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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2014
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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. |
format | Online Article Text |
id | pubmed-3969259 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
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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