Center of Functionally Integrative Neuroscience, Aarhus University, 8000 Aarhus, Denmark; Wellcome Centre for Human Neuroimaging, University College London, London WC1N 3BG, UK; Department of Experimental Psychology, University of Oxford, Oxford OX2 6GG, UK; Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, VA 24016, USA.
Fralin Biomedical Research Institute at VTC, Virginia Tech, Roanoke, VA 24016, USA; Shanghai Key Laboratory of Mental Health and Psychological Crisis Intervention, East China Normal University, Shanghai 200050, China.
Curr Biol. 2023 Nov 20;33(22):5003-5010.e6. doi: 10.1016/j.cub.2023.09.074. Epub 2023 Oct 23.
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. The LC-NA system is believed to regulate arousal and attention and is a pharmacological target in multiple clinical conditions. 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 processing and receives dense LC-NA projections, 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, 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, supported a hypothesis that pupil-NA coupling changes with cognitive state, 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.
去甲肾上腺素（NA）系统是大脑主要的神经调质系统之一；它起源于一个较小的中脑核团，蓝斑核（LC），并广泛投射到大脑中。LC-NA 系统被认为调节觉醒和注意力，是多种临床病症的药理学靶点。然而，由于缺乏人类的直接记录，我们对其在健康和疾病中的作用的理解受到了阻碍。在这里，我们通过显示可以使用用于癫痫监测的临床深度电极获得亚秒级 NA 动力学的电化学估计来解决这个问题。我们在杏仁核中进行了这些记录，杏仁核是一种支持情绪处理的古老结构，并且接收密集的 LC-NA 投射，而患者（n=3）执行视觉情感Oddball 任务。该任务旨在诱导不同的认知状态，Oddball 刺激涉及唤起情绪的图像，这些图像在唤起（低与高）和效价（负与正）方面有所不同。与理论一致，NA 估计值跟踪了注意力的情绪调节，在高唤起状态下Oddball 反应更强。瞳孔扩张的并行估计值，一种常见的 LC-NA 活动的行为代理，支持了这样一种假设，即瞳孔-NA 耦合随认知状态而变化，瞳孔和 NA 估计值在高唤起但不在低唤起状态下的Oddball 刺激中呈正相关。我们的研究提供了概念验证，即现在可以使用标准临床使用的深度电极进行神经调质监测。
