Restoring Oscillatory Dynamics in Alzheimer’s Disease: A Laminar Whole-Brain Model of Serotonergic Psychedelic Effects
Jan C. Gendra, Edmundo Lopez-Sola, Francesca Castaldo, Èlia Lleal-Custey, Roser Sanchez-Todo, Jakub Vohryzek, Ricardo Salvador, Ralph G. Andrzejak, Giulio Ruffini, The Alzheimer’s Disease Neuroimaging Initiative
bioRxiv (Cold Spring Harbor Laboratory) December 16, 2024 preprint DOI: 10.1101/2024.12.15.628565 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort with computational modeling |
|---|---|
| Sample size | 30 |
| Population | Subjects diagnosed with mild to moderate Alzheimer's disease |
| Topics | Serotonin |
| Keywords | Disease Dynamics music Laminar flow |
| Citations | 7 |
| Key findings | Simulated serotonin 2A receptor activation reproduces EEG changes (alpha suppression, gamma enhancement) that correlate with receptor distribution and suggest restored network function in Alzheimer's disease. |
Abstract
Abstract Classical serotonergic psychedelics show promise in addressing neurodegenerative disorders such as Alzheimer’s disease by modulating pathological brain dynamics. However, the precise neurobiological mechanisms underlying their effects remain elusive. This study introduces a personalized whole-brain model built upon a laminar neural mass framework to elucidate these effects. Using multimodal neuroimaging data from thirty subjects diagnosed with mild to moderate Alzheimer’s disease, we simulate the impact of serotonin 2A receptor activation, characteristic of psychedelics, on cortical dynamics. By modulating the excitability of layer 5 pyramidal neurons, our models reproduce hallmark changes in EEG power spectra observed under psychedelics, including alpha power suppression and gamma power enhancement. These spectral shifts are shown to correlate strongly with the regional distribution of serotonin 2A receptors. Furthermore, simulated EEG reveals increased complexity and entropy, suggesting restored network function. These findings underscore the potential of serotonergic psychedelics to reestablish healthy oscillatory dynamics in the prodromal and early phases of Alzheimer’s disease and offer mechanistic insights into their potential therapeutic effects in neurodegenerative disorders.
Comparable studies
Other observational and cohort studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Healthy volunteers | 2019 | Observational cohort | n = 8 |
| Memory impairment in abstinent MDMA ("Ecstasy") users Abstinent MDMA users | 1998 | Observational cohort | |
| Dynamic coupling of whole-brain neuronal and neurotransmitter systems Healthy humans | 2020 | Observational study | |
| The Serotonin System and Spiritual Experiences Normal male subjects, ages 20-45 years | 2003 | Observational cohort | n = 15 |
| Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD. Healthy human participants | 2018 | Observational study with computational modeling |
Citations in the library
Cites 34
- The entropic brain: a theory of conscious states informed by neuroimaging research with psychedelic drugs Frontiers in Human Neuroscience 2014
- REBUS and the Anarchic Brain: Toward a Unified Model of the Brain Action of Psychedelics Pharmacological Reviews June 20, 2019
- Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Current Biology April 13, 2016
- Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels Neuropsychopharmacology January 26, 2019
- Broadband Cortical Desynchronization Underlies the Human Psychedelic State Journal of Neuroscience September 18, 2013
and 29 more in the library