Cigarette Smoking and the Efficiency of the Frontoparietal Attentional Network

描述（由申请人提供）：与突然戒烟相关的注意力缺陷导致戒烟困难。与急性戒烟相关的缺陷的神经基础尚不清楚。额顶叶注意网络介导注意，并对包括梭状面区在内的感觉皮层的激活施加自上而下的注意控制。我们认为，突然停止吸烟会损害这个网络的功能效率，而急性尼古丁给药至少部分地减轻了这种损害。为了验证这一假设，我们开发了一个选择性注意任务，具有四个水平的注意/感知负荷。它使用示意性图像擦除作为目标和干扰。结合功能磁共振成像（fMRI）技术，我们将评估注意/知觉负荷与任务相关的额顶叶皮层和梭状面区fMRI信号变化之间的关系。我们将研究20名吸烟者，并使用额顶叶皮层的负荷依赖性活动作为注意力控制的指标，梭形面部区域的负荷依赖性活动作为注意力控制有效性的指标。每例受试者将在三个fMRI阶段（不同日期）进行研究，一个在自由吸烟+安慰剂后，另一个在戒烟（12小时）+安慰剂后，剩余一个在戒烟（12小时）+尼古丁（4 mg）后。我们预测，相对于自由吸烟+安慰剂后的激活，戒烟+安慰剂后的吸烟者在低注意力/感知负荷下将显示出更高的额顶叶皮层激活和类似的梭状面区激活，随着任务负荷的增加，这些脑区的激活增加较少。我们还预测，相对于戒烟+安慰剂后的激活，戒烟+尼古丁后的吸烟者在低任务负荷下的额顶叶皮层和梭状面区的激活程度较高，随着任务负荷的增加，这些脑区的激活程度增加。拟议研究的结果将阐明吸烟者的额顶叶注意力网络的功能如何受到突然戒烟和尼古丁给药的影响，还将提供一种工具，用于评估注意力如何受到戒烟与其他因素（如性别和基因型）相互作用的影响。通过阐明戒断相关注意力缺陷损伤的神经基质，这项工作可以帮助确定尼古丁依赖的治疗靶点和可能的新治疗方法。

DESCRIPTION (provided by applicant): A deficit in attention associated with abrupt cessation of smoking contributes to the difficulty of smoking cessation. The neural basis of the deficit associated with acute smoking abstinence is not well understood. The frontoparietal attentional network mediates attention and exerts top-down attentional control over the activation of sensory cortex, including the fusiform face area. We posit that abrupt cessation of cigarette smoking impairs the functional efficiency of this network, and that acute nicotine administration at least partially alleviates this impairment. To test this hypothesis, we developed a selective attention task with four levels of attention/perception load. It uses schematic images efface as target and distracters. Paired with functional magnetic resonance imaging (fMRI), our task will allow us to assess the relations between attention/perception load and task- related changes of fMRI signal in the frontoparietal cortex and the fusiform face area. We will study 20 smokers, and use load-dependent activity in the frontoparietal cortex as an indication of attentional control, and load-dependent activity in the fusiform face area as an index of the effectiveness of attentional control. Each subject will be studied in three fMRI sessions (different days), one after smoking ad libitum + placebo, the other after abstinence (12 h) + placebo, and the remaining one after abstinence (12 h) + nicotine (4 mg). We predict that, relative to activation after smoking ad libitum + placebo, smokers after abstinence + placebo will show higher activation in the frontoparietal cortex and similar activation in the fusiform face area at low attention/perception load, and less increase in activation in these brain regions as task load is increased. We also predict that, relative to activation after abstinence + placebo, smokers after abstinence + nicotine will show higher activation in the frontoparietal cortex and similar activation in the fusiform face area at low task load, and greater increases in activation in these brain areas as task load is increased. The findings from the proposed research will clarify how the function of the frontoparietal attentional network of smokers is affected by abrupt cessation of smoking and by nicotine administration, and will also provide a tool for assessing how attention is affected by the interaction of smoking cessation with other factors, such as gender and genotype. By elucidating the neural substrates of impairments in withdrawal- associated deficits in attention, this work can help identify treatment targets and possibly new approches to therapy for nicotine dependence.