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Objective <p>Post-stroke aphasia (PSA) is characterized by persistent language impairment, but its underlying physiological mechanisms remain unclear. Glymphatic dysfunction has been implicated in post-stroke pathophysiology, but its role in PSA remains unclear. The cingulo-opercular network (CON) is&#xa0;a key network implicated in language recovery after stroke. Using blood-oxygen-level-dependent (BOLD) and cerebrospinal fluid (CSF) coupling as a putative&#xa0;non-invasive marker of glymphatic function, we examined global and CON-specific alterations in patients with&#xa0;PSA and their associations with language impairment and treatment-related recovery.</p> Methods <p>We enrolled 79 patients with&#xa0;PSA and 72 healthy controls (HCs). Among the patients,&#xa0;20 underwent transcranial electrical stimulation (TES)&#xa0;targeting key CON nodes. Global and CON-specific BOLD-CSF coupling were quantified. Language function was assessed using the Western Aphasia Battery (WAB) and the Aphasia Battery of Chinese (ABC). We compared BOLD-CSF coupling between groups and examined its associations with language performance and intervention-related changes.</p> Results <p>Compared with HCs, patients with&#xa0;PSA showed significantly reduced BOLD-CSF coupling at both the global level and within the CON (all <i>p</i> &lt; 0.05). CON-specific coupling was positively associated with AQ (<i>r</i> = 0.27, <i>p</i> = 0.022), comprehension (<i>r</i> = 0.28, <i>p</i> = 0.018) and fluency (<i>r</i> = 0.23, <i>p</i> = 0.048), and showed a trend-level positive association with naming (<i>r</i> = 0.22, <i>p</i> = 0.056). After TES, the treated&#xa0;patients showed concurrent improvements in language performance and BOLD-CSF coupling. Increases in CON-specific coupling were positively associated with naming recovery (<i>r</i> = 0.59, <i>p</i> = 0.006), and this association remained significant after adjustment&#xa0;for covariates (<i>r</i> = 0.53, <i>p</i> = 0.041). AQ recovery was also associated with increased CON-specific coupling (<i>r</i> = 0.47, <i>p</i> = 0.034), with&#xa0;a trend-level association after adjustment (<i>r</i> = 0.51, <i>p</i> = 0.053).</p> Conclusions <p>Patients with&#xa0;PSA showed altered BOLD-CSF coupling, particularly within the CON, and these alterations were associated with language impairment and treatment-related recovery. These findings provide preliminary evidence that CON-specific glymphatic dysfunction may be relevant to PSA and support further investigation of the CON as a potential therapeutic target for aphasia rehabilitation.</p> <p><i>Trial Registration</i> NCT05502822, NCT07700537.</p>

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Reduced glymphatic clearance is linked to language impairments in patients with post-stroke aphasia

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月27日

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  • Yuqian Zhan,
  • Jin Li,
  • Xiaomin Pan,
  • Zhishun Gao,
  • Muen Han,
  • Qiufang Ren,
  • Jian Guan,
  • Qiang Wei,
  • Kai Wang,
  • Xiaohui Xie,
  • Tongjian Bai,
  • Panpan Hu

摘要

Objective

Post-stroke aphasia (PSA) is characterized by persistent language impairment, but its underlying physiological mechanisms remain unclear. Glymphatic dysfunction has been implicated in post-stroke pathophysiology, but its role in PSA remains unclear. The cingulo-opercular network (CON) is a key network implicated in language recovery after stroke. Using blood-oxygen-level-dependent (BOLD) and cerebrospinal fluid (CSF) coupling as a putative non-invasive marker of glymphatic function, we examined global and CON-specific alterations in patients with PSA and their associations with language impairment and treatment-related recovery.

Methods

We enrolled 79 patients with PSA and 72 healthy controls (HCs). Among the patients, 20 underwent transcranial electrical stimulation (TES) targeting key CON nodes. Global and CON-specific BOLD-CSF coupling were quantified. Language function was assessed using the Western Aphasia Battery (WAB) and the Aphasia Battery of Chinese (ABC). We compared BOLD-CSF coupling between groups and examined its associations with language performance and intervention-related changes.

Results

Compared with HCs, patients with PSA showed significantly reduced BOLD-CSF coupling at both the global level and within the CON (all p < 0.05). CON-specific coupling was positively associated with AQ (r = 0.27, p = 0.022), comprehension (r = 0.28, p = 0.018) and fluency (r = 0.23, p = 0.048), and showed a trend-level positive association with naming (r = 0.22, p = 0.056). After TES, the treated patients showed concurrent improvements in language performance and BOLD-CSF coupling. Increases in CON-specific coupling were positively associated with naming recovery (r = 0.59, p = 0.006), and this association remained significant after adjustment for covariates (r = 0.53, p = 0.041). AQ recovery was also associated with increased CON-specific coupling (r = 0.47, p = 0.034), with a trend-level association after adjustment (r = 0.51, p = 0.053).

Conclusions

Patients with PSA showed altered BOLD-CSF coupling, particularly within the CON, and these alterations were associated with language impairment and treatment-related recovery. These findings provide preliminary evidence that CON-specific glymphatic dysfunction may be relevant to PSA and support further investigation of the CON as a potential therapeutic target for aphasia rehabilitation.

Trial Registration NCT05502822, NCT07700537.