Functional consequences of acute tryptophan depletion on raphe nuclei connectivity and network organization in healthy women
Functional consequences of acute tryptophan depletion on raphe nuclei connectivity and network organization in healthy women
复制标题
DOI：
10.1016/j.neuroimage.2019.116362
复制
发表时间：
2020-02-15
期刊：
影响因子：
5.7
通讯作者：
Wagner, Gerd
中科院分区：
文献类型：
--
作者：
Baer, Karl-Juergen;Koehler, Stefanie;Wagner, Gerd
以往对中枢神经5-羟色胺（5-HT）功能的研究提供了证据，证明5-HT参与了与认知和情感加工相关的脑回路的调节。潜在的神经网络包括核心皮质下/皮质区域，例如杏仁核和内侧前额叶皮质，其被认为是由5-HT调节的。除了使用抗抑郁药之外，急性色氨酸耗竭（ATD）是一种广泛接受的技术，通过饮食和非药理学工具来操纵人体中的5-HT合成及其各自的代谢物。我们采用双盲、随机、交叉设计，两种实验挑战条件，即ATD和色氨酸（TRP）补充剂（TRYP+）作为对照。目的是扰乱5-HT的合成，并检测其对脑功能连接（FC）的上丘脑-中缝核，杏仁核和腹内侧前额叶皮层，以及使用静息状态功能磁共振成像网络组织的影响。最终分析纳入了30名健康成年女性参与者（年龄：M = 24.5 +/- 4.4岁）。ATD导致血清中TRP相对于基线降低90%。与TRYP +相比，ATD条件下中缝核到额极皮质的FC显著降低，以及右杏仁核和腹内侧前额叶皮质之间的功能耦合更大。中缝核的FC与两种挑战条件（ATD和TRYP+）的TRP变化幅度显着相关。基于网络的统计分析，使用时间序列从260个独立的解剖ROI显示更大的FC后ATD相比TRYP+在几个大脑区域的默认模式（DMN）和执行控制网络（ECN）的一部分，但也显着或视觉网络。最后，我们观察到ATD对丰富的俱乐部组织的影响，减少丰富的俱乐部系数相比TRYP+。总之，我们可以证实以前的研究结果，即假定减少大脑5-HT合成通过ATD显着改变FC中缝核以及特定的皮层下/皮层区域参与情感，但也在认知过程。此外，还证明了一些度较高的节点对所谓的富人俱乐部组织的ATD效应。这可能表明脑5-HT对来自几个脑网络的信息流的整合的影响。
Previous research on central nervous serotonin (5-HT) function provided evidence for a substantial involvement of 5-HT in the regulation of brain circuitries associated with cognitive and affective processing. The underlying neural networks comprise core subcortical/cortical regions such as amygdala and medial prefrontal cortex, which are assumed to be modulated amongst others by 5-HT. Beside the use of antidepressants, acute tryptophan depletion (ATD) is a widely accepted technique to manipulate of 5-HT synthesis and its respective metabolites in humans by means of a dietary and non-pharmacological tool. We used a double-blind, randomized, cross-over design with two experimental challenge conditions, i.e. ATD and tryptophan (TRP) supplementation (TRYP+) serving as a control. The aim was to perturb 5-HT synthesis and to detect its impact on brain functional connectivity (FC) of the upper serotonergic raphe nuclei, the amygdala and the ventromedial prefrontal cortex as well as on network organization using resting state fMRI. 30 healthy adult female participants (age: M = 24.5 +/- 4.4 yrs) were included in the final analysis. ATD resulted in a 90% decrease of TRP in the serum relative to baseline. Compared to TRYP + for the ATD condition a significantly lower FC of the raphe nucleus to the frontopolar cortex was detected, as well as greater functional coupling between the right amygdala and the ventromedial prefrontal cortex. FC of the raphe nucleus correlated significantly with the magnitude of TRP changes for both challenge conditions (ATD & TRYP+). Network-based statistical analysis using time series from 260 independent anatomical ROIs revealed significantly greater FC after ATD compared to TRYP+ in several brain regions being part of the default-mode (DMN) and the executive-control networks (ECN), but also of salience or visual networks. Finally, we observed an impact of ATD on the rich-club organization in terms of decreased rich-club coefficients compared to TRYP+.In summary we could confirm previous findings that the putative decrease in brain 5-HT synthesis via ATD significantly alters FC of the raphe nuclei as well as of specific subcortical/cortical regions involved in affective, but also in cognitive processes. Moreover, an ATD-effect on the so-called rich-club organization of some nodes with the high degree was demonstrated. This may indicate effects of brain 5-HT on the integration of information flow from several brain networks.