A network meta-analysis of effects of non-invasive neuromodulation techniques on language function in patients with aphasia after stroke

doi:10.12307/2026.820

Abstract

Abstract: OBJECTIVE: Many studies have shown that non-invasive neuromodulation techniques can effectively improve the symptoms of non-fluent aphasia after stroke. However, the optimal stimulation protocols for these techniques still need to be further verified and explored. This article used a network meta-analysis method to systematically evaluate the effects of different non-invasive neuromodulation techniques on improving the language function of patients with non-fluent aphasia after stroke.
METHODS: The CNKI, WanFang, VIP, CBM, PubMed, Cochrane Library, Embase, and Web of Science databases were searched for randomized controlled trials on the treatment of non-fluent aphasia after stroke with non-invasive neural modulation techniques, with the search ending on June 1, 2025. The control group received conventional treatment or sham stimulation, while the trial group received non-invasive neural modulation techniques in addition to the control group’s treatment. The outcome indicators were the western aphasia battery, aphasia battery of Chinese, and activity of daily living scale. The outcome measures were analyzed using both traditional meta-analysis and network meta-analysis with Stata 17.0 software, respectively. The GRADE methodology was employed to evaluate the quality of evidence pertaining to the outcome measures.
RESULTS: A total of 33 randomized controlled trials were included, involving 10 types of non-invasive neuromodulation techniques. (1) Traditional meta-analysis results showed that, low-frequency repetitive transcranial magnetic stimulation of the right Broca’s area, transcranial direct current stimulation of both Broca’s area, and transcranial direct current stimulation of the left Broca’s area improved patients’ scores on the western aphasia battery (P < 0.001). Low-frequency repetitive transcranial magnetic stimulation of the right Broca’s area, low-frequency repetitive transcranial magnetic stimulation of the posterior superior temporal gyrus, and low-frequency repetitive transcranial magnetic stimulation of the right Broca’s area combined with high-frequency repetitive transcranial magnetic stimulation of the left Broca’s area improved patients’ scores on aphasia battery of Chinese (P < 0.05). Low-frequency repetitive transcranial magnetic stimulation of the right Broca’s area, transcranial direct current stimulation of both Broca’s areas, continuous theta burst stimulation of the right Broca’s area combined with intermittent theta burst stimulation of the left Broca’s area, high-frequency repetitive transcranial magnetic stimulation of the right Broca’s area, and low-frequency repetitive transcranial magnetic stimulation of the right Broca’s area combined with high-frequency stimulation of the left Broca’s area all improved patients’ scores on the activity of daily living scale (P < 0.05). (2) The network meta-analysis results showed that low-frequency repetitive transcranial magnetic stimulation of the right Broca’s area was more effective in improving the scores of the western aphasia battery and aphasia battery of Chinese [SMD=1.13, 95%CI(0.59, 1.67), P < 0.05; SMD=4.73, 95%CI(1.28, 8.18), P < 0.05], while transcranial direct current stimulation of the bilateral Broca’s areas was more effective in improving the scores of the activity of daily living scale [SMD=1.81, 95%CI(0.51, 2.12), P < 0.05]. (3) The GRADE evidence level assessment results showed that the evidence levels for the western aphasia battery, aphasia battery of Chinese, and activity of daily living scale were all low.
CONCLUSION: Different non-invasive neuromodulation techniques can improve speech function in patients with non-fluent aphasia after stroke. Low-frequency repetitive transcranial magnetic stimulation of the right Broca’s area is significantly effective in improving multidimensional speech function, especially in spontaneous speech coherence, auditory comprehension accuracy, and naming fluency. Bilateral transcranial direct current stimulation of the Broca’s area focuses more on improving patients’ daily communication ability. However, the results are affected by the number and quality of included studies, and the level of evidence is low. More high-quality studies are needed to further verify these findings.

Key words: stroke, non-fluent aphasia, non-invasive neuromodulation technique, language function, transcranial direct current stimulation, repetitive transcranial magnetic simulation, network meta-analysis

CLC Number:

Li Sihui, Wang Qin, Cui Shenhong, Cheng Xiaofei, Feng Ziyun, Wang Dehua, Liang Chunting, Leng Jun. A network meta-analysis of effects of non-invasive neuromodulation techniques on language function in patients with aphasia after stroke[J]. Chinese Journal of Tissue Engineering Research, 2026, 30(28): 7485-7493.

