Do subjects with atypical patterns in attentional and executive behaviour show different brain network topology and react differently towards nicotine administration? The efficacy of pro-cognitive drugs like nicotine considerably varies between subjects and previous theoretical and empirical evidence suggest stronger behavioural nicotine effects in subjects with low performance. One problem is, however, how to best define low performance, especially if several cognitive functions are assessed for subject characterisation. We here present a method that used a multivariate, robust outlier detection algorithm to identify subjects with suspicious patterns of performance in attentional and executive functioning. In contrast to univariate approaches, this method is sensitive towards extreme positions within the multidimensional space that do not have to be extreme values in the individual behavioural distributions. The method was applied to a dataset of healthy, non-smoking subjects (n = 34) who were behaviorally characterised by an attention and executive function test on which N = 12 volunteers were classified as outliers. All subjects then underwent a resting-state functional magnetic resonance imaging (fMRI) scan to characterise brain network topology and an experimental behavioural paradigm under placebo and nicotine (7 mg patch) that gauged aspects of attention and executive function. Our results indicate that subjects with an atypical multivariate pattern in attention and executive functioning showed significant differences in nodal brain network integration in visual association and pre-motor brain regions during resting state. These differences in brain network topology significantly predicted larger individual nicotine effects on attentional processing. In summary, the current approach successfully identified a subgroup of healthy volunteers with low behavioural performance who differ in brain network topology and attentional benefit from nicotine.

中文翻译：

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具有极端表现模式的健康受试者的功能网络拓扑和尼古丁的益处有所不同


注意力和执行行为非典型模式的受试者是否表现出不同的大脑网络拓扑结构并对尼古丁给药有不同的反应？尼古丁等促认知药物的功效在受试者之间存在很大差异，之前的理论和经验证据表明尼古丁对表现不佳的受试者有更强的行为影响。然而，一个问题是如何最好地定义低表现，尤其是在评估多种认知功能以描述受试者特征的情况下。我们在这里提出了一种方法，该方法使用多变量、稳健的异常值检测算法来识别在注意力和执行功能方面表现可疑的受试者。与单变量方法相比，该方法对多维空间内的极端位置敏感，这些位置不一定是个体行为分布中的极值。该方法应用于健康、不吸烟受试者 (n = 34) 的数据集，这些受试者通过注意力和执行功能测试进行行为特征描述，其中 N = 12 名志愿者被归类为异常值。然后，所有受试者都接受了静息态功能磁共振成像 (fMRI) 扫描，以表征大脑网络拓扑结构，并在安慰剂和尼古丁（7 毫克贴片）下进行实验行为范式，以衡量注意力和执行功能的各个方面。我们的结果表明，注意力和执行功能具有非典型多变量模式的受试者在静息状态下视觉关联和前运动脑区域的节点脑网络整合表现出显着差异。大脑网络拓扑的这些差异显着预测了个体尼古丁对注意力处理的更大影响。 总之，当前的方法成功地识别了一组行为表现较低的健康志愿者，他们的大脑网络拓扑和尼古丁的注意力益处有所不同。