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Dynamic coupling of whole-brain neuronal and neurotransmitter systems

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  • 9566.full

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  • Morten L. Kringelbach
  • Josephine Cruzat, Pompeu Fabra University
  • ,
  • Joana Cabral
  • Gitte Moos Knudsen, University of Copenhagen
  • ,
  • Robin Carhart-Harris, Imperial College London
  • ,
  • Peter C. Whybrow, University of Oxford, University of California at Los Angeles
  • ,
  • Nikos K. Logothetis, Max Planck Institute for Biological Cybernetics, University of Manchester
  • ,
  • Gustavo Deco, Pompeu Fabra University, ICREA, Max Planck Institute for Human Cognitive and Brain Sciences, Monash University

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.

Original languageEnglish
JournalProceedings of the National Academy of Sciences
Pages (from-to)9566-9576
Number of pages11
Publication statusPublished - 2020

    Research areas

  • Neurotransmitter, PET, Psilocybin, Serotonin, Whole-brain modeling

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