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Dynamic coupling of whole-brain neuronal and neurotransmitter systems

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dc.contributor.author Kringelbach, Morten L.
dc.contributor.author Cruzat Grand, Josefina, 1983-
dc.contributor.author Cabral, Joana
dc.contributor.author Moos Knudsen, Gitte
dc.contributor.author Carhart-Harris, Robin L.
dc.contributor.author Whybrow, Peter C.
dc.contributor.author Logothetis, N.
dc.contributor.author Deco, Gustavo
dc.date.accessioned 2020-05-07T08:33:24Z
dc.date.available 2020-05-07T08:33:24Z
dc.date.issued 2020
dc.identifier.citation Kringelbach ML, Cruzat J, Cabral J, Moos Knudsen G, Carhart Harris R, Whybrow PC, Logothetis NK, Deco G. Dynamic coupling of whole-brain neuronal and neurotransmitter systems. Proc Natl Acad Sci. 2020 Apr 28;117(17):9566-76. DOI: 10.1073/pnas.1921475117
dc.identifier.issn 0027-8424
dc.identifier.uri http://hdl.handle.net/10230/44444
dc.description.abstract Remarkable progress has come from whole-brain models linking anatomy and function. Paradoxically, it is not clear how a neuronal dynamical system running in the fixed human anatomical connectome can give rise to the rich changes in the functional repertoire associated with human brain function, which is impossible to explain through long-term plasticity. Neuromodulation evolved to allow for such flexibility by dynamically updating the effectivity of the fixed anatomical connectivity. Here, we introduce a theoretical framework modeling the dynamical mutual coupling between the neuronal and neurotransmitter systems. We demonstrate that this framework is crucial to advance our understanding of whole-brain dynamics by bidirectional coupling of the two systems through combining multimodal neuroimaging data (diffusion magnetic resonance imaging [dMRI], functional magnetic resonance imaging [fMRI], and positron electron tomography [PET]) to explain the functional effects of specific serotoninergic receptor (5-HT2AR) stimulation with psilocybin in healthy humans. This advance provides an understanding of why psilocybin is showing considerable promise as a therapeutic intervention for neuropsychiatric disorders including depression, anxiety, and addiction. Overall, these insights demonstrate that the whole-brain mutual coupling between the neuronal and the neurotransmission systems is essential for understanding the remarkable flexibility of human brain function despite having to rely on fixed anatomical connectivity.
dc.description.sponsorship G.D. is supported by the Spanish Research Project PSI2016-75688-P (Agencia Estatal de Investigación/Fondo Europeo de Desarrollo Regional, European Union); by the European Union’s Horizon 2020 Research and Innovation Programme under Grant Agreements 720270 (Human Brain Project [HBP] SGA1) and 785907 (HBP SGA2); and by the Catalan Agencia de Gestión de Ayudas Universitarias Programme 2017 SGR 1545. M.L.K. is supported by the European Research Council Consolidator Grant CAREGIVING (615539); Center for Music in the Brain, funded by the Danish National Research Foundation (DNRF117); and Centre for Eudaimonia and Human Flourishing, funded by the Pettit and Carlsberg Foundations. J. Cabral is supported by the Portuguese Foundation for Science and Technology (CEECIND/03325/2017), Portugal.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher National Academy of Sciences
dc.relation.ispartof Proceedings of the National Academy of Sciences. 2020 Apr 28;117(17):9566-76
dc.rights This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title Dynamic coupling of whole-brain neuronal and neurotransmitter systems
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1073/pnas.1921475117
dc.subject.keyword Serotonin
dc.subject.keyword PET
dc.subject.keyword Psilocybin
dc.subject.keyword Neurotransmitter
dc.subject.keyword Whole-brain modeling
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/PSI2016-75688-P
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/785907
dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/615539
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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