Modulating amygdala activation to traumatic memories with a single ketamine infusion

A single low-dose infusion of ketamine, an NMDA receptor antagonist, given after recalling a traumatic memory can weaken the fear response associated with post-traumatic stress disorder. In the study, people who received ketamine showed lower activity in the amygdala and hippocampus when re-exposed to trauma memories, compared to those who received midazolam. Ketamine also reduced communication between the amygdala and hippocampus, without affecting connections to the prefrontal cortex. These changes lasted at least 30 days after treatment, suggesting that human traumatic memories can be altered during a reconsolidation window, potentially offering a new approach to treating PTSD.

Study at a glance

Abstract

NMDA receptor antagonists have a vital role in extinction, learning, and reconsolidation processes. During the reconsolidation window, memories are activated into a labile state and can be stored in an altered form. This concept might have significant clinical implications in treating PTSD. Using amygdala activity as a major biomarker of fear response, we tested the potential of a single subanesthetic intravenous infusion of ketamine (NMDA receptor antagonist) to enhance post-retrieval extinction of PTSD trauma memories. Post-extinction, ketamine recipients (vs midazolam) showed a lower amygdala and hippocampus reactivation to trauma memories. Post-retrieval ketamine administration was also associated with decreased connectivity between the amygdala and hippocampus, with no change in amygdala-vmPFC connectivity, which suggests that ketamine may enhance post-retrieval extinction of PTSD trauma memory in humans. These findings demonstrate the capacity to rewrite human traumatic memories and to modulate the fear response for at least 30 days post-extinction.