Figures/Tables 6

2.1 文献筛选结果初步检索共获得1 159篇文献，利用EndNote X9软件剔除重复文献565篇，另外剔除468篇文献与研究主题不相关的文献，依据纳入和排除标准对剩余文献进行全文阅读，最终剔除了93篇不符合标准的文献，最终纳入33项研究[17-49]。文献筛选流程见图3。 2.2 纳入文献的基本特征共纳入33篇研究，包括英文文献9篇[17-25]、中文文献24篇[26-49]，涉及2 160例脑卒中后非流畅性失语患者，年龄多在50-70岁之间，病程为1-7年，干预周期为2-6周。33项研究中，有25项研究报告了WAB评分，7项研究报告了ABC评分，8项研究报告了CADL评分；涉及10种不同的非侵入性神经调控方式，包括低频重复经颅磁刺激右侧大脑半球Broca区、高频重复经颅磁刺激右侧Broca区、低频重复经颅磁刺激颞上回后部、低频重复经颅磁刺激右侧Broca区联合高频重复经颅磁刺激左侧Broca区、经颅直流电刺激双侧大脑Broca区、连续性θ爆发刺激左侧Broca区联合间歇性θ爆发刺激右侧Broca区、经颅直流电刺激左侧大脑Broca区、连续性θ爆发刺激颞上回后部、经颅交流电刺激大脑运动辅助区、低频重复经颅磁刺激前额叶背外侧皮质。纳入文献的基本特征见表1。 2.3 纳入文献的质量评价在纳入的33篇研究中，24篇研究被评为有一定风险[26-49]，偏倚风险占比约72.7%；9篇研究被评为低风险[17-25]，偏倚风险占比约为27.3%；无高风险研究，见图4。24项研究提及随机化方案，包括随机数字表法、信封法等[17-27，31-32，35-37，41-46，48-49]；8篇研究只提及随机[28，30，33-34，38-40，47]，1篇研究按意愿分配[29]；9篇研究执行分配隐藏并报告了盲法情况[17-25]；所有研究不存在结局数据缺失及结果的选择性报告偏倚。"

2.4 传统Meta分析结果 2.4.1 WAB评分的直接Meta分析结果共纳入25项研究[17，19-28，30，34-36，39-46，48-49]，研究间异质性较高(I2=66.8%，P=0.303)，对研究进行敏感性分析，结果证实稳定性良好，见图5。参数选择刺激方式进行亚组分析来进一步明确高异质性的原因，结果表明研究间的异质性显著下降，据此推测刺激方式的差异可能是导致整体异质性较高的主要原因。研究结果显示，低频重复经颅磁刺激右侧Broca区、经颅直流电刺激双侧Broca区、经颅直流电刺激左侧Broca区对患者整体言语功能的改善程度明显优于对照组(P < 0.001)，见表2。 2.4.2 ABC评分的直接Meta分析结果共纳入7项研究[29，31-33，37-38，47]，研究间异质性较高(I2=76.7%，P < 0.001)，对研究进行敏感性分析，结果证实稳定性良好，见图6。参数选择刺激方式进行亚组分析来进一步明确高异质性的原因，结果表明研究间的异质性显著下降，据此推测刺激方式的差异可能是导致整体异质性较高的主要原因。研究结果显示，低频重复经颅磁刺激右侧Broca区、低频重复经颅磁刺激颞上回后部、低频重复经颅磁刺激右侧Broca区联合高频重复经颅磁刺激左侧Broca区对患者言语功能障碍的改善程度明显优于对照组(P < 0.05)，见表3。 2.4.3 CADL评分的直接Meta分析结果共纳入8项研究[18，26，29，33，35，40-41，45]，研究间异质性较高(I2=84.6%，P < 0.001)，对研究进行敏感性分析，结果证实稳定性良好，见图7。参数选择刺激方式进行亚组分析来进一步明确高异质性的原因，结果表明研究间的异质性显著下降，据此推测刺激方式的差异可能是导致整体异质性较高的主要原因。研究结果显示，低频重复经颅磁刺激右侧Broca区、经颅直流电刺激双侧Broca区、连续性θ爆发刺激右侧Broca区联合间歇性θ爆发刺激左侧Broca区、高频重复经颅磁刺激刺激右侧Broca区、低频重复经颅磁刺激右侧Broca区联合高频刺激左侧Broca区对患者日常生活交流能力的改善程度明显优于对照组(P < 0.05)，见表4。 2.5 网状Meta分析结果 2.5.1 WAB评分共纳入25项研究[17，19-28，30，34-36，39-46，48-49]，包括8种非侵入性神经调控技术，由于网络证据图未形成闭环，故未进行不一致性检验，见图8。网状Meta分析结果显示，低频重复经颅磁刺激右侧Broca区[SMD=1.13，95%CI(0.59，1.67)，P < 0.05]、低频重复经颅磁刺激右侧Broca区+高频重复经颅磁刺激左侧Broca区[SMD=1.25，95%CI(0.35，2.14)，P < 0.05]、经颅直流电刺激双侧Broca区[SMD=0.90，95%CI(0.43，1.38)，P < 0.05] 3种干预措施在治疗效果上明显优于常规治疗；基于现有证据，其余5种干预方式对WAB评分的改善程度尚未能证实优于常规治疗(P > 0.05)，此外，这8种不同的刺激方式对WAB评分的改善程度两两比较差异均无显著性意义(P > 0.05)，见图9。根据累积排序概率曲线下面积(surface under the cumulative ranking，SUCRA)值对不同干预措施的治疗效果进行排序，结果显示：低频重复经颅磁刺激右侧Broca区(77.2%)>低频重复经颅磁刺激右侧Broca区+高频重复经颅磁刺激左侧Broca区(68.8.%)>经颅直流电刺激双侧Broca区(65.5%)>经颅直流电刺激左侧Broca区(50.4.%)>连续性θ爆发刺激右侧Broca区+间歇性θ爆发刺激左侧Broca区(46.8%)>连续性θ爆发刺激颞上回后部(44.1%)>经颅交流电刺激大脑运动辅助区(36.4%)>低频重复经颅磁刺激背外侧前额叶皮质(32.9%)>常规治疗(24%)，见图10。 2.5.2 ABC评分共纳入7项研究[29，31-33，37-38，47]，包括4种非侵入性神经调控技术，由于网络证据图未形成闭环，故无需进行不一致性检验，见图8。由于此次研究针对ABC评分仅纳入7篇研究，在SUCRA值的排序中可能存在一定的小样本效应。网状Meta分析结果显示，低频重复经颅磁刺激右侧Broca区[SMD=4.73，95%CI(1.28，8.18)，P < 0.05]对于ABC评分的改善程度明显优于常规治疗，基于现有证据，其余3种干预方式对于ABC评分的改善程度尚未能证实优于常规治疗(P > 0.05)；此外，4种刺激方式对于WAB评分的改善程度两两比较差异均无显著性意义(P > 0.05)，见图9。"

