Noradrenaline tracks emotional modulation of attention in human amygdala

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 attention^3,4 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 processing^8,9 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.