Predictive role of endogenous phase lags between target brain regions in dual-site transcranial alternating current stimulation

Background: Dual-site transcranial alternating current stimulation (tACS) provides a promising tool for modulating interregional brain connectivity by entraining neural oscillations. However, prior studies have reported inconsistent effects on connectivity and behavioral outcomes. They often focused...

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Main Authors: Osama Elyamany, Jona Iffland, Josef Bak, Cornelius Classen, Guido Nolte, Till R. Schneider, Gregor Leicht, Christoph Mulert
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Brain Stimulation
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Online Access:http://www.sciencedirect.com/science/article/pii/S1935861X25000920
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author Osama Elyamany
Jona Iffland
Josef Bak
Cornelius Classen
Guido Nolte
Till R. Schneider
Gregor Leicht
Christoph Mulert
author_facet Osama Elyamany
Jona Iffland
Josef Bak
Cornelius Classen
Guido Nolte
Till R. Schneider
Gregor Leicht
Christoph Mulert
author_sort Osama Elyamany
collection DOAJ
description Background: Dual-site transcranial alternating current stimulation (tACS) provides a promising tool for modulating interregional brain connectivity by entraining neural oscillations. However, prior studies have reported inconsistent effects on connectivity and behavioral outcomes. They often focused on individualized stimulation-frequency as a key entrainment factor, while typically not focusing on the role of endogenous phase lags. To address this gap, we explored the predictive value of endogenous phase lags in dual-site tACS to modulate interhemispheric connectivity during dichotic listening. Methods: Thirty healthy participants (16 females) completed a dichotic listening task while undergoing simultaneous electroencephalography and tACS, including four bitemporal verum conditions with varying phase lags (0°, 45°, 90°, and 180°), and a sham condition across five sessions. Each session involved 20 min of 40-Hz tACS at a 0.5 mA peak-to-baseline amplitude applied to the temporal regions, with phase lags differing across sessions. Endogenous phase lags between the auditory cortices were calculated to explain changes in the laterality index (LI) across stimulation conditions by defining optimal and disruptive stimulation conditions for each participant. Results: Consistent with our hypothesis, our personalized analysis based on the calculated endogenous phase lags showed a significantly lower LI during the closest (optimal) stimulation condition compared to both the sham and farthest (disruptive) conditions. Conversely, the farthest stimulation condition did not statistically increase the LI compared to sham. Conclusions: These findings highlight the importance of incorporating endogenous phase dynamics into dual-site tACS protocols, paving the way for more consistent and individualized neuromodulatory interventions.
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spelling doaj-art-d4d89ac6b91e439eb6dca1a862e8a79c2025-08-20T03:08:20ZengElsevierBrain Stimulation1935-861X2025-05-0118378079310.1016/j.brs.2025.04.011Predictive role of endogenous phase lags between target brain regions in dual-site transcranial alternating current stimulationOsama Elyamany0Jona Iffland1Josef Bak2Cornelius Classen3Guido Nolte4Till R. Schneider5Gregor Leicht6Christoph Mulert7Centre of Psychiatry, Justus-Liebig University, Klinikstrasse 36, Giessen, Hessen, 35392, Germany; Centre for Mind, Brain and Behaviour (CMBB), Hans-Meerwein-Strasse 6, Marburg, 35043, Hessen, Germany; Corresponding author. Centre of Psychiatry, Justus-Liebig University, Klinikstrasse 36, Giessen, 35392, Hessen, Germany.Centre of Psychiatry, Justus-Liebig University, Klinikstrasse 36, Giessen, Hessen, 35392, GermanyCentre of Psychiatry, Justus-Liebig University, Klinikstrasse 36, Giessen, Hessen, 35392, GermanyCentre of Psychiatry, Justus-Liebig University, Klinikstrasse 36, Giessen, Hessen, 35392, GermanyDepartment of Neurophysiology and Pathophysiology, University Medical Centre Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20246, GermanyDepartment of Neurophysiology and Pathophysiology, University Medical Centre Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20246, GermanyDepartment of Psychiatry and Psychotherapy, University Medical Centre Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20246, GermanyCentre of Psychiatry, Justus-Liebig University, Klinikstrasse 36, Giessen, Hessen, 35392, Germany; Centre for Mind, Brain and Behaviour (CMBB), Hans-Meerwein-Strasse 6, Marburg, 35043, Hessen, GermanyBackground: Dual-site transcranial alternating current stimulation (tACS) provides a promising tool for modulating interregional brain connectivity by entraining neural oscillations. However, prior studies have reported inconsistent effects on connectivity and behavioral outcomes. They often focused on individualized stimulation-frequency as a key entrainment factor, while typically not focusing on the role of endogenous phase lags. To address this gap, we explored the predictive value of endogenous phase lags in dual-site tACS to modulate interhemispheric connectivity during dichotic listening. Methods: Thirty healthy participants (16 females) completed a dichotic listening task while undergoing simultaneous electroencephalography and tACS, including four bitemporal verum conditions with varying phase lags (0°, 45°, 90°, and 180°), and a sham condition across five sessions. Each session involved 20 min of 40-Hz tACS at a 0.5 mA peak-to-baseline amplitude applied to the temporal regions, with phase lags differing across sessions. Endogenous phase lags between the auditory cortices were calculated to explain changes in the laterality index (LI) across stimulation conditions by defining optimal and disruptive stimulation conditions for each participant. Results: Consistent with our hypothesis, our personalized analysis based on the calculated endogenous phase lags showed a significantly lower LI during the closest (optimal) stimulation condition compared to both the sham and farthest (disruptive) conditions. Conversely, the farthest stimulation condition did not statistically increase the LI compared to sham. Conclusions: These findings highlight the importance of incorporating endogenous phase dynamics into dual-site tACS protocols, paving the way for more consistent and individualized neuromodulatory interventions.http://www.sciencedirect.com/science/article/pii/S1935861X25000920Dichotic listeningInterhemispheric connectivityDual-siteBifocaltACSEEG
spellingShingle Osama Elyamany
Jona Iffland
Josef Bak
Cornelius Classen
Guido Nolte
Till R. Schneider
Gregor Leicht
Christoph Mulert
Predictive role of endogenous phase lags between target brain regions in dual-site transcranial alternating current stimulation
Brain Stimulation
Dichotic listening
Interhemispheric connectivity
Dual-site
Bifocal
tACS
EEG
title Predictive role of endogenous phase lags between target brain regions in dual-site transcranial alternating current stimulation
title_full Predictive role of endogenous phase lags between target brain regions in dual-site transcranial alternating current stimulation
title_fullStr Predictive role of endogenous phase lags between target brain regions in dual-site transcranial alternating current stimulation
title_full_unstemmed Predictive role of endogenous phase lags between target brain regions in dual-site transcranial alternating current stimulation
title_short Predictive role of endogenous phase lags between target brain regions in dual-site transcranial alternating current stimulation
title_sort predictive role of endogenous phase lags between target brain regions in dual site transcranial alternating current stimulation
topic Dichotic listening
Interhemispheric connectivity
Dual-site
Bifocal
tACS
EEG
url http://www.sciencedirect.com/science/article/pii/S1935861X25000920
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