Neural correlates of error monitoring modulated by atomoxetine in healthy volunteers: a randomized, placebo-controlled fMRI-study

Atomoxetine (ATMX) is a selective norepinephrine reuptake inhibitor clinically used for treatment of the attention deficit/hyperactivity disorder. In healthy controls, sub-clinical doses improved inhibitory control in combination with modulation of prefrontal cortex functioning. We investigated the effects of a clinically relevant dose of ATMX on error-monitoring as a second key component of cognitive control. 12 healthy, male volunteers were included in a randomized double-blind placebo-controlled within-subjects design to examine the effects of a single dose of ATMX(80 mg) on neural activities during a combined Eriksen-Flanker-Go/NoGo-task as measured by functional magnetic resonance imaging. Behaviorally, ATMX led to a significant increase in failed inhibition. Functionally, interaction analysis revealed a significant increase of the error signal (incorrect minus correct NoGo-trials) under ATMX in bilateral inferior frontal cortex and pre-supplementary motor area. Drug-dependent increases in error signaling did not correlate with increased error rates. Analysis of neuropsychological data indexed a significant increase in phasic alertness. Results support that a clinical dose of ATMX increases neural sensitivity for errors in healthy controls possibly due to an accentuated representation of that task set. However, this gain was accompanied by deterioration in inhibitory control possibly reflecting a shift beyond the optimal working range of the norepinephrine system.