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

PeerJ. 2016 Feb 16;4:e1710. doi: 10.7717/peerj.1710. eCollection 2016.


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 min resting state fMRI with an infusion of intravenous ketamine (target blood level = 150 ng/ml) starting at 5 min. 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 activity became negatively correlated 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.

Keywords: Anterior cingulate; Antidepressant; Depression; Ketamine; MRI.

Grant support

This work was supported by the NIHR Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, Psychology and Neuroscience, King’s College London. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.