He Yuwen, Hou Ya, Zhou Yuan, Gu Ruolei, Gao Fei, Yuan Zhen
Centre for Cognitive and Brain Sciences, University of Macau, Macau SAR, China.
Faculty of Health Sciences, University of Macau, Macau SAR, China.
Transl Psychiatry. 2025 Aug 22;15(1):307. doi: 10.1038/s41398-025-03534-w.
Language deficits are commonly observed in patients with schizophrenia, significantly impacting their quality of life. Current medicine has little curing effects on language deficits in patients with schizophrenia. Therefore, it is crucial to investigate the underlying pathology of these deficits and unravel the potential intervention targets.
We systematically reviewed fMRI publications on language processing in schizophrenia and summarized the evidence quantitatively with activation likelihood estimation algorithms following PRISMA guidelines. A total of 82 experiments involving 1538 schizophrenia patients and 1413 healthy controls were included in the current study.
Our findings revealed that the left middle frontal gyrus (MFG) and inferior frontal gyrus (IFG) were consistently related to language deficits in schizophrenia across all modalities and all contrasts. Subsequent analysis revealed increased activation in the left MFG related to language deficits in schizophrenia. Subgroup analyses uncovered modality-specific alterations. Specifically, reduced activation in bilateral MFG in language comprehension, and increased activation in left IFG in language production in schizophrenia. Further evidence in comparison analysis also uncovered greater alteration in right MFG related to comprehension than production, while greater alterations in left IFG and others related to production than comprehension in schizophrenia. Moreover, we found that age modulates the altered activation patterns in schizophrenia, while positive or negative symptoms, or sex, did not show significant correlations with these patterns.
In summary, our study highlights convergent altered activation patterns in specific brain regions and identifies several heterogeneous sources (e.g., language modality, age) contributing to language deficits in schizophrenia.
精神分裂症患者常出现语言缺陷，严重影响其生活质量。目前的药物对精神分裂症患者的语言缺陷几乎没有治疗效果。因此，研究这些缺陷的潜在病理机制并找出潜在的干预靶点至关重要。
我们系统回顾了关于精神分裂症语言处理的功能磁共振成像（fMRI）文献，并按照PRISMA指南，使用激活可能性估计算法对证据进行了定量总结。本研究共纳入了82项实验，涉及1538名精神分裂症患者和1413名健康对照者。
我们的研究结果显示，在所有模式和所有对比中，左侧额中回（MFG）和额下回（IFG）与精神分裂症的语言缺陷始终相关。随后的分析显示，精神分裂症患者左侧额中回与语言缺陷相关的激活增加。亚组分析发现了特定模式的改变。具体而言，精神分裂症患者在语言理解时双侧额中回激活减少，在语言表达时左侧额下回激活增加。比较分析中的进一步证据还发现，与表达相比，右侧额中回在理解方面的改变更大，而在精神分裂症中，左侧额下回及其他区域在表达方面的改变比理解方面更大。此外，我们发现年龄调节了精神分裂症患者激活模式的改变，而阳性或阴性症状或性别与这些模式没有显著相关性。
总之，我们的研究突出了特定脑区一致的激活模式改变，并确定了导致精神分裂症语言缺陷的几个异质性来源（如语言模式、年龄）。
