Functional Connectivity Changes Following Ketamine Administration:  Implications for Understanding Acute Antidepressant Drug Action

Introduction: Selective serotonin reuptake inhibitors (SSRI’s) are an effective treatment for many depressed patients, but their disadvantages include a wide range of side effects and a delayed treatment response. In contrast, subanesthetic doses of ketamine show acute antidepressant effects. Previous functional connectivity findings implicate the ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), key areas of the default mode network (DMN), in ketamine’s acute antidepressant effect. In addition, psilocybin has also shown acute antidepressant effects with a potential role for the claustrum, an area functionally connected to the DMN. However, pharmacological fMRI findings concerning acute antidepressant drug action may be moderated by the decision to include or exclude a controversial preprocessing step called global signal regression (GSR). In this study, we investigated ketamine’s acute effects on functional connectivity patterns in the brain in order to...Show moreIntroduction: Selective serotonin reuptake inhibitors (SSRI’s) are an effective treatment for many depressed patients, but their disadvantages include a wide range of side effects and a delayed treatment response. In contrast, subanesthetic doses of ketamine show acute antidepressant effects. Previous functional connectivity findings implicate the ventromedial prefrontal cortex (vmPFC) and posterior cingulate cortex (PCC), key areas of the default mode network (DMN), in ketamine’s acute antidepressant effect. In addition, psilocybin has also shown acute antidepressant effects with a potential role for the claustrum, an area functionally connected to the DMN. However, pharmacological fMRI findings concerning acute antidepressant drug action may be moderated by the decision to include or exclude a controversial preprocessing step called global signal regression (GSR). In this study, we investigated ketamine’s acute effects on functional connectivity patterns in the brain in order to probe the underlying mechanism of its acute antidepressant effects. Hypotheses: Ketamine acutely decreases functional connectivity between the vmPFC and PCC and between the DMN and claustrum. In addition, these findings will not be affected by the decision to include or exclude GSR. Method: Twenty volunteers were administered ketamine as well as a placebo on separate days in a randomized, double-blind, crossover design. We acquired resting-state functional magnetic resonance imaging (fMRI) data before, during and immediately after the acute phase of administration. Results: No differences in functional connectivity patterns were found between ketamine and placebo. These results were unaffected by the inclusion or exclusion of GSR. Conclusion: It remains unclear which changes in functional connectivity occur in the acute phase of ketamine administration. Future research should investigate the influence of GSR on fMRI findings.Show less

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Functional Connectivity Changes Following Ketamine Administration: Implications for Understanding Acute Antidepressant Drug Action