研究者たちは、脳のノルアドレナリンシステムを解き放つために先駆的な新しい方法を使用する(Researchers use pioneering new method to unlock brain’s noradrenaline system)

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2023-10-23 バージニア工科大学(VirginiaTech)

◆国際的な研究チームは、長らく注意欠陥・多動性障害、うつ病、不安症状の治療薬のターゲットとされてきた脳のノルアドレナリン(NA)システムに関する貴重な知見を提供しました。さらに、これに加えて、研究者が開発した画期的な方法論が注目されています。
◆この方法論を用いて、てんかんモニタリングのために通常埋め込まれる標準的な臨床電極から、実時の化学活性を記録することが可能になりました。この研究は、生体内の脳の化学反応に新たな洞察を提供し、注意欠陥・多動性障害、うつ病、不安症状など幅広い医療疾患に関連する可能性があります。

<関連情報>

ノルアドレナリンはヒト扁桃体における注意の情動変調を追跡する Noradrenaline tracks emotional modulation of attention in human amygdala

Dan Bang ,Yi Luo,Leonardo S. Barbosa,Seth R. Batten,Beniamino Hadj-Amar,Thomas Twomey,Natalie Melville,Jason P. White,Alexis Torres,Xavier Celaya,Priya Ramaiah,Samuel M. McClure,Gene A. Brewer,Robert W. Bina,Terry Lohrenz,Brooks Casas,Pearl H. Chiu,Marina Vannucci,Kenneth T. Kishida,Mark R. Witcher,P. Read Montague
Current Biology  Published:October 23, 2023
DOI:https://doi.org/10.1016/j.cub.2023.09.074

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Highlights

•Sub-second neuromodulator dynamics can be measured using clinical depth electrodes
•Noradrenaline dynamics in human amygdala reflect attention and arousal
•Coupling between noradrenaline and pupil dilation depends on cognitive state

Summary

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.

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