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Updated: Aug 15, 2026

Randomized, Triple-Blind, and Parallel-Controlled Trial of Transcranial Direct Current Stimulation for Cognitive Rehabilitation after Stroke
Published on: June 6, 2025
Effects of individualized Theta frequency high-definition transcranial alternating current stimulation on cognitive
Yulan Gao1, Fangting Duan2, Menglin Han3
1Center of Rehabilitation Medicine, Zhujiang Hospital, Southern Medical University, Guangzhou 510220, China; Department of Bone and Joint Rehabilitation, Jiangbin Hospital of Guangxi Zhuang Autonomous Region, Nanning 530000,China.
Objective:
To investigate the clinical efficacy of Individualized Theta Frequency High-Definition Transcranial Alternating Current Stimulation (ITF HD-tACS) and 5 Hz HD-tACS for patients with Post-stroke Cognitive Impairment (PSCI), and to clarify the potential neurophysiological mechanisms through electroencephalogram (EEG) analysis.
Methods:
In this single-blinded, randomized controlled trial, 34 PSCI patients meeting the inclusion criteria were randomly allocated to three groups: the individualized theta frequency group (ITF group), the 5 Hz group, or the sham stimulation group (sham group). The intervention delivered a 1 mA (peak-to-peak) current at the corresponding frequency (ITF or 5 Hz) to the left dorsolateral prefrontal cortex (DLPFC) for 10 consecutive days. We collected scale assessments and 5-min closed-eye resting-state electroencephalogram (EEG) data at two time points: baseline (T0) and the 10th day of intervention, which is after intervention initiation(T1). The assessments included the Montreal Cognitive Assessment (MoCA), Auditory Verbal Learning Test (AVLT), Digit Span Test (DST), Digit Symbol Coding Test (DSCT), Hamilton Depression Scale-17 item (HAMD-17), and Modified Barthel Index (MBI).
Results:
Behavioral results indicated that the ITF group showed the greatest change amplitude in MoCA scores (T1-T0), which was significantly different from that of the sham group (p = 0.002). Both the ITF group and the 5 Hz group demonstrated substantial improvements in orientation sub-scale scores, AVLT immediate recall, and short-delay recall (all p < 0.05). Compared with the sham group, both the ITF and 5 Hz groups exhibited an increased relative Power Spectral Density (PSD) of the theta band and a decreased relative PSD of the gamma band in the frontal region. There were significant differences in ΔPSD between each stimulation group and the sham group. Moreover, a significant positive correlation was found between frontal theta-band ΔPSD and ΔMoCA in the ITF group(p = 0.017).
Conclusion:
Theta-tACS is a promising treatment for PSCI patients. ITF-tACS may mediate cognitive improvement by modulating frontal theta oscillations. Due to its significant brain responsiveness, this approach points to an important direction for future individualized neuromodulation.
Trial Registration:
This trial was retrospectively registered in the Chinese Clinical Trial Registry, registration number ChiCTR2600121224.

