By Matthieu Aguilera (University of Strasbourg, France). November 7th, 2022.

Alzheimer’s disease (AD) is a neurodegenerative pathology characterized by a progressive and irreversible deterioration of cognitive functions, especially memory. A challenge in current research on AD is to find a reliable and early marker of the disease. Recently, our team showed that the new humanized AppNL-FxMAPT double knock-in (dKI) mouse model could generate key information on the initial disease’s stage.

To better characterize network alteration in the early stage of the disease, we performed long-term high-density EEG recording starting at 2-month of age in dKI and control littermate mice undergoing behavioral testing. Using EEG microstates dynamic analyses, our preliminary results show a decrease in microstates transition together with a reduced microstates sequences complexity starting at 4-months in dKI mice. Strikingly, these microstates dynamic alterations were concomitant with the emergence of the first recognition deficits in an object-place association task.

This prompt us to test the effect of a non-invasive visual stimulation on EEG microstates dynamic as recent studies have shown that 40 Hz gamma entrainment via visual stimulation protocol (vGENUS) reduce AD pathology (both at the behavioral and histopathological levels). We showed that vGENUS treatment effectively rescued memory deficits in the object-place association task as well as EEG microstates dynamics and complexity in dKI mice. Specifically, control mice display a distribution of dwell times in microstates manifesting a distinctive power-law shape. AD animals have a supercritical type distribution, with an excess occurrence of long permanence time (the dynamics tend to “get stuck” into microstates). The application of the vGenus protocol restores the distribution toward a power-law shape reducing the area under the supercritical bulge.

Our results therefore provide new insight into early network dynamic alterations and beneficial effects of a non-invasive gamma visual stimulation in AD, suggesting that they may have (altered) critical dynamics underpinnings.

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