The clinical effects and multimodal-fMRI of paired associative stimulation on wrist flexor spasticity after stroke

Abstract Objective: We aimed to investigate the efficacy of paired associative stimulation (PAS25) address post-stroke wrist flexor spasticity, and brain plasticity changes. Methods: Prospective randomized controlled study, 63 patients with post-stroke wrist flexor spasticity were recruited. Patients were assigned to receive LTTPO (control group, n=31) or PAS25 (study group, n=32) using a random number table. PAS25 was administered to the study group for 3 weeks, whereas the LTTPO was worn for approximately 4–6h per day over 3 weeks. Modified Ashworth Scale (MAS) was primary outcome, visual analog scale (VAS) and Fugl-Meyer Assessment (FMA) were secondary outcomes. Assessments were conducted at baseline, after 3 weeks of treatment, and at 4 and 8 weeks of follow-up. Rs-fMRI and T1 data were collected before and after treatment to observe the changes of brain plasticity. Results: The change of treatment effectiveness rate in MAS at 3 weeks exhibited a significant disparity between the two groups (77.4%vs.29%, p< 0.01). At the 4-week follow-up, significant changes were observed in MAS (96.9% vs.45.2%, p< 0.01) and FMA scores (p=0.007). Rs-fMRI results show that FC were increased between Cerebelum_Crus2_R and Frontal_Sup_Medial_R、Cingulum_Mid_R(p < 0.05, FDR). Structured T1 results show that increased grey matter density in Supp_Motor_Area、Lingual_R、Frontal_Mid_L and Frontal_Sup_Medial_R (voxel p＜0.001, cluster size＞10). Conclusion: PAS25 can relieve wrist flexor spasticity and improve the motor function of wrist, the effect is sustainable. PAS25 can alter the plasticity of the brain through a dual central-peripheral effect, which produces bidirectional regulation of the sensori-motor brain area. The effect can affect the distant brain area through the corpus callosum.