Dynamic coupling of whole-brain neuronal and neurotransmitter systems

Kringelbach, Morten L.; Cruzat, Josephine; Cabral, Joana; Knudsen, Gitte Moos; Carhart-Harris, Robin; Whybrow, Peter C.; Logothetis, Nikos K.; Deco, Gustavo

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.

Más información

Título según WOS: ID WOS:000530099500060 Not found in local WOS DB
Título de la Revista: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volumen: 117
Número: 17
Editorial: NATL ACAD SCIENCES
Fecha de publicación: 2020
Página de inicio: 9566
Página final: 9576
DOI:

10.1073/pnas.1921475117

Notas: ISI