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<article article-type="review-article" xml:lang="en" dtd-version="1.4"><processing-meta base-tagset="archiving" mathml-version="3.0" table-model="xhtml" tagset-family="jats"><restricted-by>pmc</restricted-by></processing-meta><front><journal-meta><journal-id journal-id-type="nlm-ta">J Neuroeng Rehabil</journal-id><journal-id journal-id-type="iso-abbrev">J Neuroeng Rehabil</journal-id><journal-id journal-id-type="pmc-domain-id">286</journal-id><journal-id journal-id-type="pmc-domain">jneurorehab</journal-id><journal-title-group><journal-title>Journal of NeuroEngineering and Rehabilitation</journal-title></journal-title-group><issn pub-type="epub">1743-0003</issn><publisher><publisher-name>BMC</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmcid">PMC11874405</article-id><article-id pub-id-type="pmcid-ver">PMC11874405.1</article-id><article-id pub-id-type="pmcaid">11874405</article-id><article-id pub-id-type="pmcaiid">11874405</article-id><article-id pub-id-type="pmid">40033447</article-id><article-id pub-id-type="doi">10.1186/s12984-025-01588-x</article-id><article-id pub-id-type="publisher-id">1588</article-id><article-version article-version-type="pmc-version">1</article-version><article-categories><subj-group subj-group-type="heading"><subject>Review</subject></subj-group></article-categories><title-group><article-title>Effects of brain-computer interface based training on post-stroke upper-limb rehabilitation: a meta-analysis</article-title></title-group><contrib-group><contrib contrib-type="author" equal-contrib="yes"><contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0009-0000-9748-3245</contrib-id><name name-style="western"><surname>Li</surname><given-names initials="D">Dan</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author" equal-contrib="yes"><name name-style="western"><surname>Li</surname><given-names initials="R">Ruoyu</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Song</surname><given-names initials="Y">Yunping</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff3">3</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Qin</surname><given-names initials="W">Wenting</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Sun</surname><given-names initials="G">Guangli</given-names></name><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff2">2</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Liu</surname><given-names initials="Y">Yunxi</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author"><name name-style="western"><surname>Bao</surname><given-names initials="Y">Yunjun</given-names></name><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><name name-style="western"><surname>Liu</surname><given-names initials="L">Lingyu</given-names></name><address><email>Happyneurologist@163.com</email></address><xref ref-type="aff" rid="Aff1">1</xref></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid" authenticated="false">https://orcid.org/0000-0001-7199-2578</contrib-id><name name-style="western"><surname>Jin</surname><given-names initials="L">Lingjing</given-names></name><address><email>lingjingjin@163.com</email></address><xref ref-type="aff" rid="Aff1">1</xref><xref ref-type="aff" rid="Aff3">3</xref></contrib><aff id="Aff1"><label>1</label><institution-wrap><institution-id institution-id-type="ROR">https://ror.org/03rc6as71</institution-id><institution-id institution-id-type="GRID">grid.24516.34</institution-id><institution-id institution-id-type="ISNI">0000000123704535</institution-id><institution>Department of Neurology and Neurological Rehabilitation, Shanghai Disabled Persons’ Federation Key Laboratory of Intelligent Rehabilitation Assistive Devices and Technologies, Shanghai Yangzhi Rehabilitation Hospital (Shanghai Sunshine Rehabilitation Center), School of Medicine, , </institution><institution>Tongji University, </institution></institution-wrap>Shanghai, 201619 China </aff><aff id="Aff2"><label>2</label><institution-wrap><institution-id institution-id-type="ROR">https://ror.org/0056pyw12</institution-id><institution-id institution-id-type="GRID">grid.412543.5</institution-id><institution-id institution-id-type="ISNI">0000 0001 0033 4148</institution-id><institution>Department of Sport Rehabilitation, </institution><institution>Shanghai University of Sport, </institution></institution-wrap>Shanghai, 200438 China </aff><aff id="Aff3"><label>3</label><institution-wrap><institution-id institution-id-type="ROR">https://ror.org/03rc6as71</institution-id><institution-id institution-id-type="GRID">grid.24516.34</institution-id><institution-id institution-id-type="ISNI">0000000123704535</institution-id><institution>Neurotoxin Research Center of Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Neurological Department of Tongji Hospital, School of Medicine, </institution><institution>Tongji University, </institution></institution-wrap>389 Xincun Road, Shanghai, 200065 P. R. China </aff></contrib-group><pub-date pub-type="epub"><day>3</day><month>3</month><year>2025</year></pub-date><pub-date pub-type="collection"><year>2025</year></pub-date><volume>22</volume><issue-id pub-id-type="pmc-issue-id">478636</issue-id><elocation-id>44</elocation-id><history><date date-type="received"><day>20</day><month>7</month><year>2024</year></date><date date-type="accepted"><day>21</day><month>2</month><year>2025</year></date></history><pub-history><event event-type="pmc-release"><date><day>03</day><month>03</month><year>2025</year></date></event><event event-type="pmc-live"><date><day>03</day><month>03</month><year>2025</year></date></event><event event-type="pmc-last-change"><date iso-8601-date="2025-03-06 01:25:40.563"><day>06</day><month>03</month><year>2025</year></date></event></pub-history><permissions><copyright-statement>© The Author(s) 2025</copyright-statement><copyright-year>2025</copyright-year><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/" specific-use="textmining" content-type="ccbyncndlicense">https://creativecommons.org/licenses/by-nc-nd/4.0/</ali:license_ref><license-p><bold>Open Access</bold> This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit <ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="uri" xlink:href="https://creativecommons.org/licenses/by-nc-nd/4.0/">http://creativecommons.org/licenses/by-nc-nd/4.0/</ext-link>.</license-p></license></permissions><self-uri xmlns:xlink="http://www.w3.org/1999/xlink" content-type="pmc-pdf" xlink:href="12984_2025_Article_1588.pdf"><?pdf-name 12984_2025_Article_1588.pdf?><?pdf-size 2256382?><?pdf-md5 10548e6fdf04091bfcde0ba560fbc89b?><?pdf-image-server-status NEVER_LOAD?><?pdf-cloudpmc-urn urn:app:722d/11874405/10548e6fdf04/12984_2025_Article_1588.pdf?></self-uri><abstract id="Abs1"><sec><title>Background</title><p id="Par1">Previous research has used the brain-computer interface (BCI) to promote upper-limb motor rehabilitation. However, the results of these studies were variable, leaving efficacy unclear.</p></sec><sec><title>Objectives</title><p id="Par2">This review aims to evaluate the effects of BCI-based training on post-stroke upper-limb rehabilitation and identify potential factors that may affect the outcome.</p></sec><sec><title>Design</title><p id="Par3">A meta-analysis including all available randomized-controlled clinical trials (RCTs) that reported the efficacy of BCI-based training on upper-limb motor rehabilitation after stroke.</p></sec><sec><title>Data sources and methods</title><p id="Par4">We searched PubMed, Cochrane Library, and Web of Science before September 15, 2024, for relevant studies. The primary efficacy outcome was the Fugl-Meyer Assessment-Upper extremity (FMA-UE). RevMan 5.4.1 with a random effect model was used for data synthesis and analysis. Mean difference (MD) and 95% confidence interval (95%CI) were calculated.</p></sec><sec><title>Results</title><p id="Par5">Twenty-one RCTs (<italic toggle="yes">n</italic> = 886 patients) were reviewed in the meta-analysis. Compared with control, BCI-based training exerted significant effects on FMA-UE (MD = 3.69, 95%CI 2.41–4.96, <italic toggle="yes">P</italic> &lt; 0.00001, moderate-quality evidence), Wolf Motor Function Test (WMFT) (MD = 5.00, 95%CI 2.14–7.86, <italic toggle="yes">P</italic> = 0.0006, low-quality evidence), and Action Research Arm Test (ARAT) (MD = 2.04, 95%CI 0.25–3.82, <italic toggle="yes">P</italic> = 0.03, high-quality evidence). Additionally, BCI-based training was effective on FMA-UE for both subacute (MD = 4.24, 95%CI 1.81–6.67, <italic toggle="yes">P</italic> = 0.0006) and chronic patients (MD = 2.63, 95%CI 1.50–3.76, <italic toggle="yes">P</italic> &lt; 0.00001). BCI combined with functional electrical stimulation (FES) (MD = 4.37, 95%CI 3.09–5.65, <italic toggle="yes">P</italic> &lt; 0.00001), robots (MD = 2.87, 95%CI 0.69–5.04, <italic toggle="yes">P</italic> = 0.010), and visual feedback (MD = 4.46, 95%CI 0.24–8.68, <italic toggle="yes">P</italic> = 0.04) exhibited significant effects on FMA-UE. BCI combined with FES significantly improved FMA-UE for both subacute (MD = 5.31, 95%CI 2.58–8.03, <italic toggle="yes">P</italic> = 0.0001) and chronic patients (MD = 3.71, 95%CI 2.44–4.98, <italic toggle="yes">P</italic> &lt; 0.00001), and BCI combined with robots was effective for chronic patients (MD = 1.60, 95%CI 0.15–3.05, <italic toggle="yes">P</italic> = 0.03). Better results may be achieved with daily training sessions ranging from 20 to 90 min, conducted 2–5 sessions per week for 3–4 weeks.</p></sec><sec><title>Conclusions</title><p id="Par6">BCI-based training may be a reliable rehabilitation program to improve upper-limb motor impairment and function.</p></sec><sec><title>Trial registration</title><p id="Par7">PROSPERO registration ID: CRD42022383390.</p></sec><sec><title>Supplementary Information</title><p>The online version contains supplementary material available at 10.1186/s12984-025-01588-x.