Quetiapine modulates functional connectivity in brain aggression networks
Quetiapine modulates functional connectivity in brain aggression networks
复制标题
DOI：
10.1016/j.neuroimage.2013.02.053
复制
发表时间：
2013-07-15
期刊：
影响因子：
5.7
通讯作者：
Mathiak, Klaus
中科院分区：
文献类型：
--
作者：
Klasen, Martin;Zvyagintsev, Mikhail;Mathiak, Klaus
攻击性行为与杏仁核和前额叶区域（如眶额（OFC），前扣带（ACC）和背外侧前额叶皮层（DLPFC））的情感调节网络功能障碍有关。特别是，前额叶区域被假定为通过抑制性投射控制杏仁核的活动，而这一过程可能在攻击性个体中被破坏。非典型抗精神病药奎替卡松成功地减弱了各种疾病中的攻击行为;然而，潜在的神经过程尚不清楚。前额叶-杏仁核系统的功能耦合增强可能是这些抗攻击效应的原因。据报道，暴力视频游戏中的虚拟攻击也会抑制这种网络。然而，到目前为止，还没有在体内观察到的药理学影响皮质边缘的预测在人类的攻击行为。在一项双盲、安慰剂对照研究中，在fMRI实验前连续三天给予奎替鲁肽和安慰剂。在这个实验中，在暴力视频游戏中的虚拟攻击行为和非暴力修改中的无攻击控制任务期间评估了功能性大脑连接。在虚拟攻击过程中，奎替鲁增加了ACC和DLPFC与杏仁核的功能连接，而OFC-杏仁核耦合则减弱。安慰剂组和非暴力对照组均未观察到这些效应。这些结果第一次证明了在自然环境中与攻击相关的人脑网络的药理学修饰。前额叶-杏仁核网络的暴力特异性调制似乎控制攻击行为，并为奎替鲁的抗攻击作用提供了神经生物学模型。(C)2013 Elsevier Inc. All rights reserved.
Aggressive behavior is associated with dysfunctions in an affective regulation network encompassing amygdala and prefrontal areas such as orbitofrontal (OFC), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC). In particular, prefrontal regions have been postulated to control amygdala activity by inhibitory projections, and this process may be disrupted in aggressive individuals. The atypical antipsychotic quetiapine successfully attenuates aggressive behavior in various disorders; the underlying neural processes, however, are unknown. A strengthened functional coupling in the prefrontal-amygdala system may account for these anti-aggressive effects. An inhibition of this network has been reported for virtual aggression in violent video games as well. However, there have been so far no in-vivo observations of pharmacological influences on corticolimbic projections during human aggressive behavior. In a double-blind, placebo-controlled study, quetiapine and placebo were administered for three successive days prior to an fMRI experiment. In this experiment, functional brain connectivity was assessed during virtual aggressive behavior in a violent video game and an aggression-free control task in a non-violent modification. Quetiapine increased the functional connectivity of ACC and DLPFC with the amygdala during virtual aggression, whereas OFC-amygdala coupling was attenuated. These effects were observed neither for placebo nor for the non-violent control. These results demonstrate for the first time a pharmacological modification of aggression-related human brain networks in a naturalistic setting. The violence-specific modulation of prefrontal-amygdala networks appears to control aggressive behavior and provides a neurobiological model for the anti-aggressive effects of quetiapine. (C) 2013 Elsevier Inc. All rights reserved.