To elucidate the therapeutic effects and neural mechanisms of a neuromodulatory priming strategy using intermittent theta burst stimulation (iTBS) combined with lower-limb exoskeleton robot training on functional recovery in stroke patients.

Eighty post-stroke patients with lower limb motor dysfunction were randomized into four groups (n=20 in each) :conventional rehabilitation (CR), iTBS, lower limb robot (LLR), and iTBS+LLR. All groups received conventional rehabilitation therapy. In addition, the iTBS and LLR groups received their respective interventions, while the combined group received both iTBS and robotic training. Outcome measures, including the Fugl-Meyer Assessment for Lower Extremity (FMA-LE), Modified Barthel Index (MBI), Berg Balance Scale (BBS), 3D gait analysis, and fNIRS, were assessed before and after treatment.

There were no significant differences in baseline characteristics or outcome measures among the four groups (P>0.05). Compared to baseline, all four groups exhibited statistically significant improvements in FMA-LE, MBI, and BBS scores following the intervention (P<0.001). The iTBS+LLR group demonstrated superior outcomes in FMA-LE, MBI, and BBS scores compared to other groups (P<0.05). Gait analysis indicated that all groups showed significant improvements in various gait parameters after treatment compared to pretreatment values (P<0.05). The iTBS+LLR group displayed more pronounced enhancements in temporal, spatial, and kinematic gait metrics than other groups (P<0.05). At the neurophysiological level, functional connectivity (FC) within and between regions of interest (ROIs) significantly increased in all groups after treatment (P<0.05). The iTBS+LLR group showed greater FC augmentation compared to other groups (P<0.05). The iT-BS+LLR group demonstrated broadened activation involving left and right primary motor cortex (LM1/RM1), left and right supplementary motor area (LSMA/RSMA), left and right prefrontal cortex (LPFC/RPFC), and left occipital lobe (LOL) (P<0.01). Intergroup comparisons confirmed that activation in LM1, LSMA, RS-MA, LPFC, and LOL was significantly stronger in the combined group than in the other groups (P<0.05).

Priming iTBS combined with a lower limb exoskeleton robot results in greater improvements in motor function and gait in stroke patients than either intervention alone. These benefits may be associated with enhanced motor cortical excitability, strengthened functional connectivity, and facilitation of synergistic neuroplasticity within gait-control networks.