Causal modulation of cortical amplitude coupling through dual-site amplitude-modulated tACS

BackgroundIntrinsic functional coupling at multiple temporal scales is a hallmark of human brain dynamics. Among these coupling modes, slow co-fluctuations of oscillatory amplitudes, termed amplitude coupling, are thought to represent a key organizing principle of the large-scale functional architecture, constraining and gating network activity. Yet, despite extensive correlational evidence, direct causal access to amplitude coupling remains limited, restricting insight into its functional relevance. ObjectivesHere, we investigated whether dual-site amplitude-modulated transcranial alternating current stimulation (AM-tACS) can selectively modulate interhemispheric amplitude coupling in human resting-state networks. MethodsTwenty-eight participants received AM-tACS with a carrier frequency in the beta-band whose amplitude was modulated by low-frequency, scale-free dynamics. By applying dual-site AM-tACS either coherently or incoherently across bilateral parieto-occipital cortices, we tested whether stimulation could systematically enhance or disrupt amplitude co-fluctuations in the electrophysiological aftereffect. ResultsIncoherent AM-tACS significantly reduced interhemispheric amplitude coupling between targeted parieto-occipital cortices, with the strongest effects observed in the stimulated beta-band carrier frequency range. This modulation occurred independently of changes in local power or inter-areal phase coupling, indicating a selective effect of AM-tACS on amplitude-based connectivity. Moreover, reductions in amplitude coupling were correlated with the induced electric field strength, suggesting a dose-dependent relationship between stimulation intensity and coupling modulation. ConclusionsOur findings demonstrate that dual-site AM-tACS can causally and selectively modulate amplitude coupling in the human brain. By establishing causal control over lasting amplitude coupling dynamics, this work provides a methodological foundation for future investigations into the functional and behavioral relevance of amplitude coupling in both healthy and pathological brain states. HighlightsO_LIDual-site AM-tACS selectively modulates amplitude coupling in humans C_LIO_LIAM-tACS was designed to mimic natural, scale-free amplitude fluctuations C_LIO_LIStimulation effects are spatially confined to interactions between target regions C_LIO_LIE-field strength predicts the change in amplitude coupling, suggesting a dose-response relationship C_LIO_LIAmplitude coupling modulations are not mediated by band-limited power changes C_LI