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Proc Natl Acad Sci U S A. 2018 Jan 30;115(5):E1032-E1040. doi: 10.1073/pnas.1714691115. Epub 2018 Jan 11.

Linked networks for learning and expressing location-specific threat.

Author information

Institute of Cognitive Neuroscience, University College London, London WC1N 3AZ, United Kingdom;
Section of Developmental Affective Neuroscience, National Institute of Mental Health, Bethesda, MD 20892.
Institute of Cognitive Neuroscience, University College London, London WC1N 3AZ, United Kingdom.
Institute of Neurology, University College London, London WC1N 3BG, United Kingdom.
Department of Psychology, University of York, York YO10 5DD, United Kingdom.
Department of Clinical Psychology, University College London, London WC1E 6BT, United Kingdom.
Wellcome Centre for Human Neuroimaging, University College London, London WC1N 3AR, United Kingdom.


Learning locations of danger within our environment is a vital adaptive ability whose neural bases are only partially understood. We examined fMRI brain activity while participants navigated a virtual environment in which flowers appeared and were "picked." Picking flowers in the danger zone (one-half of the environment) predicted an electric shock to the wrist (or "bee sting"); flowers in the safe zone never predicted shock; and household objects served as controls for neutral spatial memory. Participants demonstrated learning with shock expectancy ratings and skin conductance increases for flowers in the danger zone. Patterns of brain activity shifted between overlapping networks during different task stages. Learning about environmental threats, during flower approach in either zone, engaged the anterior hippocampus, amygdala, and ventromedial prefrontal cortex (vmPFC), with vmPFC-hippocampal functional connectivity increasing with experience. Threat appraisal, during approach in the danger zone, engaged the insula and dorsal anterior cingulate (dACC), with insula-hippocampal functional connectivity. During imminent threat, after picking a flower, this pattern was supplemented by activity in periaqueductal gray (PAG), insula-dACC coupling, and posterior hippocampal activity that increased with experience. We interpret these patterns in terms of multiple representations of spatial context (anterior hippocampus); specific locations (posterior hippocampus); stimuli (amygdala); value (vmPFC); threat, both visceral (insula) and cognitive (dACC); and defensive behaviors (PAG), interacting in different combinations to perform the functions required at each task stage. Our findings illuminate how we learn about location-specific threats and suggest how they might break down into overgeneralization or hypervigilance in anxiety disorders.


fMRI; hippocampus; learning; location-specific threat conditioning; navigation

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