</p></sec></abstract><kwd-group xml:lang="en"><title>Keywords</title><kwd>Brain-computer interface</kwd><kwd>Stroke</kwd><kwd>Upper-limb</kwd><kwd>Motor impairment</kwd><kwd>Rehabilitation</kwd></kwd-group><custom-meta-group><custom-meta><meta-name>pmc-status-qastatus</meta-name><meta-value>0</meta-value></custom-meta><custom-meta><meta-name>pmc-status-live</meta-name><meta-value>yes</meta-value></custom-meta><custom-meta><meta-name>pmc-status-embargo</meta-name><meta-value>no</meta-value></custom-meta><custom-meta><meta-name>pmc-status-released</meta-name><meta-value>yes</meta-value></custom-meta><custom-meta><meta-name>pmc-prop-open-access</meta-name><meta-value>yes</meta-value></custom-meta><custom-meta><meta-name>pmc-prop-olf</meta-name><meta-value>no</meta-value></custom-meta><custom-meta><meta-name>pmc-prop-manuscript</meta-name><meta-value>no</meta-value></custom-meta><custom-meta><meta-name>pmc-prop-legally-suppressed</meta-name><meta-value>no</meta-value></custom-meta><custom-meta><meta-name>pmc-prop-has-pdf</meta-name><meta-value>yes</meta-value></custom-meta><custom-meta><meta-name>pmc-prop-has-supplement</meta-name><meta-value>yes</meta-value></custom-meta><custom-meta><meta-name>pmc-prop-pdf-only</meta-name><meta-value>no</meta-value></custom-meta><custom-meta><meta-name>pmc-prop-suppress-copyright</meta-name><meta-value>no</meta-value></custom-meta><custom-meta><meta-name>pmc-prop-is-real-version</meta-name><meta-value>no</meta-value></custom-meta><custom-meta><meta-name>pmc-prop-is-scanned-article</meta-name><meta-value>no</meta-value></custom-meta><custom-meta><meta-name>pmc-prop-preprint</meta-name><meta-value>no</meta-value></custom-meta><custom-meta><meta-name>pmc-prop-in-epmc</meta-name><meta-value>yes</meta-value></custom-meta><custom-meta><meta-name>pmc-license-ref</meta-name><meta-value>CC BY-NC-ND</meta-value></custom-meta><custom-meta><meta-name>issue-copyright-statement</meta-name><meta-value>© BioMed Central Ltd., part of Springer Nature 2025</meta-value></custom-meta></custom-meta-group></article-meta></front><body><sec id="Sec1"><title>Introduction</title><p id="Par8">Stroke is the leading cause of long-term adult disability worldwide, leading to an estimated cost burden [<xref ref-type="bibr" rid="CR1">1</xref>]. Survivors of stroke frequently suffer from hemiplegia, often characterized by motor impairment (e.g., abnormal movement patterns and abnormal reflexes), poor motor function, spasticity in affected limbs, and muscle weakness, presenting a significant challenge in stroke rehabilitation [<xref ref-type="bibr" rid="CR2">2</xref>–<xref ref-type="bibr" rid="CR4">4</xref>]. Despite active treatment, 80% of people with stroke failed to achieve full recovery of motor function and disabilities of the upper limb, affecting their activities of daily living and overall quality of life substantially [<xref ref-type="bibr" rid="CR5">5</xref>]. Various rehabilitation approaches employed nowadays have some limitations [<xref ref-type="bibr" rid="CR6">6</xref>]. For example, constraint-induced movement therapy (CIMT), is often suitable for individuals with residual movement capability, and robotic therapy and neuromuscular electrical stimulation, often rely on fixed programs without brain activity significant recovery [<xref ref-type="bibr" rid="CR7">7</xref>]. Hence, finding a more effective method for upper-limb recovery after stroke remains a challenge.</p><p id="Par9">Recently several studies [<xref ref-type="bibr" rid="CR8">8</xref>–<xref ref-type="bibr" rid="CR11">11</xref>] have reported upper-limb benefits through BCI-based training. BCI, a novel technology in neurological rehabilitation, facilitates bidirectional communication between the brain and the environment by utilizing recorded brain activity [<xref ref-type="bibr" rid="CR12">12</xref>]. BCI systems can be categorized as invasive or non-invasive, depending on the location of signal acquisition. The non-invasive BCI is widely adopted due to its safety, portability, and cost-effectiveness [<xref ref-type="bibr" rid="CR13">13</xref>]. Non-invasive BCI methods for recording brain signals include electroencephalogram (EEG), magnetoencephalogram (MEG), functional near-infrared spectroscopy (fNIRS), and functional magnetic resonance imaging (fMRI), with EEG being the most commonly utilized [<xref ref-type="bibr" rid="CR14">14</xref>]. Motor imagery (MI), steady-state visual evoked potential (SSVEP), and P300 are common sources of EEG signals [<xref ref-type="bibr" rid="CR15">15</xref>]. In contrast to common rehabilitation strategies for post-stroke upper-limb motor dysfunction, BCI-based training employs a closed-loop approach called “central-peripheral-central”, offering the benefits of real-time feedback that enables self-regulation of neurophysiological activities [<xref ref-type="bibr" rid="CR16">16</xref>].</p><p id="Par10">BCI is often combined with various feedback methods such as functional electrical stimulation (FES) [<xref ref-type="bibr" rid="CR8">8</xref>, <xref ref-type="bibr" rid="CR9">9</xref>, <xref ref-type="bibr" rid="CR17">17</xref>–<xref ref-type="bibr" rid="CR21">21</xref>], robotic assistance [<xref ref-type="bibr" rid="CR10">10</xref>, <xref ref-type="bibr" rid="CR11">11</xref>, <xref ref-type="bibr" rid="CR22">22</xref>–<xref ref-type="bibr" rid="CR31">31</xref>], and visual feedback [<xref ref-type="bibr" rid="CR32">32</xref>, <xref ref-type="bibr" rid="CR33">33</xref>]. Although benefits for post-stroke upper-limb motor impairment have been reported, debates persist due to variations in training protocol. Recent systematic reviews mostly focused on the impact of different external feedback types or stroke phases [<xref ref-type="bibr" rid="CR34">34</xref>, <xref ref-type="bibr" rid="CR35">35</xref>] without analysis of the efficacy of specific external feedback across different phases. Moreover, the impact of several key clinical issues, such as the training intensity (time, sessions, and duration) was not considered appropriately. The optimal scheduling for BCI-based training has not been systematically analyzed. Addressing these aspects is essential for developing personalized training programs and enhancing the recovery of upper-limb function, daily activities, and overall quality of life in stroke patients.</p><p id="Par11">The primary objectives of this meta-analysis are as follows: (1) to investigate the clinical effects of BCI-based training on improving upper-limb motor impairment, motor function, and activities of daily living following a stroke, (2) to identify potential factors that may impact the outcomes, including stroke phases, external feedback, external feedback across stroke phases, training intensity (time, sessions, and duration) and (3) to try to determine optimal BCI-based training protocol for stroke patients.</p></sec><sec id="Sec2"><title>Methods</title><p id="Par12">We followed the guidelines provided by the Meta-Analysis of Observational Studies in Epidemiology Group, the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2020 guidelines [<xref ref-type="bibr" rid="CR36">36</xref>], the PRISMA checklist (Supplementary Table <xref rid="MOESM1" ref-type="media">S1</xref>), and the Cochrane Collaboration definition for systematic review and meta-analysis. The review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42022383390).</p><sec id="Sec3"><title>Search strategy</title><p id="Par13">We conducted a systematic search for articles on PubMed, Cochrane Library, and the Web of Science published before September 15, 2024. The search strategy included the terms: (“stroke”[Mesh] OR cerebrovascular accident OR apoplexy OR brain vascular accident OR cerebral vascular accident OR hemiplegia) AND (“Brain-Computer Interfaces”[Mesh] OR Brain Computer Interfaces OR Brain-Computer Interface OR Brain-Machine Interfaces OR Brain-Machine Interface). The detailed search strategy is presented in Supplementary Table <xref rid="MOESM1" ref-type="media">S2</xref>.</p></sec><sec id="Sec4"><title>Eligibility criteria and study selection</title><p id="Par14">We included studies that met predefined criteria, encompassing (1) RCTs, (2) All the participants included in the studies meeting the clinical diagnostic criteria of stroke or were diagnosed as having stroke by MRI or CT, and suffering from upper-limb motor dysfunction, (3) The experimental group received BCI-based training, including BCI-FES, BCI-robot, BCI-visual feedback training, (4) Control groups received sham BCI training or conventional rehabilitation training (e.g. motor therapy, occupational therapy, physical factor therapy, coordination, etc.), (5) The outcomes of these studies must include FMA-UE. The exclusion criteria included: (1) Second-hand unoriginal research (reviews, meta-analysis, letters, reports, conference abstracts), (2) Duplicated studies, (3) Studies lacking baseline data, (4) Studies with incomplete original data or data that could not be extracted, and no response from authors upon contact, (5) Studies without FMA-UE. In cases of multiple articles using the same data, the one published earlier will be selected. Two reviewers (RL and WQ) independently evaluated the eligibility of the included articles, and disagreements were resolved through consensus during a meeting.</p></sec><sec id="Sec5"><title>Data extraction</title><p id="Par15">Data extraction was conducted by two independent reviewers (DL and YB). The extracted information from each study included the first author’s name, year of publication, participant age, stroke phases, interventions and control details, outcome measures, external feedback, sample size, and follow-up evaluation after interventions. If the mean and SD of change scores were shown in the articles, they were extracted. If not explicitly stated, change scores were calculated using the following formula based on the principles of the Cochrane Handbook for Systematic Reviews of Interventions [<xref ref-type="bibr" rid="CR37">37</xref>]. In cases where studies reported median and interquartile range, we converted these values to mean and SD estimates using the transformations: mean ≈ median and standard deviation = IQR × 1.35.<disp-formula id="Equa"><alternatives><tex-math id="M1"><?equation-image-name M1.gif?><?equation-image-status READY?><?equation-image-md5 6cefe662ef29ab724de941aa55cf621a?><?equation-image-cloudpmc-urn urn:cdn:blobs/722d/11874405/6cefe662ef29/M1.gif?>\documentclass[12pt]{minimal}
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				\begin{document}$$\:{\text{M}\text{e}\text{a}\text{n}}_{change}={\text{M}\text{e}\text{a}\text{n}}_{final}-{\text{M}\text{e}\text{a}\text{n}}_{baseline};$$\end{document}</tex-math><graphic xmlns:xlink="http://www.w3.org/1999/xlink" position="anchor" orientation="portrait" xlink:href="12984_2025_1588_Article_Equa.gif"><?image-name 12984_2025_1588_Article_Equa.gif?><?image-size 1178?><?image-md5 5dbf422a80c7401830d1ee583dffd33a?><?image-image-server-status NEVER_LOAD?><?image-scaled-height 19?><?image-scaled-width 274?><?image-cloudpmc-urn urn:cdn:blobs/722d/11874405/5dbf422a80c7/12984_2025_1588_Article_Equa.gif?><?thumb-name 12984_2025_1588_Article_Equa.gif?><?thumb-size 1178?><?thumb-md5 5dbf422a80c7401830d1ee583dffd33a?><?thumb-image-server-status NEVER_LOAD?><?thumb-scaled-height 19?><?thumb-scaled-width 274?><?thumb-cloudpmc-urn urn:cdn:blobs/722d/11874405/5dbf422a80c7/12984_2025_1588_Article_Equa.gif?></graphic></alternatives></disp-formula><disp-formula id="Equb"><alternatives><tex-math id="M2"><?equation-image-name M2.gif?><?equation-image-status READY?><?equation-image-md5 f3797ae3c19bd8a17dc600d35bbbe539?><?equation-image-cloudpmc-urn urn:cdn:blobs/722d/11874405/f3797ae3c19b/M2.gif?>\documentclass[12pt]{minimal}
