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Human Hippocampus Arbitrates Approach-Avoidance Conflict

Animal models of human anxiety often invoke a conflict between approach and avoidance [1, 2]. In these, a key behavioral assay comprises passive avoidance of potential threat and inhibition, both thought to be controlled by ventral hippocampus [2–6]. Efforts to translate these approaches to clinical...

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Autores principales: Bach, Dominik R., Guitart-Masip, Marc, Packard, Pau A., Miró, Júlia, Falip, Mercè, Fuentemilla, Lluís, Dolan, Raymond J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969259/
https://www.ncbi.nlm.nih.gov/pubmed/24560572
http://dx.doi.org/10.1016/j.cub.2014.01.046
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author Bach, Dominik R.
Guitart-Masip, Marc
Packard, Pau A.
Miró, Júlia
Falip, Mercè
Fuentemilla, Lluís
Dolan, Raymond J.
author_facet Bach, Dominik R.
Guitart-Masip, Marc
Packard, Pau A.
Miró, Júlia
Falip, Mercè
Fuentemilla, Lluís
Dolan, Raymond J.
author_sort Bach, Dominik R.
collection PubMed
description Animal models of human anxiety often invoke a conflict between approach and avoidance [1, 2]. In these, a key behavioral assay comprises passive avoidance of potential threat and inhibition, both thought to be controlled by ventral hippocampus [2–6]. Efforts to translate these approaches to clinical contexts [7, 8] are hampered by the fact that it is not known whether humans manifest analogous approach-avoidance dispositions and, if so, whether they share a homologous neurobiological substrate [9]. Here, we developed a paradigm to investigate the role of human hippocampus in arbitrating an approach-avoidance conflict under varying levels of potential threat. Across four experiments, subjects showed analogous behavior by adapting both passive avoidance behavior and behavioral inhibition to threat level. Using functional magnetic resonance imaging (fMRI), we observe that threat level engages the anterior hippocampus, the human homolog of rodent ventral hippocampus [10]. Testing patients with selective hippocampal lesions, we demonstrate a causal role for the hippocampus with patients showing reduced passive avoidance behavior and inhibition across all threat levels. Our data provide the first human assay for approach-avoidance conflict akin to that of animal anxiety models. The findings bridge rodent and human research on passive avoidance and behavioral inhibition and furnish a framework for addressing the neuronal underpinnings of human anxiety disorders, where our data indicate a major role for the hippocampus.
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spelling pubmed-39692592014-03-31 Human Hippocampus Arbitrates Approach-Avoidance Conflict Bach, Dominik R. Guitart-Masip, Marc Packard, Pau A. Miró, Júlia Falip, Mercè Fuentemilla, Lluís Dolan, Raymond J. Curr Biol Report Animal models of human anxiety often invoke a conflict between approach and avoidance [1, 2]. In these, a key behavioral assay comprises passive avoidance of potential threat and inhibition, both thought to be controlled by ventral hippocampus [2–6]. Efforts to translate these approaches to clinical contexts [7, 8] are hampered by the fact that it is not known whether humans manifest analogous approach-avoidance dispositions and, if so, whether they share a homologous neurobiological substrate [9]. Here, we developed a paradigm to investigate the role of human hippocampus in arbitrating an approach-avoidance conflict under varying levels of potential threat. Across four experiments, subjects showed analogous behavior by adapting both passive avoidance behavior and behavioral inhibition to threat level. Using functional magnetic resonance imaging (fMRI), we observe that threat level engages the anterior hippocampus, the human homolog of rodent ventral hippocampus [10]. Testing patients with selective hippocampal lesions, we demonstrate a causal role for the hippocampus with patients showing reduced passive avoidance behavior and inhibition across all threat levels. Our data provide the first human assay for approach-avoidance conflict akin to that of animal anxiety models. The findings bridge rodent and human research on passive avoidance and behavioral inhibition and furnish a framework for addressing the neuronal underpinnings of human anxiety disorders, where our data indicate a major role for the hippocampus. Cell Press 2014-03-03 /pmc/articles/PMC3969259/ /pubmed/24560572 http://dx.doi.org/10.1016/j.cub.2014.01.046 Text en © 2014 The Authors http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Report
Bach, Dominik R.
Guitart-Masip, Marc
Packard, Pau A.
Miró, Júlia
Falip, Mercè
Fuentemilla, Lluís
Dolan, Raymond J.
Human Hippocampus Arbitrates Approach-Avoidance Conflict
title Human Hippocampus Arbitrates Approach-Avoidance Conflict
title_full Human Hippocampus Arbitrates Approach-Avoidance Conflict
title_fullStr Human Hippocampus Arbitrates Approach-Avoidance Conflict
title_full_unstemmed Human Hippocampus Arbitrates Approach-Avoidance Conflict
title_short Human Hippocampus Arbitrates Approach-Avoidance Conflict
title_sort human hippocampus arbitrates approach-avoidance conflict
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3969259/
https://www.ncbi.nlm.nih.gov/pubmed/24560572
http://dx.doi.org/10.1016/j.cub.2014.01.046
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