Aging populations face significant cognitive challenges, particularly in working memory (WM). Transcranial alternating current stimulation (tACS) offer promising avenues for cognitive enhancement, especially when inspired by brain physiology. This study (NCT04986787) explores the effect of multifocal tACS on WM performance in healthy older adults, focusing on fronto-parietal network modulation. Individualized physiology-inspired tACS applied to the fronto-parietal network was investigated in two blinded cross-over experiments. The first experiment involved monofocal/bifocal theta-tACS to the fronto-parietal network, while in the second experiment cross-frequency theta-gamma interactions between these regions were explored. Participants have done online WM tasks under the stimulation conditions. Network connectivity was assessed via rs-fMRI and multichannel electroencephalography. Prefrontal monofocal theta tACS modestly improved WM accuracy over sham (d = 0.30). Fronto-parietal stimulation enhanced WM task processing speed, with the strongest effects for bifocal in-phase theta tACS (d = 0.41). Cross-frequency stimulations modestly boosted processing speed with or without impairing task accuracy depending on the stimulation protocol. This research adds to the understanding of physiology-inspired brain stimulation for cognitive enhancement in older subjects.

1st Department of Neurology Faculty of Medicine and St Anne's University Hospital Masaryk University Brno Czech Republic

Applied Neuroscience Research Group Central European Institute of Technology Masaryk University Brno Czech Republic

Brain and Mind Research Central European Institute of Technology Masaryk University Brno Czech Republic

Clinical Neuroscience University of Geneva Medical School Geneva Switzerland

International Clinical Research Center Faculty of Medicine and St Anne's University Hospital Masaryk University Brno Czech Republic

Neuro 10 Institute Chemin des Mines 9 1202 CH Geneva Switzerland

Neuro 10 Institute EPFL Valais Clinique Romande de Réadaptation Sion Switzerland

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