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				\begin{document}$$\:{SD}_{change}=\sqrt{\begin{aligned}&amp;{SD}_{baseline}^{2}+{SD}_{final}^{2}\cr&amp;\quad-(2\times\:\text{C}\text{o}\text{r}\text{r}\times\:{SD}_{baseline}\times\:{SD}_{final})\end{aligned}}$$\end{document}</tex-math><graphic xmlns:xlink="http://www.w3.org/1999/xlink" position="anchor" orientation="portrait" xlink:href="12984_2025_1588_Article_Equb.gif"><?image-name 12984_2025_1588_Article_Equb.gif?><?image-size 2283?><?image-md5 e4ba9938850507eb639d1f0f92f679a0?><?image-image-server-status NEVER_LOAD?><?image-scaled-height 53?><?image-scaled-width 400?><?image-cloudpmc-urn urn:cdn:blobs/722d/11874405/e4ba99388505/12984_2025_1588_Article_Equb.gif?><?thumb-name 12984_2025_1588_Article_Equb.gif?><?thumb-size 2283?><?thumb-md5 e4ba9938850507eb639d1f0f92f679a0?><?thumb-image-server-status NEVER_LOAD?><?thumb-scaled-height 53?><?thumb-scaled-width 400?><?thumb-cloudpmc-urn urn:cdn:blobs/722d/11874405/e4ba99388505/12984_2025_1588_Article_Equb.gif?></graphic></alternatives></disp-formula></p></sec><sec id="Sec6"><title>Quality assessment</title><p id="Par16">The quality and risk of bias for included studies were independently assessed by two reviewers (GS and YL). The tool chosen for the quality appraisal of this meta-analysis was the Physiotherapy Evidence Database (PEDro) scale since it is an effective and reliable scoring tool for evaluating methodological quality within the physiotherapy profession and has been used frequently in systematic reviews and meta-analysis [<xref ref-type="bibr" rid="CR38">38</xref>]. The PEDro scale comprises 11 items, addressing aspects including the risk of bias in randomization, allocation concealment, blinding, dropout rate, intention to treat, and data reporting. Except for the first item, each of the remaining 10 items receives 1 point if a clinical controlled trial fulfills the criterion, and the final score is determined by summing these points. Studies with a PEDro score of 9–10 are classified as “excellent” quality, 6–8 as “good” quality, 4–5 as “fair” quality, and below 4 as “poor” quality [<xref ref-type="bibr" rid="CR38">38</xref>, <xref ref-type="bibr" rid="CR39">39</xref>]. Additionally, the risk of bias in included studies was assessed using the items of the Cochrane Risk of Bias tool (ROB) and recorded in Review Manager 5.4.1, consisting of random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, and selective reporting. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines for systematic reviews were used to evaluate the quality of outcomes [<xref ref-type="bibr" rid="CR40">40</xref>]. In instances of disagreement, a third reviewer (YS) was consulted, and consensus was reached.</p></sec><sec id="Sec7"><title>Statistical analysis</title><sec id="Sec8"><title>Effect size calculation</title><p id="Par17">Upper-limb motor impairment, motor function, and activities of daily living were the focused outcomes in our meta-analysis. The FMA-UE is the most frequently utilized clinical measurement for detecting the recovery of motor impairments in the paretic upper limbs of stroke patients [<xref ref-type="bibr" rid="CR41">41</xref>], and it was adopted as the primary outcome measure in this study. Assessments of upper-limb motor function included WMFT [<xref ref-type="bibr" rid="CR42">42</xref>] and ARAT [<xref ref-type="bibr" rid="CR43">43</xref>]. Modified Barthel Index (MBI) was used to assess activities of daily living [<xref ref-type="bibr" rid="CR44">44</xref>]. MD and 95%CI for each statistical analysis were calculated to assess the efficacy of BCI-based training, and the difference was significant when the test level was <italic toggle="yes">P</italic> &lt; 0.05. RevMan 5.4.1 was used for data synthesis and analysis.</p></sec><sec id="Sec9"><title>Heterogeneity analysis</title><p id="Par18">The chi-square test and I<sup>2</sup> test were used to estimate statistical heterogeneity between trials. The statistical heterogeneity was categorized as negligible or small heterogeneity (0-40%), moderate heterogeneity (30-60%), substantial heterogeneity (50-90%), and considerable heterogeneity (&gt; 75%) [<xref ref-type="bibr" rid="CR45">45</xref>]. If the chi-square test was <italic toggle="yes">P</italic> &gt; 0.1 or I<sup>2</sup> &lt; 50%, the studies were assessed as having high homogeneity, and the fixed-effects model was used for meta-analysis. If the chi-square test was <italic toggle="yes">P</italic> &lt; 0.1 or I<sup>2</sup> &gt; 50%, the studies were assessed as having significant heterogeneity, and the random-effects model was used for meta-analysis. A subgroup or sensitivity analysis was conducted to explore the potential sources of clinical heterogeneity within the included studies and verify the reliability of the results. Leave-one-out sensitivity analysis was performed.</p></sec><sec id="Sec10"><title>Publication bias</title><p id="Par19">A funnel plot analysis was performed to assess the potential for publication bias in the meta-analysis, applicable when the number of included studies exceeded ten. In the event of symmetry in the distribution of effect sizes around the pooled mean effect size, this would indicate an absence of publication bias, assuming that any observed variability is attributable to random sampling error.</p></sec><sec id="Sec11"><title>Subgroup analysis</title><p id="Par20">Subgroup analysis was performed based on different follow-up (≤ 3 months vs.&gt;3 months), stroke phases (subacute: 7 days to 6 months from stroke onset vs. chronic: &gt;6 months from stroke onset [<xref ref-type="bibr" rid="CR46">46</xref>]), external feedback combined with BCI (BCI-FES vs. BCI-robot vs. BCI-visual feedback), external feedback and stroke phases (BCI-FES on subacute vs. BCI-FES on chronic, BCI-robot on subacute vs. BCI-robot on chronic). Additionally, to provide a reference for clinical training intensity settings for BCI-based training, we have subdivided the intervention intensity into the following categories: training time per day (&lt; 20 min vs. 20 min vs. 30–40 min vs. 60 min vs. 60–90 min vs. 90 min), training sessions per week (2–3 sessions vs. 5 sessions), total training sessions (≤ 10 sessions vs. 10–20 sessions vs. ≥20 sessions), training duration (2 weeks vs. 3–4 weeks vs. &gt; 4 weeks). The outcome measure for all subgroup analysis was the FMA-UE.</p></sec></sec></sec><sec id="Sec12"><title>Results</title><sec id="Sec13"><title>Search results</title><p id="Par21">The search strategy yielded 3773 articles from various sources: 1092 from PubMed, 272 from Cochrane Library, 2409 from Web of Science, and 1 from other sources. After removing duplicates, patents, books, and conference proceedings, the titles and abstracts of 2192 articles were screened for possible inclusion. Subsequently, 409 articles were assessed for eligibility through full-text screening. Finally, 21 articles, involving 886 patients were included in the meta-analysis. The flowchart of the search strategy and selection steps is presented in Fig. <xref rid="Fig1" ref-type="fig">1</xref>, and the main characteristics of the included studies are detailed in Table <xref rid="Tab1" ref-type="table">1</xref> and Supplementary Table <xref rid="MOESM1" ref-type="media">S3</xref>-<xref rid="MOESM1" ref-type="media">S4</xref>.</p></sec><sec id="Sec14"><title>Methodological quality and risk of bias</title><p id="Par22">According to the PEDro scale (Supplementary Table <xref rid="MOESM1" ref-type="media">S5</xref>), quality assessment was conducted for the included RCTs. Eighteen RCTs (85.7%) were classified as “good” quality studies, while five RCTs (14.3%) were classified as fair quality studies, with no studies identified as “poor” quality. Figures <xref rid="Fig2" ref-type="fig">2</xref> and <xref rid="Fig3" ref-type="fig">3</xref> show the results of the RoB evaluation. The qualitative assessment showed a low risk of missing outcome data and selection of the reported results. Moreover, studies showed some concerns in the randomization process, allocation concealment, and measurement of outcomes. As blinding of participants and intervention providers was not feasible, the studies mainly focused on blinding outcome assessors, which might cause a high risk of performance bias (<xref rid="Tab2" ref-type="table">2</xref>).</p><p id="Par23">
<fig id="Fig1" position="float" orientation="portrait"><label>Fig. 1</label><caption><p>PRISMA flow chart of study selection</p></caption><graphic xmlns:xlink="http://www.w3.org/1999/xlink" id="d33e526" position="float" orientation="portrait" xlink:href="12984_2025_1588_Fig1_HTML.jpg"><?image-name 12984_2025_1588_Fig1_HTML.jpg?><?image-size 59268?><?image-md5 5c6922667c0b5ec02d44244fb23bd6d4?><?image-image-server-status LOAD_COMPLETED?><?image-original-height 1188?><?image-original-width 2008?><?image-scaled-height 396?><?image-scaled-width 669?><?image-cloudpmc-urn urn:cdn:blobs/722d/11874405/5c6922667c0b/12984_2025_1588_Fig1_HTML.jpg?><?thumb-name 12984_2025_1588_Fig1_HTML.gif?><?thumb-size 3939?><?thumb-md5 fbf6f5f7b5ec3716d970533bc4f8a051?><?thumb-image-server-status NEVER_LOAD?><?thumb-scaled-height 80?><?thumb-scaled-width 135?><?thumb-cloudpmc-urn urn:cdn:blobs/722d/11874405/fbf6f5f7b5ec/12984_2025_1588_Fig1_HTML.gif?></graphic></fig>
</p><p id="Par24">
