Comparative Efficacy of iTBS and rTMS in Treating Post-Stroke Cognitive Impairment: A Double-Blind Randomized Controlled Trial

Objective: To compare the therapeutic effect of intermittent theta burst stimulation (iTBS) and repetitive transcranial magnetic stimulation (rTMS) on cognitive function in patients with post-stroke cognitive impairment (PSCI) and investigate underlying neuroelectrophysiological mechanisms using microstate analysis. Methods: In this randomized, double-blind, sham-controlled trial, 45 patients with PSCI were assigned 2:2:1 to iTBS, rTMS, and sham groups, with stimulation targeting the left dorsolateral prefrontal cortex. All participants also received therapist-delivered cognitive training in addition to stimulation. Outcomes were evaluated before (T0) and 10 days after (T1). The primary outcome measure was Montreal Cognitive Assessment (MoCA) score. Secondary outcomes were auditory verbal learning test, Wechsler Adult Intelligence Scale-Ⅲ digit symbol coding test and digit span test scores as well as microstate indices. Results: ΔMoCA(T1-T0) scores were significantly improved in both the iTBS (median [interquartile range]: 2.00 [1.00, 4.00]) and rTMS groups (2.00 [1.00, 3.00]) compared with sham group ( P < .05). There was no significant difference in ΔMoCA between the 2 active protocols. Significant within-group improvements in memory and working memory were observed in the iTBS group ( P < .05). Both iTBS and rTMS group showed significantly increased microstate C parameters between T0 and T1 ( P < .05). Furthermore, the transition probabilities in the iTBS group showed more diversity between microstates, while the other groups showed no significant transformation. Conclusion: iTBS and 5-Hz rTMS were effective in improving overall cognitive ability in PSCI, and iTBS may represent a practical, time-efficient alternative to 5-Hz rTMS. EEG microstate suggested distinct modulation patterns, serving as a useful exploratory tool. Clinical Trial Registry Name: Effect of different transcranial magnetic stimulation protocols on cognitive function in patients with post-stroke cognitive impairment. Clinical Trial Registration-URL: https://www.chictr.org.cn/ Clinical Trial Registration Number: ChiCTR2200064233.