Priming Intermittent Theta Burst Stimulation for Hemiparetic Upper Limb After Stroke: A Randomized Controlled Trial

BACKGROUNDIntermittent theta burst stimulation (iTBS) creates a state with increased excitability that permits treatment modalities to induce neuroplasticity and motor learning. Continuous theta burst stimulation before iTBS may induce metaplasticity and boost the facilitatory effect of iTBS. This study investigated the effects of priming iTBS (ie, applying continuous theta burst stimulation before iTBS) on poststroke hemiparetic upper limb recovery. METHODSIn this randomized controlled trial, 42 patients with chronic stroke were recruited and randomly allocated to 10 sessions of either priming iTBS, nonpriming iTBS, or sham stimulation to the ipsilesional motor cortex, immediately before robot-assisted training. Outcomes included Fugl-Meyer Assessment-Upper Extremity, Action Research Arm Test and mean movement velocity during each robot-assisted training session. Twenty-one patients were enrolled for measuring the sensorimotor beta event-related desynchronization induced by either mirror visual feedback or movement. RESULTSThe Fugl-Meyer Assessment-Upper Extremity scores revealed a significant time-by-group interaction (P=0.011). Priming and nonpriming iTBS were both superior to sham stimulation in post hoc comparisons; however, the superiority was diminished at follow-up. Among patients with a higher functioning upper limb, priming iTBS yielded a significantly greater improvement in Fugl-Meyer Assessment-Upper Extremity scores than nonpriming iTBS (P=0.025) and sham stimulation (P=0.029) did. No significant interaction was found when analyzing the Action Research Arm Test and mean movement velocity. Priming iTBS enhanced the patients' mirror visual feedback-induced high beta sensorimotor event-related desynchronization over their ipsilesional hemisphere. CONCLUSIONSPriming and nonpriming iTBS are both superior to sham stimulation in enhancing treatment gains from robot-assisted training, and patients with a higher functioning upper limb may experience more benefits from priming iTBS. Priming iTBS may facilitate poststroke motor learning by enhancing the permissiveness of the ipsilesional sensorimotor area to therapeutic sensory modalities, such as the mirror visual feedback. REGISTRATIONURL: https://www. CLINICALTRIALSgov; Unique identifier: NCT04034069.