Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD.
Gustavo Deco, Josephine Cruzat, Joana Cabral, Gitte M. Knudsen, Robin Carhart-Harris, Peter C. Whybrow, Nikos K. Logothetis, Morten L. Kringelbach
Current Biology September 27, 2018 DOI: 10.1016/j.cub.2018.07.083 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study with computational modeling Peer reviewed |
|---|---|
| Population | Healthy human participants |
| Intervention | Lysergic acid diethylamide (LSD) |
| Topics | LSD Serotonin |
| Keywords | LSD Brain Effects Serotonin receptors Neuropharmacology |
| Citations | 246 |
| Key findings | LSD's effects on brain dynamics are causally explained by non-linear interactions between anatomical connectivity, 5-HT2A receptor density distribution, and neuromodulation of neuronal gain. |
Abstract
Understanding the underlying mechanisms of the human brain in health and disease will require models with necessary and sufficient details to explain how function emerges from the underlying anatomy and is shaped by neuromodulation. Here, we provide such a detailed causal explanation using a whole-brain model integrating multimodal imaging in healthy human participants undergoing manipulation of the serotonin system. Specifically, we combined anatomical data from diffusion magnetic resonance imaging (dMRI) and functional magnetic resonance imaging (fMRI) with neurotransmitter data obtained with positron emission tomography (PET) of the detailed serotonin 2A receptor (5-HT2AR) density map. This allowed us to model the resting state (with and without concurrent music listening) and mechanistically explain the functional effects of 5-HT2AR stimulation with lysergic acid diethylamide (LSD) on healthy participants. The whole-brain model used a dynamical mean-field quantitative description of populations of excitatory and inhibitory neurons as well as the associated synaptic dynamics, where the neuronal gain function of the model is modulated by the 5-HT2AR density. The model identified the causative mechanisms for the non-linear interactions between the neuronal and neurotransmitter system, which are uniquely linked to (1) the underlying anatomical connectivity, (2) the modulation by the specific brainwide distribution of neurotransmitter receptor density, and (3) the non-linear interactions between the two. Taking neuromodulatory activity into account when modeling global brain dynamics will lead to novel insights into human brain function in health and disease and opens exciting possibilities for drug discovery and design in neuropsychiatric disorders.
Comparable studies
Other observational and cohort studies on LSD, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Increased Global Functional Connectivity Correlates with LSD-Induced Ego Dissolution. Human participants | 2016 | Observational cohort | |
| Increased spontaneous MEG signal diversity for psychoactive doses of ketamine, LSD and psilocybin Humans | 2017 | Observational study | |
| Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. USA adult respondents from the National Survey on Drug Use and Health (2008-2012) | 2015 | Observational cohort | n = 190,000 |
| Psychedelics not linked to mental health problems or suicidal behavior: A population study Randomly selected United States adults | 2015 | Observational cohort | n = 135,095 |
| Long-lasting subjective effects of LSD in normal subjects Healthy participants | 2017 | Observational cohort | n = 16 |
Citations in the library
Cited by 75
- Dynamic coupling of whole-brain neuronal and neurotransmitter systems Proceedings of the National Academy of Sciences April 13, 2020
- The neural basis of psychedelic action. Nature Neuroscience October 24, 2022
- LSD alters dynamic integration and segregation in the human brain. Neuroimage February 15, 2021
- Receptor-informed network control theory links LSD and psilocybin to a flattening of the brain's control energy landscape. Nature Communications October 3, 2022
- How do psychedelics work? Current Opinion in Psychiatry 2019
and 70 more in the library
Cites 13
- A default mode of brain function Proceedings of the National Academy of Sciences January 16, 2001
- Neural correlates of the LSD experience revealed by multimodal neuroimaging. Proceedings of the National Academy of Sciences April 11, 2016
- Psychedelics and the essential importance of context. Journal of Psychopharmacology February 15, 2018
- The paradoxical psychological effects of lysergic acid diethylamide (LSD) Psychological Medicine February 5, 2016
- Connectome-harmonic decomposition of human brain activity reveals dynamical repertoire re-organization under LSD. Scientific Reports December 15, 2017
and 8 more in the library