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) were applied to ensure comprehensive reporting of acupuncture details (e.g., needle depth, retention time). Discrepancies were resolved through discussion among all researchers.</p>
</sec>
<sec>
<label>2.6</label>
<title>Quality assessment</title>
<p>Two researchers (Qin and Li) assessed the methodological quality of RCTs using the Cochrane Risk of Bias 2.0 tool (RoB 2). The RoB results were classified as high risk, low risk, or some concerns. Disagreements were resolved through consensus.</p>
</sec>
<sec>
<label>2.7</label>
<title>Synthesis methods</title>
<p>Due to methodological heterogeneity among the included studies, a descriptive analysis was conducted. The synthesis aimed to provide neuroimaging evidence supporting the clinical efficacy of acupuncture for PISCI.</p></sec></sec>
<sec sec-type="results" id="s3">
<label>3</label>
<title>Results</title>
<sec>
<label>3.1</label>
<title>Study selection</title>
<p>A comprehensive search across multiple databases initially retrieved 1,582 records. After removing duplicates using reference management software, 1,115 records remained. Titles, abstracts, and keywords were then screened against the eligibility criteria, yielding 54 potentially relevant studies. Following full-text assessment, 8 studies (<xref ref-type="bibr" rid="B56">Li, 2023</xref>; <xref ref-type="bibr" rid="B84">Su, 2016</xref>; <xref ref-type="bibr" rid="B92">Wang et al., 2014</xref>, <xref ref-type="bibr" rid="B91">2021</xref>; <xref ref-type="bibr" rid="B95">Wang, 2021</xref>; <xref ref-type="bibr" rid="B109">Xiao and Yu, 2024</xref>; <xref ref-type="bibr" rid="B118">Yu et al., 2021</xref>; <xref ref-type="bibr" rid="B122">Zhang et al., 2020</xref>) were included for analysis. The PRISMA flowchart of the search and selection process is shown in <xref ref-type="fig" rid="F1">Figure 1</xref>.</p>
<fig position="float" id="F1">
<label>Figure 1</label>
<caption><p>Flow chart of selection process.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnins-19-1629305-g0001.tif">
<alt-text content-type="machine-generated">Flowchart of a study selection process. It begins with 1,582 records identified, reduced to 1,115 after removing duplicates. Records were screened, excluding 1,061 for various reasons like ineligible interventions and non-eligible subjects. Fifty-four full-text articles were assessed, with 46 excluded. Finally, eight studies were included in the review. The stages are labeled: Identification, Screening, Eligibility, and Included.</alt-text>
</graphic>
</fig>
</sec>
<sec>
<label>3.2</label>
<title>Study characteristics</title>
<p><xref ref-type="table" rid="T3">Table 3</xref> summarizes characteristics of the 8 included studies, published between 2014 and 2024. These studies comprised 5 RCTs and 3 non-RCTs, all conducted in China.</p>
<table-wrap position="float" id="T3">
<label>Table 3</label>
<caption><p>Characteristics of studies included in the systematic review.</p></caption>
<table frame="box" rules="all">
<thead>
<tr>
<th valign="top" align="left"><bold>Study</bold></th>
<th valign="top" align="left"><bold>Study type</bold></th>
<th valign="top" align="center"><bold>Year</bold></th>
<th valign="top" align="left"><bold>Sample Size (T/C)</bold></th>
<th valign="top" align="left"><bold>Gender (%males)</bold></th>
<th valign="top" align="left"><bold>Age (years)</bold></th>
<th valign="top" align="left"><bold>Time since stroke</bold></th>
<th valign="top" align="left"><bold>Treatment courses</bold></th>
<th valign="top" align="left"><bold>Type of T patient</bold></th>
<th valign="top" align="left"><bold>Type of C patient</bold></th>
<th valign="top" align="left"><bold>Intervention (T)</bold></th>
<th valign="top" align="left"><bold>Intervention (C)</bold></th>
<th valign="top" align="left"><bold>Imaging modality</bold></th>
<th valign="top" align="left"><bold>Clinical outcomes</bold></th>
<th valign="top" align="left"><bold>Analytical approaches</bold></th>
<th valign="top" align="left"><bold>Scan T</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Wei Xiao</td>
<td valign="top" align="left">RCT</td>
<td valign="top" align="center">2024</td>
<td valign="top" align="left">25(17/8)</td>
<td valign="top" align="left">52%</td>
<td valign="top" align="left">T: 63.00 &#x000B1; 6.34 C: 58.25 &#x000B1; 6.60</td>
<td valign="top" align="left">Within 3 months</td>
<td valign="top" align="left">2 weeks</td>
<td valign="top" align="left">PISCI</td>
<td valign="top" align="left">PISCI</td>
<td valign="top" align="left">Acupuncture</td>
<td valign="top" align="left">Sham acupuncture</td>
<td valign="top" align="left">rs-fMRI</td>
<td valign="top" align="left">MMSE, MoCA</td>
<td valign="top" align="left">DC</td>
<td valign="top" align="left">/</td>
</tr>
<tr>
<td valign="top" align="left">Xiayu Li</td>
<td valign="top" align="left">Non-RCT</td>
<td valign="top" align="center">2023</td>
<td valign="top" align="left">32(16/16)</td>
<td valign="top" align="left">75%</td>
<td valign="top" align="left">T: 60.5 &#x000B1; 1.2 C: 61.5 &#x000B1; 1.2</td>
<td valign="top" align="left">Within 6 months</td>
<td valign="top" align="left">12 weeks</td>
<td valign="top" align="left">PISCI</td>
<td valign="top" align="left">HC</td>
<td valign="top" align="left">&#x0201C;Regulating Mind and Enlightening Wisdom&#x0201D; acupuncture</td>
<td valign="top" align="left">/</td>
<td valign="top" align="left">rs-fMRI</td>
<td valign="top" align="left">MMSE, MoCA, WMS-RC</td>
<td valign="top" align="left">FALFF, ReHo, DC</td>
<td valign="top" align="left">3.0 T</td>
</tr>
<tr>
<td valign="top" align="left">Fei Wang</td>
<td valign="top" align="left">RCT</td>
<td valign="top" align="center">2021</td>
<td valign="top" align="left">80(40/40)</td>
<td valign="top" align="left">63%</td>
<td valign="top" align="left">T: 66 &#x000B1; 8 C: 67 &#x000B1; 9</td>
<td valign="top" align="left">Within 30 days</td>
<td valign="top" align="left">8 weeks</td>
<td valign="top" align="left">PISCI</td>
<td valign="top" align="left">PISCI</td>
<td valign="top" align="left">Acupuncture and Cognitive Training</td>
<td valign="top" align="left">Cognitive Training</td>
<td valign="top" align="left">rs-fMRI</td>
<td valign="top" align="left">MMSE, MoCA, NIHSS, FMA, MBI</td>
<td valign="top" align="left">FC (ROI)</td>
<td valign="top" align="left">3.0 T</td>
</tr>
<tr>
<td valign="top" align="left">Ran Wang</td>
<td valign="top" align="left">Non-RCT</td>
<td valign="top" align="center">2021</td>
<td valign="top" align="left">36(22/14)</td>
<td valign="top" align="left">42%</td>
<td valign="top" align="left">T: 60.14 &#x000B1; 8.46 C: 56.71 &#x000B1; 4.68</td>
<td valign="top" align="left">/</td>
<td valign="top" align="left">2 weeks</td>
<td valign="top" align="left">PISCI</td>
<td valign="top" align="left">HC</td>
<td valign="top" align="left">Acupuncture</td>
<td valign="top" align="left">/</td>
<td valign="top" align="left">rs-fMRI</td>
<td valign="top" align="left">MMSE, MoCA</td>
<td valign="top" align="left">FC (DC, local efficiency)</td>
<td valign="top" align="left">3.0T</td>
</tr>
<tr>
<td valign="top" align="left">Yanli Yu</td>
<td valign="top" align="left">RCT</td>
<td valign="top" align="center">2021</td>
<td valign="top" align="left">60(30/30)</td>
<td valign="top" align="left">58%</td>
<td valign="top" align="left">T: 59 &#x000B1; 3 C: 59 &#x000B1; 3</td>
<td valign="top" align="left">More than 3 weeks</td>
<td valign="top" align="left">4 weeks</td>
<td valign="top" align="left">PISCI</td>
<td valign="top" align="left">PISCI</td>
<td valign="top" align="left">Bo&#x00027;s Abdominal Acupuncture and Cognitive Training</td>
<td valign="top" align="left">Cognitive Training</td>
<td valign="top" align="left">rs-fMRI</td>
<td valign="top" align="left">MoCA, TMT, AVLT, DS</td>
<td valign="top" align="left">ALFF</td>
<td valign="top" align="left">/</td>
</tr>
<tr>
<td valign="top" align="left">Jianbo Zhang</td>
<td valign="top" align="left">RCT</td>
<td valign="top" align="center">2020</td>
<td valign="top" align="left">60(30/30)</td>
<td valign="top" align="left">63%</td>
<td valign="top" align="left">T: 70.10 &#x000B1; 4.51 C: 69.03 &#x000B1; 4.70</td>
<td valign="top" align="left">More than 2 weeks</td>
<td valign="top" align="left">6 weeks</td>
<td valign="top" align="left">PISCI</td>
<td valign="top" align="left">PISCI</td>
<td valign="top" align="left">Scalp electro acupuncture and Computer-Assisted Training</td>
<td valign="top" align="left">Computer-Assisted Training</td>
<td valign="top" align="left">MRS</td>
<td valign="top" align="left">MoCA</td>
<td valign="top" align="left">Metabolic Ration</td>
<td valign="top" align="left">3.0T</td>
</tr>
<tr>
<td valign="top" align="left">Mengrun Sun</td>
<td valign="top" align="left">Non-RCT</td>
<td valign="top" align="center">2016</td>
<td valign="top" align="left">60(30/30)</td>
<td valign="top" align="left">52%</td>
<td valign="top" align="left">T: 68.23 &#x000B1; 5.99 C: 70.87 &#x000B1; 7.32</td>
<td valign="top" align="left">Within 2 weeks</td>
<td valign="top" align="left">4 weeks</td>
<td valign="top" align="left">PISCI</td>
<td valign="top" align="left">PISCI</td>
<td valign="top" align="left">Acupuncture and nimodipine</td>
<td valign="top" align="left">Nimodipine</td>
<td valign="top" align="left">MRS</td>
<td valign="top" align="left">MMSE, MoCA</td>
<td valign="top" align="left">Metabolic Ration</td>
<td valign="top" align="left">3.0T</td>
</tr>
<tr>
<td valign="top" align="left">Fang Wang</td>
<td valign="top" align="left">RCT</td>
<td valign="top" align="center">2014</td>
<td valign="top" align="left">60(30/30)</td>
<td valign="top" align="left">52%</td>
<td valign="top" align="left">45-80</td>
<td valign="top" align="left">3-6 months</td>
<td valign="top" align="left">12 weeks</td>