根据SUCRA值对不同干预措施的治疗效果进行排序，结果显示：低频重复经颅磁刺激右侧Broca区(76.8%)>低频重复经颅磁刺激颞上回后部(65.2%)>高频重复经颅磁刺激右侧Broca区(46.5%)>低频重复经颅磁刺激右侧Broca区+高频重复经颅磁刺激左侧Broca区(44.3%)>常规治疗(17.3%)，见图10。由于该结局指标仅纳入7项研究，低频重复经颅磁刺激颞上回后部仅来自顾海萍等[32]的1项研究，试验组样本量为50例，低频重复经颅磁刺激右侧Broca区+高频重复经颅磁刺激左侧Broca区仅来自王洪崑[37]的1项研究，试验组样本量为40例，可能存在小样本效应，SUCRA值的排序结果需谨慎解释。 2.5.3 CADL评分共纳入8项研究[18，26，29，33，35，40-41，45]，共5种非侵入性神经调控技术，由于网络证据图未形成闭环，故无需进行不一致性检验，见图8。网状Meta分析结果显示，经颅直流电刺激双侧Broca区[SMD=1.81，95%CI(0.51，2.12)，P < 0.05]、低频重复经颅磁刺激右侧Broca区[SMD=1.36，95%CI(0.31，2.42)，P < 0.05] 2种干预对日常生活交流能力的改善程度明显优于常规治疗，基于现有证据，其余3种刺激方式对CADL评分的改善程度尚未能证实优于常规治疗(P > 0.05)；此外，5种刺激方式对于CADL评分的改善程度两两比较差异均无显著性意义(P > 0.05)，见图9。根据SUCRA值对不同干预措施的治疗效果进行排序，结果显示：经颅直流电刺激双侧Broca区(73.5%)>高频重复经颅磁刺激右侧Broca区(63.8%)>连续性θ爆发刺激右侧Broca区+间歇性θ爆发刺激左侧Broca区(62.8%)>低频重复经颅磁刺激右侧Broca区(57%)>低频重复经颅磁刺激右侧Broca区+高频重复经颅磁刺激左侧Broca区(37.3%)>常规治疗(5.6%)，见图10。由于该结局指标纳入的研究仅为8项，连续性θ爆发刺激右侧Broca区+间歇性θ爆发刺激左侧Broca区仅来自曾贞等[26]的1项研究，试验组样本量为35例，低频重复经颅磁刺激右侧Broca区+高频重复经颅磁刺激左侧Broca区仅来自代锋等[29]的1项研究，试验组样本量为48例，可能存在小样本效应，SUCRA值的排序结果需谨慎解释。 2.6 发表偏倚此次研究仅对纳入研究≥10篇的WAB评分结局指标绘制漏斗图，并进行Egger检验评估研究的偏倚风险，结果显示散点在漏斗图中呈非对称性分布，散点集中在漏斗图上方，而底部散点数量少且分布散乱，个别散点偏离漏斗图的预设范围，进一步进行Egger检验，WAB评分P=0.047 7，提示存在一定的发表偏倚风险及小样本效应，见图11。 2.7 GRADE证据分级结果由于多项研究在随机化方面对于盲法、分配隐藏情况描述不清，研究可能存在一定的发表偏倚，因此对偏倚风险此项进行降级；研究的3项结局指标在进行直接Meta分析时异质性较高，根据不同干预方式进行亚组分析和敏感性分析，结果显示异质性检验I2≤50%且敏感性分析结果较稳健，故不一致性不予降级；所纳入研究的结局指标与评估目的相关性较强且不存在最小临床差异的相关问题，故间接性和精确性不予降级；研究绘制了3项结局指标的漏斗图显示散点分布不均，有少量散落在漏斗图底部和范围之外，并且对WAB评分进行Egger检验(P=0.047 7)，提示存在一定的发表偏倚，故对发表偏倚项进行降级。具体结果见表5。"

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