==== Front bioRxiv BIORXIV bioRxiv Cold Spring Harbor Laboratory 10.1101/2023.06.11.544491 preprint 1 Article Resting-state EEG signatures of Alzheimer’s disease are driven by periodic but not aperiodic changes Kopčanová Martina http://orcid.org/0009-0004-0300-3343 Tait Luke http://orcid.org/0000-0002-2351-5328 Donoghue Thomas http://orcid.org/0000-0001-5911-0472 Stothart George http://orcid.org/0000-0003-1323-1580 Smith Laura http://orcid.org/0000-0003-3275-1530 Flores Sandoval Aimee Arely Davila-Perez Paula http://orcid.org/0000-0003-3596-1429 Buss Stephanie Shafi Mouhsin M. Pascual-Leone Alvaro http://orcid.org/0000-0001-8975-0382 Fried Peter J. Benwell Christopher S.Y. http://orcid.org/0000-0002-4157-4049 12 6 2023 2023.06.11.544491http://biorxiv.org/lookup/doi/10.1101/2023.06.11.544491 nihpp-2023.06.11.544491.pdf Abstract Electroencephalography (EEG) has shown potential for identifying early-stage biomarkers of neurocognitive dysfunction associated with dementia due to Alzheimer’s disease (AD). A large body of evidence shows that, compared to healthy controls (HC), AD is associated with power increases in lower EEG frequencies (delta and theta) and decreases in higher frequencies (alpha and beta), together with slowing of the peak alpha frequency. However, the pathophysiological processes underlying these changes remain unclear. For instance, recent studies have shown that apparent shifts in EEG power from high to low frequencies can be driven either by frequency specific periodic power changes or rather by non-oscillatory (aperiodic) changes in the underlying 1/f slope of the power spectrum. Hence, to clarify the mechanism(s) underlying the EEG alterations associated with AD, it is necessary to account for both periodic and aperiodic characteristics of the EEG signal. Across two independent datasets, we examined whether resting-state EEG changes linked to AD reflect true oscillatory (periodic) changes, changes in the aperiodic (non-oscillatory) signal, or a combination of both. We found strong evidence that the alterations are purely periodic in nature, with decreases in oscillatory power at alpha and beta frequencies (AD < HC) leading to lower (alpha + beta) / (delta + theta) power ratios in AD. Aperiodic EEG features did not differ between AD and HC. By replicating the findings in two cohorts, we provide robust evidence for purely oscillatory pathophysiology in AD and against aperiodic EEG changes. We therefore clarify the alterations underlying the neural dynamics in AD and emphasise the robustness of oscillatory AD signatures, which may further be used as potential prognostic or interventional targets in future clinical investigations. ==== Body pmc