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  Whole-brain multimodal neuroimaging model using serotonin receptor maps explains non-linear functional effects of LSD

Deco, G., Cruzal, J., Cabal, J., Knudsen, G. M., Carhart-Harris, R. L., Whybrow, P. C., 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.e6. doi:10.1016/j.cub.2018.07.083.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0003-BAB7-D Version Permalink: http://hdl.handle.net/21.11116/0000-0003-CA7E-D
Genre: Journal Article


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Deco, Gustavo1, 2, 3, 4, Author              
Cruzal, Josephine1, Author
Cabal, Joana5, 6, 7, Author
Knudsen, Gitte M.8, 9, Author
Carhart-Harris , Robin L.10, Author
Whybrow, Peter C.11, Author
Logothetis, Nikos K.12, 13, Author
Kringelbach, Morten L.5, 6, 7, 14, Author
1Center for Brain and Cognition, University Pompeu Fabra, Barcelona, Spain, ou_persistent22              
2Catalan Institution for Research and Advanced Studies (ICREA), University Pompeu Fabra, Barcelona, Spain, ou_persistent22              
3Department Neuropsychology, MPI for Human Cognitive and Brain Sciences, Max Planck Society, ou_634551              
4School of Psychological Sciences, Monash University, Melbourne, Australia, ou_persistent22              
5Department of Psychiatry, University of Oxford, United Kingdom, ou_persistent22              
6Center for Music in the Brain, Aarhus University, Denmark, ou_persistent22              
7ICVS - Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, Braga, Portugal, ou_persistent22              
8Center for Integrated Molecular Brain Imaging (CIMBI), Copenhagen, Denmark, ou_persistent22              
9Faculty of Health and Medical Sciences, University of Copenhagen, Denmark, ou_persistent22              
10Psychedelic Research Group, Division of Brain Sciences, Faculty of Medicine, Imperial College London, United Kingdom, ou_persistent22              
11Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, CA, USA, ou_persistent22              
12Max Planck Institute for Biological Cybernetics, Tübingen, Germany, ou_persistent22              
13Centre for Imaging Sciences, University of Manchester, United Kingdom, ou_persistent22              
14Institut d’études avancées de Paris, France, ou_persistent22              


Free keywords: Whole-brain modeling; Serotonin; LSD; PET; 5-HT; Drug discovery; Neuromodulation; Music; Psychedelics; fMRI
 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.


Language(s): eng - English
 Dates: 2018-06-212018-05-092018-07-312018-09-272018-10-08
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: DOI: 10.1016/j.cub.2018.07.083
Other: Epub 2018
PMID: 30270185
 Degree: -



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Project information

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Project name : The Dynamical and Structural Basis of Human Mind Complexity: Segregation and Integration of Information and Processing in the Brain / DYSTRUCTURE
Grant ID : 295129
Funding program : Funding Programme 7
Funding organization : European Commission (EC)
Project name : Spanish National Project Complexity of Brain States
Grant ID : PSI2016-75688-P
Funding program : -
Funding organization : Spanish Research Agency (AEI) and the European Regional Development Fund (ERDF)
Project name : Human Brain Project Specific Grant Agreement 2 / HBP SGA2
Grant ID : 785907
Funding program : Horizon 2020
Funding organization : European Commission (EC)
Project name : The plasticity of parental caregiving: characterizing the brain mechanisms underlying normal and disrupted development of parenting / CAREGIVING
Grant ID : 615539
Funding program : Funding Programme 7
Funding organization : European Commission (EC)
Project name : -
Grant ID : DNRF117
Funding program : -
Funding organization : Danish National Research Foundation
Project name : -
Grant ID : -
Funding program : -
Funding organization : Alex Mosley Charitable Trust
Project name : -
Grant ID : -
Funding program : -
Funding organization : Beckley Foundation
Project name : -
Grant ID : NORTE-01-0145-FEDER-000023
Funding program : European Regional Development Fund
Funding organization : European Commission (EC)
Project name : -
Grant ID : 2010-5364
Funding program : -
Funding organization : Lundbeck Foundation

Source 1

Title: Current Biology
  Other : Curr. Biol.
Source Genre: Journal
Publ. Info: London, UK : Cell Press
Pages: - Volume / Issue: 28 (19) Sequence Number: - Start / End Page: 3065 - 3074.e6 Identifier: ISSN: 0960-9822
CoNE: https://pure.mpg.de/cone/journals/resource/954925579107