<table-wrap id="Tab1" position="float" orientation="portrait"><label>Table 1</label><caption><p>Characteristics of the included studies</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" colspan="1" rowspan="1">Study</th><th align="left" colspan="1" rowspan="1">Time from stroke onset</th><th align="left" colspan="1" rowspan="1">Stroke phases</th><th align="left" colspan="1" rowspan="1">Experimental interventions</th><th align="left" colspan="1" rowspan="1">Control interventions</th><th align="left" colspan="1" rowspan="1">BCI training intensity</th><th align="left" colspan="1" rowspan="1">Outcome measures</th><th align="left" colspan="1" rowspan="1">Follow-up</th><th align="left" colspan="1" rowspan="1">Sample size</th><th align="left" colspan="1" rowspan="1">PEDro</th></tr></thead><tbody><tr><td align="left" colspan="1" rowspan="1">Ang, 2014</td><td align="left" colspan="1" rowspan="1"><p>E: 285.7 ± 64.0 d</p><p>C: 454.4 ± 109.6 d</p></td><td align="left" colspan="1" rowspan="1">chronic</td><td align="left" colspan="1" rowspan="1">BCI-HK + con-rehab</td><td align="left" colspan="1" rowspan="1"><p>HK: HK + con-rehab</p><p>SAT: con-rehab</p></td><td align="left" colspan="1" rowspan="1"><p>60 min /d, 3 d/wk,</p><p>6 wks, 18 sessions</p></td><td align="left" colspan="1" rowspan="1">FMA-UE</td><td align="left" colspan="1" rowspan="1"><p>6 wks</p><p>18 wks</p></td><td align="left" colspan="1" rowspan="1"><p>E: 6</p><p>C: 8/7</p></td><td char="." align="char" colspan="1" rowspan="1">7</td></tr><tr><td align="left" colspan="1" rowspan="1">Ang, 2015</td><td align="left" colspan="1" rowspan="1"><p>E: 383.0 ± 290.8 d</p><p>C: 234.7 ± 183.8 d</p></td><td align="left" colspan="1" rowspan="1">chronic</td><td align="left" colspan="1" rowspan="1">BCI-Manus robot</td><td align="left" colspan="1" rowspan="1">Manus robot</td><td align="left" colspan="1" rowspan="1"><p>90 min/d, 3 d/wk,</p><p>4 wks,12 sessions</p></td><td align="left" colspan="1" rowspan="1">FMA-UE</td><td align="left" colspan="1" rowspan="1">8 wks</td><td align="left" colspan="1" rowspan="1"><p>E: 11</p><p>C: 14</p></td><td char="." align="char" colspan="1" rowspan="1">7</td></tr><tr><td align="left" colspan="1" rowspan="1">Biasiucci, 2018</td><td align="left" colspan="1" rowspan="1"><p>E: 39.8 ± 45.9 m</p><p>C: 33.5 ± 30.5 m</p></td><td align="left" colspan="1" rowspan="1">chronic</td><td align="left" colspan="1" rowspan="1">BCI-FES + con-rehab</td><td align="left" colspan="1" rowspan="1">sham FES + con-rehab</td><td align="left" colspan="1" rowspan="1"><p>60 min/d, 2 d/wk,</p><p>5 wks, 10 sessions</p></td><td align="left" colspan="1" rowspan="1"><p>FMA-UE</p><p>MRC</p><p>MAS</p><p>ESS</p></td><td align="left" colspan="1" rowspan="1">6–12 m</td><td align="left" colspan="1" rowspan="1"><p>E: 14</p><p>C: 13</p></td><td char="." align="char" colspan="1" rowspan="1">8</td></tr><tr><td align="left" colspan="1" rowspan="1">Chen, 2020</td><td align="left" colspan="1" rowspan="1"><p>E: 3.1 ± 1.7 m</p><p>C: 3.9 ± 1.5 m</p></td><td align="left" colspan="1" rowspan="1">subacute</td><td align="left" colspan="1" rowspan="1">BCI-exoskeleton + con-rehab</td><td align="left" colspan="1" rowspan="1">sham BCI + con-rehab</td><td align="left" colspan="1" rowspan="1"><p>19.5 min/d, 3 d/wk,</p><p>4 wks, 12 sessions</p></td><td align="left" colspan="1" rowspan="1">FMA-UE</td><td align="left" colspan="1" rowspan="1">—</td><td align="left" colspan="1" rowspan="1"><p>E: 7</p><p>C: 7</p></td><td char="." align="char" colspan="1" rowspan="1">6</td></tr><tr><td align="left" colspan="1" rowspan="1">Cheng, 2020</td><td align="left" colspan="1" rowspan="1"><p>E: 476.8 ± 302.0 d</p><p>C: 890.2 ± 257.2 d</p></td><td align="left" colspan="1" rowspan="1">chronic</td><td align="left" colspan="1" rowspan="1">BCI-SRG + con-rehab</td><td align="left" colspan="1" rowspan="1">SRG + con-rehab</td><td align="left" colspan="1" rowspan="1"><p>90 min /d, 3 d/ wk,</p><p>6 wks, 18 sessions</p></td><td align="left" colspan="1" rowspan="1"><p>FMA-UE</p><p>ARAT</p></td><td align="left" colspan="1" rowspan="1"><p>6 wks</p><p>18 wks</p></td><td align="left" colspan="1" rowspan="1"><p>E: 5</p><p>C: 5</p></td><td char="." align="char" colspan="1" rowspan="1">6</td></tr><tr><td align="left" colspan="1" rowspan="1">Curado, 2015</td><td align="left" colspan="1" rowspan="1"><p>E: 5.6 ± 3.9 y</p><p>C: 5.5 ± 6.1 y</p></td><td align="left" colspan="1" rowspan="1">chronic</td><td align="left" colspan="1" rowspan="1">BCI-orthosis + con-rehab</td><td align="left" colspan="1" rowspan="1">sham BCI + con-rehab</td><td align="left" colspan="1" rowspan="1"><p>60 min/d, 5 d/wk,</p><p>4 wks, 20 sessions</p></td><td align="left" colspan="1" rowspan="1">FMA-UE</td><td align="left" colspan="1" rowspan="1">—</td><td align="left" colspan="1" rowspan="1"><p>E: 16</p><p>C: 14</p></td><td char="." align="char" colspan="1" rowspan="1">6</td></tr><tr><td align="left" colspan="1" rowspan="1">Frolov, 2017</td><td align="left" colspan="1" rowspan="1"><p>E: 8.4 ± 6.9 m</p><p>C: 10.9 ± 7.9 m</p></td><td align="left" colspan="1" rowspan="1">subacute and chronic</td><td align="left" colspan="1" rowspan="1">BCI-exoskeleton + con-rehab</td><td align="left" colspan="1" rowspan="1">sham BCI</td><td align="left" colspan="1" rowspan="1"><p>30 min/d, 5 d/wk,</p><p>2 wks, 10 sessions</p></td><td align="left" colspan="1" rowspan="1">FMA-UE, ARAT</td><td align="left" colspan="1" rowspan="1">—</td><td align="left" colspan="1" rowspan="1"><p>E: 55</p><p>C: 19</p></td><td char="." align="char" colspan="1" rowspan="1">6</td></tr><tr><td align="left" colspan="1" rowspan="1">Fu, 2023</td><td align="left" colspan="1" rowspan="1"><p>E: 77.5 (33.8, 175.3) d</p><p>C: 64.0 (37.0, 150.0) d</p></td><td align="left" colspan="1" rowspan="1">unclear</td><td align="left" colspan="1" rowspan="1">BCI-hand robot + con-rehab</td><td align="left" colspan="1" rowspan="1">con-rehab</td><td align="left" colspan="1" rowspan="1"><p>30 min/d, 5 d/wk,</p><p>4 wks, 20 sessions</p></td><td align="left" colspan="1" rowspan="1">FMA-UE</td><td align="left" colspan="1" rowspan="1">—</td><td align="left" colspan="1" rowspan="1"><p>E: 30</p><p>C: 31</p></td><td char="." align="char" colspan="1" rowspan="1">6</td></tr><tr><td align="left" colspan="1" rowspan="1">Guo, 2022</td><td align="left" colspan="1" rowspan="1"><p>E: 12.5 ± 7.1 m</p><p>C: 10.9 ± 7.9 m</p></td><td align="left" colspan="1" rowspan="1">chronic</td><td align="left" colspan="1" rowspan="1">BCI-SRG + con-rehab</td><td align="left" colspan="1" rowspan="1"><p>Robotic: SRG</p><p>control: con-rehab</p></td><td align="left" colspan="1" rowspan="1"><p>60 min/d, 5 d/wk,</p><p>2 wks, 10 sessions</p></td><td align="left" colspan="1" rowspan="1"><p>FMA-UE</p><p>WMFT</p><p>MAS</p></td><td align="left" colspan="1" rowspan="1">12 wks</td><td align="left" colspan="1" rowspan="1"><p>E: 10</p><p>C: 10/10</p></td><td char="." align="char" colspan="1" rowspan="1">5</td></tr><tr><td align="left" colspan="1" rowspan="1">Kim, 2016</td><td align="left" colspan="1" rowspan="1"><p>E: 8.3 ± 2.0 m</p><p>C: 7.8 ± 1.8 m</p></td><td align="left" colspan="1" rowspan="1">chronic</td><td align="left" colspan="1" rowspan="1">BCI-FES + con-rehab</td><td align="left" colspan="1" rowspan="1">con-rehab</td><td align="left" colspan="1" rowspan="1"><p>30 min/d, 3 d/wk,</p><p>4 wks, 12 sessions</p></td><td align="left" colspan="1" rowspan="1"><p>FMA-UE</p><p>MAL</p><p>MBI</p><p>ROM</p></td><td align="left" colspan="1" rowspan="1">—</td><td align="left" colspan="1" rowspan="1"><p>E: 15</p><p>C: 15</p></td><td char="." align="char" colspan="1" rowspan="1">7</td></tr><tr><td align="left" colspan="1" rowspan="1">Lee, 2020</td><td align="left" colspan="1" rowspan="1"><p>E: 7.5 ± 1.6 m</p><p>C: 8.3 ± 2.0 m</p></td><td align="left" colspan="1" rowspan="1">chronic</td><td align="left" colspan="1" rowspan="1">BCI-FES + con-rehab</td><td align="left" colspan="1" rowspan="1">FES + con-rehab</td><td align="left" colspan="1" rowspan="1"><p>30 min/d, 5 d/wk,</p><p>4 wks, 20 sessions</p></td><td align="left" colspan="1" rowspan="1"><p>FMA-UE</p><p>WMFT</p><p>MAL</p><p>MBI</p></td><td align="left" colspan="1" rowspan="1">—</td><td align="left" colspan="1" rowspan="1"><p>E: 13</p><p>C: 13</p></td><td char="." align="char" colspan="1" rowspan="1">7</td></tr><tr><td align="left" colspan="1" rowspan="1">Li, 2014</td><td align="left" colspan="1" rowspan="1"><p>E: 2.2 ± 1.8 m</p><p>C: 2.8 ± 2.0 m</p></td><td align="left" colspan="1" rowspan="1">subacute</td><td align="left" colspan="1" rowspan="1">BCI-FES + con-rehab</td><td align="left" colspan="1" rowspan="1">FES + con-rehab</td><td align="left" colspan="1" rowspan="1"><p>60–90 min/d, 3 d/wk,</p><p>8 wks, 24 sessions</p></td><td align="left" colspan="1" rowspan="1"><p>FMA-UE</p><p>ARAT</p></td><td align="left" colspan="1" rowspan="1">—</td><td align="left" colspan="1" rowspan="1"><p>E: 7</p><p>C: 7</p></td><td char="." align="char" colspan="1" rowspan="1">7</td></tr><tr><td align="left" colspan="1" rowspan="1">Li, 2022</td><td align="left" colspan="1" rowspan="1"><p>E: 4.0 (2.0, 11.3) m</p><p>C: 4.3 ± 2.60 m</p></td><td align="left" colspan="1" rowspan="1">subacute</td><td align="left" colspan="1" rowspan="1">BCI-exoskeleton + con-rehab</td><td align="left" colspan="1" rowspan="1">con-rehab</td><td align="left" colspan="1" rowspan="1"><p>60 min/d, 5d/wk,</p><p>2 wks, 10 sessions</p></td><td align="left" colspan="1" rowspan="1"><p>FMA-UE</p><p>WMFT MBI</p></td><td align="left" colspan="1" rowspan="1">2 wks</td><td align="left" colspan="1" rowspan="1"><p>E: 12</p><p>C: 12</p></td><td char="." align="char" colspan="1" rowspan="1">5</td></tr><tr><td align="left" colspan="1" rowspan="1">Liu, 2023</td><td align="left" colspan="1" rowspan="1"><p>E: 52.5 (45.0, 59.3) d</p><p>C: 18.0 (9.8, 23.0) d</p></td><td align="left" colspan="1" rowspan="1">subacute</td><td align="left" colspan="1" rowspan="1">BCI-FES + con-rehab</td><td align="left" colspan="1" rowspan="1">FES + con-rehab</td><td align="left" colspan="1" rowspan="1"><p>20 min/d, 5d/wk,</p><p>3wks, 15 sessions</p></td><td align="left" colspan="1" rowspan="1"><p>FMA-UE</p><p>WMFT</p><p>MBI</p></td><td align="left" colspan="1" rowspan="1">—</td><td align="left" colspan="1" rowspan="1"><p>E: 30</p><p>C: 30</p></td><td char="." align="char" colspan="1" rowspan="1">8</td></tr><tr><td align="left" colspan="1" rowspan="1">Ma, 2023</td><td align="left" colspan="1" rowspan="1"><p>E: 5.90 ± 2.99 m</p><p>C: 6.45 ± 3.38 m</p></td><td align="left" colspan="1" rowspan="1">unclear</td><td align="left" colspan="1" rowspan="1">BCI-exoskeleton + con-rehab</td><td align="left" colspan="1" rowspan="1">con-rehab</td><td align="left" colspan="1" rowspan="1"><p>40 min/d, 5d/wk,</p><p>2 wks, 10 sessions</p></td><td align="left" colspan="1" rowspan="1">FMA-UE</td><td align="left" colspan="1" rowspan="1">—</td><td align="left" colspan="1" rowspan="1"><p>E: 20</p><p>C: 20</p></td><td char="." align="char" colspan="1" rowspan="1">7</td></tr><tr><td align="left" colspan="1" rowspan="1">Miao, 2020</td><td align="left" colspan="1" rowspan="1"><p>E: 18.3 ± 10.9 m</p><p>C: 11.1 ± 5.0 m</p></td><td align="left" colspan="1" rowspan="1">chronic</td><td align="left" colspan="1" rowspan="1">BCI-FES + con-rehab</td><td align="left" colspan="1" rowspan="1">con-rehab</td><td align="left" colspan="1" rowspan="1"><p>16 min/d, 3 d/wk,</p><p>4 wks, 12 sessions</p></td><td align="left" colspan="1" rowspan="1">FMA-UE</td><td align="left" colspan="1" rowspan="1">—</td><td align="left" colspan="1" rowspan="1"><p>E: 8</p><p>C: 8</p></td><td char="." align="char" colspan="1" rowspan="1">5</td></tr><tr><td