Implicit Memory Under Sedation and Anesthesia: From the ED to the Lab and Back

Background: Sedation and anesthesia aims to induce unconsciousness and prevent memory of unpleasant experiences. Patients’ explicit recall occurs in a fraction of the cases. Moreover, even without explicit recall, implicit memory can form and lead to trauma and other physiological insults. The amygdala and the prefrontal cortex participate in forging and retrieving emotional and valence-driven learning. We hypothesized that this circuitry plays an active role in formation of aversive associations under sedation and anesthesia.

Methods: We recorded the activity of single neurons in the amygdala and the medial-prefrontal-cortex of sedated/anesthetized monkeys undergoing aversive tone-odor conditioning, and further tested recall after recovery. We used a wide range of therapeutic doses of ketamine - a non-competitive NMDA-receptor-antagonist; and midazolam - a GABA-co-agonist.

Results: Seventy-six full sessions from two non-human primates entered analysis. We recorded 172 amygdala and 189 dACC neurons respectively. We found behavioral evidence for aversive memory formation under both anesthetics and in all doses. Under anesthesia, we found behavioral evidence of memory formation in 46% of sessions. Increased single-neuron responses in 16.2% of amygdala and 18.7% medial-prefrontal-cortex units during acquisition (namely under anesthesia) were correlated with memory formation, and response magnitude predicted post-anesthesia retention.

Conclusions: Unconditioned responses under anesthesia did not differ in magnitude from saline controls suggesting that stimulus valence is maintained can lead to associative memory formation under different anesthetic doses and agents, and that the amygdala- medial-prefrontal-cortex circuitry plays a major role in acquisition and maintenance of these memories. The findings may serve development of monitoring strategies and improved protocols for sedated and anesthetized patients.