Effects of Serial Ketamine Infusions on Corticolimbic Functional Connectivity in Major Depression

Megha M. Vasavada, Joana Loureiro, Antoni Kubicki, Ashish Sahib, Benjamin Wade, Gerhard Hellemann, Randall T. Espinoza, Eliza Congdon, Katherine L. Narr, Amber M. Leaver*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Background: Ketamine is a highly effective antidepressant for patients with treatment-resistant major depressive disorder (MDD). Resting-state functional magnetic resonance imaging studies show disruptions of functional connectivity (FC) between limbic regions and resting-state networks (RSNs) in MDD, including the default mode network, central executive network (CEN), and salience network (SN). Here, we investigated whether serial ketamine treatments change FC between limbic structures and RSNs. Methods: Patients with MDD (n = 44) were scanned at baseline (time 1 [T1]) and 24 hours after the first (T2) and fourth (T3) infusions of ketamine. Healthy control subjects (n = 50) were scanned at baseline, with a subgroup (n = 17) being rescanned at 2 weeks. Limbic regions included the amygdala and hippocampus, and RSNs included the default mode network, CEN, and SN. Results: Ketamine increased right amygdala FC to the right CEN (p = .05), decreased amygdala FC to the left CEN (p = .005) at T2 versus T1 (p = .015), which then increased at T3 versus T2 (p = .002), and decreased left amygdala FC to the SN (p = .016). Decreased left amygdala to SN FC at T2 predicted improvements in anxiety at T3 (p = .006). Ketamine increased right hippocampus FC to the left CEN (p = .001), and this change at T2 predicted decreased anhedonia at T3 (p = .005). Conclusions: Ketamine modulates FC between limbic regions and RSNs implicated in MDD. Increases in FC between limbic regions and the CEN suggest that ketamine may be involved in restoring top-down control of emotion processing. FC decreases between the left amygdala and SN suggest that ketamine may ameliorate MDD-related dysconnectivity in these circuits. Early FC changes between limbic regions and RSNs may be predictive of clinical improvements.

Original languageEnglish (US)
Pages (from-to)735-744
Number of pages10
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Issue number7
StatePublished - Jul 2021


  • Antidepressant treatment
  • Functional connectivity
  • Ketamine
  • Major depression
  • Mood disorders
  • Personalized medicine

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Clinical Neurology
  • Cognitive Neuroscience
  • Biological Psychiatry


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