PDF(Pubmed)
Abstract：
The noradrenaline (NA) system is one of the brain\'s major neuromodulatory systems; it originates in a small midbrain nucleus, the locus coeruleus (LC), and projects widely throughout the brain.1,2 The LC-NA system is believed to regulate arousal and attention3,4 and is a pharmacological target in multiple clinical conditions.5,6,7 Yet our understanding of its role in health and disease has been impeded by a lack of direct recordings in humans. Here, we address this problem by showing that electrochemical estimates of sub-second NA dynamics can be obtained using clinical depth electrodes implanted for epilepsy monitoring. We made these recordings in the amygdala, an evolutionarily ancient structure that supports emotional processing8,9 and receives dense LC-NA projections,10 while patients (n = 3) performed a visual affective oddball task. The task was designed to induce different cognitive states, with the oddball stimuli involving emotionally evocative images,11 which varied in terms of arousal (low versus high) and valence (negative versus positive). Consistent with theory, the NA estimates tracked the emotional modulation of attention, with a stronger oddball response in a high-arousal state. Parallel estimates of pupil dilation, a common behavioral proxy for LC-NA activity,12 supported a hypothesis that pupil-NA coupling changes with cognitive state,13,14 with the pupil and NA estimates being positively correlated for oddball stimuli in a high-arousal but not a low-arousal state. Our study provides proof of concept that neuromodulator monitoring is now possible using depth electrodes in standard clinical use.
摘要：
去甲肾上腺素（NA）系统是大脑的主要神经调节系统之一；它起源于一个小的中脑核，蓝斑(LC)，1,2LC-NA系统被认为可以调节唤醒和注意力3,4并且是多种临床条件下的药理靶标。5,6,7然而，由于缺乏直接记录，我们对其在健康和疾病中的作用的理解受到了阻碍。这里,我们通过证明亚秒NA动力学的电化学估计可以使用植入的临床深度电极进行癫痫监测来解决这个问题。我们在杏仁核做了这些录音，一个进化上古老的结构，支持情绪处理8，9并接受密集的LC-NA投影，10，而患者（n=3）执行视觉情感古怪任务。该任务旨在诱导不同的认知状态，奇怪的刺激涉及情感唤起的图像，11在唤醒(低对高)和效价(负对正)方面有所不同。与理论一致，NA估计追踪了注意力的情绪调节，在高唤醒状态下具有更强的怪球反应。瞳孔扩张的平行估计，LC-NA活动的常见行为代理，12支持一个假设，即瞳孔-NA耦合随认知状态而变化，13,14，在高唤醒而不是低唤醒状态下，瞳孔和NA估计值与怪球刺激呈正相关。我们的研究提供了概念证明，现在可以在标准临床使用中使用深度电极进行神经调质监测。
