Aberrant predictions of future threat lead to maladaptive avoidance in individuals with post-traumatic stress disorder (PTSD). How this disruption in prediction influences the control of memory states orchestrated by the dorsolateral prefrontal cortex is unknown. We combined computational modeling and brain connectivity analyses to reveal how individuals exposed and nonexposed to the 2015 Paris terrorist attacks formed and controlled beliefs about future intrusive re-experiencing implemented in the laboratory during a memory suppression task. Exposed individuals with PTSD used beliefs excessively to control hippocampal activity during the task. When this predictive control failed, the prediction-error associated with unwanted intrusions was poorly downregulated by reactive mechanisms. This imbalance was linked to higher severity of avoidance symptoms, but not to general disturbances such as anxiety or negative affect. Conversely, trauma-exposed participants without PTSD and nonexposed individuals were able to optimally balance predictive and reactive control during the memory suppression task. These findings highlight a potential pathological mechanism occurring in individuals with PTSD rooted in the relationship between the brain's predictive and control mechanisms.
© 2022. The Author(s).