Abstract
BACKGROUND: Diaphragmatic dysfunction following stroke severely impacts patient prognosis. However, the central neuromodulatory mechanisms of External Diaphragmatic Nerve Stimulation (EDNS) across different stroke subtypes, including ischemic Stroke (IS) and Intracerebral Hemorrhage (ICH), remain unclear. OBJECTIVE: To investigate the immediate effects of EDNS on peripheral Diaphragm Excursion (DE) and central cortical activation in stroke patients, and to compare the response heterogeneity between IS and ICH subtypes. METHODS: This prospective observational study included 50 convalescent stroke patients (30 IS and 20 ICH) and 15 age- and sex-matched healthy Controls (HC). All participants received a single 20-min EDNS intervention. DE was measured using M-mode ultrasound at three time points (pre-, during, and post-intervention). Concurrently, functional Near-Infrared Spectroscopy (fNIRS) was used to synchronize monitoring of cortical activation across 10 Regions of Interest (ROIs). Data were strictly evaluated using non-parametric tests with false discovery rate (FDR) correction. RESULTS: EDNS intervention significantly improved immediate diaphragmatic function across all groups. DE in the IS group increased from 1.67 ± 0.29 cm at baseline to 1.92 ± 0.33 cm during intervention (p < 0.01), and in the ICH group from 1.64 ± 0.26 cm to 1.87 ± 0.31 cm (p < 0.01). However, t the spatial pattern of central activation exhibited significant heterogeneity: the HC group showed no significant activation in any ROI (p > 0.05); the IS group activated a broad "cognitive-sensory" activation pattern, including the bilateral Dorsolateral Prefrontal Cortex (DLPFC) (p < 0.05) and bilateral Somatosensory Association Cortex (SAC) (p < 0.01); whereas the ICH group activated only a localized sensory region (Right SAC, p = 0.046). Furthermore, the magnitude of DE improvement was significantly positively correlated with the intensity of Right DLPFC activation only in the IS group (Spearman's ρ = 0.386, p = 0.035), with no such correlation observed in the ICH group (p > 0.05). CONCLUSION: Although EDNS universally improves immediate diaphragmatic function in both IS and ICH patients, the underlying central neuromodulatory mechanisms are subtype-specific. IS patients appear to preserve a "top-down" cognitive-sensory regulation pathway (DLPFC-SAC) and central-peripheral coupling, whereas the central response in ICH patients is limited to basic sensory processing (SAC) with a lack of such coupling. This mechanistic disparity suggests that rehabilitation strategies for IS patients might benefit from integrating cognitive engagement, highlighting the necessity of tailoring personalized respiratory rehabilitation protocols based on stroke pathology.