Ketamine modulates subgenual cingulate connectivity with the memory-related neural circuit – a mechanism of relevance to resistant depression?

Background: Ketamine has been reported to have efficacy as an antidepressant in several studies of treatment-resistant depression. In this study, we investigate whether an acute administration of ketamine leads to reductions in the functional connectivity of subgenual anterior cingulate cortex (sgACC) with other brain regions. Methods: Thirteen right-handed healthy male subjects underwent a 15 minute resting state fMRI with an infusion of intravenous ketamine (target blood level=150ng/ml) starting at 5 minutes. We used a seed region centred on the sgACC and assessed functional connectivity before and during ketamine administration. Results: Before ketamine administration, positive coupling with the sgACC seed region was observed in a large cluster encompassing the anterior cingulate and negative coupling was observed with the anterior cerebellum. Following ketamine administration, sgACC coupling decreased with the brainstem, hippocampus, parahippocampal gyrus, retrosplenial cortex, and thalamus. Discussion: Ketamine reduced functional connectivity of the sgACC with brain regions implicated in emotion, memory and mind wandering. It is possible the therapeutic effects of ketamine may be mediated via this mechanism, although further work is required to test this hypothesis.