Comparative Efficacy of Dual- vs. Single-Node tACS in Amnestic Mild Cognitive Impairment: Behavioral and EEG Evidence
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Background The efficacy of current transcranial stimulation in cognitive disorders is limited by single-node intervention. Recent evidence indicates that amnestic mild cognitive impairment (aMCI) is associated with dysconnectivity in the frontoparietal network (FPN) and theta oscillations; modulating the FPN with theta-frequency stimulation represents a promising intervention for aMCI. Methods We developed a noninvasive transcranial alternating current stimulation (tACS) protocol for modulating long-range theta interactions within the FPN in aMCI patients. Thirty patients with aMCI were randomly assigned to 2 mA, 6 Hz, 25 min, and 10 sessions of dual-node tACS applied over right FPN (i.e., the DLPFC and the posterior parietal cortex) or single-node tACS over right DLPFC, followed by clinical visits at 4 weeks after treatment. Participants also undergone EEG recordings during resting state, 2-back working memory, and associative memory task before and after intervention. Results Compared with single-node stimulation, dual-node stimulation produced more sgnificant improvements in global cognition, as measured by Montreal Cognitive Assessment. Dual-node stimulation enhanced resting-state theta power in dorsolateral and midline prefrontal cortices. Furthermore, dual-node stimulation was also superior to single-site stimulation in improving memory performance and network dynamics, including theta-gamma phase-amplitude coupling in right dorsolateral prefrontal cortex during the working memory task and right frontal-to-parietal theta-phase synchronization during the associative memory task. Conclusion This study demonstrates behavioural benefits and neural mechanisms of dual-node stimulation in ameliorating cognitive impairment, providing a promising approach for achieving network-level intervention in cognitive disorders. Trial registration Chinese Clinical Trial Registry, ChiCTR2200058652 Registration Date
