Research master thesis | Psychology (research) (MSc)
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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...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
Research master thesis | Psychology (research) (MSc)
closed access
Introduction: The default mode network (DMN) is a large intrinsic network in the brain, which seems to be affected in depressed patients. Also, aberrant heart rate variability (HRV) is often found...Show moreIntroduction: The default mode network (DMN) is a large intrinsic network in the brain, which seems to be affected in depressed patients. Also, aberrant heart rate variability (HRV) is often found in this population. Ketamine is thought to be a fast-acting antidepressant and has shown to have an effect on HRV and intrinsic brain connectivity. In this study, the effect of HRV on resting-state functional connectivity of the DMN and brain activity of areas within the DMN that were significantly correlated with HRV was examined. Also, it was investigated whether ketamine moderated this relationship. Method: Twelve healthy men received an intravenous ketamine or placebo infusion on two occasions. Resting-state functional connectivity and HRV were measured before, during, and after infusion. Dual-regression was used to obtain DMN connectivity scores, while a whole brain analysis was done to determine which brain areas were correlated with HRV. Raw digitized electrocardiogram (EKG), obtained with a pulse oximeter, was analyzed in order to extract HRV data. Multilevel analysis was used to determine the effect of HRV and ketamine on resting-state functional connectivity in the DMN and brain activity in the subgenual anterior cingulate cortex (sgACC), right dorsolateral prefrontal cortex (dlPFC), and the left postcentral gyrus. Results: DMN connectivity strength was negatively related to HRV, but positively related to activity of the right dlPFC and the left postcentral gyrus for the placebo condition. Ketamine was associated with a more profound effect of HRV on DMN connectivity and brain activity within the postcentral gyrus. Discussion: The present results complement recent studies that show that HRV is associated with connectivity strength in the DMN. Implications for the relevance of using ketamine in depressed patients are discussed. Initial increases of DMN connectivity are followed by a decrease in the DMN, which may be beneficial for depressed patients who generally show hyperconnectivity within the DMN. Results thus imply that ketamine has a moderating role in this.Show less