Structural–Functional Connectivity Coupling in Motor–Brain Networks Following Acute Ischemic Stroke

Abstract Background: Structural connectivity (SC) and functional connectivity (FC) are pivotal for motor recovery after stroke, yet their interplay (SC-FC coupling) within the motor network during the acute phase of ischemic stroke remains poorly understood. Objective: This study aimed to investigate SC-FC coupling in the motor network of patients with acute ischemic stroke (AIS) and elucidate its relationship with motor function. Methods: We prospectively enrolled 55 patients within one week of AIS onset and 55 baseline-matched healthy controls (HC). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI). We compared the motor network SC and FC metrics between the two groups. Mediation analysis was employed to explore the interplay among SC, FC, and motor function and further analyze the associations between SC-FC coupling levels and motor function. Results: The study included 55 patients (mean age ± standard deviation (SD): 57.75 ± 13.00 years; 36 males) and 55 HC (mean age ± SD: 57.09 ± 10.74 years; 33 males). Compared with HC, patients with AIS demonstrated significantly reduced SC and FC strength within the motor network ( P <0.05). The altered SC and FC metrics were significantly negatively correlated with motor function scores ( P <0.05). Notably, mediation analysis revealed that the SC between the ipsilesional thalamus (THA) and contralesional putamen (PUT) influenced motor function through its effect on interhemispheric precentral gyrus (PreCG) FC. Crucially, the level of SC-FC coupling was significantly negatively correlated with motor function scores ( r = -0.27, P = 0.04). Conclusion: Our findings revealed synergistic alterations in the SC between the ipsilesional THA and contralesional PUT, as well as in the FC of the interhemispheric PreCG, in patients with AIS, indicating a pathological coupling effect. Furthermore, stronger SC-FC coupling is significantly associated with poorer motor function outcomes. Therefore, targeting this specific SC-FC coupling pattern, particularly by modulating interhemispheric PreCG FC, may represent a promising neuromodulation strategy to promote motor recovery in AIS patients.