The Effect of Atomoxetine on the Functional Connectivity of Large-Scale Brain Networks

Atomoxetine 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...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 Network analyses were conducted on unpublished functional magnetic resonance (fMRI)-data collected by Chamberlain and colleagues (2009) in a double-blind, placebo-controlled, within-subjects, crossover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

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The Effect of Atomoxetine on the Functional Connectivity of Large-Scale Brain Networks