Fürtinger Stefan, Zinn Joel C, Simonyan Kristina
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America; Department of Otolaryngology, Icahn School of Medicine at Mount Sinai, New York, New York, United States of America.
PLoS Comput Biol. 2014 Nov 13;10(11):e1003924. doi: 10.1371/journal.pcbi.1003924. eCollection 2014 Nov.
Assessing brain activity during complex voluntary motor behaviors that require the recruitment of multiple neural sites is a field of active research. Our current knowledge is primarily based on human brain imaging studies that have clear limitations in terms of temporal and spatial resolution. We developed a physiologically informed non-linear multi-compartment stochastic neural model to simulate functional brain activity coupled with neurotransmitter release during complex voluntary behavior, such as speech production. Due to its state-dependent modulation of neural firing, dopaminergic neurotransmission plays a key role in the organization of functional brain circuits controlling speech and language and thus has been incorporated in our neural population model. A rigorous mathematical proof establishing existence and uniqueness of solutions to the proposed model as well as a computationally efficient strategy to numerically approximate these solutions are presented. Simulated brain activity during the resting state and sentence production was analyzed using functional network connectivity, and graph theoretical techniques were employed to highlight differences between the two conditions. We demonstrate that our model successfully reproduces characteristic changes seen in empirical data between the resting state and speech production, and dopaminergic neurotransmission evokes pronounced changes in modeled functional connectivity by acting on the underlying biological stochastic neural model. Specifically, model and data networks in both speech and rest conditions share task-specific network features: both the simulated and empirical functional connectivity networks show an increase in nodal influence and segregation in speech over the resting state. These commonalities confirm that dopamine is a key neuromodulator of the functional connectome of speech control. Based on reproducible characteristic aspects of empirical data, we suggest a number of extensions of the proposed methodology building upon the current model.
评估在需要募集多个神经位点的复杂自主运动行为期间的大脑活动是一个活跃的研究领域。我们目前的知识主要基于人脑成像研究,这些研究在时间和空间分辨率方面存在明显局限性。我们开发了一种具有生理学依据的非线性多房室随机神经模型,以模拟复杂自主行为(如言语产生)期间与神经递质释放耦合的功能性大脑活动。由于其对神经放电的状态依赖性调制,多巴胺能神经传递在控制言语和语言的功能性脑回路组织中起关键作用,因此已被纳入我们的神经群体模型。本文给出了所提出模型解的存在性和唯一性的严格数学证明,以及数值逼近这些解的计算有效策略。使用功能网络连通性分析静息状态和句子产生期间的模拟大脑活动,并采用图论技术突出两种状态之间的差异。我们证明,我们的模型成功地再现了静息状态和言语产生之间经验数据中看到的特征变化,并且多巴胺能神经传递通过作用于潜在的生物随机神经模型,在模拟的功能连通性中引起显著变化。具体而言,言语和静息状态下的模型网络和数据网络都具有特定任务的网络特征:模拟和经验功能连通性网络在言语状态下都比静息状态显示出节点影响力和分离度的增加。这些共性证实多巴胺是言语控制功能连接组的关键神经调节因子。基于经验数据可重复的特征方面,我们建议在当前模型的基础上对所提出的方法进行一些扩展。