Leila Halavi Anjar, Amir Ghasemi Jangjoo, Touraj Hashemi, Davood Khezerloo, Hassan Sabouri Moghaddam
Objective To investigate whether transcranial direct current stimulation (tDCS) can mitigate radiotherapy-induced cognitive impairment and modulate cortical activity, as measured by quantitative electroencephalography (QEEG), in patients undergoing whole-brain radiotherapy (WBRT). Methods In this randomized, sham-controlled pretest–posttest study, 40 right-handed adults with brain metastases scheduled for WBRT were assigned to either active tDCS (n = 20) or sham stimulation (n = 20). For tDCS stimulation (2mA, 20 sessions), two electrode montages were applied over the dorsolateral prefrontal cortex (DLPFC) and supraorbital regions. Cognitive performance was assessed using a computerized 2-back task (working memory) and the continuous performance test (CPT) for sustained attention. Resting-state QEEG was recorded before and after treatment to quantify absolute beta and theta power. Peripheral blood samples were analyzed by Western blot to evaluate expression of DYRK1A, MMP2, MMP9, and VEGF. Multivariate ANCOVA was used to control for baseline differences. Results Active tDCS significantly improved cognitive performance compared with sham stimulation. N-back correct response increased from 2.96 ± 1.53 to 4.75 ± 0.55 (about 60.47% improvement, p < 0.001), and CPT correct responses increased from 13.20 ± 2.52 to 18.80 ± 1.39 (about 42.42% improvement, p < 0.01). QEEG analysis showed a significant reduction in absolute beta power (17.41 ± 4.30 to 11.46 ± 3.15 μV², about 51.19% reduction, p < 0.001), and theta power (33.41 ± 5.20 to 18.15 ± 4.50 μV², about 84.07% reduction, p=0.002). Western blot results indicated that tDCS significantly attenuated the post-radiotherapy upregulation of stress- and inflammation-related proteins. Conclusion tDCS was associated with improved short-term cognitive performance during WBRT and may improve working memory and sustained attention, normalize aberrant beta–theta EEG activity, and reduce the expression of peripheral biomarkers. These findings support tDCS as a potential noninvasive adjunctive strategy for preserving cognitive function in patients undergoing WBRT.