Research master thesis | Psychology (research) (MSc)
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Atomoxetine is a prescription drug often used to restore executive (or cognitive) functioning in patients with attention-deficit/hyperactivity disorder and other neuropsychiatric conditions....Show moreAtomoxetine is a prescription drug often used to restore executive (or cognitive) functioning in patients with attention-deficit/hyperactivity disorder and other neuropsychiatric conditions. Moreover, this drug may potentially be ingested by healthy individuals who seek to improve their cognitive performance. However, the effect of atomoxetine on healthy brain functioning remains largely unclear. Network approaches have become useful for studying how the functional connectivity between brain regions may enhance or hinder executive functioning. Accordingly, to further examine the underlying mechanisms of action of atomoxetine, it is relevant to explore how this drug influences the functional connectivity of a large-scale brain network involved in the control of top-down processes: the executive control network (ECN). The aim of this study was thus to investigate the effect of atomoxetine (40 mg) on the functional connectivity of the ECN in healthy volunteers (n = 15). Network analyses were conducted on unpublished functional magnetic resonance (fMRI)-data collected by Chamberlain and colleagues (2009) in a double-blind, placebo-controlled, within-subjects, crossover design in which participants completed a goal-directed fMRI-task (i.e., the temporal discounting task), probing the ECN. Contrary to expectations, a paired-samples permutation test, corrected for multiple comparisons by means of a threshold free cluster enhancement, revealed that the functional connectivity of the participants’ ECN does not increase significantly after ingesting atomoxetine as compared to placebo (p > .05 corrected). Nevertheless, exploratory analyses indicated that, relative to placebo, atomoxetine significantly strengthens the functional connectivity of a frontoparietal network highly associated with cognition and language paradigms (t(14) = 7.61, p = .003). Together, these results suggest that, in healthy individuals, atomoxetine might not have enhancing effects on the processes supported by the ECN but (potentially) on those supported by a frontoparietal network. Atomoxetine might thus have beneficial effects in the cognitive performance of healthy individuals by facilitating certain processes associated with both cognition and language. Further research is however warranted to corroborate these findings in confirmatory studies and enhance the understanding of the underlying mechanisms of action of atomoxetine in healthy brain functioning.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
