Department of Psychiatry, University of Oxford, Oxford OX3 7JX, United Kingdom;
Center for Music in the Brain, Department of Clinical Medicine, Aarhus University, DK-8000 Aarhus C, Denmark.
Proc Natl Acad Sci U S A. 2020 Apr 28;117(17):9566-9576. doi: 10.1073/pnas.1921475117. Epub 2020 Apr 13.
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-HTR) 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.
从连接解剖结构和功能的全脑模型中取得了显著的进展。矛盾的是，目前尚不清楚在固定的人类解剖连接组中运行的神经元动力学系统如何产生与人类大脑功能相关的丰富功能变化，而长期可塑性无法对此进行解释。神经调节通过动态更新固定解剖连接的有效性，从而进化出这种灵活性。在这里，我们引入了一个理论框架，用于对神经元和神经递质系统之间的动态相互耦合进行建模。我们证明，通过将两种系统通过结合多模态神经影像学数据（扩散磁共振成像[dMRI]、功能磁共振成像[fMRI]和正电子发射断层扫描[PET]）进行双向耦合，该框架对于深入理解全脑动力学至关重要，以解释特定 5-羟色胺能受体（5-HTR）刺激在健康人类中使用裸盖菇素产生的功能影响。这一进展提供了一种理解为什么裸盖菇素作为一种治疗包括抑郁、焦虑和成瘾在内的神经精神疾病的干预手段具有很大潜力的原因。总的来说，这些见解表明，尽管必须依赖于固定的解剖连接，但神经元和神经传递系统之间的全脑相互耦合对于理解人类大脑功能的显著灵活性是至关重要的。
