Ettinger Ulrich, Williams Steven C R, Patel Dhanesh, Michel Tanja M, Nwaigwe Agwawumma, Caceres Alejandro, Mehta Mitul A, Anilkumar Anantha P, Kumari Veena
Centre for Neuroimaging Sciences, Institute of Psychiatry, King's College London, DeCrespigny Park, PO89, London SE5 8AF, UK.
Neuroimage. 2009 Apr 1;45(2):549-61. doi: 10.1016/j.neuroimage.2008.12.029. Epub 2008 Dec 30.
The present study used functional magnetic resonance imaging (fMRI) to investigate the neural mechanisms of nicotine effects on antisaccades (an oculomotor measure of the conflict between a reflexive response and a spatially complex volitional response) and prosaccades (involving reflexive overt attentional shifts). Given the known inter-individual variability in drug response we aimed to identify oculomotor variables and brain areas in which significant inter-individual heterogeneity in response to nicotine is observed. To do so we calculated within-session intraclass correlation (ICC) coefficients over measurements obtained before and after nicotine/placebo administration and reasoned that a significant reduction in ICC with nicotine compared to placebo would reflect the operation of significant inter-individual response heterogeneity. Thirteen light-to-moderate smokers and 11 non-smokers completed fMRI during antisaccades before and after subcutaneous injection of 12 microg/kg nicotine or saline placebo in a double-blind, randomised, cross-over design. All participants were healthy, right-handed males. Nicotine and placebo were given on separate occasions approximately 1 week apart with time of injection kept constant. Nicotine significantly reduced antisaccade latencies in both groups. At the level of brain function, during antisaccades the blood oxygen level dependent (BOLD) response in the left frontal eye field was non-significantly reduced by nicotine while it significantly increased following placebo in non-smokers, but there was no discernible effect in smokers. During prosaccades, it was found that deactivation areas (posterior cingulate gyrus and precuneus; right superior temporal gyrus) showed enhanced deactivations following nicotine administration in both groups. ICC analysis identified significant inter-individual response heterogeneity in antisaccade reflexive errors in smokers, and in a number of brain regions, particularly in non-smokers. These findings suggest that nicotine has beneficial effects at the cognitive level and leads to reductions in task-related activations and further decreases of BOLD in deactivation areas. The comparison of within-session ICCs across drug conditions suggests that the effects of nicotine are subject to inter-individual variability at behavioural and neural levels.
本研究采用功能磁共振成像（fMRI）来探究尼古丁对反扫视（一种衡量反射性反应与空间复杂意志反应之间冲突的眼动指标）和正扫视（涉及反射性明显注意力转移）影响的神经机制。鉴于已知药物反应存在个体间差异，我们旨在确定眼动变量和脑区，在这些变量和脑区中观察到对尼古丁反应存在显著的个体间异质性。为此，我们计算了尼古丁/安慰剂给药前后测量值的组内类内相关系数（ICC），并推断与安慰剂相比，尼古丁使ICC显著降低将反映出显著的个体间反应异质性。13名轻度至中度吸烟者和11名非吸烟者在双盲、随机、交叉设计中，于皮下注射12微克/千克尼古丁或生理盐水安慰剂前后进行反扫视时完成了fMRI。所有参与者均为健康的右利手男性。尼古丁和安慰剂在不同时间给药，间隔约1周，注射时间保持恒定。尼古丁显著缩短了两组的反扫视潜伏期。在脑功能水平上，在反扫视期间，左额叶眼区的血氧水平依赖（BOLD）反应在尼古丁作用下无显著降低，而在非吸烟者中，安慰剂作用后该反应显著增加，但在吸烟者中未观察到明显影响。在正扫视期间，发现失活区域（后扣带回和楔前叶；右侧颞上回）在两组中尼古丁给药后失活增强。ICC分析确定吸烟者在反扫视反射错误方面以及在一些脑区，特别是非吸烟者中存在显著的个体间反应异质性。这些发现表明，尼古丁在认知水平上具有有益作用，并导致与任务相关的激活减少以及失活区域BOLD进一步降低。跨药物条件的组内ICC比较表明，尼古丁的作用在行为和神经水平上存在个体间差异。
