Hippocampal dysfunction effects on context memory: possible etiology for posttraumatic stress disorder

Abstract

Hippocampal volume reductions and functional impairments are reliable findings in posttraumatic stress disorder (PTSD) imaging studies. However, it is not clear if and how hippocampal dysfunction contributes to the etiology and maintenance of PTSD. Individuals with PTSD are often described as showing fear responses to trauma reminders outside of contexts in which these cues would reasonably predict danger. Animal studies suggest that the hippocampus is required to form and recall associations between contextual stimuli and aversive events. For example, the hippocampus is critical for encoding memories in which a complex configuration of multiple cues is associated with the aversive event. Conversely, the hippocampus is not required for associations with discrete cues. In animal studies, if configural memory is disrupted, learning strategies using discrete cue associations predominate. These data suggest poor hippocampal function could bias the organism toward forming multiple simple cue associations during trauma, thus increasing the chances of fear responses in multiple environments (or contexts) in which these cues may be present. Here we will examine clinical and preclinical literature to support a theory of hippocampal dysfunction as a primary contributory factor to the etiology of PTSD, and discuss future research required to test these hypotheses. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.

Figure 1

Schematic representation of the role of hippocampal function in context fear memory. Here we suggest that such a shift to a predominantly elemental strategy would thus allow elemental cues to have a much larger role in behavioral responses to the environment, with each discrete cue encoded during trauma able to induce conditioned fear responses across multiple contexts. The left side of the figure demonstrates how normal hippocampal function allows for the formation of a conjunctive context representation consisting of a combination of individual elements. This conjunctive representation is then associated with the traumatic event (in this case an exploding grenade). Upon later exposure to a single element of the original context (in this case the garbage bag), no fear response is triggered. The right side of the figure demonstrates how impaired hippocampal function precludes formation of a conjunctive representation. Instead, each individual element of the context is independently associated with the traumatic event. Due to this single-element association, later exposure to only the garbage bag (independent of other contextual elements) is then sufficient to trigger a fear response.