align="left" colspan="1" rowspan="1">Mihara, 2013</td><td align="left" colspan="1" rowspan="1"><p>E: 146.6 ± 36.2 d</p><p>C: 123.4 ± 38.3 d</p></td><td align="left" colspan="1" rowspan="1">subacute</td><td align="left" colspan="1" rowspan="1">BCI-visual feedback + con-rehab</td><td align="left" colspan="1" rowspan="1">sham BCI + con-rehab</td><td align="left" colspan="1" rowspan="1"><p>20 min/d, 3 d/wk,</p><p>2 wks,6 sessions</p></td><td align="left" colspan="1" rowspan="1"><p>FMA-UE</p><p>ARAT</p></td><td align="left" colspan="1" rowspan="1">2 wks</td><td align="left" colspan="1" rowspan="1"><p>E: 10</p><p>C: 10</p></td><td char="." align="char" colspan="1" rowspan="1">8</td></tr><tr><td align="left" colspan="1" rowspan="1">Pichiorri, 2015</td><td align="left" colspan="1" rowspan="1"><p>E: 2.7 ± 1.7 m</p><p>C: 2.5 ± 1.2 m</p></td><td align="left" colspan="1" rowspan="1">subacute</td><td align="left" colspan="1" rowspan="1">BCI-virtual feedback + con-rehab</td><td align="left" colspan="1" rowspan="1">MI + con-rehab</td><td align="left" colspan="1" rowspan="1"><p>60 min/d, 3 d/wk,</p><p>4 wks, 12 sessions</p></td><td align="left" colspan="1" rowspan="1"><p>FMA-UE</p><p>NIHSS</p><p>MRC</p><p>MAS</p></td><td align="left" colspan="1" rowspan="1">—</td><td align="left" colspan="1" rowspan="1"><p>E: 14</p><p>C: 14</p></td><td char="." align="char" colspan="1" rowspan="1">7</td></tr><tr><td align="left" colspan="1" rowspan="1">Ramos-Murguialday, 2013</td><td align="left" colspan="1" rowspan="1"><p>E: 66.0 ± 45.0 m</p><p>C: 71.0 ± 72.0 m</p></td><td align="left" colspan="1" rowspan="1">chronic</td><td align="left" colspan="1" rowspan="1">BCI-orthosis + con-rehab</td><td align="left" colspan="1" rowspan="1">sham BCI + con-rehab</td><td align="left" colspan="1" rowspan="1"><p>60 min/d, 5 d/wk,</p><p>4 wks, 20 sessions</p></td><td align="left" colspan="1" rowspan="1"><p>FMA-UE</p><p>MAL</p><p>AS</p><p>GAS</p></td><td align="left" colspan="1" rowspan="1">6 m</td><td align="left" colspan="1" rowspan="1"><p>E: 16</p><p>C: 16</p></td><td char="." align="char" colspan="1" rowspan="1">8</td></tr><tr><td align="left" colspan="1" rowspan="1">Wang, 2024</td><td align="left" colspan="1" rowspan="1"><p>E: 15 (8–21) d</p><p>C: 13 (8 − 1) d</p></td><td align="left" colspan="1" rowspan="1">subacute</td><td align="left" colspan="1" rowspan="1">BCI-FES + con-rehab</td><td align="left" colspan="1" rowspan="1">con-rehab</td><td align="left" colspan="1" rowspan="1"><p>30 min/d, 5 d/wk,</p><p>4 wks, 20 sessions</p></td><td align="left" colspan="1" rowspan="1"><p>FMA-UE</p><p>ARAT</p><p>WMFT</p><p>MAS</p><p>IADL</p></td><td align="left" colspan="1" rowspan="1">2 m</td><td align="left" colspan="1" rowspan="1"><p>E: 150</p><p>C: 146</p></td><td char="." align="char" colspan="1" rowspan="1">7</td></tr><tr><td align="left" colspan="1" rowspan="1">Wu, 2020</td><td align="left" colspan="1" rowspan="1"><p>E: 2.1 ± 0.3 m</p><p>C: 2.0 (1.5, 3.0) m</p></td><td align="left" colspan="1" rowspan="1">subacute</td><td align="left" colspan="1" rowspan="1">BCI-exoskeleton + con-rehab</td><td align="left" colspan="1" rowspan="1">con-rehab</td><td align="left" colspan="1" rowspan="1"><p>60 min/d, 5 d/wk,</p><p>4 wks, 20 sessions</p></td><td align="left" colspan="1" rowspan="1"><p>FMA-UE</p><p>ARAT</p><p>WMFT</p></td><td align="left" colspan="1" rowspan="1">—</td><td align="left" colspan="1" rowspan="1"><p>E: 14</p><p>C: 11</p></td><td char="." align="char" colspan="1" rowspan="1">6</td></tr></tbody></table><table-wrap-foot><p>Abbreviations: E: Experimental group, C: Control group, BCI: Brain-Computer interface, FES: Functional electric stimulation, con-rehab: Conventional rehabilitation, m: Months, d: Days, SAT: Standard Arm Therapy, FMA-UE: Fugl-Meyer assessment-upper extremity, ARAT: Action research arm test, WMFT: Wolf motor function Test, MBI: modified Barthel index, NIHSS: National Institutes of Health Stroke Scale, IADL: Instrumental Activity of Daily Living, MAS: modified Ashworth scale, AS: Ashworth scale, MRC: Medical Research Council Scale, MAL: Motor Activity Log, GAS: Goal Attainment Scale, ESS: European Stroke Scale</p></table-wrap-foot></table-wrap>
</p><p id="Par25">
<table-wrap id="Tab2" position="float" orientation="portrait"><label>Table 2</label><caption><p>GRADE quality of evidence assessment of individual outcome measures for the efficacy of BCI-based training in the improvement of upper-limb recovery</p></caption><table frame="hsides" rules="groups"><thead><tr><th align="left" rowspan="2" colspan="1">Outcome measure</th><th align="left" rowspan="2" colspan="1">Number of participants</th><th align="left" colspan="2" rowspan="1">Heterogeneity</th><th align="left" rowspan="2" colspan="1">Model of analysis</th><th align="left" colspan="2" rowspan="1">Group effect value</th><th align="left" rowspan="2" colspan="1">MD</th><th align="left" rowspan="2" colspan="1">95%CI</th><th align="left" rowspan="2" colspan="1">Grade</th></tr><tr><th align="left" colspan="1" rowspan="1">I<sup>2</sup></th><th align="left" colspan="1" rowspan="1">
<italic toggle="yes">P</italic>
</th><th align="left" colspan="1" rowspan="1">Z</th><th align="left" colspan="1" rowspan="1">
<italic toggle="yes">P</italic>
</th></tr></thead><tbody><tr><td align="left" colspan="1" rowspan="1">FMA-UE</td><td align="left" colspan="1" rowspan="1">886 (21 RCT)</td><td align="left" colspan="1" rowspan="1">70%</td><td char="." align="char" colspan="1" rowspan="1">&lt; 0.00001</td><td align="left" colspan="1" rowspan="1">Random effect</td><td char="." align="char" colspan="1" rowspan="1">5.65</td><td char="." align="char" colspan="1" rowspan="1">&lt; 0.00001</td><td char="." align="char" colspan="1" rowspan="1">3.69</td><td char="." align="char" colspan="1" rowspan="1">[2.41, 4.96]</td><td align="left" colspan="1" rowspan="1">Moderate</td></tr><tr><td align="left" colspan="1" rowspan="1">WMFT</td><td align="left" colspan="1" rowspan="1">451 (6 RCT)</td><td align="left" colspan="1" rowspan="1">79%</td><td char="." align="char" colspan="1" rowspan="1">0.0002</td><td align="left" colspan="1" rowspan="1">Random effect</td><td char="." align="char" colspan="1" rowspan="1">3.43</td><td char="." align="char" colspan="1" rowspan="1">0.0006</td><td char="." align="char" colspan="1" rowspan="1">5.00</td><td char="." align="char" colspan="1" rowspan="1">[2.14, 7.86]</td><td align="left" colspan="1" rowspan="1">Low</td></tr><tr><td align="left" colspan="1" rowspan="1">ARAT</td><td align="left" colspan="1" rowspan="1">412 (6 RCT)</td><td align="left" colspan="1" rowspan="1">38%</td><td char="." align="char" colspan="1" rowspan="1">0.18</td><td align="left" colspan="1" rowspan="1">Fixed effect</td><td char="." align="char" colspan="1" rowspan="1">2.23</td><td char="." align="char" colspan="1" rowspan="1">0.03</td><td char="." align="char" colspan="1" rowspan="1">2.04</td><td char="." align="char" colspan="1" rowspan="1">[0.25, 3.82]</td><td align="left" colspan="1" rowspan="1">High</td></tr><tr><td align="left" colspan="1" rowspan="1">MBI</td><td align="left" colspan="1" rowspan="1">140 (4 RCT)</td><td align="left" colspan="1" rowspan="1">94%</td><td char="." align="char" colspan="1" rowspan="1">&lt; 0.00001</td><td align="left" colspan="1" rowspan="1">Random effect</td><td char="." align="char" colspan="1" rowspan="1">1.89</td><td char="." align="char" colspan="1" rowspan="1">0.06</td><td char="." align="char" colspan="1" rowspan="1">7.46</td><td char="." align="char" colspan="1" rowspan="1">[-0.29, 15.22]</td><td align="left" colspan="1" rowspan="1">Low</td></tr></tbody></table></table-wrap>
</p><p id="Par26">
<fig id="Fig2" position="float" orientation="portrait"><label>Fig. 2</label><caption><p>Risk of bias summary</p></caption><graphic xmlns:xlink="http://www.w3.org/1999/xlink" id="d33e1261" position="float" orientation="portrait" xlink:href="12984_2025_1588_Fig2_HTML.jpg"><?image-name 12984_2025_1588_Fig2_HTML.jpg?><?image-size 367516?><?image-md5 8fe865020b4eb088b8d9222966f24bfa?><?image-image-server-status LOAD_COMPLETED?><?image-original-height 2216?><?image-original-width 767?><?image-scaled-height 2216?><?image-scaled-width 767?><?image-cloudpmc-urn urn:cdn:blobs/722d/11874405/8fe865020b4e/12984_2025_1588_Fig2_HTML.jpg?><?thumb-name 12984_2025_1588_Fig2_HTML.gif?><?thumb-size 10323?><?thumb-md5 4e0b5e2947ef6f69ff4f0d5355ec11ef?><?thumb-image-server-status NEVER_LOAD?><?thumb-scaled-height 289?><?thumb-scaled-width 100?><?thumb-cloudpmc-urn urn:cdn:blobs/722d/11874405/4e0b5e2947ef/12984_2025_1588_Fig2_HTML.gif?></graphic></fig>
</p><p id="Par27">
<fig id="Fig3" position="float" orientation="portrait"><label>Fig. 3</label><caption><p>Risk of bias graph</p></caption><graphic xmlns:xlink="http://www.w3.org/1999/xlink" id="d33e1271" position="float" orientation="portrait" xlink:href="12984_2025_1588_Fig3_HTML.jpg"><?image-name 12984_2025_1588_Fig3_HTML.jpg?><?image-size 52594?><?image-md5 a9e5b437b083e970007e230e89d5bb86?><?image-image-server-status LOAD_COMPLETED?><?image-original-height 546?><?image-original-width 1488?><?image-scaled-height 273?><?image-scaled-width 744?><?image-cloudpmc-urn urn:cdn:blobs/722d/11874405/a9e5b437b083/12984_2025_1588_Fig3_HTML.jpg?><?thumb-name 12984_2025_1588_Fig3_HTML.gif?><?thumb-size 3951?><?thumb-md5 b2a56a21ad039ea6bf2635cd58146a13?><?thumb-image-server-status NEVER_LOAD?><?thumb-scaled-height 73?><?thumb-scaled-width 200?><?thumb-cloudpmc-urn urn:cdn:blobs/722d/11874405/b2a56a21ad03/12984_2025_1588_Fig3_HTML.gif?></graphic></fig>
</p><p id="Par28">
<fig id="Fig4" position="float" orientation="portrait"><label>Fig. 4</label><caption><p>Evaluating effects of BCI-based training in improving upper-limb rehabilitation after stroke compared to control interventions. The analysis includes assessments of FMA-UE, WMFT, ARAT, and MBI, and the follow-up of FMA-UE after finishing the intervention</p></caption><graphic xmlns:xlink="http://www.w3.org/1999/xlink" id="d33e1281" position="float" orientation="portrait" xlink:href="12984_2025_1588_Fig4_HTML.jpg"><?image-name 12984_2025_1588_Fig4_HTML.jpg?><?image-size 38299?><?image-md5 6a91eaa8167ecc13c11812e0d7761d67?><?image-image-server-status LOAD_COMPLETED?><?image-original-height 801?><?image-original-width 1488?><?image-scaled-height 401?><?image-scaled-width 744?><?image-cloudpmc-urn urn:cdn:blobs/722d/11874405/6a91eaa8167e/12984_2025_1588_Fig4_HTML.jpg?><?thumb-name 12984_2025_1588_Fig4_HTML.gif?><?thumb-size 2924?><?thumb-md5 c6c5182a2ec079afc4efde8ba9b0eeee?><?thumb-image-server-status NEVER_LOAD?><?thumb-scaled-height 80?><?thumb-scaled-width 148?><?thumb-cloudpmc-urn urn:cdn:blobs/722d/11874405/c6c5182a2ec0/12984_2025_1588_Fig4_HTML.gif?></graphic></fig>
