Ketamine reduces spontaneous brain activity in three subregions of the anterior cingulate cortex (ACC) during administration in healthy people. Lamotrigine, which inhibits glutamate release, attenuates this effect only in the ventral ACC subregions, suggesting glutamate involvement there. ACC activity returns to baseline 24 hours later, though group differences persist between the lamotrigine and ketamine groups. Trait negative emotionality is closely linked to activity changes in the subgenual ACC after ketamine. These findings clarify how ketamine affects different ACC subregions and may relate to its antidepressant mechanisms.
Ketamine infusion significantly increased functional connectivity between the pregenual anterior cingulate cortex and the dorsomedial prefrontal cortex during a working memory task, and between the pregenual anterior cingulate cortex and the left insula during rest. These effects were absent when participants were pretreated with lamotrigine, a glutamate-release inhibitor. The findings suggest that ketamine's beneficial effects on brain communication, observed in psychiatric conditions linked to chronic stress, may depend on glutamate release.