Restoring Oscillatory Dynamics in Alzheimer’s Disease: A Laminar Whole-Brain Model of Serotonergic Psychedelic Effects
bioRxiv (Cold Spring Harbor Laboratory) December 16, 2024 Jan C. Gendra, Edmundo Lopez-Sola, Francesca Castaldo et al. 7 citations preprint
Classical serotonergic psychedelics may help treat neurodegenerative disorders like Alzheimer's disease by altering pathological brain dynamics. Using multimodal neuroimaging data from thirty subjects with mild to moderate Alzheimer's disease, a personalized whole-brain model based on a laminar neural mass framework simulated the effects of serotonin 2A receptor activation. Modulating the excitability of layer 5 pyramidal neurons reproduced hallmark EEG changes seen under psychedelics, including alpha power suppression and gamma power enhancement. These spectral shifts correlated strongly with regional serotonin 2A receptor distribution. Simulated EEG also showed increased complexity and entropy, suggesting restored network function, offering mechanistic insights into potential therapeutic effects in early Alzheimer's disease.