| Paper: | PS-1B.12 | ||
| Session: | Poster Session 1B | ||
| Location: | H Fläche 1.OG | ||
| Session Time: | Saturday, September 14, 16:30 - 19:30 | ||
| Presentation Time: | Saturday, September 14, 16:30 - 19:30 | ||
| Presentation: | Poster | ||
| Publication: | 2019 Conference on Cognitive Computational Neuroscience, 13-16 September 2019, Berlin, Germany | ||
| Paper Title: | Mechanisms of the non-linear interactions between the neuronal and neurotransmitter systems explained by causal whole-brain modeling | ||
| Manuscript: | Click here to view manuscript | ||
| License: |  This work is licensed under a Creative Commons Attribution 3.0 Unported License. |
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| DOI: | https://doi.org/10.32470/CCN.2019.1095-0 | ||
| Authors: | Josephine Cruzat, Universitat Pompeu Fabra, Spain; Joana Cabral, University of Minho, Portugal; Gitte Moos Knudsen, Copenhagen University, Denmark; Robin Carhart-Harris, Imperial College London, United Kingdom; Peter C. Whybrow, University of California, Los Angeles, United States; Nikos K. Logothetis, Max Planck Institute for Biological Cybernetics, Germany; Morten L. Kringelbach, University of Oxford, United Kingdom; Gustavo Deco, Universitat Pompeu Fabra, Spain | ||
| Abstract: | Although a variety of studies have shown the role of neurotransmitters at the neuronal level, their impact on the dynamics of the system at a macroscopic scale is poorly understood. Here, we provide a causal explanation using the first whole-brain model integrating multimodal imaging in healthy human participants undergoing manipulation of the serotonin system. Specifically, we combined anatomical and functional data with a detailed map of the serotonin 2A receptor (5-HT2AR) densities obtained with positron emission tomography (PET). This allowed us to model the resting state and mechanistically explain the functional effects of 5-HT2AR stimulation with lysergic acid diethylamide (LSD). 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 results show that the precise distribution of 5-HT2AR is crucial to predict the neuromodulatory effects of LSD. The model identified the causative mechanisms for the non-linear interactions between the neuronal and neurotransmitter system, which are uniquely linked to the underlying neuroanatomical network, the modulation by the specific brain-wide distribution of neurotransmitter receptors, and the non-linear interactions between the two. | ||