Dynamic coupling of whole-brain neuronal and neurotransmitter systems
Cabral, J., Carhart-Harris, R. L., Cruzat, J., Deco, G., Knudsen, G. M., Kringelbach, M. L., Logothetis, N. K., Whybrow, P. C.
This computational paper (2020) describes a model that predicts whole-brain activity in light of the functional coupling between neuroanatomical and neuromodulatory systems and applies this model to demonstrate how the effects of psilocybin on the brain arise out of the mutual interaction between serotonergic (5-HT2A) receptor modulation and the anatomy of the raphe nucleus. The results provide evidence for how the integration of dMRI (anatomy), fMRI (functional neuronal activity), and PET (neurotransmitter system) at the whole-brain level is necessary for properly predicting brain dynamics as a result of the mutual coupling between a dual system.
Abstract
Introduction: 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.Methods: Here, we introduce a theoretical framework modelling the dynamical mutual coupling between the neuronal and neurotransmitter systems.Results: 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.Discussion: 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.