Tuesday, May 19, 2020

Closing the gap between mind and brain - The dynamic connectome and psilocybin

Quiroga summaries elegant work by Kringelbach et al.,
...who provide a framework for incorporating into the connectome the dynamic variations caused by neuromodulatory systems...The main tenet of [their work] is that neurotransmitters’ systems can modulate the connectome over time, thus enabling a plethora of behaviors with the same underlying structural connectivity. To this end, a modeling approach is presented, in which the structural connectivity is estimated through diffusion MRI, and is coupled to the neurotransmitter system, estimated from positron electron tomography data. Both systems are portrayed by a set of mutually coupled dynamic equations, which are used to fit the functional connectivity, obtained from functional MRI. This approach was tested by exploring the effects that a psychedelic drug (psilocybin) had on neuronal activity, showing that the dynamically coupled neuronal and neuromodulatory systems give a significantly better fit to the measured data, compared to alternative models in which both systems were uncoupled, or in which the neuromodulatory system, rather than being dynamically updated, was frozen in time.
I pass on the Kringelbach et al. significance statement (not distinguished by its modesty) and abstract. The article is open source,and has excellent graphics and figures.  

Significance
In a technical tour de force, we have created a framework demonstrating the underlying fundamental principles of bidirectional coupling of neuronal and neurotransmitter dynamical systems. Specifically, in the present study, we combined multimodal neuroimaging data to causally explain the functional effects of specific serotoninergic receptor (5-HT2AR) stimulation with psilocybin in healthy humans. Longer term, this could provide a better understanding of why psilocybin is showing considerable promise as a therapeutic intervention for neuropsychiatric disorders including depression, anxiety, and addiction.
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.

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