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Modulating amygdala activation to traumatic memories with a single ketamine infusion

Duek, O.; Li, Y.; Kelmendi, B.; Amen, S.; Gordon, C.; Milne, M.; Krystal, J. H.; Levy, I.; Harpaz-Rotem, I.

2021-07-09 psychiatry and clinical psychology
10.1101/2021.07.07.21260166 medRxiv
Show 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.

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