Filbey Francesca M, Dunlop Joseph
Center for BrainHealth, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75235, USA.
Center for BrainHealth, School of Behavioral and Brain Sciences, University of Texas at Dallas, Richardson, TX 75235, USA.
Drug Alcohol Depend. 2014 Jul 1;140:101-11. doi: 10.1016/j.drugalcdep.2014.04.002. Epub 2014 Apr 13.
Emergent studies show that similar to other substances of abuse, cue-reactivity to cannabis is also associated with neural response in the brain's reward pathway (Filbey et al., 2009). However, the inter-relatedness of brain regions during cue-reactivity in cannabis users remains unknown.
In this study, we conducted a series of investigations to determine functional connectivity during cue-reactivity in 71 cannabis users. First, we used psychophysiological interaction (PPI) analysis to examine coherent neural response to cannabis cues. Second, we evaluated whether these patterns of network functional connectivity differentiated dependent and non-dependent users. Finally, as an exploratory analysis, we determined the directionality of these connections via Granger connectivity analyses.
PPI analyses showed reward network functional connectivity with the nucleus accumbens (NAc) seed region during cue exposure. Between-group contrasts found differential effects of dependence status. Dependent users (N=31) had greater functional connectivity with amygdala and anterior cingulate gyrus (ACG) seeds while the non-dependent users (N=24) had greater functional connectivity with the NAc, orbitofrontal cortex (OFC) and hippocampus seeds. Granger analyses showed that hippocampal and ACG activation preceded neural response in reward areas.
Both PPI and Granger analyses demonstrated strong functional coherence in reward regions during exposure to cannabis cues in current cannabis users. Functional connectivity (but not regional activation) in the reward network differentiated dependent from non-dependent cannabis users. Our findings suggest that repeated cannabis exposure causes observable changes in functional connectivity in the reward network and should be considered in intervention strategies.
紧急研究表明，与其他成瘾物质类似，对大麻的线索反应性也与大脑奖赏通路中的神经反应相关（菲尔贝等人，2009年）。然而，大麻使用者在线索反应过程中脑区的相互关联性仍不明确。
在本研究中，我们进行了一系列调查，以确定71名大麻使用者在线索反应过程中的功能连接性。首先，我们使用心理生理交互作用（PPI）分析来检查对大麻线索的连贯神经反应。其次，我们评估了这些网络功能连接模式是否能区分依赖和非依赖使用者。最后，作为探索性分析，我们通过格兰杰连接性分析确定了这些连接的方向性。
PPI分析显示，在线索暴露期间，奖赏网络与伏隔核（NAc）种子区域存在功能连接。组间对比发现了依赖状态的不同影响。依赖使用者（N = 31）与杏仁核和前扣带回皮质（ACG）种子的功能连接更强，而非依赖使用者（N = 24）与NAc、眶额皮质（OFC）和海马体种子的功能连接更强。格兰杰分析表明，海马体和ACG的激活先于奖赏区域的神经反应。
PPI和格兰杰分析均表明，当前大麻使用者在接触大麻线索期间，奖赏区域存在强大的功能连贯性。奖赏网络中的功能连接（而非区域激活）区分了依赖和非依赖大麻使用者。我们的研究结果表明，反复接触大麻会导致奖赏网络功能连接发生可观察到的变化，在干预策略中应予以考虑。
