A virtual clinical trial of psychedelics to treat patients with disorders of consciousness
Naji Alnagger, Paolo Cardone, Charlotte Martial, Yonatan Sanz Perl, Iván Mindlin, Jacobo Sitt, Leor Roseman, Robin Carhart‐Harris, David Nutt, Pablo Mallaroni, Natasha L. Mason, Johannes G. Ramaekers, Vincent Bonhomme, Steven Laureys, Gustavo Deco, Olivia Gosseries, Pablo Núñez, Jitka Annen
bioRxiv (Cold Spring Harbor Laboratory) August 19, 2024 preprint DOI: 10.1101/2024.08.16.608251 via OpenAlex
Summary
AI-generated from the abstractDisorders of consciousness, such as unresponsive wakefulness syndrome (UWS) and minimally conscious state (MCS), have few treatments. Using whole-brain computational models built from individual patients' fMRI and diffusion-weighted imaging data, this virtual clinical trial simulated the effects of LSD and psilocybin. The psychedelics shifted the brains of patients with disorders of consciousness closer to a critical dynamical state, with a larger effect in MCS patients. In UWS patients, the treatment response depended on structural connectivity, whereas in MCS patients it aligned with baseline functional connectivity. These results provide a computational foundation for considering psychedelics in treating disorders of consciousness and highlight the role of computational modeling in drug discovery and personalized medicine.
Study at a glance
| Characteristics | Computational modeling study (virtual clinical trial) |
|---|---|
| Population | Patients with disorders of consciousness (unresponsive wakefulness syndrome and minimally conscious state) |
| Interventions | LSD psilocybin |
| Keywords | Persistent vegetative state Consciousness Psychotherapist Clinical psychology |
| Citations | 3 |
| Key finding | LSD and psilocybin shift the brains of patients with disorders of consciousness closer to criticality, with a greater effect in minimally conscious state patients and a response that correlates with structural connectivity in unresponsive wakefulness syndrome patients and with baseline functional connectivity in minimally conscious state patients. |
Abstract
Disorders of consciousness (DoC), including the unresponsive wakefulness syndrome (UWS) and the minimally conscious state (MCS), have limited treatment options. Recent research suggests that psychedelic drugs, known for their complexity-enhancing properties, could be promising treatments for DoC. This study uses whole-brain computational models to explore this potential. We created individualised models for DoC patients, optimised with empirical fMRI and diffusion-weighted imaging (DWI) data, and simulated the administration of LSD and psilocybin. We used an in-silico perturbation protocol to distinguish between different states of consciousness, including DoC, anaesthesia, and the psychedelic state, and assess the dynamical stability of the brains of DoC patients pre- and post-psychedelic simulation. Our findings indicate that LSD and psilocybin shift DoC patients' brains closer to criticality, with a greater effect in MCS patients. In UWS patients, the treatment response correlates with structural connectivity, while in MCS patients, it aligns with baseline functional connectivity. This virtual clinical trial lays a computational foundation for using psychedelics in DoC treatment and highlights the future role of computational modelling in drug discovery and personalised medicine.