<td valign="top" align="left">PISCI</td>
<td valign="top" align="left">PISCI</td>
<td valign="top" align="left">Acupuncture and nimodipine</td>
<td valign="top" align="left">Nimodipine</td>
<td valign="top" align="left">MRS</td>
<td valign="top" align="left">MoCA</td>
<td valign="top" align="left">Metabolic Ration</td>
<td valign="top" align="left">3.0 T</td>
</tr></tbody>
</table>
<table-wrap-foot>
<p>T, treatment group; C, control group; HC, healthy control; MMSE, Mini-Mental State Examination; MoCA, Montreal Cognitive Assessment; WMS-RC, Wechsler Memory Scale-Revised in China; AVLT, auditory verbal learning test; DS, digital span; TMT, Trail Making Test; FC: functional connectivity; DC: degree centrality, FALFF, fractional amplitude of low frequency fluctuation; ReHo, regional homogeneity; ALFF, amplitude of low-frequency fluctuation; ROI: region of interest; rs-fMRI, resting-state functional magnetic resonance imaging; NIHSS, National Institute of Health stroke scale; FMA, Fugl-Meyer assessment; MBI, modified Barthel index.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec>
<label>3.3</label>
<title>Quality assessment</title>
<p>The risk of bias assessment for the included RCTs is presented in <xref ref-type="fig" rid="F2">Figure 2</xref>. Of the five RCTs, two were judged to have a high risk of bias, and three were rated as having some concerns according to the RoB 2 tool. Regarding the randomization process, all studies presented certain issues due to inadequate reporting of random sequence generation or allocation concealment. With respect to deviations from the intended interventions, none of the studies blinded acupuncturists, which is expected given the nature of the intervention. Three studies reported participant blinding and were rated as low risk; the remaining two raised some concerns due to unclear blinding descriptions. Risk of bias due to missing outcome data was generally low across all studies. Measurement of the outcome was rated as low risk in all studies. In terms of the selection of the reported result, potential bias may exist due to the lack of complete study protocols or trial registration information.</p>
<fig position="float" id="F2">
<label>Figure 2</label>
<caption><p>Risk of bias graph and summary.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnins-19-1629305-g0002.tif">
<alt-text content-type="machine-generated">Risk of bias assessment consisting of a graph and summary chart. The top graph shows risk levels in five studies, with categories D1 to D5, indicating risks as low (green), some concerns (yellow), and high (red). The bottom chart summarizes the risks as percentages for overall bias and specific criteria, displaying green, yellow, and red bars to denote risk levels.</alt-text>
</graphic>
</fig>
</sec>
<sec>
<label>3.4</label>
<title>Participants</title>
<p>A total of 397 participants were included across the eight studies, comprising 367 patients with PISCI and 30 healthy controls. Sample sizes ranged from 25 to 80. Two studies compared PISCI patients with healthy controls, while six enrolled only PISCI patients. The age of PISCI patients ranged from 45 to 80 years. All studies reported gender; in total, there were 237 males and 150 females, and only one study had a male proportion below 50%.</p>
</sec>
<sec>
<label>3.5</label>
<title>Intervention</title>
<p>In accordance with STRICTA, acupuncture details are summarized in <xref ref-type="table" rid="T4">Table 4</xref>. All studies reported the theoretical rationale for acupoint selection. The number of needles used per session ranged from 1 to 22 across studies. Among all studies, GV20 (6/8, 75%) was the most frequently used acupoint, followed by EX-HN1 (5/8, 62.5%), and both GV24 and LR3 (4/8, 50% each) (<xref ref-type="fig" rid="F3">Figure 3</xref>). Acupuncture types included scalp acupuncture (1/8, 12.5%), abdominal acupuncture (1/8, 12.5%), and body acupuncture (6/8, 75%). Manual acupuncture predominated (7/8, 87.5%), while electro acupuncture was used in one study (1/8, 12.5%). Needle insertion depth was reported in six studies (15-50 mm) and a specific needling response (e.g., &#x0201C;Deqi&#x0201D;) was described in five studies (5/8, 62.5%). Except for one study, all reported total treatment sessions, ranging from 10 to 72 over 2 to 12 weeks. Practitioner qualifications were reported in three studies (3/8, 37.5%).</p>
<table-wrap position="float" id="T4">
<label>Table 4</label>
<caption><p>Details of included studies according to Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA).</p></caption>
<table frame="box" rules="all">
<thead>
<tr>
<th valign="top" align="left"><bold>Study</bold></th>
<th valign="top" align="left" colspan="3"><bold>1.Acupuncture rational</bold></th>
<th valign="top" align="left" colspan="7"><bold>2.Details of needling</bold></th>
<th valign="top" align="left" colspan="2"><bold>3.Treatment regimen</bold></th>
<th valign="top" align="left" colspan="2"><bold>4.Other components of treatment</bold></th>
<th valign="top" align="left"><bold>5.Practitioner background</bold></th>
<th valign="top" align="left" colspan="2"><bold>6.Control or comparator interventions</bold></th>
</tr>
<tr>
<th/>
<th valign="top" align="left"><bold>1a</bold></th>
<th valign="top" align="left"><bold>1b</bold></th>
<th valign="top" align="left"><bold>1c</bold></th>
<th valign="top" align="left"><bold>2a</bold></th>
<th valign="top" align="left"><bold>2b</bold></th>
<th valign="top" align="left"><bold>2c</bold></th>
<th valign="top" align="left"><bold>2d</bold></th>
<th valign="top" align="left"><bold>2e</bold></th>
<th valign="top" align="left"><bold>2f</bold></th>
<th valign="top" align="left"><bold>2g</bold></th>
<th valign="top" align="center"><bold>3a</bold></th>
<th valign="top" align="left"><bold>3b</bold></th>
<th valign="top" align="left"><bold>4a</bold></th>
<th valign="top" align="left"><bold>4b</bold></th>
<th valign="top" align="left"><bold>5</bold></th>
<th valign="top" align="left"><bold>6a</bold></th>
<th valign="top" align="left"><bold>6b</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Wei Xiao</td>
<td valign="top" align="left">TCM</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">NA</td>
<td valign="top" align="left">7</td>
<td valign="top" align="left">PC6, GV20, EX-HN1</td>
<td valign="top" align="left">20-25mm</td>
<td valign="top" align="left">Deqi</td>
<td valign="top" align="left">Manual</td>
<td valign="top" align="left">30min</td>
<td valign="top" align="left">Needle brand: Jiangsu Medical Supplies Factory Co., Ltd.</td>
<td valign="top" align="center">NR</td>
<td valign="top" align="left">Duration: 2 weeks</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">Y</td>
</tr>
<tr>
<td valign="top" align="left">Xiayu Li</td>
<td valign="top" align="left">TCM</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">NA</td>
<td valign="top" align="left">22</td>
<td valign="top" align="left">GV20, EX-HN1, GV26, ST2, GB20, GB12, BL10, PC6, HT7, ST40, SP6, LR3</td>
<td valign="top" align="left">15mm-30mm</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">Manual</td>
<td valign="top" align="left">30min</td>
<td valign="top" align="left">Diameter and length: 0.25mm &#x000D7; 40mm Needle brand: Hwato</td>
<td valign="top" align="center">36</td>
<td valign="top" align="left">Frequency: three times per week Duration: 12 weeks</td>
<td valign="top" align="left">Conventional therapy</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
</tr>
<tr>
<td valign="top" align="left">Fei Wang</td>
<td valign="top" align="left">TCM</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">NA</td>
<td valign="top" align="left">1</td>
<td valign="top" align="left">GV20, GV24</td>
<td valign="top" align="left">20&#x02013;30mm</td>
<td valign="top" align="left">Deqi</td>
<td valign="top" align="left">Manual</td>
<td valign="top" align="left">30min</td>
<td valign="top" align="left">Diameter and length: 0.35 &#x000D7; 25mm Needle brand: Hwato</td>
<td valign="top" align="center">28</td>
<td valign="top" align="left">Frequency: every other day Duration: 8 weeks</td>
<td valign="top" align="left">Cognitive Training</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
</tr>
<tr>
<td valign="top" align="left">Ran Wang</td>
<td valign="top" align="left">TCM</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">NA</td>
<td valign="top" align="left">7</td>
<td valign="top" align="left">PC6, GV20, EX-HN1</td>
<td valign="top" align="left">20&#x02013;25mm</td>
<td valign="top" align="left">Deqi</td>
<td valign="top" align="left">Manual</td>
<td valign="top" align="left">30min</td>
<td valign="top" align="left">Diameter and length: 0.35 &#x000D7; 50mm</td>
<td valign="top" align="center">10</td>
<td valign="top" align="left">Frequency: five times per week Duration:2 weeks</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">NA</td>
<td valign="top" align="left">NA</td>
</tr>
<tr>
<td valign="top" align="left">Jianbo Zhang</td>
<td valign="top" align="left">TCM</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">NA</td>
<td valign="top" align="left">5</td>
<td valign="top" align="left">MS1, MS6 (bilateral)</td>
<td valign="top" align="left">15-20mm</td>
<td valign="top" align="left">Deqi</td>
<td valign="top" align="left">Electronic</td>
<td valign="top" align="left">30min</td>
<td valign="top" align="left">Diameter and length: 0.30 &#x000D7; 25mm&#x00026; 0.25 &#x000D7; 40mm Needle brand: Dongbang Electroacupuncture apparatus: KWD-808I</td>
<td valign="top" align="center">30</td>
<td valign="top" align="left">Frequency: five times per week Duration:6weeks</td>
<td valign="top" align="left">Computer-Assisted Training</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
</tr>
<tr>
<td valign="top" align="left">Yanli Yu</td>
