Network-specific enhancement of global blood-oxygen-level-dependent signals and CSF coupling after language therapy in post-stroke aphasia

Abstract Emerging evidence indicates that stroke may impair glymphatic function by disrupting cerebrospinal fluid (CSF) clearance. The coupling between global blood-oxygen-level-dependent signals and CSF flow has been proposed as a noninvasive biomarker of glymphatic activity. However, it remains unclear whether this coupling can be modulated through rehabilitation. This study investigated whether language therapy in patients with post-stroke aphasia enhances global blood-oxygen-level-dependent–CSF coupling, thereby reflecting potential restoration of fluid–brain interaction. This longitudinal observational study was conducted at a single center and included 20 patients with post-stroke aphasia and 35 age- and sex- balanced healthy controls. All participants underwent MRI scanning, including resting-state blood-oxygen-level-dependent and structural imaging. Among the post-stroke aphasia group, 14 patients completed both pre- and post-treatment assessments after undergoing a standardized 4-week speech-language therapy program. The Western Aphasia Battery was used to quantify language deficits and monitor treatment-related changes. Global blood-oxygen-level-dependent–CSF coupling was quantified using cross-correlation analysis across the whole brain and four predefined language-related resting-state networks. At baseline, patients exhibited significantly reduced global blood-oxygen-level-dependent–CSF coupling compared to healthy controls (P < 0.05). Following therapy, coupling significantly increased within the language, salience, and dorsal attention networks, whereas coupling within the default mode network significantly decreased (all P < 0.05). Notably, increased global blood-oxygen-level-dependent–CSF coupling in specific networks was significantly correlated with improvements in targeted language functions, such as object naming, responsive naming, and auditory word recognition (P < 0.05). These findings suggest that language rehabilitation enhances neurophysiological coupling between brain activity and CSF flow, potentially reflecting restoration of fluid–brain interaction in post-stroke aphasia.