Ketamine attenuates habenula activity in response to aversive outcomes during Pavlovian learning
bioRxiv (Cold Spring Harbor Laboratory) February 10, 2026 Erdem Pulcu, Sara Costi, Pilar Artiach-Hortelano et al.
A single sub-anesthetic dose of ketamine reduces activity in the lateral habenula, a small midbrain structure involved in aversive learning, when healthy volunteers expect or experience unpleasant stimuli a day later. In a randomized trial with 70 adults, those who received ketamine showed attenuated habenula responses during an aversive Pavlovian conditioning task measured with 7-Tesla functional neuroimaging. Preliminary evidence suggests that reduced habenula activity during aversive learning may weaken the emotional impact of negative memories. These results support preclinical models of how ketamine may rapidly relieve depression by acting on the human habenula.