<td valign="top" align="left">TCM</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">NA</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">CV 12, CV 10, CV 6, CV 4, bilateral ST24, bilateral ST26, bilateral LI,4, bilateral LR3, shangfengshidian, shangfengshishangdian, shangdengshiwaidian, xiafengshidian, and xiafengshixiadian of affected side</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">Manual</td>
<td valign="top" align="left">30min</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="center">20</td>
<td valign="top" align="left">Frequency: five times per week Duration: 4 weeks</td>
<td valign="top" align="left">Cognitive Training</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">NR</td>
</tr>
<tr>
<td valign="top" align="left">Mengrun Sun</td>
<td valign="top" align="left">TCM</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">NA</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">GV20, GV24, EX-HN1, LR3, LI4, SP6, ST40, ST36</td>
<td valign="top" align="left">15mm-50mm</td>
<td valign="top" align="left">Deqi</td>
<td valign="top" align="left">Manual</td>
<td valign="top" align="left">30min</td>
<td valign="top" align="left">Needle brand: Jiajian</td>
<td valign="top" align="center">24</td>
<td valign="top" align="left">Frequency: six times per week Duration:4 weeks</td>
<td valign="top" align="left">Nimodipine</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
</tr>
<tr>
<td valign="top" align="left">Fang Wang</td>
<td valign="top" align="left">TCM</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">NA</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">GV20, GV24, EX-HN1, LI4, LR3, SP6, ST40, CV12, ST36</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">Manual</td>
<td valign="top" align="left">30min</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="center">72</td>
<td valign="top" align="left">Frequency: six times per week Duration:12 weeks</td>
<td valign="top" align="left">Nimodipine</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
<td valign="top" align="left">Y</td>
</tr></tbody>
</table>
<table-wrap-foot>
<p>1a, Style of acupuncture; 1b, Reasoning for provided treatment, based on historical context, literature sources, or consensus methods, with references where appropriate; 1c, Extent to which treatment varied; 2a, Number of needle insertions per subject per session; 2b, Names; 2c, Depth of insertion, based on a specified unit of measurement, or on a particular tissue level; 2d, Response sought; 2e, Needle stimulation; 2f, Needle retention time; 2g, Needle type; 3a, Number of treatment sessions; 3b, Frequency and duration of treatment sessions; 4a, Details of other interventions administered to the acupuncture group; 4b, Setting and context of treatment, including instructions to practitioners, information and explanations to patients; 5, Description of participating acupuncturists; 6a, The rationale for the control or comparator in the context of the research question, with sources that justify this choice; 6b, A precise description of the control or comparator. If sham acupuncture or any other type of acupuncture-like control was used, provide details as in items 1&#x02013;3 above; TCM, Traditional Chinese Medicine; Y, yes; NA, not application; NR, not reported. MS1, middle line of forehead; MS2, anterior oblique parietotemporal line.</p>
</table-wrap-foot>
</table-wrap>
<fig position="float" id="F3">
<label>Figure 3</label>
<caption><p>Frequency of acupoint usage in included studies (<italic>n</italic> = 8).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnins-19-1629305-g0003.tif">
<alt-text content-type="machine-generated">Bar chart showing the frequency of acupoint usage in eight studies. GV20 is the most used acupoint in six studies. Other acupoints like EX-HN1 and LR3 appear in five and four studies, respectively. Many acupoints, such as CV16, ST24, and others, are used in only one study.</alt-text>
</graphic>
</fig>
</sec>
<sec>
<label>3.6</label>
<title>Comparison</title>
<p>Four types of comparisons were identified across the eight studies: acupuncture vs. sham acupuncture (1/8, 12.5%); acupuncture plus drug vs. drug alone (2/8, 25.0%); acupuncture vs. healthy volunteers (2/8, 25.0%); and acupuncture plus cognitive training vs. cognitive training alone (3/8, 37.5%).</p>
</sec>
<sec>
<label>3.7</label>
<title>Clinical outcomes</title>
<p>PISCI was assessed across multiple domains. All studies used MoCA to evaluate cognitive function, with most (62.5%) also employing MMSE. Additional cognitive measures and assessments of neurological, motor, and daily living functions were used in individual studies (detailed in <xref ref-type="table" rid="T3">Table 3</xref>).</p>
</sec>
<sec>
<label>3.8</label>
<title>Neuroimaging results</title>
<sec>
<label>3.8.1</label>
<title>MRI imaging analysis methods</title>
<p>Five studies (5/8, 62.5%) used rs-fMRI, employing analytical methods including fALFF/ALFF, ReHo, DC, and functional connectivity (FC). Three studies (3/8, 37.5%) used MRS to evaluate metabolic ratios (NAA/Cr, Cho/Cr, MI/Cr). Scanner specifications varied: although two studies (2/8, 25%) did not report the MRI scanner model, the remaining six used 3.0-T scanners from manufacturers including Siemens and GE. Imaging acquisition parameters showed heterogeneity across studies, with TR (repetition time) ranging from 1,500-3,000 ms in rs-fMRI studies and TE (echo time) ranging from 30-40 ms. Preprocessing steps and analytical software also varied, with studies using different sequences and voxel sizes. All studies focused on sustained post-treatment effects of acupuncture. Complete technical specifications are provided in <xref ref-type="table" rid="T5">Table 5</xref>. Detailed neuroimaging findings are provided in the <xref ref-type="supplementary-material" rid="SM1">Supplementary material</xref>.</p>
<table-wrap position="float" id="T5">
<label>Table 5</label>
<caption><p>Imaging parameters of the included studies.</p></caption>
<table frame="box" rules="all">
<thead>
<tr>
<th valign="top" align="left"><bold>Study</bold></th>
<th valign="top" align="left"><bold>Scanner</bold></th>
<th valign="top" align="center"><bold>Field strength</bold></th>
<th valign="top" align="left"><bold>Type</bold></th>
<th valign="top" align="center"><bold>TR (ms)</bold></th>
<th valign="top" align="center"><bold>TE (ms)</bold></th>
<th valign="top" align="left"><bold>Sequence</bold></th>
<th valign="top" align="left"><bold>Voxel size</bold></th>
<th valign="top" align="left"><bold>Key metric</bold></th>
<th valign="top" align="left"><bold>Location</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Wei Xiao</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="center">NR</td>
<td valign="top" align="left">rs-fMRI</td>
<td valign="top" align="center">NR</td>
<td valign="top" align="center">NR</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">DC</td>
<td valign="top" align="left">Whole brain</td>
</tr>
<tr>
<td valign="top" align="left">Xiayu Li</td>
<td valign="top" align="left">Siemens Skyra</td>
<td valign="top" align="center">3.0T</td>
<td valign="top" align="left">rs-fMRI</td>
<td valign="top" align="center">2000</td>
<td valign="top" align="center">30</td>
<td valign="top" align="left">ep2d-bold-rest</td>
<td valign="top" align="left">3 &#x000D7; 3 &#x000D7; 3 mm3</td>
<td valign="top" align="left">fALFF, ReHo, DC</td>
<td valign="top" align="left">Whole brain</td>
</tr>
<tr>
<td valign="top" align="left">Fei Wang</td>
<td valign="top" align="left">Siemens Skyra</td>
<td valign="top" align="center">3.0T</td>
<td valign="top" align="left">rs-fMRI</td>
<td valign="top" align="center">3000</td>
<td valign="top" align="center">40</td>
<td valign="top" align="left">Single-shot EPI</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">FC (Hippocampus)</td>
<td valign="top" align="left">Bilateral Hippocampus</td>
</tr>
<tr>
<td valign="top" align="left">Ran Wang</td>
<td valign="top" align="left">GE MR750</td>
<td valign="top" align="center">3.0T</td>
<td valign="top" align="left">rs-fMRI</td>
<td valign="top" align="center">2000</td>
<td valign="top" align="center">30</td>
<td valign="top" align="left">rs-fMRI</td>
<td valign="top" align="left">3 &#x000D7; 3 &#x000D7; 3 mm3</td>
<td valign="top" align="left">Graph Theory</td>
<td valign="top" align="left">Whole brain</td>
</tr>
<tr>
<td valign="top" align="left">Yanli Yu</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="center">NR</td>
<td valign="top" align="left">rs-fMRI</td>
<td valign="top" align="center">NR</td>
<td valign="top" align="center">NR</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">ALFF</td>
<td valign="top" align="left">Whole brain</td>
</tr>
<tr>
<td valign="top" align="left">Jianbo Zhang</td>
<td valign="top" align="left">Siemens Prisma</td>
<td valign="top" align="center">3.0T</td>
<td valign="top" align="left">MRS</td>
<td valign="top" align="center">2000</td>
<td valign="top" align="center">144</td>
<td valign="top" align="left">PRESS</td>
<td valign="top" align="left">1 &#x000D7; 1 &#x000D7; 1 cm3</td>
<td valign="top" align="left">NAA, Cr, Cho, MI</td>
<td valign="top" align="left">Lesion area</td>
</tr>
<tr>
<td valign="top" align="left">Mengrun Su</td>
<td valign="top" align="left">Siemens</td>
<td valign="top" align="center">3.0T</td>
<td valign="top" align="left">MRS</td>
<td valign="top" align="center">1500</td>
<td valign="top" align="center">30</td>
<td valign="top" align="left">PRESS</td>
<td valign="top" align="left">2 &#x000D7; 2 &#x000D7; 2 cm</td>
<td valign="top" align="left">NAA, Cr, Cho, MI</td>
<td valign="top" align="left">Bilateral frontal white matter</td>
</tr>
<tr>
<td valign="top" align="left">Fang Wang</td>
<td valign="top" align="left">GE GEMS</td>
<td valign="top" align="center">3.0T</td>
