Dual Transcranial Direct Current Stimulation Modulates Hierarchical Functional Network Organization in Post-Stroke Cognitive Impairment: A Randomized Controlled Trial.
Wang Y, Liu W, et al. • CNS neuroscience & therapeutics • 2026
Dual-tDCS over bilateral DLPFC safely improves cognitive recovery in PSCI, with clinical gains associated with rs-fMRI alterations in regional synchronization, inter-regional connectivity, and global topology, suggesting a potential biomarker for monitoring tDCS efficacy.
Key Findings
Results
Active dual-tDCS produced significantly greater improvements in MoCA scores compared to sham stimulation in PSCI patients.
MoCA improvement: tDCS group 5.74 ± 2.76 vs. sham group 2.69 ± 2.69 (t = 4.799, p < 0.001)
Randomized, double-blind, sham-controlled trial with 74 PSCI patients (active tDCS n = 38, sham n = 36)
Both groups received conventional therapy alongside their assigned stimulation condition
Results
Active dual-tDCS produced significantly greater improvements in attention and memory domains compared to sham stimulation.
Secondary outcome measures included the Stroop Test (ST), Trail Making Test (TMT), and Wechsler Memory Scale (WMS)
Additional secondary measures included MMSE and Barthel Index (BI)
Specific domain-level improvements in attention and memory were statistically significant versus sham
Results
Active dual-tDCS increased regional homogeneity (ReHo) in the right middle temporal gyrus and left inferior frontal gyrus.
ReHo changes were assessed via resting-state fMRI in a subgroup of 36 participants (18 per group)
Increased ReHo was observed in the right middle temporal gyrus (MTG) and left inferior frontal gyrus (IFG)
Results were corrected for multiple comparisons using family-wise error (FWE) correction (p < 0.05, FWE-corrected)
ReHo represents regional synchronization at the local neural level
Results
Active dual-tDCS reduced functional connectivity between the right MTG–left superior frontal gyrus and left IFG–cerebellum pairs.
Functional connectivity (FC) was reduced between right MTG and left superior frontal gyrus (p < 0.05, FWE-corrected)
FC was also reduced between left IFG and cerebellum (p < 0.05, FWE-corrected)
These inter-regional connectivity changes were detected in the rs-fMRI subgroup of 36 participants
Results
Active dual-tDCS increased small-worldness and global efficiency of functional brain network topology.
Both small-worldness and global efficiency increased significantly in the tDCS group (p < 0.05)
Network topology was assessed using graph-theoretic analysis of rs-fMRI data
These global topology changes represent the highest level of the hierarchical functional network organization examined
Results
Neuroimaging alterations in regional synchronization, inter-regional connectivity, and global topology correlated with clinical cognitive recovery.
Partial correlations were used to assess associations between neuroimaging alterations and clinical improvements
Changes in ReHo, FC, small-worldness, and global efficiency all correlated with clinical recovery outcomes
Authors suggest these neuroimaging measures represent potential biomarkers for monitoring tDCS efficacy
Results
Adverse events associated with dual-tDCS were rare and self-limiting in PSCI patients.
No serious adverse events were reported in the active tDCS group
The safety profile supports use of dual-tDCS at 2.0 mA for 20 min/day over 20 sessions in stroke rehabilitation
Authors concluded the intervention was 'safe' for cognitive recovery in PSCI
What This Means
This research suggests that a non-invasive brain stimulation technique called transcranial direct current stimulation (tDCS), applied to both sides of the prefrontal cortex (a brain region involved in thinking and decision-making), can meaningfully improve cognitive function in people who develop cognitive problems after a stroke. In this study, patients who received active tDCS alongside their usual rehabilitation therapy showed roughly twice the improvement on a standard cognitive test (MoCA) compared to patients who received fake (sham) stimulation, with the real treatment group improving by about 5.7 points versus 2.7 points. Improvements were also seen in specific areas like attention and memory.
The study used brain imaging (resting-state fMRI) in a subgroup of patients to look at what was happening inside the brain. This research suggests that tDCS changed brain activity at multiple levels simultaneously: locally (how synchronized activity was within individual brain regions), between regions (how different brain areas communicate with each other), and globally (how efficiently the entire brain network is organized). Notably, regions involved in language, memory, and executive function—including the middle temporal gyrus and inferior frontal gyrus—showed changes, and these brain changes were statistically linked to how much patients improved cognitively.
The treatment was well tolerated, with only rare and mild side effects. This research suggests that tDCS may offer a safe and effective add-on therapy for post-stroke cognitive impairment, and that brain imaging measures could potentially serve as biomarkers to track whether the treatment is working for individual patients—a step toward more personalized stroke rehabilitation.
Wang Y, Liu W, Yang W, Hu J, Cheng X, Yu H, et al.. (2026). Dual Transcranial Direct Current Stimulation Modulates Hierarchical Functional Network Organization in Post-Stroke Cognitive Impairment: A Randomized Controlled Trial.. CNS neuroscience & therapeutics. https://doi.org/10.1002/cns.71111