Dopamine-induced changes in neural network patterns supporting aversive conditioning
Dopamine-induced changes in neural network patterns supporting aversive conditioning
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DOI：
10.1016/j.brainres.2009.11.064
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发表时间：
2010-02-08
期刊：
影响因子：
2.9
通讯作者：
McIntosh, Anthony Randal
中科院分区：
文献类型：
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作者：
Diaconescu, Andreea Oliviana;Menon, Mahesh;McIntosh, Anthony Randal
本论文的目的是评估多巴胺（DA）传递改变对人类介导厌恶性条件反射的脑区之间的功能连接的影响。为此，我们分析了以前发表的数据集，从一个双盲设计结合功能磁共振成像（fMRI）记录，其中健康志愿者被随机分配到三个药物组之一：安非他明（间接DA激动剂），氟哌啶醇（DA D2受体拮抗剂），和安慰剂。参与者暴露于一个厌恶的经典条件反射范式，使用皮肤电刺激作为非条件刺激（US），视觉线索作为条件刺激（CS），其中一种颜色（CS+），其次是美国在33%的试验和另一种颜色（CS-）没有后果。所有参与者都报告了对刺激意外事件的认识。组分析的fMRI数据显示，左腹侧纹状体（VS）和杏仁核激活响应CS+在所有三组。由于这两个区域的激活模式和厌恶性条件反射的记录，这两个区域被用作功能连接分析的种子。为了限制获得的功能网络与条件反应有关，我们还将种子活性与皮肤电反应（GSR）相关联。在安慰剂组中，右侧腹侧被盖区/黑质（VTA/SN）、双侧尾状核、右侧海马旁回、左侧顶下小叶（IPL）、双侧中央后回、双侧额中（BA 46）、眶额和腹内侧。前额叶皮层（PFC，BA 10/11）与VS和杏仁核种子相关，与CS+相比，通过安非他明增强多巴胺传递与CS+和CS-条件下左VS种子和DA调节的区域（如左VTA/SN，右尾状核，左杏仁核，左侧额中回（BA 46），双侧PFC腹内侧（BA 10）。通过氟哌啶醇阻断多巴胺传递与包括左杏仁核种子和右杏仁核、左前扣带回和左前额叶在内的交替区域网络的显著功能连接有关。（BA 24/32）、双侧IPL（BA 40）、楔前叶（BA 7）、中央后回、额中回（BA 46）和辅助运动区（SMA，BA 6）的CS+与CS-这些数据提供了深入了解DA剂的纹状体，边缘系统和前额区之间的功能连接的不同影响。(c)2009 Elsevier B. V.保留所有权利，
The aim of the present paper is to assess the effects of altered dopamine (DA) transmission on the functional connectivity among brain regions mediating aversive conditioning in humans. To this aim, we analyzed a previous published data set from a double-blind design combined with functional magnetic resonance imaging (fMRI) recordings in which healthy volunteers were randomly assigned to one of three drug groups: amphetamine (an indirect DA agonist), haloperidol (DA D2 receptor antagonist), and placebo. Participants were exposed to an aversive classical conditioning paradigm using cutaneous electrical stimulation as the unconditioned stimulus (US), and visual cues as the conditioned stimuli (CS) where one colour (CS+) was followed by the US in 33% of the trials and another colour (CS-) had no consequences. All participants reported awareness of stimulus contingencies. Group analysis of fMRI data revealed that the left ventral striatum (VS) and amygdala activated in response to the CS+ in all the three groups. Because of their activation patterns and documented involvement in aversive conditioning, both regions were used as seeds in the functional connectivity analysis. To constrain the functional networks obtained to relate to the conditioned response, we also correlated seed activity with the Galvanic Skin Response (GSR). In the placebo group, the right ventral tegmental area/substantia nigra (VTA/SN), bilateral caudate, right parahippocampal gyrus, left inferior parietal lobule (IPL), bilateral postcentral gyrus, bilateral middle frontal (BA 46), orbitofrontal, and ventromedial. prefrontal cortices (PFC, BA 10/11) correlated with the VS and amygdala seeds in response to the CS+ compared to the CS- Enhancing dopamine transmission via amphetamine was associated with reduced task differences and significant functional connectivity for both CS+ and CS- conditions between the left VS seed and regions modulated by DA, such as the left VTA/SN, right caudate, left amygdala, left middle frontal gyrus (BA 46), and bilateral ventromedial PFC (BA 10). Blocking dopamine transmission via haloperidol was associated with significant functional connectivity across an alternate network of regions including the left amygdala seed and the right insula, the left ACC (BA 24/32), bilateral IPL (BA 40), precuneus (BA 7), post-central gyrus, middle frontal gyrus (BA 46), and supplementary motor area (SMA, BA 6) to the CS+ versus the CS- These data provide insight into the distinct effects of DA agents on the functional connectivity between striatal, limbic, and prefrontal areas. (c) 2009 Elsevier B.V. All rights reserved,