Anglia Ruskin University
Download file
Download file
2 files

Prefrontal cortex activation and stopping performance underlie the beneficial effects of atomoxetine on response inhibition in healthy and cocaine use disorder volunteers

Download all (3.67 MB)
journal contribution
posted on 2023-08-30, 19:02 authored by Peter Zhukovsky, Sharon Morein-Zamir, Hisham Ziauddeen, Emilio Fernandez-Egea, Chun Meng, Ralf Regenthal, Barbara J. Sahakian, Edward T. Bullmore, Trevor W. Robbins, Jeffrey W. Dalley, Karen D. Ersche
Background- Impaired response inhibition in individuals with cocaine use disorder (CUD) is hypothesised to depend on deficient noradrenergic signalling in cortico-striatal networks. Remediation of noradrenergic neurotransmission with selective norepinephrine reuptake inhibitors such as atomoxetine may therefore have clinical utility to improve response inhibitory control in CUD. Methods- We carried out a randomised, double-blind, placebo-controlled, crossover study with 26 CUD participants and 28 control volunteers investigating the neural substrates of stop-signal inhibitory control. The effects of a single dose of atomoxetine (40 mg) were compared with placebo on stop-signal reaction time performance and functional network connectivity using dynamic causal modelling. Results- We found that atomoxetine speeded Go response times in both control and CUD participants. Improvements in stopping efficiency on atomoxetine were conditional on baseline (placebo) stopping performance and were directly associated with increased inferior frontal gyrus activation. Further, stopping performance, task-based brain activation and effective connectivity were similar in the two groups. Dynamic causal modelling of effective connectivity of multiple prefrontal and basal ganglia regions replicated and extended previous models of network function underlying inhibitory control to CUD and control volunteers and showed subtle effects of atomoxetine on prefrontal-basal ganglia interactions. Conclusions- These findings demonstrate that atomoxetine improves response inhibition in a baseline-dependent manner in control and in CUD participants. Our results emphasize inferior frontal cortex function as a future treatment target due to its key role in improving response inhibition in CUD.



  • Yes



Issue number


Page range


Publication title

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging





File version

  • Accepted version


  • eng

Legacy posted date


Legacy creation date


Legacy Faculty/School/Department

Faculty of Science & Engineering

Usage metrics

    ARU Outputs


    No categories selected