Noradrenaline tracks emotional modulation of attention in human amygdala

dc.contributor.authorBang, Danen
dc.contributor.authorLuo, Yien
dc.contributor.authorBarbosa, Leonardo S.en
dc.contributor.authorBatten, Seth R.en
dc.contributor.authorHadj-Amar, Beniaminoen
dc.contributor.authorTwomey, Thomasen
dc.contributor.authorMelville, Natalieen
dc.contributor.authorWhite, Jason P.en
dc.contributor.authorTorres, Alexisen
dc.contributor.authorCelaya, Xavieren
dc.contributor.authorRamaiah, Priyaen
dc.contributor.authorMcClure, Samuel M.en
dc.contributor.authorBrewer, Gene A.en
dc.contributor.authorBina, Robert W.en
dc.contributor.authorLohrenz, Terryen
dc.contributor.authorCasas, Brooksen
dc.contributor.authorChiu, Pearl H.en
dc.contributor.authorVannucci, Marinaen
dc.contributor.authorKishida, Kenneth T.en
dc.contributor.authorWitcher, Mark R.en
dc.contributor.authorMontague, P. Readen
dc.date.accessioned2023-10-23T18:51:39Zen
dc.date.available2023-10-23T18:51:39Zen
dc.date.issued2023-11-20en
dc.description.abstractThe 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 lowarousal state. Our study provides proof of concept that neuromodulator monitoring is now possible using depth electrodes in standard clinical use.en
dc.description.sponsorshipThis work was supported by the Lundbeck Foundation (D.B., R368-2021-325), the Wellcome Trust (D.B., 213630/Z/ 18/Z; P.R.M., 091188/Z/10/Z), the Swartz Foundation (P.R.M., 2019-11), NIHNCATS (K.T.K., KL2TR001421), NIH-NIDA (K.T.K., R01-DA048096), NIHNINDS (K.T.K. and P.R.M., R01-NS092701), NIH-NIMH (K.T.K., R01- MH121099; K.T.K., M.V., and P.R.M., R01-MH124115; P.H.C. and P.R.M., R01-MH122512; B.C. and P.R.M., R01-MH122948; P.H.C., R01-127773), VA-RR&D (B.C., D2354R), a donation by Steve Neumann (A.T., X.C., and G.A.B.), and a Virginia Tech Foundation Seale Innovation Award (P.R.M., FY22). The Wellcome Centre for Human Neuroimaging is supported by core funding from the Wellcome Trust (203147/Z/16/Z).en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1016/j.cub.2023.09.074en
dc.identifier.urihttp://hdl.handle.net/10919/116531en
dc.language.isoenen
dc.publisherElsevieren
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.titleNoradrenaline tracks emotional modulation of attention in human amygdalaen
dc.title.serialCurrent Biologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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