High-Intensity Transcranial Alternating Current Stimulation for Post-Stroke Cognitive Impairment: A Triple-Blind...

Non-invasive neuromodulation for post-stroke cognitive impairment (PSCI) holds promise, but high-level evidence is lacking, partly due to the challenge of targeting single brain regions in a condition with diverse lesions and multi-network dysfunction.

The present study aimed to evaluate the effect of high-intensity transcranial alternating current stimulation (Hi-tACS) on cognitive function in patients with PSCI.

In this triple-blind, randomized, sham-controlled trial, PSCI patients were randomized to receive either active or sham Hi-tACS. The tACS group received active Hi-tACS at 15 mA and 77.5 Hz for 40 minutes, twice daily, 5 days a week for 2 weeks. The sham group used identical devices without current delivery. The primary outcome was the change in Montreal Cognitive Assessment (MoCA) score. Secondary outcomes included Digit Span Test and cerebral oxyhemoglobin (HbO) concentration changes measured by functional near-infrared spectroscopy (fNIRS).

The tACS group (n=34) showed higher MoCA response rates than the sham group (n=34) immediately after treatment (73.5% vs 38.2%, P=0.003) and at the 4-week post-treatment follow-up (88.2% vs 55.9%, P=0.003). Improvements in forward and backward digit span were also greater in the tACS group at both assessments. The intention-to-treat analysis of all 70 randomized participants yielded results consistent with the per-protocol analysis. Exploratory fNIRS analyses identified greater HbO increases in the left, right, and medial prefrontal regions in the tACS group at T1 after FDR correction (all q=0.033), whereas no regional difference remained significant at T2.

Hi-tACS improved global cognition and working memory in patients with PSCI and was generally well tolerated. Exploratory fNIRS findings suggested possible accompanying changes in cortical activation and network organization but did not establish a neurophysiological mechanism. Importantly, as a broad-network stimulation approach, Hi-tACS may reduce reliance on selecting a single precise target, a potential practical advantage in heterogeneous PSCI.