Department of Clinical Neurosciences and Cambridge University Hospital NHS Trust, University of Cambridge, Herchel Smith Building, Robinson Way, Cambridge, CB2 0SZ, UK.
Centre for Neuroimaging Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.
Psychopharmacology (Berl). 2022 Feb;239(2):365-376. doi: 10.1007/s00213-021-05998-2. Epub 2021 Oct 25.
The effects of atomoxetine (ATO) on response inhibition have been typically examined using the stop signal task (SST) which is however confounded by attentional capture. The right inferior frontal cortex (rIFC) has been implicated in the modulation of ATO on inhibitory control, but a precise characterisation of its role is complicated by its functional inhomogeneity.
The current study aimed to directly investigate the effect of ATO in the SST using the imaging contrast unconfounded by attentional capture, to test the specific drug actions in functionally dissociable rIFC subregions, and to explore the role of locus coeruleus (LC), the main source of cortical noradrenaline, in mediating the drug effects.
This imaging study investigated the effect of ATO (40 mg) in 18 human participants during a modified SST that unconfounds attention from inhibition. Functional definitions for rIFC subdivisions were adopted in the analyses to isolate attention and inhibition during action cancellation. The LC integrity was measured in vivo using a neuromelanin-sensitive sequence.
We identified one mechanism of ATO modulation specific to inhibitory control: ATO enhanced activity in pre-supplementary area (pre-SMA) for motor inhibition, and the recruitment of temporoparietal junction (TPJ) and inferior frontal junction (IFJ) for functional integration during response inhibition. Moreover, drug-related behavioural and neural responses correlated with variations in LC integrity.
These findings provide a more nuanced and precise understanding of the effects of ATO on specific and domain general aspects of stopping.
阿托莫西汀（ATO）对反应抑制的影响通常使用停止信号任务（SST）进行检查，但该任务受到注意力捕获的混淆。右侧额下回（rIFC）被认为在调节 ATO 对抑制控制的作用，但由于其功能异质性，其作用的精确特征变得复杂。
本研究旨在使用不受注意力捕获影响的成像对比直接研究 ATO 在 SST 中的作用，测试 rIFC 功能可分离亚区中特定药物的作用，并探索蓝斑（LC）在介导药物作用中的作用，LC 是皮质去甲肾上腺素的主要来源。
这项影像学研究调查了在修改后的 SST 中 ATO（40mg）对 18 名人类参与者的影响，该 SST 可将注意力与抑制分开。在分析中采用了 rIFC 细分的功能定义，以在动作取消过程中隔离注意力和抑制。LC 完整性在体内使用神经黑色素敏感序列进行测量。
我们确定了 ATO 调节抑制控制的一种特定机制：ATO 增强了运动抑制的补充前区（pre-SMA）的活动，以及招募颞顶联合区（TPJ）和下额额联合区（IFJ）进行反应抑制的功能整合。此外，与药物相关的行为和神经反应与 LC 完整性的变化相关。
这些发现为 ATO 对停止的特定和领域普遍方面的影响提供了更细致和精确的理解。
