Comparative efficacy of dual- vs. single-node tACS in amnestic mild cognitive impairment: behavioral and EEG evidence

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 abnormal theta oscillations. Modulating the FPN with theta-frequency stimulation therefore represents a promising intervention for aMCI. We developed a noninvasive transcranial alternating current stimulation (tACS) protocol to modulate long-range theta interactions within the FPN in aMCI patients. Thirty patients with aMCI were randomly assigned to receive 10 sessions (2 mA, 6 Hz, 25 min per session) of either dual-node tACS applied over the right FPN (i.e., the dorsolateral prefrontal cortex, DLPFC, and the posterior parietal cortex, PPC) or single-node tACS over the right DLPFC alone. Participants also undergone EEG recordings during resting state, a 2-back working memory, and an associative memory task before and after intervention. Compared with single-node stimulation, dual-node stimulation produced more significant improvements in global cognition, as measured by Montreal Cognitive Assessment. Dual-node stimulation also enhanced resting-state theta power in dorsolateral and midline prefrontal cortices. Furthermore, dual-node stimulation was superior to single-site stimulation in improving memory performance and network dynamics. Specifically, it enhanced theta-gamma phase-amplitude coupling in right DLPFC during the working memory task and increased right frontal-to-parietal theta-phase synchronization during the associative memory task. This study provides preliminary evidence that dual-node tACS targeted over the FPN may offer behavioral and neurophysiological benefits over single-node stimulation in aMCI. Trial registration: Chinese Clinical Trial Registry, ChiCTR2200058652; Registration Date: 2022-03-13.