Gamma transcranial alternating current stimulation prevents scopolamine-induced damage to EEG activity and spatial memory

Background Dementia is a serious public health concern, primarily caused by Alzheimer's disease (AD). Transcranial alternating current stimulation (tACS) can improve cognitive function by modulating neural oscillations. While tACS shows therapeutic potential for dementia, its preventive effects remain unknown. Because tACS has long-lasting modulatory effects, we propose that these offline effects may help prevent dementia. Objective This study aims to determine whether pre-administered 40 Hz tACS prevents scopolamine-induced impairment of electroencephalogram (EEG) activity and spatial cognition. Scopolamine induces cholinergic dysfunction in animal models, mimicking AD-related behavioral and EEG abnormalities. Methods Scopolamine (3 mg/kg, i.p.) was administered to induce a mouse model of dementia. Prior to induction, tACS targeting the prefrontal cortex (PFC) and/or hippocampus (Hip) was performed for five days (40 Hz, 300 μA, 20 min/day). EEG activity was recorded from the PFC and Hip during spontaneous and task-related (Y-maze) states. In addition, spatial memory was evaluated using the Barnes maze test, and general activity including locomotion and anxiety was evaluated using the open field test. Results Scopolamine reduced spontaneous EEG activity in gamma frequency band and task-related PFC EEG activity across multiple frequency bands. Prior Hip tACS prevented these EEG reductions. Behaviorally, scopolamine induced spatial memory deficits and increased locomotion and anxiety-like behaviors. Notably, dual-site tACS reversed memory impairment and PFC tACS reduced locomotion. In addition, tACS had little effect on anxiety. Conclusions Prior gamma tACS exerts region-specific protection against scopolamine-induced EEG and behavioral impairments, providing first evidence for its potential as a preventive strategy for dementia-related deficits.