<td valign="top" align="left">MRS</td>
<td valign="top" align="center">NR</td>
<td valign="top" align="center">NR</td>
<td valign="top" align="left">PRESS</td>
<td valign="top" align="left">NR</td>
<td valign="top" align="left">NAA, Cr, Cho</td>
<td valign="top" align="left">Hippocampus</td>
</tr></tbody>
</table>
<table-wrap-foot>
<p>NR, not reported; TR, repetition time; TE, echo time; rs-fMRI, resting-state functional magnetic resonance imaging; MRS, magnetic resonance spectroscopy; fALFF, fractional amplitude of low-frequency fluctuation; ALFF, amplitude of low-frequency fluctuation; ReHo, regional homogeneity; DC, degree centrality; FC, functional connectivity; NAA, N-acetylaspartate; Cr, creatine; Cho, choline; MI, myo-inositol; PRESS, point resolved spectroscopy; EPI, echo-planar imaging. Scanner field strength was 3.0 Tesla (T) for all studies where reported.</p>
</table-wrap-foot>
</table-wrap>
</sec>
<sec>
<label>3.8.2</label>
<title>Acupuncture-induced neuroimaging changes</title>
<p>To assess the consistency of findings across studies, we conducted a systematic synthesis of neuroimaging outcomes across all included studies (<xref ref-type="table" rid="T6">Table 6</xref>), explicitly indicating the direction of change (increase or decrease) for each metric. Despite heterogeneity in study design and analysis methods, notable consistency emerged in several key regions. Resting-state fMRI demonstrated consistent patterns in several brain regions: bilateral lingual gyrus, bilateral fusiform gyrus, bilateral para hippocampal gyrus (all showing increased activity), and right angular gyrus (decreased activity). MRS findings showed consistency across all three studies, with NAA/Cr ratios consistently increasing and Cho/Cr and MI/Cr consistently decreasing following acupuncture treatment.</p>
<table-wrap position="float" id="T6">
<label>Table 6</label>
<caption><p>Direction of neuroimaging changes after acupuncture treatment.</p></caption>
<table frame="box" rules="all">
<thead>
<tr>
<th valign="top" align="left"><bold>Brain region</bold></th>
<th valign="top" align="left"><bold>Metric</bold></th>
<th valign="top" align="left"><bold>Studies</bold></th>
<th valign="top" align="left"><bold>Direction</bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left" colspan="4"><bold>A. Resting-state fMRI findings</bold></td>
</tr>
<tr>
<td valign="top" align="left">L. Parahippocampal gyrus</td>
<td valign="top" align="left">DC, Local efficiency</td>
<td valign="top" align="left">Wei Xiao, Ran Wang</td>
<td valign="top" align="left">&#x02191;&#x02191; (2/2)</td>
</tr>
<tr>
<td valign="top" align="left">R. Parahippocampal gyrus</td>
<td valign="top" align="left">ALFF</td>
<td valign="top" align="left">Yanli Yu</td>
<td valign="top" align="left">&#x02191; (1/1)</td>
</tr>
<tr>
<td valign="top" align="left">Hippocampus-prefrontal cortex</td>
<td valign="top" align="left">FC</td>
<td valign="top" align="left">Fei Wang</td>
<td valign="top" align="left">&#x02191; (1/1)</td>
</tr>
<tr>
<td valign="top" align="left">L. Fusiform gyrus</td>
<td valign="top" align="left">DC, fALFF, Local efficiency</td>
<td valign="top" align="left">Wei Xiao, Xiayu Li, Ran Wang</td>
<td valign="top" align="left">&#x02191;<italic>&#x02191;&#x02191;</italic> (3/3)</td>
</tr>
<tr>
<td valign="top" align="left">L. Lingual gyrus</td>
<td valign="top" align="left">DC</td>
<td valign="top" align="left">Wei Xiao 2024, Ran Wang</td>
<td valign="top" align="left">&#x02191;&#x02191; (2/2)</td>
</tr>
<tr>
<td valign="top" align="left">R. Lingual gyrus</td>
<td valign="top" align="left">DC</td>
<td valign="top" align="left">Wei Xiao, Ran Wang</td>
<td valign="top" align="left">&#x02191;&#x02191; (2/2)</td>
</tr>
<tr>
<td valign="top" align="left">R. Inferior occipital gyrus</td>
<td valign="top" align="left">DC, Local efficiency</td>
<td valign="top" align="left">Wei Xiao, Ran Wang</td>
<td valign="top" align="left">&#x02191;&#x02191; (2/2)</td>
</tr>
<tr>
<td valign="top" align="left">L. Posterior cingulate gyrus</td>
<td valign="top" align="left">DC</td>
<td valign="top" align="left">Wei Xiao</td>
<td valign="top" align="left">&#x02191; (1/1)</td>
</tr>
<tr>
<td valign="top" align="left">L. Anterior cingulate cortex</td>
<td valign="top" align="left">ALFF</td>
<td valign="top" align="left">Yanli Yu</td>
<td valign="top" align="left">&#x02191; (1/1)</td>
</tr>
<tr>
<td valign="top" align="left">Transverse temporal gyrus</td>
<td valign="top" align="left">DC, Local efficiency</td>
<td valign="top" align="left">Wei Xiao, Ran Wang</td>
<td valign="top" align="left">&#x02191;&#x02191; (2/2)</td>
</tr>
<tr>
<td valign="top" align="left">L. Thalamus</td>
<td valign="top" align="left">ALFF</td>
<td valign="top" align="left">Yanli Yu</td>
<td valign="top" align="left">&#x02191; (1/1)</td>
</tr>
<tr>
<td valign="top" align="left">R. Insula</td>
<td valign="top" align="left">ALFF</td>
<td valign="top" align="left">Yanli Yu</td>
<td valign="top" align="left">&#x02191; (1/1)</td>
</tr>
<tr>
<td valign="top" align="left">R. Superior occipital gyrus</td>
<td valign="top" align="left">fALFF</td>
<td valign="top" align="left">Xiayu Li</td>
<td valign="top" align="left">&#x02193; (1/1)</td>
</tr>
<tr>
<td valign="top" align="left">R. Angular gyrus</td>
<td valign="top" align="left">DC, Local efficiency</td>
<td valign="top" align="left">Wei Xiao, Ran Wang</td>
<td valign="top" align="left">&#x02193;&#x02193; (2/2)</td>
</tr>
<tr>
<td valign="top" align="left">L. Inferior frontal gyrus</td>
<td valign="top" align="left">ALFF</td>
<td valign="top" align="left">Yanli Yu</td>
<td valign="top" align="left">&#x02193; (1/1)</td>
</tr>
<tr>
<td valign="top" align="left">L. Inferior temporal gyrus</td>
<td valign="top" align="left">ALFF</td>
<td valign="top" align="left">Yanli Yu</td>
<td valign="top" align="left">&#x02193; (1/1)</td>
</tr>
<tr>
<td valign="top" align="left">R. Inferior temporal gyrus</td>
<td valign="top" align="left">ALFF</td>
<td valign="top" align="left">Yanli Yu</td>
<td valign="top" align="left">&#x02193; (1/1)</td>
</tr>
<tr>
<td valign="top" align="left">L. Middle temporal gyrus</td>
<td valign="top" align="left">ALFF</td>
<td valign="top" align="left">Yanli Yu</td>
<td valign="top" align="left">&#x02193; (1/1)</td>
</tr>
<tr>
<td valign="top" align="left">L. Superior parietal lobule</td>
<td valign="top" align="left">ALFF</td>
<td valign="top" align="left">Yanli Yu</td>
<td valign="top" align="left">&#x02193; (1/1)</td>
</tr>
<tr>
<td valign="top" align="left">L. Posterior cerebellum</td>
<td valign="top" align="left">ALFF</td>
<td valign="top" align="left">Yanli Yu</td>
<td valign="top" align="left">&#x02193; (1/1)</td>
</tr>
<tr>
<td valign="top" align="left">L. Inferior occipital gyrus</td>
<td valign="top" align="left">DC vs. ALFF</td>
<td valign="top" align="left">&#x02191;: Wei Xiao, Ran Wang; &#x02193;: Yanli Yu</td>
<td valign="top" align="left">Divergent: &#x02191;&#x02191; (2/3) vs. &#x02193; (1/3)<sup>&#x0002A;</sup></td>
</tr>
<tr>
<td valign="top" align="left" colspan="4"><bold>B. Magnetic resonance spectroscopy findings</bold></td>
</tr>
<tr>
<td valign="top" align="left"><bold>Metabolite ratio</bold></td>
<td valign="top" align="left"><bold>ROI locations</bold></td>
<td valign="top" align="left"><bold>Studies</bold></td>
<td valign="top" align="left"><bold>Direction</bold></td>
</tr>
<tr>
<td valign="top" align="left">NAA/Cr</td>
<td valign="top" align="left">Infarct area, frontal WM, hippocampus</td>
<td valign="top" align="left">Jianbo Zhang, Mengrun Su, Fang Wang</td>
<td valign="top" align="left">&#x02191;<italic>&#x02191;&#x02191;</italic> (3/3)</td>
</tr>
<tr>
<td valign="top" align="left">Cho/Cr</td>
<td valign="top" align="left">Infarct area, hippocampus</td>
<td valign="top" align="left">Jianbo Zhang, Fang Wang</td>
<td valign="top" align="left">&#x02193;&#x02193; (2/2)</td>
</tr>
<tr>
<td valign="top" align="left">MI/Cr</td>
<td valign="top" align="left">Infarct area, frontal WM</td>
<td valign="top" align="left">Jianbo Zhang, Mengrun Su</td>
<td valign="top" align="left">&#x02193;&#x02193; (2/2)</td>
</tr></tbody>
</table>
<table-wrap-foot>
<p>L, left; R, right. &#x02191; indicates increased activity; &#x02193; indicates decreased activity. Numbers in parentheses indicate the number of studies showing the finding (e.g., &#x02191;<italic>&#x02191;&#x02191;</italic> (3/3) means 3 out of 3 studies showed an increase). <sup>&#x0002A;</sup>Indicates divergent findings: DC showed increased activity in 2 studies, while ALFF showed decreased activity in 1 study. ALFF, amplitude of low-frequency fluctuation; fALFF, fractional ALFF; DC, degree centrality; FC, functional connectivity. WM, white matter; NAA/Cho/MI, N-acetylaspartate/choline/myo-inositol; Cr, creatine.</p>
</table-wrap-foot>
</table-wrap>
<sec>
<label>3.8.2.1</label>
<title>Acupuncture-induced changes in brain activity</title>
<p>Five rs-fMRI studies evaluated acupuncture&#x00027;s effects on brain functional activity in PISCI (<xref ref-type="fig" rid="F4">Figure 4</xref>). Acupuncture-induced brain changes primarily involved regions associated with memory, executive function, visuospatial processing, and attention.</p>
<fig position="float" id="F4">
<label>Figure 4</label>
<caption><p>Brain regions changes induced by acupuncture. The figure shows a dorsal view of the brain. Red spheres = increased activity; Blue spheres = decreased activity. Increased Activity (Red): LPHG, Left Parahippocampal Gyrus; LPCC, Left Posterior Cingulate Cortex; LFFG, Left Fusiform Gyrus; LHG, Left Heschl&#x00027;s Gyrus; LLG, Left Lingual Gyrus; RLG, Right Lingual Gyrus; RIOG, Right Inferior Occipital Gyrus; RPHG, Right Parahippocampal Gyrus; LThal, Left Thalamus; RIns, Right Insula; LACC, Left Anterior Cingulate Cortex. Decreased Activity (Blue): RAG, Right Angular Gyrus; ROFCmid, Right Orbital Middle Frontal Gyrus; RSOG, Right Superior Occipital Gyrus; LCbP, Left Cerebellum Posterior Lobe; LITG, Left Inferior Temporal Gyrus; RITG, Right Inferior Temporal Gyrus; LIFG, Left Inferior Frontal Gyrus; LMTG, Left Middle Temporal Gyrus; LSPL, Left Superior Parietal Lobule.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnins-19-1629305-g0004.tif">