</p></sec><sec id="Sec15"><title>Effects on upper-limb motor impairment</title><sec id="Sec16"><title>FMA-UE</title><p id="Par29">The findings indicated that BCI-based training significantly improved FMA-UE scores (random, MD = 3.69, 95%CI 2.41–4.96, <italic toggle="yes">P</italic> &lt; 0.00001) (Fig. <xref rid="Fig4" ref-type="fig">4</xref>). There was substantial heterogeneity among the included studies (I<sup>2</sup> = 70%, <italic toggle="yes">P</italic> &lt; 0.00001). Leave-one-out sensitivity analysis revealed 2 studies contributing most to heterogeneity [<xref ref-type="bibr" rid="CR11">11</xref>, <xref ref-type="bibr" rid="CR31">31</xref>]. The heterogeneity was reduced significantly after excluding the two studies (I<sup>2</sup> = 46%). The results also showed that BCI-based training significantly improved FMA-UE scores (random, MD = 3.16, 95%CI 2.10–4.22, <italic toggle="yes">P</italic> &lt; 0.00001) (Supplementary Fig <xref rid="MOESM1" ref-type="media">S1</xref>-<xref rid="MOESM1" ref-type="media">S4</xref>). In addition, In case of excluding studies with PEDro score &lt; 6 [<xref ref-type="bibr" rid="CR18">18</xref>, <xref ref-type="bibr" rid="CR21">21</xref>, <xref ref-type="bibr" rid="CR29">29</xref>], the results also favored the benefits of BCI-based training (random, MD = 3.91, 95%CI 2.53–5.30, <italic toggle="yes">P</italic> &lt; 0.00001) (Supplementary Fig <xref rid="MOESM1" ref-type="media">S5</xref>-<xref rid="MOESM1" ref-type="media">S6</xref>).</p><p id="Par30">Furthermore, BCI-based training not only showed better effects compared to sham BCI (random, MD = 2.92, 95%CI 1.51–4.33, <italic toggle="yes">P</italic> &lt; 0.0001), with moderate heterogeneity (I<sup>2</sup> = 52%, <italic toggle="yes">P</italic> = 0.01) but compared to conventional rehabilitation (random, MD = 5.03, 95%CI 3.12–6.94, <italic toggle="yes">P</italic> &lt; 0.00001), with considerable heterogeneity (I<sup>2</sup> = 75%, <italic toggle="yes">P</italic> &lt; 0.0001) (Supplementary Fig <xref rid="MOESM1" ref-type="media">S7</xref>-<xref rid="MOESM1" ref-type="media">S8</xref>). Besides, 5 of the 21 studies used the MAS or AS to assess spasticity [<xref ref-type="bibr" rid="CR8">8</xref>–<xref ref-type="bibr" rid="CR10">10</xref>, <xref ref-type="bibr" rid="CR29">29</xref>, <xref ref-type="bibr" rid="CR33">33</xref>] and consistently reported that BCI-based training did not improve MAS or AS scores compared with control interventions.</p></sec></sec><sec id="Sec17"><title>Effects on upper-limb motor function</title><sec id="Sec18"><title>WMFT</title><p id="Par31">The WMFT scores of the affected side were significantly longer in the intervention group than in the control group (random, MD = 5.00, 95%CI 2.14–7.86, <italic toggle="yes">P</italic> = 0.0006), with considerable heterogeneity (I<sup>2</sup> = 79%, <italic toggle="yes">P</italic> = 0.0002). Leave-one-out sensitivity analysis revealed 2 studies contributing most to heterogeneity [<xref ref-type="bibr" rid="CR11">11</xref>, <xref ref-type="bibr" rid="CR20">20</xref>]. The heterogeneity was decreased significantly after excluding the two studies (I<sup>2</sup> = 0%). The results also showed that BCI-based training significantly improved WMFT scores (random, MD = 2.96, 95%CI 2.06–3.87, <italic toggle="yes">P</italic> &lt; 0.00001) (Fig. <xref rid="Fig4" ref-type="fig">4</xref> and Supplementary Fig <xref rid="MOESM1" ref-type="media">S9</xref>-<xref rid="MOESM1" ref-type="media">S10</xref>).</p></sec><sec id="Sec19"><title>ARAT</title><p id="Par32">The pooled results showed that BCI-based training exhibited significant improvements in ARAT scores (fixed, MD = 2.04, 95%CI 0.25–3.82, <italic toggle="yes">P</italic> = 0.03), with small heterogeneity (I<sup>2</sup> = 35%, <italic toggle="yes">P</italic> = 0.18) (Fig. <xref rid="Fig4" ref-type="fig">4</xref> and Supplementary Fig <xref rid="MOESM1" ref-type="media">S11</xref>).</p></sec></sec><sec id="Sec20"><title>Effects on activities of daily living</title><sec id="Sec21"><title>MBI</title><p id="Par33">We found no statistically significant improvement in MBI scores (random, MD = 7.46, 95%CI -0.29-15.22, P = 0.06), with considerable heterogeneity (I2 = 94%, P &lt; 0.00001). Sensitive exclusion analysis indicated that BCI-based training produced a statistically significant improvement in MBI after excluding the studies of Liu et al. [20] (random, MD = 3.60, 95%CI 0.17–7.03, P = 0.04), with moderate heterogeneity (I2 = 55%, P = 0.11). (Fig. 4 and Supplementary Fig S12-S <xref rid="Tab2" ref-type="table">Table 2</xref></p></sec></sec><sec id="Sec22"><title>Subgroup analysis</title><sec id="Sec23"><title>Follow-up</title><p id="Par35">The aggregated findings from follow-up assessments demonstrated that the effects of BCI-based training on FMA-UE could be sustained for both a short time (random, MD = 3.22, 95%CI 1.10–5.34, <italic toggle="yes">P</italic> = 0.003) with moderate heterogeneity (I<sup>2</sup> = 46%, <italic toggle="yes">P</italic> = 0.09) and a longer duration after intervention (random, MD = 1.49, 95%CI 0.03–2.96, <italic toggle="yes">P</italic> = 0.05) with small heterogeneity (I<sup>2</sup> = 23%, <italic toggle="yes">P</italic> = 0.27) (Fig. <xref rid="Fig4" ref-type="fig">4</xref> and Supplementary Fig <xref rid="MOESM1" ref-type="media">S14</xref>-<xref rid="MOESM1" ref-type="media">S15</xref>).</p><p id="Par36">
<fig id="Fig5" position="float" orientation="portrait"><label>Fig. 5</label><caption><p>Subgroup meta-analysis assessing the effectiveness of BCI-based training in enhancing FMA-UE across distinct stroke phases and comparing the efficacy of BCI combined with different external devices in post-stroke upper-limb motor recovery</p></caption><graphic xmlns:xlink="http://www.w3.org/1999/xlink" id="d33e1476" position="float" orientation="portrait" xlink:href="12984_2025_1588_Fig5_HTML.jpg"><?image-name 12984_2025_1588_Fig5_HTML.jpg?><?image-size 43191?><?image-md5 8d44486afd0abbd6cb89b496aa0c678d?><?image-image-server-status LOAD_COMPLETED?><?image-original-height 1101?><?image-original-width 2004?><?image-scaled-height 367?><?image-scaled-width 668?><?image-cloudpmc-urn urn:cdn:blobs/722d/11874405/8d44486afd0a/12984_2025_1588_Fig5_HTML.jpg?><?thumb-name 12984_2025_1588_Fig5_HTML.gif?><?thumb-size 3236?><?thumb-md5 596764fc3f6ada19cec075171adf8708?><?thumb-image-server-status NEVER_LOAD?><?thumb-scaled-height 80?><?thumb-scaled-width 145?><?thumb-cloudpmc-urn urn:cdn:blobs/722d/11874405/596764fc3f6a/12984_2025_1588_Fig5_HTML.gif?></graphic></fig>
</p></sec></sec><sec id="Sec24"><title>Stroke phases</title><p id="Par37">Compared with control interventions, our analysis demonstrated that BCI-based training significantly impacted FMA-UE for subacute patients (random, MD = 4.24, 95%CI 1.81–6.67, <italic toggle="yes">P</italic> = 0.0006) with considerable heterogeneity (I<sup>2</sup> = 77%, <italic toggle="yes">P</italic> &lt; 0.0001) and chronic patients (random, MD = 2.63, 95%CI 1.50–3.76, <italic toggle="yes">P</italic> &lt; 0.00001) with small heterogeneity (I<sup>2</sup> = 26%, <italic toggle="yes">P</italic> = 0.20) (Fig. <xref rid="Fig5" ref-type="fig">5</xref> and Supplementary Fig <xref rid="MOESM1" ref-type="media">S16</xref>-<xref rid="MOESM1" ref-type="media">S17</xref>).</p></sec><sec id="Sec25"><title>External feedback</title><p id="Par38">Compared with control interventions, the subgroup analysis revealed that BCI combined with FES (random, MD = 4.37, 95%CI 3.09–5.65, <italic toggle="yes">P</italic> &lt; 0.00001), BCI combined with robots (random, MD = 2.87, 95%CI 0.69–5.04, <italic toggle="yes">P</italic> = 0.010), and BCI combined with visual feedback (random, MD = 4.46, 95%CI 0.24–8.68, <italic toggle="yes">P</italic> = 0.04) exhibited significant effects on FMA-UE (Fig. <xref rid="Fig4" ref-type="fig">4</xref>). The three subgroups had small heterogeneity (I<sup>2</sup> = 36%, <italic toggle="yes">P</italic> = 0.15), considerable heterogeneity (I<sup>2</sup> = 81%, <italic toggle="yes">P</italic> &lt; 0.00001), and small heterogeneity (I<sup>2</sup> = 27%, <italic toggle="yes">P</italic> = 0.24), respectively (Fig. <xref rid="Fig5" ref-type="fig">5</xref> and Supplementary Fig <xref rid="MOESM1" ref-type="media">S18</xref>-<xref rid="MOESM1" ref-type="media">S19</xref>).</p><p id="Par39">Further analysis indicated that BCI combined with FES was superior to both sham BCI (random, MD = 4.94, 95%CI 2.73–7.15, <italic toggle="yes">P</italic> &lt; 0.0001), with moderate heterogeneity (I<sup>2</sup> = 58%, <italic toggle="yes">P</italic> = 0.07) and conventional rehabilitation (random, MD = 3.81, 95%CI 2.30–5.32, <italic toggle="yes">P</italic> &lt; 0.00001), with negligible heterogeneity (I<sup>2</sup> = 0%, <italic toggle="yes">P</italic> = 0.49). BCI combined with robots was superior to both sham BCI (random, MD = 1.58, 95%CI 0.31–2.85, <italic toggle="yes">P</italic> = 0.01), with negligible heterogeneity (I<sup>2</sup> = 0%, <italic toggle="yes">P</italic> = 0.44) and conventional rehabilitation (random, MD = 5.73, 95%CI 3.13–8.33, <italic toggle="yes">P</italic> &lt; 0.0001), with considerable heterogeneity (I<sup>2</sup> = 78%, <italic toggle="yes">P</italic> = 0.004) (Supplementary Fig <xref rid="MOESM1" ref-type="media">S20</xref>-<xref rid="MOESM1" ref-type="media">S22</xref>).</p></sec><sec id="Sec26"><title>External feedback across stroke phases</title><p id="Par40">Compared with control interventions, further analysis indicated significant improvement in FMA-UE through the combination of BCI and FES both for subacute patients (random, MD = 5.31, 95%CI 2.58–8.03, <italic toggle="yes">P</italic> = 0.0001), with substantial heterogeneity (I<sup>2</sup> = 60%, <italic toggle="yes">P</italic> = 0.08) and chronic patients (random, MD = 3.71, 95%CI 2.44–4.98, <italic toggle="yes">P</italic> &lt; 0.00001) with negligible heterogeneity (I<sup>2</sup> = 0%, <italic toggle="yes">P</italic> = 0.54). Compared with control interventions, the combination of BCI and robots improved FMA-UE for chronic patients (random, MD = 1.60, 95%CI 0.15–3.05, <italic toggle="yes">P</italic> = 0.03), with small heterogeneity (I<sup>2</sup> = 10%, <italic toggle="yes">P</italic> = 0.35), but not subacute patients (random, MD = 2.82, 95%CI -2.97-8.61, <italic toggle="yes">P</italic> = 0.34), with considerable heterogeneity (I<sup>2</sup> = 89%, <italic toggle="yes">P</italic> &lt; 0.00001) (Fig. <xref rid="Fig5" ref-type="fig">5</xref> and Supplementary Fig <xref rid="MOESM1" ref-type="media">S23</xref>-<xref rid="MOESM1" ref-type="media">S25</xref>).</p><p id="Par41">
