Wang Guo-Ying, van Eijk Julia, Demirakca Traute, Sack Markus, Krause-Utz Annegret, Cackowski Sylvia, Schmahl Christian, Ende Gabriele
Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.
Department of Neuroimaging, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Germany.
Neuroimage. 2017 Feb 15;147:164-174. doi: 10.1016/j.neuroimage.2016.12.013. Epub 2016 Dec 7.
Impulsivity often develops from disturbed inhibitory control, a function mainly regulated by γ-Aminobutyric acid (GABA) levels in the anterior cingulate cortex (ACC) and the fronto-striatal system. In this study, we combined MRS GABA measurements and fMRI to investigate neurochemical and neurofunctional correlates of interference inhibition, further emphasizing the direct relationship between those two systems, as well as their relations to impulsivity in patients with BPD. In addition to BOLD activation, task-dependent functional connectivity was assessed by a generalized psychophysiological interactions approach. Full factorial analyses were performed via SPM to examine the main effect (within-group associations) as well as the interaction term (group differences in the association slope). The UPPS scales were used to evaluate impulsivity traits. Compared to healthy controls (HCs), BPD patients exhibited significantly less ACC-caudate functional connectivity during interference inhibition. ACC GABA levels in BPD patients but not in HCs were positively related to the magnitude of activation in several fronto-striatal regions (e.g. ACC, frontal regions, putamen, caudate,) and the strength of ACC-caudate functional connectivity during interference inhibition. The strength of the correlations of GABA with connectivity significantly differs between the two groups. Moreover, among all the UPPS impulsivity subscales, UPPS sensation seeking in the BPD group was related to GABA and was also negatively related to the task-dependent BOLD activation and functional connectivity in the fronto-striatal network. Finally, mediation analyses revealed that the magnitude of activation in the caudate and the strength of ACC-caudate functional connectivity mediated the relationship between ACC GABA levels and UPPS sensation seeking in patients with BPD. Our findings suggest a disconnectivity of the fronto-striatal network in BPD patients during interference inhibition, particularly for patients with higher impulsivity. The ACC GABAergic system seems to play a crucial role in regulating regional BOLD activations and functional connectivity in this network, which are further associated with impulsive sensation seeking in BPD.
冲动性通常源于抑制控制障碍，这一功能主要受前扣带回皮质（ACC）和额纹状体系统中γ-氨基丁酸（GABA）水平的调节。在本研究中，我们结合磁共振波谱（MRS）对GABA的测量和功能磁共振成像（fMRI）来研究干扰抑制的神经化学和神经功能相关性，进一步强调这两个系统之间的直接关系，以及它们与边缘型人格障碍（BPD）患者冲动性的关系。除了血氧水平依赖（BOLD）激活外，还通过广义心理生理交互作用方法评估任务依赖性功能连接。通过统计参数映射（SPM）进行全因子分析，以检验主效应（组内关联）以及交互项（关联斜率的组间差异）。使用UPPS量表来评估冲动性特质。与健康对照组（HCs）相比，BPD患者在干扰抑制期间表现出显著更少的ACC-尾状核功能连接。BPD患者而非HCs的ACC GABA水平与几个额纹状体区域（如ACC、额叶区域、壳核、尾状核）的激活程度以及干扰抑制期间ACC-尾状核功能连接的强度呈正相关。两组之间GABA与连接性的相关性强度存在显著差异。此外，在所有UPPS冲动性分量表中，BPD组的UPPS寻求刺激与GABA相关，并且也与额纹状体网络中任务依赖的BOLD激活和功能连接呈负相关。最后，中介分析表明，尾状核的激活程度和ACC-尾状核功能连接的强度介导了BPD患者ACC GABA水平与UPPS寻求刺激之间的关系。我们的研究结果表明，BPD患者在干扰抑制期间额纹状体网络存在脱节，尤其是对于冲动性较高的患者。ACC GABA能系统似乎在调节该网络中的区域BOLD激活和功能连接方面起着关键作用，而这又进一步与BPD中的冲动性寻求刺激相关。