<alt-text content-type="machine-generated">Diagram of a human brain viewed from above, showing labeled regions. Red and blue dots indicate specific areas, with a color-coded scale on the right. Regions include ROFCmid, LIFG, LACC, and others.</alt-text>
</graphic>
</fig>
<sec>
<label>3.8.2.1.1</label>
<title>Memory-related regions</title>
<p>Enhanced activity was observed in memory structures across multiple studies. The para hippocampal gyrus showed increased activity in 3/5 studies (60%), with elevated ALFF in the right para hippocampal gyru and increased DC and local efficiency in the left para hippocampal gyrus. Hippocampal frontal connectivity was strengthened bilaterally, with enhanced connections between the left hippocampus and right middle/inferior frontal gyri, and between the right hippocampus and left frontal regions and parietal lobe. The left thalamus also showed increased ALFF.</p></sec>
<sec>
<label>3.8.2.1.2</label>
<title>Executive function-related regions</title>
<p>Executive networks showed mixed modulation patterns. Hippocampal-frontal connectivity was enhanced bilaterally, and the left anterior cingulate gyrus exhibited increased ALFF. The left posterior cingulate gyrus showed increased DC. However, decreased activity occurred in the left inferior frontal gyrus (reduced ALFF) and right orbitofrontal cortex (decreased DC).</p></sec>
<sec>
<label>3.8.2.1.3</label>
<title>Visuospatial processing regions</title>
<p>The fusiform gyrus, critical for visual object recognition, showed consistent increases across 3/5 studies (60%), with elevated fALFF, increased DC and increased local efficiency. The lingual gyrus also demonstrated enhanced activity in 3/5 studies (60%), with increased DC and node centrality bilaterally. Occipital regions showed mixed patterns: the left inferior occipital gyrus showed increased DC and node centrality but decreased ALFF, the right inferior occipital gyrus showed increased local efficiency, and the right superior occipital gyrus exhibited decreased fALFF.</p></sec>
<sec>
<label>3.8.2.1.4</label>
<title>Attention-related regions</title>
<p>The cingulate cortex showed increased activity in 2/5 studies (40%): left anterior cingulate gyrus and left posterior cingulate gyrus. The right insula demonstrated increased ALFF. Conversely, the right angular gyrus showed decreased DC and local efficiency, and the left superior parietal lobule showed reduced ALFF.</p></sec>
<sec>
<label>3.8.2.1.5</label>
<title>Other regions</title>
<p>The left transverse temporal gyrus showed increased DC and local efficiency. Decreased activity was observed in bilateral inferior temporal gyri, left middle temporal gyrus, and left posterior cerebellar lobe.</p></sec></sec>
<sec>
<label>3.8.2.2</label>
<title>Acupuncture-induced changes in brain metabolism</title>
<p>Three studies (<xref ref-type="bibr" rid="B84">Su, 2016</xref>; <xref ref-type="bibr" rid="B92">Wang et al., 2014</xref>; <xref ref-type="bibr" rid="B122">Zhang et al., 2020</xref>) used MRS to assess metabolite ratios in regions including the infarct area, hippocampus, and frontal white matter. Among the three studies that employed MRS, all observed significant increases in NAA/Cr after acupuncture. Two of these three studies also reported reductions in MI/Cr, and two observed decreases in Cho/Cr.</p></sec>
</sec>
<sec>
<label>3.8.3</label>
<title>Correlation between neuroimaging and clinical outcomes</title>
<p>Three studies (3/8, 37.5%) examined associations between acupuncture-related brain changes and cognitive test scores. Two studies found a negative correlation between the area under the curve (AUC) of DC in the left inferior occipital gyrus and MoCA scores after acupuncture. One study did not identify any significant correlations between fALFF, ReHo, or DC values in altered regions and neuropsychological scores.</p></sec>
<sec>
<label>3.8.4</label>
<title>Potential brain network changes induced by acupuncture</title>
<p>Affected regions mapped onto several functional networks (<xref ref-type="fig" rid="F5">Figure 5</xref>): the default mode network (DMN; para hippocampal gyrus, posterior cingulate gyrus, middle temporal gyrus, angular gyrus); the central executive network (CEN; orbitofrontal cortex, inferior frontal gyrus, superior parietal lobule); the salience network (SN; insula, anterior cingulate gyrus); and the visual network (VN; lingual gyrus, inferior occipital gyrus, fusiform gyrus). <xref ref-type="fig" rid="F6">Figure 6</xref> illustrates the modulation of brain regions within brain networks and associated changes in FC.</p>
<fig position="float" id="F5">
<label>Figure 5</label>
<caption><p>Brain networks potentially induced by acupuncture. Lateral view (left hemisphere) showing four major functional networks potentially modulated by acupuncture treatment. Default Mode Network (DMN, orange): PHG, Parahippocampal Gyrus; PCC, Posterior Cingulate Cortex; MTG, Middle Temporal Gyrus; AG, Angular Gyrus. Central Executive Network (CEN, yellow): MFG, Middle Frontal Gyrus; IFG, Inferior Frontal Gyrus; SPL, Superior Parietal Lobule. Salience Network (SN, green): Ins, Insula; ACC, Anterior Cingulate Cortex. Visual Network (VN, blue): LG, Lingual Gyrus; IOG, Inferior Occipital Gyrus; FFG, Fusiform Gyrus.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnins-19-1629305-g0005.tif">
<alt-text content-type="machine-generated">Illustration of the human brain with colored lines indicating four networks: Default Mode Network (orange), Central Executive Network (red), Salience Network (green), and Visual Network (blue). Colored dots mark regions such as SPL, ACC, IFG, MTG, and others linked to these networks.</alt-text>
</graphic>
</fig>
<fig position="float" id="F6">
<label>Figure 6</label>
<caption><p>Brain network alterations in regional activity and functional connectivity after acupuncture. The figure shows brain activity changes and functional connectivity alterations across four views (left lateral, right lateral, left medial, right medial). Colored spheres represent network nodes with activity changes; red lines indicate significantly enhanced functional connectivity between regions. Sphere size encoding: Smallest spheres = decreased activity; Largest spheres = increased activity; Medium-sized spheres = regions showing functional connectivity changes only (without significant local activity changes). Network color coding: Orange = DMN, Yellow = CEN, Green = SN, Blue = VN. DMN (orange): LHipp, left hippocampus; RHipp, right hippocampus; LPHG, left parahippocampal gyrus; RPHG, right parahippocampal gyrus; LPCC, left posterior cingulate cortex; RAG, right angular gyrus; CEN (yellow): LSFG, left superior frontal gyrus; LMFG, left middle frontal gyrus; RMFG, right middle frontal gyrus; LIFG, left inferior frontal gyrus; RIFG, right inferior frontal gyrus; LSPL, left superior parietal lobule; SN (green): LACC, left anterior cingulate cortex; RIns, right Insula; VN (blue): LFFG, left fusiform gyrus; LLG, left lingual gyrus; RLG, right lingual gyrus; LIOG, left inferior occipital gyrus; RIOG, right inferior occipital gyrus.</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fnins-19-1629305-g0006.tif">
<alt-text content-type="machine-generated">Diagram of the human brain showing labeled regions with colored spheres on lateral and medial views of the left and right hemispheres. Connections between specific regions are illustrated with red lines in the central image. Different colors represent distinct brain regions.</alt-text>
</graphic>
</fig>
</sec>
<sec>
<label>3.8.5</label>
<title>Correlation between neuroimaging findings and detailed acupuncture</title>
<p>None of the included studies directly analyzed associations between specific acupuncture parameters and neuroimaging outcomes; however, a descriptive analysis can be conducted based on STRICTA details and study results.</p>
<p>Among the five rs-fMRI studies, most employed prescriptions centered on GV20 (4/5, 80%) and EX-HN1 (3/5, 60%), often combined with PC6 (3/5, 60%). Only one study used scalp acupuncture (1/5, 20%). In these studies focusing on vertex acupoints, neuroimaging results demonstrated increased activity in the left fusiform gyrus (3/5, 60%), para hippocampal gyrus (3/5, 60%), cingulate gyrus (2/5, 40%), and bilateral lingual gyri (2/5, 40%), alongside decreased activity in the right angular gyrus (2/5, 40%). Regarding techniques, four studies used manual acupuncture (4/5, 80%) and one used electro acupuncture (1/5, 20%). The electro acupuncture study reported reduced ALFF in the left inferior occipital gyrus, whereas two manual acupuncture studies showed increased DC and node centrality in the same region.</p>
<p>Three additional studies used MRS with target regions including the area of cerebral infarction, bilateral frontal lobe white matter, and the hippocampal region. Frequently selected acupoints included LI4 (3/3, 100%), LR3 (3/3, 100%), GV24 (2/3, 66.7%), EX-HN1 (2/3, 66.7%), and GV20 (2/3, 66.7%); all used manual acupuncture. MRS findings consistently demonstrated increased NAA/Cr ratios (3/3, 100%), together with decreased Cho/Cr (3/3, 100%) and MI/Cr (2/3, 66.7%).</p></sec>
</sec>
</sec>
<sec sec-type="discussion" id="s4">
<label>4</label>
<title>Discussion</title>
