L-DOPA modulates activity in the vmPFC, nucleus accumbens, and VTA during threat extinction learning in humans

Learning to be safe is central for adaptive behaviour when threats are no longer present. Detecting the absence of an expected threat is key for threat extinction learning and an essential process for the behavioural treatment of anxiety-related disorders. One possible mechanism underlying extinctio...

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Autores principales:	Roland Esser, Christoph W Korn, Florian Ganzer, Jan Haaker
Formato:	article
Lenguaje:	EN
Publicado:	eLife Sciences Publications Ltd 2021
Materias:	nucleus accumbens vmPFC amygdala Dopamine Medicine R Science Q Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0ea2256eede44a7ca9dc2266ab1c7a66
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spelling	oai:doaj.org-article:0ea2256eede44a7ca9dc2266ab1c7a662021-11-15T07:05:10ZL-DOPA modulates activity in the vmPFC, nucleus accumbens, and VTA during threat extinction learning in humans10.7554/eLife.652802050-084Xe65280https://doaj.org/article/0ea2256eede44a7ca9dc2266ab1c7a662021-09-01T00:00:00Zhttps://elifesciences.org/articles/65280https://doaj.org/toc/2050-084XLearning to be safe is central for adaptive behaviour when threats are no longer present. Detecting the absence of an expected threat is key for threat extinction learning and an essential process for the behavioural treatment of anxiety-related disorders. One possible mechanism underlying extinction learning is a dopaminergic mismatch signal that encodes the absence of an expected threat. Here we show that such a dopamine-related pathway underlies extinction learning in humans. Dopaminergic enhancement via administration of L-DOPA (vs. Placebo) was associated with reduced retention of differential psychophysiological threat responses at later test, which was mediated by activity in the ventromedial prefrontal cortex that was specific to extinction learning. L-DOPA administration enhanced signals at the time-point of an expected, but omitted threat in extinction learning within the nucleus accumbens, which were functionally coupled with the ventral tegmental area and the amygdala. Computational modelling of threat expectancies further revealed prediction error encoding in nucleus accumbens that was reduced when L-DOPA was administered. Our results thereby provide evidence that extinction learning is influenced by L-DOPA and provide a mechanistic perspective to augment extinction learning by dopaminergic enhancement in humans.Roland EsserChristoph W KornFlorian GanzerJan HaakereLife Sciences Publications Ltdarticlenucleus accumbensvmPFCamygdalaDopamineMedicineRScienceQBiology (General)QH301-705.5ENeLife, Vol 10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	nucleus accumbens vmPFC amygdala Dopamine Medicine R Science Q Biology (General) QH301-705.5
spellingShingle	nucleus accumbens vmPFC amygdala Dopamine Medicine R Science Q Biology (General) QH301-705.5 Roland Esser Christoph W Korn Florian Ganzer Jan Haaker L-DOPA modulates activity in the vmPFC, nucleus accumbens, and VTA during threat extinction learning in humans
description	Learning to be safe is central for adaptive behaviour when threats are no longer present. Detecting the absence of an expected threat is key for threat extinction learning and an essential process for the behavioural treatment of anxiety-related disorders. One possible mechanism underlying extinction learning is a dopaminergic mismatch signal that encodes the absence of an expected threat. Here we show that such a dopamine-related pathway underlies extinction learning in humans. Dopaminergic enhancement via administration of L-DOPA (vs. Placebo) was associated with reduced retention of differential psychophysiological threat responses at later test, which was mediated by activity in the ventromedial prefrontal cortex that was specific to extinction learning. L-DOPA administration enhanced signals at the time-point of an expected, but omitted threat in extinction learning within the nucleus accumbens, which were functionally coupled with the ventral tegmental area and the amygdala. Computational modelling of threat expectancies further revealed prediction error encoding in nucleus accumbens that was reduced when L-DOPA was administered. Our results thereby provide evidence that extinction learning is influenced by L-DOPA and provide a mechanistic perspective to augment extinction learning by dopaminergic enhancement in humans.
format	article
author	Roland Esser Christoph W Korn Florian Ganzer Jan Haaker
author_facet	Roland Esser Christoph W Korn Florian Ganzer Jan Haaker
author_sort	Roland Esser
title	L-DOPA modulates activity in the vmPFC, nucleus accumbens, and VTA during threat extinction learning in humans
title_short	L-DOPA modulates activity in the vmPFC, nucleus accumbens, and VTA during threat extinction learning in humans
title_full	L-DOPA modulates activity in the vmPFC, nucleus accumbens, and VTA during threat extinction learning in humans
title_fullStr	L-DOPA modulates activity in the vmPFC, nucleus accumbens, and VTA during threat extinction learning in humans
title_full_unstemmed	L-DOPA modulates activity in the vmPFC, nucleus accumbens, and VTA during threat extinction learning in humans
title_sort	l-dopa modulates activity in the vmpfc, nucleus accumbens, and vta during threat extinction learning in humans
publisher	eLife Sciences Publications Ltd
publishDate	2021
url	https://doaj.org/article/0ea2256eede44a7ca9dc2266ab1c7a66
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L-DOPA modulates activity in the vmPFC, nucleus accumbens, and VTA during threat extinction learning in humans

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