The escalating global burden of age-related neurodegenerative diseases and associated healthcare costs necessitates innovative interventions to stabilize or enhance cognitive functions. Deficits in working memory (WM) are linked to alterations in prefrontal theta–gamma cross-frequency coupling. Low-intensity transcranial alternating current stimulation (tACS) has emerged as a non-invasive, low-cost approach capable of modulating ongoing oscillations in targeted brain areas through entrainment. This study investigates the impact of multi-session peak-coupled theta–gamma cross-frequency tACS administered to the dorsolateral prefrontal cortex (DLPFC) on WM performance in older adults. In a randomized, sham-controlled, triple-blinded design, 77 participants underwent 16 stimulation sessions over six weeks while performing n-back tasks. Signal detection measures revealed increased 2-back sensitivity and robust modulations of response bias, indicating improved WM and decision-making adaptations, respectively. No effects were observed in the 1-back condition, emphasizing dependencies on cognitive load. Repeated tACS reinforces behavioral changes, indicated by increasing effect sizes. This study supports prior research correlating prefrontal theta–gamma coupling with WM processes and provides unique insights into the neurocognitive benefits of repeated tACS intervention. The well-tolerated and highly effective multi-session tACS intervention among the elderly underscores its therapeutic potential in vulnerable populations.

与年龄相关的神经退行性疾病和相关医疗费用的全球负担不断升级，需要创新的干预措施来稳定或增强认知功能。工作记忆（WM）缺陷与前额叶 theta-gamma 交叉频率耦合的变化有关。低强度经颅交流电刺激 (tACS) 已成为一种非侵入性、低成本的方法，能够通过夹带调节目标大脑区域的持续振荡。本研究调查了对背外侧前额叶皮层 (DLPFC) 进行多次峰值耦合 θ-γ 交叉频率 tACS 对老年人 WM 表现的影响。在一项随机、假对照、三盲设计中，77 名参与者在六周内接受了 16 次刺激，同时执行n -back 任务。信号检测措施显示出 2-back 灵敏度的增加和响应偏差的稳健调节，分别表明 WM 和决策适应能力得到改善。在 1-back 条件下没有观察到任何影响，强调了对认知负荷的依赖性。重复的 tACS 会强化行为改变，表现为效应大小的增加。这项研究支持了先前将前额叶 theta-gamma 耦合与 WM 过程相关联的研究，并为重复 tACS 干预的神经认知益处提供了独特的见解。老年人中耐受性良好且高效的多次 tACS 干预强调了其对弱势群体的治疗潜力。