Please use this identifier to cite or link to this item: http://hdl.handle.net/1822/57826

TitleWhole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD
Author(s)Deco, Gustavo
Cruzat, Josephine
Cabral, Joana
Knudsen, Gitte M.
Carhart-Harris, Robin L.
Whybrow, Peter C.
Logothetis, Nikos K.
Kringelbach, Morten L.
KeywordsWhole-brain modeling
Serotonin
LSD
PET
5-HT
Drug discovery
Neuromodulation
Music
Psychedelics
fMRI
Issue date8-Oct-2018
PublisherCell Press
JournalCurrent Biology
CitationDeco, G., Cruzat, J., Cabral, J., Knudsen, G. M., Carhart-Harris, R. L., et. al.(2018) Whole-brain multimodal neuroimaging model using serotonin receptor maps explains non-linear functional effects of LSD. Current biology, 28(19), 3065-3074
Abstract(s)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.
Typearticle
URIhttp://hdl.handle.net/1822/57826
DOI10.1016/j.cub.2018.07.083
ISSN0960-9822
e-ISSN1879-0445
Publisher versionhttps://www.sciencedirect.com/science/article/pii/S0960982218310455
Peer-Reviewedyes
AccessembargoedAccess (1 Year)
Appears in Collections:ICVS - Artigos em Revistas Internacionais com Referee


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