Whole-Brain Multimodal Neuroimaging Model Using Serotonin Receptor Maps Explains Non-linear Functional Effects of LSD

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    Gustavo Deco, Monash Univ, Monash University, Sch Psychol Sci, Josephine Cruzat, Univ Pompeu Fabra, Pompeu Fabra University, Dept Informat & Commun Technol, Computat Neurosci Grp, Ctr Brain & Cognit,
  • Joana Cabral
  • Gitte M. Knudsen, Univ Copenhagen, University of Copenhagen, Dept Large Anim Sci, Fac Med & Hlth Sci, Robin L. Carhart-Harris, Imperial Coll London, Imperial College London, Div Brain Sci, Ctr Psychiat, Psychedel Res Grp, Peter C. Whybrow, Univ Calif Los Angeles, University of California System, University of California Los Angeles, Semel Inst Neurosci & Human Behav, Nikos K. Logothetis, Univ Manchester, University of Manchester, Imaging Sci & Biomed Engn,
  • Morten L. Kringelbach

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.

Original languageEnglish
JournalCurrent Biology
Issue number19
Pages (from-to)3065-+
Number of pages16
Publication statusPublished - 8 Oct 2018

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