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Curr Biol. 2014 Mar 3;24(5):541-7. doi: 10.1016/j.cub.2014.01.046. Epub 2014 Feb 20.

Human hippocampus arbitrates approach-avoidance conflict.

Author information

1
Wellcome Trust Centre for Neuroimaging, University College London, London WC1N 3BG, UK; Berlin School of Mind and Brain, Humboldt University Berlin, 10099 Berlin, Germany; Psychiatric Hospital, University of Zurich, 8032 Zurich, Switzerland. Electronic address: dominik.bach@uzh.ch.
2
Wellcome Trust Centre for Neuroimaging, University College London, London WC1N 3BG, UK; Age Research Center, Karolinska Institute, 17111 Stockholm, Sweden.
3
Cognition and Brain Plasticity Unit, Institute of Biomedicine Research of Bellvitge (IDIBELL), 08908 Barcelona, Spain.
4
Cognition and Brain Plasticity Unit, Institute of Biomedicine Research of Bellvitge (IDIBELL), 08908 Barcelona, Spain; Epilepsy Unit, University Hospital of Bellvitge, 08907 Barcelona, Spain.
5
Epilepsy Unit, University Hospital of Bellvitge, 08907 Barcelona, Spain.
6
Cognition and Brain Plasticity Unit, Institute of Biomedicine Research of Bellvitge (IDIBELL), 08908 Barcelona, Spain; Department of Basic Psychology, University of Barcelona, 08007 Barcelona, Spain.
7
Wellcome Trust Centre for Neuroimaging, University College London, London WC1N 3BG, UK; Berlin School of Mind and Brain, Humboldt University Berlin, 10099 Berlin, Germany.

Erratum in

  • Curr Biol. 2014 Jun 16;24(12):1435.

Abstract

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

PMID:
24560572
PMCID:
PMC3969259
DOI:
10.1016/j.cub.2014.01.046
[Indexed for MEDLINE]
Free PMC Article

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