<p>This SR evaluated neuroimaging studies on acupuncture for PISCI in accordance with PRISMA. Eight studies (<italic>n</italic> = 397) were included. The primary objective was to summarize neuroimaging evidence on the effects of acupuncture in PISCI and to explore potential neural mechanisms.</p>
<sec>
<label>4.1</label>
<title>Characteristics of included neuroimaging studies</title>
<p>All included studies were conducted in China, reflecting the widespread clinical use of acupuncture in that context. However, the lack of studies from other countries may limit generalizability to populations with different cultural backgrounds and acceptance of acupuncture. The included studies comprised five RCTs and three non-RCTs. Quality assessment revealed that two RCTs were at high risk of bias, primarily due to inadequately reported randomization process and lack of allocation concealment; the remaining three were judged to have &#x0201C;some concerns,&#x0201D; largely related to deviations from intended interventions and incomplete outcome reporting. These methodological weaknesses represent critical threats to internal validity and indicate that findings should be interpreted with caution. Future research should adhere closely to methodological standards outlined in the Cochrane Handbook for Systematic Reviews of Interventions to improve rigor and transparency, thereby enhancing the overall credibility of the evidence.</p>
<p>All included studies had small sample sizes (fewer than 80 participants), which fundamentally limits statistical power and reproducibility. Prior research has shown that (<xref ref-type="bibr" rid="B41">Klapwijk et al., 2021</xref>) small neuroimaging samples may overestimate effect sizes and reduce reproducibility. Without predefined analysis plans, especially for ROI analyses, the risk of false positives further increases (<xref ref-type="bibr" rid="B22">Gentili et al., 2021</xref>). Cross-validation may mitigate this risk but cannot fully compensate for inadequate sample sizes (<xref ref-type="bibr" rid="B24">Goltermann et al., 2023</xref>). Additionally, all studies recruited participants from tertiary care centers, potentially limiting generalizability to community settings. Future studies should increase sample sizes and standardize data-analysis pipelines. Regarding participant characteristics, seven of the eight studies included more men than women, consistent with the higher global incidence of ischemic stroke in males, especially under the age of 75 (<xref ref-type="bibr" rid="B12">de Miguel-Yanes et al., 2021</xref>). Sex may influence neural repair and cognitive recovery after stroke (<xref ref-type="bibr" rid="B67">Madsen and Guo, 2020</xref>; <xref ref-type="bibr" rid="B127">Zinman et al., 2023</xref>); thus, future trials should explicitly include sex as a biological variable.</p>
<p>Cross-study replication of findings strengthens the credibility of the evidence. Among the five rs-fMRI studies, several brain regions showed consistent changes: the para hippocampal gyrus, fusiform gyrus, and lingual gyrus demonstrated enhanced activity across independent different studies. In contrast, changes in other regions were reported in single studies only, representing preliminary observations requiring validation. However, due to the limited number of included studies and methodological heterogeneity, quantitative meta-analysis was not feasible, which constrained our ability to estimate pooled effect sizes and assess publication bias. Notably, the predominance of positive findings among small-sample studies suggests potential publication bias, although formal statistical testing was not possible due to insufficient study numbers.</p>
<p>The included studies varied widely in acupuncture methods, acupoint selections, and treatment protocols. Seven studies used manual acupuncture, one used electro acupuncture, and only five reported practitioner qualifications. Variability in techniques, needle retention time, and stimulation intensity could influence treatment effects and reproducibility (<xref ref-type="bibr" rid="B113">Yang et al., 2013</xref>). Several studies did not fully comply with STRICTA, with incomplete reporting of details such as deqi sensations or acupoint rationale; only five studies described patient responses to acupuncture. Evidence suggests that (<xref ref-type="bibr" rid="B53">Li et al., 2015a</xref>; <xref ref-type="bibr" rid="B78">Shi et al., 2016</xref>) deqi is associated with activation of regions such as the insula and cingulate gyrus, potentially underlying central effects of acupuncture. Standardization and consistent adherence to STRICTA are therefore critical for improving comparability and reliability.</p>
<p>Regarding acupoint selection, GV20 and EX-HN1 were most frequently used; both are located at the vertex. Unlike distal points commonly used for Alzheimer&#x00027;s disease (AD) or mild cognitive impairment (MCI) (<xref ref-type="bibr" rid="B115">Yin et al., 2023a</xref>,<xref ref-type="bibr" rid="B116">b</xref>), these acupoints directly stimulate cortical regions beneath the skull. Neuroimaging studies indicate that (<xref ref-type="bibr" rid="B14">Deng et al., 2015</xref>; <xref ref-type="bibr" rid="B44">Kong et al., 2024</xref>; <xref ref-type="bibr" rid="B103">Wei et al., 2021</xref>) these regions correspond to prefrontal and parietal cortices&#x02014;areas related to executive function, attention, and working memory. Animal research further suggests that (<xref ref-type="bibr" rid="B126">Zheng et al., 2020</xref>) GV20 may promote neuroplasticity and neurotrophic factor expression, potentially improving cognitive function.</p>
<p>For outcome measurement, the most commonly used cognitive assessment tools were MoCA and MMSE. Numerous studies indicate that MoCA is more sensitive than MMSE for detecting MCI, making it suitable for identifying early post-stroke cognitive deficits (<xref ref-type="bibr" rid="B17">Dong et al., 2014</xref>; <xref ref-type="bibr" rid="B51">Lestari et al., 2017</xref>; <xref ref-type="bibr" rid="B73">Pendlebury et al., 2012</xref>). MMSE is more commonly used for dementia screening and for assessing overall cognitive function (<xref ref-type="bibr" rid="B40">Kawada, 2018</xref>; <xref ref-type="bibr" rid="B64">Lyrakos et al., 2014</xref>). Additional tools included WMS-RC, TMT, AVLT, and DS. WMS-RC is widely used in China for assessing verbal and visual memory (<xref ref-type="bibr" rid="B15">Ding et al., 2009</xref>). TMT is sensitive to attentional and executive dysfunction and, when combined with MoCA, can improve screening accuracy for post-stroke vascular cognitive impairment (VCI) (<xref ref-type="bibr" rid="B17">Dong et al., 2014</xref>; <xref ref-type="bibr" rid="B43">Kodama et al., 2022</xref>). AVLT assesses auditory-verbal memory (<xref ref-type="bibr" rid="B110">Xin-Xian, 2012</xref>), while the DS evaluates working memory and correlates with daily functional status (<xref ref-type="bibr" rid="B21">Fitri et al., 2020</xref>; <xref ref-type="bibr" rid="B52">Leung et al., 2011</xref>). Overall, although MoCA and MMSE remain the primary screening tools in PISCI, they have limitations for domain-specific deficits. Future studies should incorporate more targeted assessments (e.g., AVLT, DS, TMT) and consider emerging approaches such as digital cognitive tools (<xref ref-type="bibr" rid="B3">Bateh et al., 2025</xref>) or virtual reality-integrated cognitive tasks (<xref ref-type="bibr" rid="B25">Gunawan et al., 2024</xref>) to enhance comprehensiveness and sensitivity.</p>
</sec>
<sec>
<label>4.2</label>
<title>Findings of acupuncture treatment on neuroimaging of PISCI</title>
<p>In this SR, rs-fMRI and MRS were used to investigate the effects of acupuncture on brain functional activity and neurometabolic levels. It should be noted that all included studies reported within-group pre-post comparisons as their primary outcome. Two studies included healthy controls as normative references, but the primary analysis in all studies focused on within-group pre-post changes in acupuncture-treated PISCI patients. Therefore, the findings below reflect treatment-associated changes from pre- to post-treatment. However, studies varied in design (some lacked parallel control groups while others were randomized controlled trials), which should be considered when interpreting causal implications.</p>
<p>Rs-fMRI, a non-invasive BOLD-based technique, characterizes regional neural activity and large-scale network organization during rest (<xref ref-type="bibr" rid="B125">Zhen et al., 2018</xref>) and has been widely applied in studies of cognitive impairment and post-stroke brain functional reorganization (<xref ref-type="bibr" rid="B8">Cha et al., 2015</xref>; <xref ref-type="bibr" rid="B23">Golestani et al., 2013</xref>). Common rs-fMRI metrics include ALFF/fALFF (amplitude of spontaneous activity) (<xref ref-type="bibr" rid="B96">Wang et al., 2023</xref>), ReHo (local synchronization) (<xref ref-type="bibr" rid="B30">Han et al., 2018</xref>), and FC (interregional coupling) (<xref ref-type="bibr" rid="B34">Hua et al., 2024</xref>). FC analyses are often combined with graph theory to extract the topological features of brain networks. Frequently used graph-based indicators include DC and local efficiency. DC refers to the number of connections a given brain region has with other regions, indicating its hub-like role within the network (<xref ref-type="bibr" rid="B47">Kuhnert et al., 2012</xref>). Local efficiency measures the efficiency of information transmission among neighboring nodes, reflecting the integrative capacity of local subnetworks (<xref ref-type="bibr" rid="B77">Sang et al., 2020</xref>). Integrating these multilevel metrics provides a comprehensive framework for probing central regulatory mechanisms of acupuncture in PISCI.</p>
