Transcutaneous electrical stimulation enhances episodic memory encoding via a noradrenaline-attention network, with associated neuroinflammatory changes.

Attention plays a central role in learning and memory processes. Prior research has demonstrated how goal-directed attention influences successful performance on both attention and working memory tasks. However, an important question remains about whether long-term memory outcomes can be reliably enhanced by targeting attention processes. To test the hypothesis that 40 Hz Non-invasive Transcutaneous Electrical Stimulation of the Greater Occipital Nerve (NITESGON) would enhance long-term memory encoding by upregulating theta activity in the dorsal attention network. We also hypothesized that this would be in association with upregulated noradrenaline activity and downregulated cytokine activity. In two double-blinded experiments, learning and memory were tested via a Swahili-English word-association task completed on 2 visits (separated by 1 week). 60 individuals were randomized to assess 40 Hz NITESGON's effect compared to active-control (1 Hz) or sham conditions. Before and after stimulation, rs-EEG assessed theta activity in the dorsal attention network, and saliva measures were collected incl. salivary alpha amylase (sAA; a proxy for noradrenaline activity) and cytokines (IL-6, IL-1β and TNF-α). Participants receiving 40 Hz NITESGON learned and remembered more words than control or sham groups. There were no significant differences in consolidation between the groups. 40 Hz NITESGON was associated with increased theta activity in the dorsal attention network, and this activation was associated with enhanced learning but not memory performance. The 40 Hz NITESGON group had significantly upregulated sAA post-stimulation, with this associated with learning and memory (supporting a LC-NA mechanism). Modulation of IL-1β and TNF-α were not frequency specific. However, modulation of IL-6 was specific to 40 Hz and was associated with memory outcomes. 40 Hz NITESGON can activate a noradrenaline - dorsal attention network, to facilitate goal-directed attention during encoding stages of a long-term memory task, in association with neuroinflammatory changes.