Effect of heart rate variability and the moderating effect of ketamine on resting-state brain connectivity in the default mode network

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 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),...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

Leiden University Student Repository

Documents

In Collections

Effect of heart rate variability and the moderating effect of ketamine on resting-state brain connectivity in the default mode network