TY - JOUR
T1 - Dual-site theta stimulation modulates connectivity, but not sequence memory in older adults
AU - Ehrhardt, Nina M.
AU - Lodema, D. Yorben
AU - Fleischmann, Robert
AU - Grittner, Ulrike
AU - Hayek, Dayana
AU - Hanna, Jevri
AU - Malinowski, Robert
AU - Li, Shu Chen
AU - Thielscher, Axel
AU - Flöel, Agnes
AU - Antonenko, Daria
N1 - Publisher Copyright:
© The Author(s) 2026. Published by Oxford University Press on behalf of the Guarantors of Brain. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
PY - 2026
Y1 - 2026
N2 - Understanding and modulating memory functions in older adults continues to be a fundamental challenge for neuroscientific research. Given age-associated declines in long-range connectivity, network approaches targeting these connections are of particular interest. We investigated whether dual-site transcranial alternating current stimulation can modulate episodic (sequential) memory in cognitively healthy older adults (N = 44, aged 60–80 years). In a sham-controlled crossover design, participants received in-phase (0°) and anti-phase (180°) transcranial alternating current stimulation during a temporal order memory task, with a counterbalanced order of conditions. We computed source analysis-based weighted phase lag indices and corrected amplitude envelope correlation between left hemispheric fronto-parietal stimulation targets from resting-state electroencephalography to quantify modulation of functional connectivity, and conducted analyses of phase angles between these targets. No overall memory effects were observed in either active stimulation conditions, compared with sham. However, the results showed an interaction between memory modulation and age, indicating that the older the participants the higher the memory improvement in the anti-phase condition. Functional coupling increase was observed in both anti- and in-phase conditions as an elevated weighted phase lag indices theta change, compared with sham. No differences were observed for weighted phase lag indices in other frequency bands (alpha, beta) or for the corrected amplitude envelope correlation (theta, alpha, beta). Theta phase angle shifts were increased in the anti-phase compared with the sham condition. Further, in the anti-phase condition, the increase in theta connectivity was linked to age and memory improvement, indicating a potential mechanistic link between neurophysiological and cognitive outcomes. In sum, our findings suggest that dual-site anti-phase stimulation may increase functional connectivity in older adults with large interindividual variability in memory effects, warranting further investigation to optimize stimulation strategies.
AB - Understanding and modulating memory functions in older adults continues to be a fundamental challenge for neuroscientific research. Given age-associated declines in long-range connectivity, network approaches targeting these connections are of particular interest. We investigated whether dual-site transcranial alternating current stimulation can modulate episodic (sequential) memory in cognitively healthy older adults (N = 44, aged 60–80 years). In a sham-controlled crossover design, participants received in-phase (0°) and anti-phase (180°) transcranial alternating current stimulation during a temporal order memory task, with a counterbalanced order of conditions. We computed source analysis-based weighted phase lag indices and corrected amplitude envelope correlation between left hemispheric fronto-parietal stimulation targets from resting-state electroencephalography to quantify modulation of functional connectivity, and conducted analyses of phase angles between these targets. No overall memory effects were observed in either active stimulation conditions, compared with sham. However, the results showed an interaction between memory modulation and age, indicating that the older the participants the higher the memory improvement in the anti-phase condition. Functional coupling increase was observed in both anti- and in-phase conditions as an elevated weighted phase lag indices theta change, compared with sham. No differences were observed for weighted phase lag indices in other frequency bands (alpha, beta) or for the corrected amplitude envelope correlation (theta, alpha, beta). Theta phase angle shifts were increased in the anti-phase compared with the sham condition. Further, in the anti-phase condition, the increase in theta connectivity was linked to age and memory improvement, indicating a potential mechanistic link between neurophysiological and cognitive outcomes. In sum, our findings suggest that dual-site anti-phase stimulation may increase functional connectivity in older adults with large interindividual variability in memory effects, warranting further investigation to optimize stimulation strategies.
KW - ageing
KW - episodic memory
KW - large-scale brain oscillations
KW - non-invasive brain stimulation
KW - transcranial alternating stimulation
UR - https://www.scopus.com/pages/publications/105038684758
U2 - 10.1093/braincomms/fcag153
DO - 10.1093/braincomms/fcag153
M3 - Article
AN - SCOPUS:105038684758
SN - 2632-1297
VL - 8
JO - Brain communications
JF - Brain communications
IS - 3
M1 - fcag153
ER -