Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Roc Boronat 138, 08018 Barcelona, Spain; Institució Catalana de la Recerca i Estudis Avançats (ICREA), Passeig Lluís Companys 23, 08010 Barcelona, Spain; Department of Neuropsychology, Max Planck Institute for Human Cognitive and Brain Sciences, 04103 Leipzig, Germany; School of Psychological Sciences, Monash University, Melbourne, Clayton VIC 3800, Australia.
Center for Brain and Cognition, Computational Neuroscience Group, Department of Information and Communication Technologies, Universitat Pompeu Fabra, Roc Boronat 138, 08018 Barcelona, Spain.
Curr Biol. 2018 Oct 8;28(19):3065-3074.e6. doi: 10.1016/j.cub.2018.07.083. Epub 2018 Sep 27.
Understanding the underlying mechanisms of the human brain in health and disease will require models with necessary and sufficient details to explain how function emerges from the underlying anatomy and is shaped by neuromodulation. Here, we provide such a detailed causal explanation using a whole-brain model integrating multimodal imaging in healthy human participants undergoing manipulation of the serotonin system. Specifically, we combined anatomical data from diffusion magnetic resonance imaging (dMRI) and functional magnetic resonance imaging (fMRI) with neurotransmitter data obtained with positron emission tomography (PET) of the detailed serotonin 2A receptor (5-HTR) density map. This allowed us to model the resting state (with and without concurrent music listening) and mechanistically explain the functional effects of 5-HTR stimulation with lysergic acid diethylamide (LSD) on healthy participants. The whole-brain model used a dynamical mean-field quantitative description of populations of excitatory and inhibitory neurons as well as the associated synaptic dynamics, where the neuronal gain function of the model is modulated by the 5-HTR density. The model identified the causative mechanisms for the non-linear interactions between the neuronal and neurotransmitter system, which are uniquely linked to (1) the underlying anatomical connectivity, (2) the modulation by the specific brainwide distribution of neurotransmitter receptor density, and (3) the non-linear interactions between the two. Taking neuromodulatory activity into account when modeling global brain dynamics will lead to novel insights into human brain function in health and disease and opens exciting possibilities for drug discovery and design in neuropsychiatric disorders.
理解人类大脑在健康和疾病中的潜在机制需要具有必要和充分细节的模型，以解释功能如何从潜在的解剖结构中出现，并受到神经调制的影响。在这里，我们使用一个整合了健康人类参与者的多模态成像的全脑模型提供了这样一个详细的因果解释，这些参与者的血清素系统受到了操纵。具体来说，我们将扩散磁共振成像（dMRI）和功能磁共振成像（fMRI）的解剖数据与正电子发射断层扫描（PET）获得的神经递质数据结合起来，获得了详细的血清素 2A 受体（5-HTR）密度图。这使我们能够模拟静息状态（伴有和不伴有同时的音乐聆听），并从机制上解释 LSD 对健康参与者的 5-HTR 刺激对功能的影响。全脑模型使用了兴奋性和抑制性神经元群体的动力平均场定量描述以及相关的突触动力学，其中模型的神经元增益函数由 5-HTR 密度调制。该模型确定了神经元和神经递质系统之间非线性相互作用的因果机制，这些机制与（1）潜在的解剖连接，（2）特定的全脑神经递质受体密度调制，以及（3）两者之间的非线性相互作用，具有独特的联系。在对全局大脑动力学进行建模时考虑到神经调制活动，将为健康和疾病中的人类大脑功能提供新的见解，并为神经精神障碍的药物发现和设计开辟令人兴奋的可能性。
