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

Background: 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...

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Main Authors: Elva Arulchelvan, Sven Vanneste
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Brain Stimulation
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Online Access:http://www.sciencedirect.com/science/article/pii/S1935861X25000105
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author Elva Arulchelvan
Sven Vanneste
author_facet Elva Arulchelvan
Sven Vanneste
author_sort Elva Arulchelvan
collection DOAJ
description Background: 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. Objective: 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 hypothesised that this would be in association with upregulated noradrenaline activity and downregulated cytokine activity. Methods: 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). Results: 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. Conclusion: 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.
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spelling doaj-art-0b9684ddb9fb4eaa906ff565ec66c89d2025-08-20T02:17:27ZengElsevierBrain Stimulation1935-861X2025-01-0118119120710.1016/j.brs.2025.01.008Transcutaneous electrical stimulation enhances episodic memory encoding via a noradrenaline-attention network, with associated neuroinflammatory changesElva Arulchelvan0Sven Vanneste1Lab for Clinical and Integrative Neuroscience, Trinity Institute for Neuroscience, School of Psychology, Trinity College Dublin, IrelandLab for Clinical and Integrative Neuroscience, Trinity Institute for Neuroscience, School of Psychology, Trinity College Dublin, Ireland; Global Brain Health Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; Corresponding author. Lab for Clinical & Integrative Neuroscience, School of Psychology, Global Brain Health Institute, Institute of Neuroscience, Trinity College Dublin, College Green 2, Dublin, Ireland.Background: 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. Objective: 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 hypothesised that this would be in association with upregulated noradrenaline activity and downregulated cytokine activity. Methods: 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). Results: 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. Conclusion: 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.http://www.sciencedirect.com/science/article/pii/S1935861X25000105TranscranialTranscutaneousElectrical stimulationEpisodic memoryAttention networkLocus coeruleus
spellingShingle Elva Arulchelvan
Sven Vanneste
Transcutaneous electrical stimulation enhances episodic memory encoding via a noradrenaline-attention network, with associated neuroinflammatory changes
Brain Stimulation
Transcranial
Transcutaneous
Electrical stimulation
Episodic memory
Attention network
Locus coeruleus
title Transcutaneous electrical stimulation enhances episodic memory encoding via a noradrenaline-attention network, with associated neuroinflammatory changes
title_full Transcutaneous electrical stimulation enhances episodic memory encoding via a noradrenaline-attention network, with associated neuroinflammatory changes
title_fullStr Transcutaneous electrical stimulation enhances episodic memory encoding via a noradrenaline-attention network, with associated neuroinflammatory changes
title_full_unstemmed Transcutaneous electrical stimulation enhances episodic memory encoding via a noradrenaline-attention network, with associated neuroinflammatory changes
title_short Transcutaneous electrical stimulation enhances episodic memory encoding via a noradrenaline-attention network, with associated neuroinflammatory changes
title_sort transcutaneous electrical stimulation enhances episodic memory encoding via a noradrenaline attention network with associated neuroinflammatory changes
topic Transcranial
Transcutaneous
Electrical stimulation
Episodic memory
Attention network
Locus coeruleus
url http://www.sciencedirect.com/science/article/pii/S1935861X25000105
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AT svenvanneste transcutaneouselectricalstimulationenhancesepisodicmemoryencodingviaanoradrenalineattentionnetworkwithassociatedneuroinflammatorychanges