%0 Journal Article
%A Javed, Ehtasham
%A Suárez Méndez, Isabel
%A Susi, Gianluca
%A Verdejo Román, Juan
%A Matias Palva, J
%A Maestu Unturbe, Fernando
%A Palva, Satu
%T A shift towards super-critical brain dynamics predicts Alzheimer’s disease progression
%D 2024
%@ 0270-6474
%U https://hdl.handle.net/20.500.14352/116402
%X Alzheimer’s disease (AD) is the most common form of dementia with continuum of disease progression of increasing severity from subjective cognitive decline (SCD) to mild cognitive impairment (MCI), and lastly to AD. The transition from MCI to AD has been linked to brain hyper-synchronization, but the underlying mechanisms leading to this are unknown. Here, we hypothesized that excessive excitation in AD disease progression would shift brain dynamics towards supercriticality across an extended regime of critical-like dynamics. In this framework, healthy brain activity during aging preserves operation at near the critical phase transition at balanced excitation-inhibition (E/I). To test this hypothesis, we used source-reconstructed resting-state MEG data from a cross-sectional cohort (N=343) of individuals with SCD, MCI and healthy controls (HC) as well as from a longitudinal cohort (N=45) of MCI patients. We then assessed brain criticality by quantifying long-range temporal correlations (LRTCs) and functional EI (fE/I) of neuronal oscillations. LRTCs were attenuated in SCD in spectrally and anatomically constrained regions while this breakdown was progressively more widespread in MC. In parallel, fE/I was increased in the MCI but not in the SC cohort. Both observations also predicted the disease progression in the longitudinal cohort. Finally, using machine learning trained on functional (LRTCs, fE/I) and structural (MTL volumes) features, we show that LRTCs and f/EI are the most informative features for accurate classification of individuals with SCD while structural changes accurate classify the individuals with MCI. These findings establish that a shift towards super-critical brain dynamics reflects early AD disease progression.
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