High-Frequency rTMS Broadly Ameliorates Working Memory and Cognitive Symptoms in Stroke Patients: A Randomized Controlled Trial

Objective. To explore the efficacy and tolerability of high-frequency repetitive transcranial magnetic stimulation (rTMS) in the treatment of post-stroke working memory (WM) impairment and its changes in brain function. Methods. In the present randomized, double-blinded, sham-controlled design, 10 Hz rTMS was administered to the left dorsolateral prefrontal cortex (DLPFC) of patients with post-stroke WM impairment for 14 days. Measures included WM (primary outcome), comprehensive neuropsychological tests, and the functional near-infrared spectroscopy test. Patients were assessed at baseline, after the intervention (week 2), and 4 weeks after treatment cessation (week 6). Results. Of 123 stroke patients, 82 finished the trial. The rTMS group showed more WM improvement at week 2 (t = 5.55, P < .001) and week 6 (t = 2.11, P = .045) than the sham group. Most of the neuropsychological test scores were markedly improved in the rTMS group. In particular, the rTMS group exhibited significantly higher oxygenated hemoglobin content and significantly stronger functional connectivity in the left DLPFC, right pre-motor cortex (PMC), and right superior parietal lobule (SPL) at weeks 2 and 6. Dropout rates were equal (18% [9/50 cases] in each group), and headaches were the most common side effect (rTMS: 36% [18/50 cases]; sham: 30% [15/50 cases]). Conclusions. High-frequency rTMS was effective in improving post-stroke WM impairment, with good tolerability, and the efficacy lasted up to 4 weeks, which may be due to the activation of the left DLPFC, right PMC, and right SPL brain regions and their synergistic enhancement of neural remodeling.