Ethoexperimental differentiation of human brain activity during threat-related pursuit and goal conflict

Evidence from functional magnetic resonance imaging (fMRI) suggests that in humans, as in rodents, the midbrain activates during imminent (proximate) threat-related pursuit and mediates panic whereas the hippocampus is activated by goal conflict and mediates anxiety. To date studies have used tasks that present only one or other of these contexts, precluding within-subjects comparison of brain activity during the two contexts. We sought a new perspective on human responses to pursuit and goal conflict by comparing, within-subjects and within one paradigm, the degree of neural dissociation between these two challenges. We did this by translating the Mouse Defense Test Battery (MDTB) for use during fMRI. In this ethoexperimental paradigm we repeatedly exposed participants to pursuit and goal conflict, with and without threat of electric shock. Moreover, the runway design of the MDTB allowed the effect of threat distance on brain activation to be evaluated independently of context. Consistent with earlier research, we found that imminent threat activated the midbrain and that this effect was significantly stronger during the pursuit condition than during goal conflict. Also consistent with earlier research, we found that hippocampal activation was significantly greater during goal conflict than pursuit by imminent threat. Finally, we found that hippocampal activation during goal conflict plus imminent threat was significantly negatively correlated with neuroticism scores, suggesting that anxiety-proneness impairs capacity to process goal conflict effectively under threat.