Whole-brain modelling supports the use of serotonergic psychedelics for the treatment of disorders of consciousness
I Mindlin, R Herzog, L Belloli, D Manasova, M Monge-Asensio, J. Vohryzek, A. Escrichs, N Alnagger, P Núñez, Ml Kringelbach, G Deco, E Tagliazucchi, L Naccache, B Rohaut, Jd Sitt, Y Sanz Perl
bioRxiv Preprint Server December 29, 2023 preprint DOI: 10.1101/2023.12.29.573603 via bioRxiv
Summary
AI-generated from the abstractDisorders of consciousness involve impaired awareness with few non-invasive treatment options. Researchers used computer models to simulate how activating certain receptors, particularly serotonergic and opioid receptors, alters whole-brain dynamics in patients. The simulations shifted patients' brain activity patterns toward those seen in conscious, awake individuals. This effect depended on the density of activated receptors across the brain. The results suggest whole-brain modeling can help identify new pharmacological treatments and support the potential of serotonergic psychedelics to accelerate recovery of consciousness.
Study at a glance
| Characteristics | In silico simulation |
|---|---|
| Population | Patients with disorders of consciousness |
| Citations | 7 |
| Key finding | Simulated activation of serotonergic and opioid receptors shifted brain dynamics of DoC patients toward patterns typical of conscious individuals, mediated by receptor density. |
Abstract
Disorders of consciousness (DoC) are a challenging and complex group of neurological conditions characterised by absent or impaired awareness. The current range of therapeutic options for DoC patients is limited, offering few non-invasive pharmacological alternatives. This situation has sprung a growing interest in the development of novel treatments, such as the proposal to study the efficacy of 5HT2A receptor agonists (also known as psychedelics) to restore impaired consciousness. Given the ethical implications of exploring novel compounds in non-communicative individuals, we assessed in silico their effects in the whole-brain dynamics of DoC patients. We embedded the whole-brain activity of patients in a low-dimensional space, and then used this representation to visualise the effects of simulated neuromodulation across a range of receptors representing potential drug targets. Our findings show that activation of serotonergic and opioid receptors shifted brain dynamics of DoC patients towards patterns typically seen in conscious and awake individuals, and that this effect was mediated by the brain-wide density of activated receptors. These results showcase the role of whole-brain models in the discovery of novel pharmacological treatments for neuropsychiatric conditions, while also supporting the feasibility of accelerating the recovery of consciousness with serotonergic psychedelics.