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

Zhukovsky, Peter and Morein-Zamir, Sharon and Ziauddeen, Hisham and Fernandez-Egea, Emilio and Meng, Chun and Regenthal, Ralf and Sahakian, Barbara J. and Bullmore, Edward T. and Robbins, Trevor W. and Dalley, Jeffrey W. and Ersche, Karen D. (2021) Prefrontal cortex activation and stopping performance underlie the beneficial effects of atomoxetine on response inhibition in healthy and cocaine use disorder volunteers. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging. ISSN 2451-9022

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Official URL: http://dx.doi.org/10.1016/j.bpsc.2021.08.010

Abstract

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.

Item Type: Journal Article
Keywords: Impulsivity, Stop Signal Task, fMRI, Cocaine Addiction, Connectivity, DCM, Norepinephrine
Faculty: Faculty of Science & Engineering
SWORD Depositor: Symplectic User
Depositing User: Symplectic User
Date Deposited: 10 Sep 2021 12:51
Last Modified: 10 Sep 2021 12:52
URI: https://arro.anglia.ac.uk/id/eprint/706913

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