<fig id="Fig6" position="float" orientation="portrait"><label>Fig. 6</label><caption><p>Subgroup meta-analysis of the efficacy of BCI-based training in improving FMA-UE with varying training intensity</p></caption><graphic xmlns:xlink="http://www.w3.org/1999/xlink" id="d33e1647" position="float" orientation="portrait" xlink:href="12984_2025_1588_Fig6_HTML.jpg"><?image-name 12984_2025_1588_Fig6_HTML.jpg?><?image-size 74923?><?image-md5 160a5ec07423153e2cc2546eefc6d554?><?image-image-server-status LOAD_COMPLETED?><?image-original-height 1077?><?image-original-width 1488?><?image-scaled-height 539?><?image-scaled-width 744?><?image-cloudpmc-urn urn:cdn:blobs/722d/11874405/160a5ec07423/12984_2025_1588_Fig6_HTML.jpg?><?thumb-name 12984_2025_1588_Fig6_HTML.gif?><?thumb-size 3183?><?thumb-md5 8056974b7523991e8bdd461d2ff57c0a?><?thumb-image-server-status NEVER_LOAD?><?thumb-scaled-height 80?><?thumb-scaled-width 110?><?thumb-cloudpmc-urn urn:cdn:blobs/722d/11874405/8056974b7523/12984_2025_1588_Fig6_HTML.gif?></graphic></fig>
</p></sec><sec id="Sec27"><title>Training time per day</title><p id="Par42">Compared with control interventions, subgroup analysis of &lt; 20 min per day, there was no significant improvement in FMA-UE (random, MD = 2.87, 95%CI -0.19-5.92, <italic toggle="yes">P</italic> = 0.07) with negligible heterogeneity (I<sup>2</sup> = 0%, <italic toggle="yes">P</italic> = 0.77). In the subgroup of 20 min per day, a significant improvement in FMA-UE was shown (random, MD = 5.30, 95%CI 1.17–9.42, <italic toggle="yes">P</italic> = 0.01) with substantial heterogeneity (I<sup>2</sup> = 65%, <italic toggle="yes">P</italic> = 0.09). In the subgroup of 30–40 min, a significant improvement in FMA-UE was shown (random, MD = 3.92, 95%CI 2.18–5.66, <italic toggle="yes">P</italic> &lt; 0.0001) with substantial heterogeneity (I<sup>2</sup> = 65%, <italic toggle="yes">P</italic> = 0.010). In the subgroup of 60 min per day, a significant improvement in FMA-UE was shown (random, MD = 4.06, 95%CI 1.40–6.71, <italic toggle="yes">P</italic> = 0.0003) with considerable heterogeneity (I<sup>2</sup> = 80%, <italic toggle="yes">P</italic> = 0.0001). Only one study [<xref ref-type="bibr" rid="CR18">18</xref>] reported a training time of 60–90 min per day, which showed a significant improvement in FMA-UE (random, MD = 5.94, 95%CI 0.38–11.50, <italic toggle="yes">P</italic> = 0.04). In the subgroup of 90 min per day (random, MD = -1.80, 95%CI -5.42-1.82, <italic toggle="yes">P</italic> = 0.33) with negligible heterogeneity (I<sup>2</sup> = 0%, <italic toggle="yes">P</italic> = 0.81) per day, there was no significant improvement in FMA-UE (Fig. <xref rid="Fig6" ref-type="fig">6</xref> and Supplementary Fig <xref rid="MOESM1" ref-type="media">S28</xref>-<xref rid="MOESM1" ref-type="media">S29</xref>).</p></sec><sec id="Sec28"><title>Training sessions per week</title><p id="Par43">Compared with control interventions, the findings revealed that BCI-based training was effective in improving FMA-UE for 2–3 sessions per week (random, MD = 3.52, 95%CI 1.54–5.50, <italic toggle="yes">P</italic> = 0.0005), with substantial heterogeneity (I<sup>2</sup> = 73%, <italic toggle="yes">P</italic> &lt; 0.0001) and 5 sessions per week (random, MD = 3.83, 95%CI 2.11–5.54, <italic toggle="yes">P</italic> &lt; 0.00001), with substantial heterogeneity (I<sup>2</sup> = 70%, <italic toggle="yes">P</italic> = 0.0008) (Fig. <xref rid="Fig6" ref-type="fig">6</xref> and Supplementary Fig <xref rid="MOESM1" ref-type="media">S24</xref>-<xref rid="MOESM1" ref-type="media">S25</xref>).</p></sec><sec id="Sec29"><title>Total BCI-based training sessions</title><p id="Par44">Subgroup analysis of total training sessions ≤ 10 sessions, a significant improvement in FMA-UE was shown (random, MD = 3.44, 95%CI 0.79–6.09, <italic toggle="yes">P</italic> = 0.01), with substantial heterogeneity (I<sup>2</sup> = 65%, <italic toggle="yes">P</italic> = 0.01). In the subgroup of 10–20 sessions, a significant improvement in FMA-UE was shown (random, MD = 2.93, 95%CI 0.45–5.42, <italic toggle="yes">P</italic> = 0.02), with substantial heterogeneity (I<sup>2</sup> = 70%, <italic toggle="yes">P</italic> = 0.001). In the subgroup of ≥ 20 sessions, a significant improvement in FMA-UE was shown (random, MD = 4.38, 95%CI 2.33–6.42, <italic toggle="yes">P</italic> &lt; 0.0001), with considerable heterogeneity (I<sup>2</sup> = 80%, <italic toggle="yes">P</italic> &lt; 0.0001) (Fig. <xref rid="Fig6" ref-type="fig">6</xref> and Supplementary Fig <xref rid="MOESM1" ref-type="media">S30</xref>-<xref rid="MOESM1" ref-type="media">S31</xref>).</p></sec><sec id="Sec30"><title>Training duration</title><p id="Par45">Compared with control interventions, subgroup analysis of training duration &lt; 2 weeks, showed no significant improvement in FMA-UE (random, MD = 3.06, 95%CI -0.35-6.48, <italic toggle="yes">P</italic> = 0.08), with substantial heterogeneity (I<sup>2</sup> = 72%, <italic toggle="yes">P</italic> = 0.006). Subgroup analysis of 3–4 weeks showed that BCI-based training could significantly improve FMA-UE (random, MD = 4.24, 95%CI 2.68–5.79, <italic toggle="yes">P</italic> &lt; 0.00001), with substantial heterogeneity (I<sup>2</sup> = 74%, <italic toggle="yes">P</italic> &lt; 0.00001). However, in the subgroup of &gt; 4 weeks, a significant improvement in FMA-UE was not observed (random, MD = 2.18, 95%CI -1.21-5.57, <italic toggle="yes">P</italic> = 0.21), with substantial heterogeneity (I<sup>2</sup> = 60%, <italic toggle="yes">P</italic> = 0.06) (Fig. <xref rid="Fig6" ref-type="fig">6</xref> and Supplementary Fig <xref rid="MOESM1" ref-type="media">S32</xref>-<xref rid="MOESM1" ref-type="media">S33</xref>).</p></sec></sec><sec id="Sec31"><title>Discussion</title><p id="Par46">The meta-analysis explored the efficacy of BCI-based training on upper-limb function in stroke patients, revealing significant enhancements in upper-limb motor impairment and function, and this improvement can be maintained or continued to increase after intervention. Besides, the efficacy of BCI-based training varied with stroke phases, external feedback types, and training intensity. Our present work could give a new insight into BCI-based training for stroke survivors.</p><p id="Par47">Subgroup analysis revealed the effectiveness of BCI-based training for both subacute and chronic stroke patients. The initial six months post-stroke play a crucial role in shaping the recovery trajectory [<xref ref-type="bibr" rid="CR47">47</xref>]. However, many stroke patients miss that time window and only obtain limited functional gains during the chronic phase [<xref ref-type="bibr" rid="CR48">48</xref>]. Patients in the chronic phase can still exhibit enduring and extensive cortical reorganization through reinforcement learning and programmed memory, leading to positive prognostic outcomes [<xref ref-type="bibr" rid="CR49">49</xref>]. BCI-based training facilitates safe and repetitive rehabilitation training, allowing for maximum patient participation [<xref ref-type="bibr" rid="CR50">50</xref>, <xref ref-type="bibr" rid="CR51">51</xref>], enhancing early recovery, and overcoming later functional plateaus.</p><p id="Par48">Clinically, different studies have used different types of external feedback to apply to stroke patients. Our results showed that BCI-FES, BCI-robot, and BCI-visual feedback can significantly improve motor impairment. These findings underscored the distinctive benefits of the active closed-loop feedback inherent to the “central-peripheral-central” paradigm of BCI-based training. The enduring benefits of BCI-based training are likely due to its capacity to enhance motor recovery, cortical reorganization, and functional restoration, resulting in long-term improvements in motor impairment [<xref ref-type="bibr" rid="CR8">8</xref>, <xref ref-type="bibr" rid="CR52">52</xref>]. During BCI-based training, patients develop movement intentions to move the paralyzed limb, and the coupling of external feedback devices completes the loop between cortical activity and movement [<xref ref-type="bibr" rid="CR10">10</xref>, <xref ref-type="bibr" rid="CR53">53</xref>, <xref ref-type="bibr" rid="CR54">54</xref>]. This process enables participants to consciously regulate sensorimotor oscillations, generating afferent feedback activity that may restore corticospinal and corticomuscular connections, fostering neuroplasticity and improving motor impairment [<xref ref-type="bibr" rid="CR25">25</xref>, <xref ref-type="bibr" rid="CR55">55</xref>, <xref ref-type="bibr" rid="CR56">56</xref>].</p><p id="Par49">In addition, subgroup analysis revealed that BCI-FES is effective for both subacute and chronic stroke patients, whereas BCI-robot is beneficial exclusively for the chronic phase and not for subacute patients. This suggested that for subacute stroke patients, BCI-FES may be more potent in enhancing upper-limb motor impairment compared to BCI-robot. Furthermore, in chronic stroke patients, BCI-FES yielded a higher improvement than BCI-robot. This disparity may arise from FES facilitating voluntary muscle contraction, providing rich proprioceptive and somatosensory information feedback, and increasing perfusion to the sensory-motor cortex [<xref ref-type="bibr" rid="CR57">57</xref>–<xref ref-type="bibr" rid="CR59">59</xref>]. The efficacy of BCI-robot may also be influenced by the type of robot used, as differences in materials, joints, and training protocols can affect joint mobility, proprioceptive stimuli, and patient experience [<xref ref-type="bibr" rid="CR60">60</xref>–<xref ref-type="bibr" rid="CR62">62</xref>]. The robots used in these studies included end-effector [<xref ref-type="bibr" rid="CR22">22</xref>, <xref ref-type="bibr" rid="CR23">23</xref>], hand exoskeleton [<xref ref-type="bibr" rid="CR11">11</xref>, <xref ref-type="bibr" rid="CR24">24</xref>, <xref ref-type="bibr" rid="CR26">26</xref>, <xref ref-type="bibr" rid="CR28">28</xref>, <xref ref-type="bibr" rid="CR30">30</xref>], arm and hand orthosis [<xref ref-type="bibr" rid="CR10">10</xref>, <xref ref-type="bibr" rid="CR27">27</xref>], and soft robotic gloves [<xref ref-type="bibr" rid="CR25">25</xref>, <xref ref-type="bibr" rid="CR29">29</xref>]. While the pooled results from our studies leaned towards BCI combined with visual feedback, some researchers, such as Ono et al. [<xref ref-type="bibr" rid="CR63">63</xref>] have posited that proprioceptive feedback generated by real motion is more advantageous. Therefore, FES may be more favorable external feedback for BCI in upper-limb recovery following a stroke. Combining BCI with FES may be a more favorable option for patients in both the subacute and chronic phase.