Mapping the effects of atomoxetine during response inhibition across cortical territories and the locus coeruleus

TY - JOUR

T1 - Mapping the effects of atomoxetine during response inhibition across cortical territories and the locus coeruleus

AU - Ye, Rong

AU - Mazibuko, Ndabezinhle

AU - Teichert, Jens

AU - Regenthal, Ralf

AU - Kehagia, Angie A.

AU - Mehta, Mitul A.

N1 - Funding Information: This study was funded from departmental sources. Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

PY - 2021/10/25

Y1 - 2021/10/25

N2 - Rationale: The effects of atomoxetine (ATO) on response inhibition have been typically examined using the stop signal task (SST) which is however confounded by attentional capture. The right inferior frontal cortex (rIFC) has been implicated in the modulation of ATO on inhibitory control, but a precise characterisation of its role is complicated by its functional inhomogeneity. Objectives: The current study aimed to directly investigate the effect of ATO in the SST using the imaging contrast unconfounded by attentional capture, to test the specific drug actions in functionally dissociable rIFC subregions, and to explore the role of locus coeruleus (LC), the main source of cortical noradrenaline, in mediating the drug effects. Methods: This imaging study investigated the effect of ATO (40 mg) in 18 human participants during a modified SST that unconfounds attention from inhibition. Functional definitions for rIFC subdivisions were adopted in the analyses to isolate attention and inhibition during action cancellation. The LC integrity was measured in vivo using a neuromelanin-sensitive sequence. Results: We identified one mechanism of ATO modulation specific to inhibitory control: ATO enhanced activity in pre-supplementary area (pre-SMA) for motor inhibition, and the recruitment of temporoparietal junction (TPJ) and inferior frontal junction (IFJ) for functional integration during response inhibition. Moreover, drug-related behavioural and neural responses correlated with variations in LC integrity. Conclusions: These findings provide a more nuanced and precise understanding of the effects of ATO on specific and domain general aspects of stopping.

AB - Rationale: The effects of atomoxetine (ATO) on response inhibition have been typically examined using the stop signal task (SST) which is however confounded by attentional capture. The right inferior frontal cortex (rIFC) has been implicated in the modulation of ATO on inhibitory control, but a precise characterisation of its role is complicated by its functional inhomogeneity. Objectives: The current study aimed to directly investigate the effect of ATO in the SST using the imaging contrast unconfounded by attentional capture, to test the specific drug actions in functionally dissociable rIFC subregions, and to explore the role of locus coeruleus (LC), the main source of cortical noradrenaline, in mediating the drug effects. Methods: This imaging study investigated the effect of ATO (40 mg) in 18 human participants during a modified SST that unconfounds attention from inhibition. Functional definitions for rIFC subdivisions were adopted in the analyses to isolate attention and inhibition during action cancellation. The LC integrity was measured in vivo using a neuromelanin-sensitive sequence. Results: We identified one mechanism of ATO modulation specific to inhibitory control: ATO enhanced activity in pre-supplementary area (pre-SMA) for motor inhibition, and the recruitment of temporoparietal junction (TPJ) and inferior frontal junction (IFJ) for functional integration during response inhibition. Moreover, drug-related behavioural and neural responses correlated with variations in LC integrity. Conclusions: These findings provide a more nuanced and precise understanding of the effects of ATO on specific and domain general aspects of stopping.

KW - Atomoxetine

KW - Functional magnetic resonance imaging

KW - Locus coeruleus

KW - Response inhibition

KW - Stop signal task

UR - http://www.scopus.com/inward/record.url?scp=85117797353&partnerID=8YFLogxK

U2 - 10.1007/s00213-021-05998-2

DO - 10.1007/s00213-021-05998-2

M3 - Article

AN - SCOPUS:85117797353

SN - 0033-3158

JO - Psychopharmacology

JF - Psychopharmacology

ER -