Human Hippocampus Arbitrates Approach-Avoidance Conflict
2014 (English)In: Current Biology, ISSN 0960-9822, E-ISSN 1879-0445, Vol. 24, no 5, 541-547 p.Article in journal (Refereed) Published
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 . 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.
Place, publisher, year, edition, pages
2014. Vol. 24, no 5, 541-547 p.
Biochemistry and Molecular Biology Cell Biology
IdentifiersURN: urn:nbn:se:su:diva-102462DOI: 10.1016/j.cub.2014.01.046ISI: 000332412400022OAI: oai:DiVA.org:su-102462DiVA: diva2:710785
FunderWellcome trust, 098362/Z/12/Z, 091593/Z/10/Z
Other Funding Agencies:
Senate of Berlin; Ramon y Cajal program; Spanish Government PSI2010-15024 2014-04-082014-04-072014-04-08Bibliographically approved