</p><p id="Par50">Regarding training intensity, the majority of researchers opted for a training frequency of 3–5 sessions per week. Moreover, a training duration of 3–4 weeks appeared to be optimal. In general, more intense exercise is associated with more benefits [<xref ref-type="bibr" rid="CR64">64</xref>]. However, our analysis showed that training for less than 20 min or up to 90 min per day and training 2 weeks or longer than 4 weeks did not significantly improve motor impairment. On the one hand, inadequate daily training durations may preclude meaningful improvement, whereas excessively long sessions could precipitate fatigue and distraction [<xref ref-type="bibr" rid="CR26">26</xref>], on the other hand, the small number of included studies and the high heterogeneity caused the bias of the results [<xref ref-type="bibr" rid="CR25">25</xref>]. More high-quality studies are needed to bring more reliable results. Drawing from the subgroup analysis, we can offer tentative recommendations on training intensity: daily training sessions ranging from 20 to 90 min, conducted 2–5 sessions per week for 3–4 weeks, may yield the most favorable results.</p><p id="Par51">MBI scores were not improved compared with the control group after BCI-based training in our analysis. MBI focuses on independence from the activities of daily living, rather than on a single motor function. The functional improvement observed may have not yet been translated into the practical use of the upper limbs for activities of daily living. It is noteworthy to highlight that spasticity is a prevalent complication among stroke survivors, with a notable impact on upper-limb recovery. Interestingly, 5 studies [<xref ref-type="bibr" rid="CR8">8</xref>–<xref ref-type="bibr" rid="CR10">10</xref>, <xref ref-type="bibr" rid="CR29">29</xref>, <xref ref-type="bibr" rid="CR33">33</xref>] consistently demonstrated that BCI-based training did not confer greater improvements in MAS or AS scores compared with control interventions. This observation suggests that BCI-based training may not substantially influence spasticity associated with stroke. More effective rehabilitation strategies for spasticity need further exploration.</p><p id="Par52">Conventional rehabilitation therapies also play a key role in clinical recovery. The studies included in our analysis predominantly encompassed conventional rehabilitation programs that involved physical therapy (e.g. exercise therapy, passive mobilization, stretching, and physical factor therapy) [<xref ref-type="bibr" rid="CR8">8</xref>–<xref ref-type="bibr" rid="CR11">11</xref>, <xref ref-type="bibr" rid="CR17">17</xref>–<xref ref-type="bibr" rid="CR22">22</xref>, <xref ref-type="bibr" rid="CR24">24</xref>–<xref ref-type="bibr" rid="CR33">33</xref>] and more than half of the studies also incorporated occupational therapy [<xref ref-type="bibr" rid="CR9">9</xref>–<xref ref-type="bibr" rid="CR11">11</xref>, <xref ref-type="bibr" rid="CR20">20</xref>, <xref ref-type="bibr" rid="CR24">24</xref>, <xref ref-type="bibr" rid="CR28">28</xref>–<xref ref-type="bibr" rid="CR33">33</xref>]. A few studies mentioned acupuncture [<xref ref-type="bibr" rid="CR18">18</xref>] and cognitive therapy [<xref ref-type="bibr" rid="CR33">33</xref>]. Overall, conventional rehabilitation pathways were generally consistent across the studies.</p><p id="Par53">BCI-based training holds promise for patients with motor impairment, bridging the gap between motor intention and actual movement. Beyond stroke phases, external feedback, and training intensity, BCI accuracy is always crucial for the efficiency of BCI-based training. Considering moderate to severe brain deficits of stroke patients, motor-related cortical activities may be decreased or even hindered [<xref ref-type="bibr" rid="CR65">65</xref>], which causes difficulties in detecting motor intention. Much effort has been made to solve the problem, including sophisticated algorithms [<xref ref-type="bibr" rid="CR66">66</xref>], user training [<xref ref-type="bibr" rid="CR67">67</xref>], and sensor fusion [<xref ref-type="bibr" rid="CR68">68</xref>]. Recently, non-invasive brain stimulation techniques, such as anodal transcranial direct current stimulation (tDCS) [<xref ref-type="bibr" rid="CR69">69</xref>] and repetitive transcranial magnetic stimulation (rTMS) [<xref ref-type="bibr" rid="CR70">70</xref>], have been considered to be feasible in enhancing BCI performance. These approaches offer novel solutions to address BCI inefficiency, potentially advancing the clinical application of BCI-based stroke rehabilitation.</p><p id="Par54">Finally, given the current findings and the PEDro scale assessment in our analysis, future studies should explore the dose-response relationship of BCI-based training, optimize treatment regimens, and incorporate long-term follow-up to assess the sustainability of the benefits of BCI-based training. Secondly, an individualized BCI-based training program should be developed according to the characteristics and rehabilitation stage of the patient. In addition, the high methodological quality of the study design was ensured by clear criteria, randomization, blinding, and adequate sample size. These recommendations aim to advance the research and application of BCI in stroke rehabilitation.</p><p id="Par55">Limitations: Our study is subject to several limitations. Firstly, the analysis was based on a limited number of randomized clinical trials (21 studies involving 886 patients). Secondly, for a robust subgroup meta-analysis, it is recommended to include at least 5 clinical trials in each subgroup [<xref ref-type="bibr" rid="CR35">35</xref>]. In some of our subgroup analysis, this criterion was not met. Additionally, this study did not involve the interaction between drug use and BCI-based training. It is suggested that future clinical research should add more details of medication to provide a more meaningful reference for clinical practice. Lastly, as with any meta-analysis, the possibility of publication bias is a concern, as evidenced by the asymmetric appearance of the funnel plot in our analysis.</p></sec><sec id="Sec32"><title>Conclusion</title><p id="Par56">In summary, BCI-based training emerges as an effective strategy for upper-limb rehabilitation following a stroke. The combination of BCI with FES appears particularly promising, catering to patients in both the subacute and chronic phases. A training intensity of 20 to 90 min per day, 2–5 sessions per week for 3–4 weeks may be most recommended. In both research and clinical contexts, careful consideration of stroke phases and the selection of external feedback is crucial. Future investigations should prioritize enhancing BCI accuracy, and refining and standardizing study designs for BCI-based training.</p></sec><sec id="Sec33" sec-type="supplementary-material"><title>Electronic supplementary material</title><p>Below is the link to the electronic supplementary material.</p><p>
<supplementary-material content-type="local-data" id="MOESM1" position="float" orientation="portrait"><media xmlns:xlink="http://www.w3.org/1999/xlink" xlink:href="12984_2025_1588_MOESM1_ESM.pdf" position="float" orientation="portrait"><?suppdata-name 12984_2025_1588_MOESM1_ESM.pdf?><?suppdata-size 3271597?><?suppdata-md5 969d41ccdb32d91af8fc00855a733207?><?suppdata-image-server-status NEVER_LOAD?><?suppdata-mime-type application?><?suppdata-mime-sub-type pdf?><?suppdata-cloudpmc-urn urn:app:722d/11874405/969d41ccdb32/12984_2025_1588_MOESM1_ESM.pdf?><caption><p>Supplementary Material 1</p></caption></media></supplementary-material>
</p></sec></body><back><fn-group><fn><p><bold>Publisher’s note</bold></p><p>Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.</p></fn><fn><p>Dan Li and Ruoyu Li contributed equally to this work.</p></fn></fn-group><ack><title>Acknowledgements</title><p>None.</p></ack><notes notes-type="author-contribution"><title>Author contributions</title><p>DL, RL, and LJ initiated and organized the project. DL, RL, and WQ reviewed references and conducted this meta-analysis. DL, LL, and GS reviewed references and interpreted data. DL, RL, and YS drafted the manuscript. LJ and LL revised the manuscript. All authors have given final approval for the current version to be published. All authors read and approved the final manuscript.</p></notes><notes notes-type="funding-information"><title>Funding</title><p>This research was supported by National Key Research and Development Program (2023YFC3604500), National Clinical Key Specialty Construction Project of China (Z155080000004), Shanghai Rehabilitation Medical Research Center (Top Priority Research Center of Shanghai) (2023ZZ02027), Shanghai Clinical Research Ward (SHDC2023CRW018B), Shanghai Hospital Development Center Foundation—Shanghai Municipal Hospital Rehabilitation Medicine Specialty Alliance (SHDC22023304), Science and Technology Innovation Program of Shanghai Municipal Science and Technology (22Y31900200 and 22Y31900203).</p></notes><notes notes-type="data-availability"><title>Data availability</title><p>No datasets were generated or analysed during the current study.</p></notes><notes><title>Declarations</title><notes id="FPar1"><title>Ethics approval and consent to participate</title><p id="Par57">Not applicable.</p></notes><notes id="FPar2"><title>Consent for publication</title><p id="Par58">Not applicable.</p></notes><notes id="FPar3" notes-type="COI-statement"><title>Competing interests</title><p id="Par59">The authors declare no competing interests.</p></notes></notes><ref-list id="Bib1"><title>References</title><ref id="CR1"><label>1.</label><citation-alternatives><element-citation id="ec-CR1" publication-type="journal"><person-group person-group-type="author"><name name-style="western"><surname>Global</surname><given-names>regional</given-names></name></person-group><article-title>National burden of stroke and its risk factors, 1990–2019: a systematic analysis for the global burden of disease study 2019</article-title><source>Lancet Neurol</source><year>2021</year><volume>20</volume><issue>10</issue><fpage>795</fpage><lpage>820</lpage><pub-id pub-id-type="doi">10.1016/S1474-4422(21)00252-0</pub-id><pub-id pub-id-type="pmid">34487721</pub-id><pub-id pub-id-type="pmcid">PMC8443449</pub-id></element-citation><mixed-citation id="mc-CR1" publication-type="journal">Global regional. National burden of stroke and its risk factors, 1990–2019: a systematic analysis for the global burden of disease study 2019. Lancet Neurol. 2021;20(10):795–820.<pub-id pub-id-type="pmid">34487721</pub-id>
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