<p>MRS, a non-invasive metabolic technique, quantifies relative concentrations of brain metabolites (e.g., NAA, Cho, and MI) to assess neuronal function, glial activity, and inflammation (<xref ref-type="bibr" rid="B88">Tumati et al., 2013</xref>). The included studies demonstrated that acupuncture significantly increased NAA/Cr in the hippocampus and prefrontal cortex and reduced MI/Cr, suggesting improved neuronal function and attenuated inflammatory responses. One study reported a positive correlation between NAA/Cr and cognitive scores, supporting its potential as a neuroimaging biomarker for PISCI (<xref ref-type="bibr" rid="B70">Meng et al., 2016</xref>). It should be noted that MRS-derived metabolite ratios may vary depending on both the anatomical region examined and the post-stroke recovery phase. Previous studies included in this review measured metabolite levels from different brain regions, such as the hippocampus, frontal white matter, or peri-infarct cortex, and at various stages of stroke recovery (acute, subacute, or chronic). These regional and temporal differences can independently influence NAA, Cho, and MI concentrations, reflecting distinct metabolic and reparative processes at different stages of neural reorganization. Therefore, while the current synthesis demonstrates a generally consistent pattern, these results should be interpreted as reflecting an overall trend toward metabolic improvement rather than a precise quantitative convergence. Future studies with standardized voxel placement, acquisition parameters, and longitudinal follow-up are needed to clarify how acupuncture modulates regional and temporal metabolic dynamics after stroke.</p>
<p>Notably, most included studies used single-modality imaging, with limited multimodal integration, which may constrain comprehensive mechanistic understanding. Different techniques offer complementary strengths: DTI reflects post-stroke white matter microstructural damage and remodeling (<xref ref-type="bibr" rid="B2">Auriat et al., 2015</xref>); fNIRS, with high temporal resolution and portability, enables real-time prefrontal hemodynamic monitoring during acupuncture (<xref ref-type="bibr" rid="B1">Annavarapu et al., 2018</xref>); and Electroencephalogram and Magnetoencephalography (EEG/MEG) capture rapid, acupuncture-related electrophysiological activity (<xref ref-type="bibr" rid="B28">Hall et al., 2014</xref>). Future research should adopt multimodal strategies to elucidate acupuncture-mediated central mechanisms and provide robust evidence for precise interventions.</p>
<p>The included studies focused on the sustained effects of acupuncture in PISCI patients. One study revealed that acupuncture significantly enhanced hippocampus-prefrontal functional connectivity (including the middle, inferior, and superior frontal gyri). Consistent with this, a multimodal MRI study (<xref ref-type="bibr" rid="B33">Hosseini et al., 2016</xref>) identified hippocampal structural damage as closely associated with cognitive dysfunction and as a major predictor of post-stroke dementia. The hippocampus plays a central role in PSCI, with functional damage strongly linked to declines in memory and learning capacity (<xref ref-type="bibr" rid="B13">Delattre et al., 2017</xref>; <xref ref-type="bibr" rid="B42">Kliper et al., 2016</xref>). The prefrontal cortex supports executive function, attention, and memory, and reduced connectivity in this region has been associated with cognitive decline (<xref ref-type="bibr" rid="B54">Li et al., 2015b</xref>). By enhancing connectivity within this pathway, acupuncture may promote neuroplasticity and network reorganization, thereby improving cognitive function after stroke (<xref ref-type="bibr" rid="B16">Ding et al., 2014</xref>; <xref ref-type="bibr" rid="B111">Yang et al., 2014</xref>).</p>
<p>This review also indicates that acupuncture modulates several cognition-related regions, including the para hippocampal gyrus, fusiform gyrus, inferior occipital gyrus, cingulate gyrus, transverse temporal gyrus, lingual gyrus, and angular gyrus. The para hippocampal gyrus links the hippocampus with other cortical areas and is essential for memory encoding and spatial navigation. Studies have shown that both the hippocampus and para hippocampal gyrus often show concomitant abnormalities in PISCI and AD, which relate to memory impairment (<xref ref-type="bibr" rid="B38">Jung et al., 2020</xref>; <xref ref-type="bibr" rid="B63">Lu et al., 2024</xref>). The fusiform gyrus, implicated in visual recognition, exhibits abnormalities in PISCI (<xref ref-type="bibr" rid="B10">Cheng et al., 2021</xref>), and serves as an early biomarker in AD/MCI (<xref ref-type="bibr" rid="B7">Cai et al., 2015</xref>; <xref ref-type="bibr" rid="B104">Whitwell et al., 2007</xref>). The lingual and inferior occipital gyri, components of the visual network, may affect visuospatial abilities and information processing after stroke (<xref ref-type="bibr" rid="B80">Smagula et al., 2018</xref>). The cingulate gyrus is a hub for attention and executive control and has been associated with impaired cognitive regulation post-stroke (<xref ref-type="bibr" rid="B49">Lang et al., 2023</xref>). The transverse temporal gyrus, primarily involved in auditory processing, may signal language-related cognitive impairment when disrupted, particularly in left-hemisphere stroke (<xref ref-type="bibr" rid="B13">Delattre et al., 2017</xref>). The angular gyrus contributes to semantic processing, attentional regulation, and working memory; decreased functional connectivity of this region has been linked to lower MoCA scores in PISCI (<xref ref-type="bibr" rid="B37">Jiang et al., 2014</xref>). Collectively, these regions support multiple cognitive domains, including memory, executive function, attentional control, and visual perception. Dysfunction of these regions is closely associated with PISCI. The present findings suggest that acupuncture may modulate these regions and support network-level reorganization. Future work should clarify the roles of these brain areas across cognitive domains and identify the principal pathways and targets through which acupuncture exerts its effects.</p>
<p>Acupuncture may also modulate several functional brain networks implicated in PISCI, including the DMN, CEN, SN, and VN. The DMN, associated with high-level cognitive processes, often shows reduced connectivity after stroke, correlating with cognitive decline (<xref ref-type="bibr" rid="B120">Yue et al., 2023</xref>). The CEN, responsible for executive control and working memory, typically shows hypo-activation post-stroke; acupuncture may help modulate this reduction (<xref ref-type="bibr" rid="B32">Hoffmann, 2020</xref>). The SN functions as a regulatory switch between the DMN and CEN and frequently demonstrates impaired efficiency in PISCI; acupuncture may help restore this modulatory role (<xref ref-type="bibr" rid="B97">Wang et al., 2024a</xref>). The VN, which supports visual information processing, can also be disrupted after a stroke; acupuncture may aid the recovery of visual perception and related functions (<xref ref-type="bibr" rid="B60">Liu et al., 2017</xref>). Recent neuroimaging studies increasingly highlight abnormalities in both static and dynamic connectivity within and between the DMN, CEN, and SN in stroke-related cognitive deficits (<xref ref-type="bibr" rid="B89">Veldsman et al., 2020</xref>; <xref ref-type="bibr" rid="B99">Wang et al., 2024b</xref>; <xref ref-type="bibr" rid="B120">Yue et al., 2023</xref>). These findings suggest that acupuncture may support cognitive recovery by modulating network connectivity, particularly in attention, memory, and executive control. Further research is needed to clarify how acupuncture influences network interactions and contributes to reorganization after stroke.</p>
<p>However, it is important to note that most included studies employed rs-fMRI to examine spontaneous brain activity and functional connectivity, without task-based validation to directly link observed neural changes to specific cognitive processes. As a result, the functional interpretation of regional activation changes remains correlational and inferential. For example, while altered activity in the fusiform or lingual gyrus may be associated with visual processing, without concurrent cognitive task performance, we cannot definitively establish whether these neural changes translate into measurable improvements in visuospatial function. Future studies should incorporate task-based fMRI paradigms that probe memory, attention, executive function, and other cognitive domains to validate the functional relevance of acupuncture-induced neural modulation.</p>
</sec>
<sec>
<label>4.3</label>
<title>Potential factors influencing the neural effects of acupuncture</title>
<p>Although this SR provides a preliminary synthesis of neuroimaging evidence on acupuncture for PISCI, it is important to note that multiple factors may modulate acupuncture-induced brain functional changes.</p>
<p>Intervention-related parameters represent a key set of determinants. Evidence suggests that timing may critically influence neuroplasticity and functional recovery. One study reported (<xref ref-type="bibr" rid="B58">Li et al., 2024</xref>) that treatment initiated during the acute stage of stroke was associated with a lower risk of disability at 6 months, and another neuroimaging study (<xref ref-type="bibr" rid="B100">Wang et al., 2022b</xref>) showed stronger neural responses when acupuncture was applied within the 1<sup>st</sup> month after stroke, indicating a time-dependent effect. Moreover, differences in treatment dose, such as duration, frequency, and stimulation intensity, also play an essential role. An fMRI study (<xref ref-type="bibr" rid="B108">Xiang et al., 2021</xref>) revealed frequency-dependent alterations in BOLD oscillations linked to analgesia, and an animal experiment demonstrated (<xref ref-type="bibr" rid="B99">Wang et al., 2024b</xref>) that moderate-intensity stimulation produced optimal analgesic and immune regulatory effects. Acupoint selection likewise contributes to variability. Although GV20 and EX-HN1 were commonly selected in included studies, different acupoints or combinations can elicit distinct activation patterns. Studies have indicated that (<xref ref-type="bibr" rid="B119">Yuan et al., 2021</xref>) stimulation of language-related acupoints induced different cortical activations, and in hypertension (<xref ref-type="bibr" rid="B121">Zhang et al., 2019</xref>), combined LR3&#x0002B;KI3 stimulation activated broader frontal, insular, and parietal regions than single-point interventions.</p>
