Neurology · Medical Literature
Efficacy and Mechanisms of Combined Central-Peripheral Magnetic Stimulation on Prefrontal-Sensorimotor Cortex Connectivity in Post-Stroke Dysphagia after Supratentorial Stroke: A Randomized, Single-Blind, Parallel-Controlled Trial.
Abstract
Combined central-peripheral magnetic stimulation shows promise for post-stroke dysphagia (PSD), but its neural mechanisms remain unclear. We evaluated the its efficacy and cortical mechanisms in PSD patients. In this single-blind, parallel-controlled trial, 44 PSD patients were randomized to four groups: active-rTMS + active-rPMS, active-rTMS + sham-rPMS, sham-rTMS + active-rPMS, or sham-rTMS + sham-rPMS. Clinical scales, such as functional oral intake scale (FOIS) and Penetration-Aspiration Scale (PAS), and Videofluoroscopic Swallowing Study (VFSS) were accessed before, after intervention. Cortical activation during rest and swallowing task was measured by functional near-infrared spectroscopy (fNIRS). Significant interaction effects (time × intervention) were found for FOIS (Wald χ2 = 39.816, p < 0.001) and PAS scores (Wald χ2 = 45.433, p < 0.001), with the active-rTMS + active-rPMS group showing the most pronounced therapeutic gains. Concurrently, this group displayed significant improvements of laryngeal vestibular closure duration (LCD, MD = -3.598, 95% CI -4.177 to -3.019, adjusted p < 0.001) and superior hyoid excursion (SHE, MD = -3.708, 95% CI -4.213 to -3.18, adjusted p < 0.001). Neurophysiologically, increased functional connectivity (FC) within the ipsilesional prefrontal-sensorimotor network was observed and the changes of FC in ipsilesional M1 and S1 is significantly correlated with the change magnitude of LCD (rs = 0.78, p = 0.004) and SHE (rs = 0.67, P = 0.023). The combined central-peripheral magnetic stimulation robustly improved swallowing function, temporal and kinematic sequence of swallowing, and sensori-motor connectivity in PSD patients, representing a promising neuromodulatory therapy for PSD.
Clinical relevance
Post-stroke dysphagia (PSD) affects a substantial proportion of supratentorial stroke survivors and carries significant risks of aspiration pneumonia, malnutrition, and mortality, yet neuromodulatory treatment options remain limited and mechanistically poorly understood. This trial addresses a critical gap by evaluating whether combining cortically-directed repetitive TMS (rTMS) with peripherally-directed repetitive peripheral magnetic stimulation (rPMS) yields superior swallowing recovery compared to either modality alone, while simultaneously interrogating the underlying prefrontal-sensorimotor cortical network mechanisms via fNIRS. Clinicians managing PSD should attend to these findings now as they provide both efficacy data and neurophysiological mechanistic evidence to guide rational combination neuromodulation protocols.
Key findings
1. Significant time × intervention interaction effects were demonstrated for the Functional Oral Intake Scale (FOIS; Wald χ² = 39.816, p < 0.001) and the Penetration-Aspiration Scale (PAS; Wald χ² = 45.433, p < 0.001), with the combined active-rTMS + active-rPMS group achieving the most pronounced therapeutic gains across both clinical endpoints. 2. Combined stimulation produced significant improvement in laryngeal vestibule closure duration (LCD; MD = −3.598, 95% CI −4.177 to −3.019, adjusted p < 0.001) on VFSS, indicating faster and more protective laryngeal closure during the pharyngeal swallow phase. 3. Superior hyoid excursion (SHE) improved significantly in the combined group (MD = −3.708, 95% CI −4.213 to −3.180, adjusted p < 0.001), reflecting enhanced hyolaryngeal biomechanics critical to upper esophageal sphincter opening. 4. fNIRS neuroimaging revealed increased functional connectivity (FC) within the ipsilesional prefrontal-sensorimotor cortical network specifically in the active-rTMS + active-rPMS group, implicating perilesional network reorganization as a key mechanism of recovery. 5. Changes in ipsilesional primary motor cortex (M1) and primary somatosensory cortex (S1) FC were significantly correlated with improvement in LCD (Spearman rs = 0.78, p = 0.004) and SHE (rs = 0.67, p = 0.023), providing direct neurophysiological correlates of swallowing kinematic gains. 6. The four-arm parallel design (active-rTMS + active-rPMS; active-rTMS + sham-rPMS; sham-rTMS + active-rPMS; sham-rTMS + sham-rPMS; n = 44 total) allowed factorial decomposition of central vs. peripheral stimulation contributions, demonstrating that synergistic combination—not either modality alone—drove maximal benefit.
Practice implications
Clinicians should consider combined rTMS (targeting ipsilesional cortical swallowing areas) plus rPMS (targeting peripheral oropharyngeal or cervical musculature) as a preferred neuromodulatory strategy over unimodal magnetic stimulation for PSD patients following supratentorial stroke, given demonstrated superiority on both functional oral intake and aspiration-penetration metrics. Patient selection should prioritize supratentorial stroke survivors with confirmed PSD on VFSS or FEES, and treatment response monitoring should incorporate objective kinematic VFSS parameters—particularly LCD and SHE—as these biomechanical surrogates correlate directly with ipsilesional M1/S1 connectivity changes and may serve as imaging-informed biomarkers of neuromodulatory efficacy. Future implementation should await replication in larger, double-blind trials with longer follow-up, as this study was limited by a small sample (n = 44), single-blind design, and absence of reported durability data beyond the acute post-intervention timepoint.