<p>In addition, stroke-related clinical characteristics significantly affect the therapeutic effects of acupuncture. In acute ischemic stroke (<xref ref-type="bibr" rid="B87">Tsai et al., 2024</xref>), greater neurological impairment limited the extent of functional recovery achieved with acupuncture, although anti-inflammatory benefits were still observed. Lesion location is a key factor influencing acupuncture effects. A study of post-stroke dysphagia suggested that (<xref ref-type="bibr" rid="B76">Qiu et al., 2021</xref>) efficacy depended on lesion distribution in the brainstem and cortico-subcortical extension region, and another study reported (<xref ref-type="bibr" rid="B124">Zhang et al., 2024</xref>) distinct acupuncture-induced activation patterns across infarct locations. Furthermore, ischemia duration determines the degree of neuronal necrosis and the therapeutic window. An animal experiment demonstrated that (<xref ref-type="bibr" rid="B27">Guo et al., 2025</xref>) acupuncture administered within 24 h after ischemia significantly reduced infarct volume and improved neurological scores, whereas delayed intervention produced weaker effects.</p>
<p>Overall, the included studies did not sufficiently address these factors, limiting understanding of neural effects. Future research should incorporate intervention parameters and stroke characteristics into study design and adhere to STRICTA and the Consolidated Standards of Reporting Trials (CONSORT) guidelines to ensure transparency and scientific rigor.</p>
</sec>
<sec>
<label>4.4</label>
<title>Comparison with other studies</title>
<p>A study of neuroimaging in AD (<xref ref-type="bibr" rid="B115">Yin et al., 2023a</xref>) reported acupuncture-induced activation in the hippocampus, prefrontal cortex, and parietal regions, along with enhanced integration of the DMN, CEN, and fronto parietal network (FPN). Another review focused on MCI (<xref ref-type="bibr" rid="B116">Yin et al., 2023b</xref>) highlighted modulation of the anterior cingulate cortex and insula, involving the DMN and SN. An fMRI meta-analysis (<xref ref-type="bibr" rid="B65">Ma et al., 2022</xref>) further revealed increased activation in the thalamic, frontal, and cingulate regions in MCI after acupuncture, suggesting potential benefits for attention and executive function. While broadly consistent, these studies differ in focus. The present review targets PISCI and indicates modulation of visual-related brain regions (lingual gyrus, inferior occipital gyrus, fusiform gyrus), which are less reported in AD or MCI. This discrepancy may reflect the heterogeneity of stroke lesions, which can affect motor, language, and visual systems in addition to memory, complicating cognitive assessment (<xref ref-type="bibr" rid="B93">Wang, 2020</xref>). Thus, cognitive impairment after stroke may involve multimodal sensory and attentional deficits beyond memory decline. These findings contribute to a more comprehensive understanding of the neural mechanisms underlying acupuncture in PISCI and provide a comparative framework for evaluating differential effects across cognitive disorders. Future research should include cross-condition comparisons, multimodal imaging, and task-based designs to better characterize the neural substrates of acupuncture.</p>
</sec>
<sec>
<label>4.5</label>
<title>Limitations</title>
<p>This review has several limitations. First, most included studies had small sample sizes and heterogeneous designs, potentially affecting the generalizability. Second, key factors such as stroke type, lesion location, recovery phase, concurrent rehabilitation programs, and pharmacotherapy were rarely reported or controlled across studies, which may influence brain reorganization and intervention efficacy. Without systematic control of these variables, the specific contribution of acupuncture may be overstated. Future studies should employ stricter protocols for documenting and adjusting for these clinical factors. Third, variability in imaging protocols, analysis methods, and outcome measures precluded meta-analysis or quantitative integration.</p>
<p>Fourth, only eight studies were included in the final analysis, and several were dissertations, which may limit the representativeness and robustness. Fifth, formal assessment of publication bias was not feasible due to the small number of studies and the absence of pooled quantitative data; nevertheless, the predominance of positive findings suggests that potential publication bias cannot be ruled out. Finally, all included studies were conducted in China, which may limit the generalizability due to potential cultural and methodological factors. Cultural factors such as patient expectations and beliefs about acupuncture, which vary across populations, may influence placebo responses and neural patterns. Acupuncture practice varies internationally in practitioner training, technique standardization, and acupoint selection, potentially affecting neural responses. Cross-country differences in neuroimaging protocols and population characteristics (e.g., stroke etiology, genetic backgrounds) may also impact comparability. While the consistency across multiple independent Chinese studies supports reliability, international multicenter studies with standardized protocols are needed to validate whether these mechanisms generalize across diverse populations and cultural contexts.</p></sec>
</sec>
<sec id="s5">
<label>5</label>
<title>Conclusions</title>
<p>This review provides preliminary neuroimaging evidence supporting the potential benefits of acupuncture for PISCI. The findings suggest that the possible mechanisms of acupuncture for PISCI involve changes in the activity and enhanced functional connectivity of cognition-related brain regions. Additionally, acupuncture may influence brain networks and regulate neurochemical metabolites within cognition-related regions. However, as this field remains in its early stages, further validation is needed. Future studies should focus on well-designed, multicenter randomized controlled trials (RCTs) with large sample sizes and incorporate multiple neuroimaging techniques to better clarify and verify the neural mechanisms of acupuncture in PISCI.</p></sec>
</body>
<back>
<sec sec-type="data-availability" id="s6">
<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="s7">
<title>Author contributions</title>
<p>CQ: Conceptualization, Writing &#x02013; original draft, Writing &#x02013; review &#x00026; editing. BZ: Data curation, Writing &#x02013; review &#x00026; editing. XY: Data curation, Writing &#x02013; review &#x00026; editing. YC: Methodology, Writing &#x02013; review &#x00026; editing. ZM: Methodology, Writing &#x02013; review &#x00026; editing. BL: Project administration, Supervision, Writing &#x02013; review &#x00026; editing.</p>
</sec>
<sec sec-type="COI-statement" id="conf1">
<title>Conflict of interest</title>
<p>The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p>
</sec>
<sec sec-type="ai-statement" id="s9">
<title>Generative AI statement</title>
<p>The author(s) declared that generative AI was used in the creation of this manuscript. During the preparation of this manuscript the author(s) used AI in order to improve language.</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="s10">
<title>Publisher&#x00027;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="s11">
<title>Supplementary material</title>
<p>The Supplementary Material for this article can be found online at: <ext-link ext-link-type="uri" xlink:href="https://www.frontiersin.org/articles/10.3389/fnins.2025.1629305/full#supplementary-material">https://www.frontiersin.org/articles/10.3389/fnins.2025.1629305/full#supplementary-material</ext-link></p>
<supplementary-material xlink:href="Data_Sheet_1.docx" id="SM1" mimetype="application/vnd.openxmlformats-officedocument.wordprocessingml.document" xmlns:xlink="http://www.w3.org/1999/xlink"/></sec>
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<fn fn-type="custom" custom-type="edited-by" id="fn0001">
<p>Edited by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/937688/overview">Pradeep Kumar</ext-link>, All India Institute of Medical Sciences, India</p>
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<fn fn-type="custom" custom-type="reviewed-by" id="fn0002">
<p>Reviewed by: <ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/85139/overview">Kathrin Kollndorfer</ext-link>, Medical University of Vienna, Austria</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2598494/overview">Wei Liu</ext-link>, Guangzhou University of Chinese Medicine, China</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/2964879/overview">Chrismawan Ardianto</ext-link>, Airlangga University, Indonesia</p>
<p><ext-link ext-link-type="uri" xlink:href="https://loop.frontiersin.org/people/3157154/overview">Fang Liu</ext-link>, Hubei University of Chinese Medicine, China</p></fn>
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