fMRI activation during response inhibition and error processing: the role of the DAT1 gene in typically developing adolescents and those diagnosed with ADHD

Wouter Braet, Katherine Johnson, Claire Tobin, Ruth Acheson, Caroline McDonnell, Ziarih Hawi, Edwina Barry, Aisling Mulligan, Michael Gill, Mark Bellgrove, Ian Robertson, Hugh Garavan

Research output: Contribution to journalArticleResearchpeer-review

37 Citations (Scopus)

Abstract

The DAT1 gene codes for the dopamine transporter, which clears dopamine from the synaptic cleft, and a variant of this gene has previously been associated with compromised response inhibition in both healthy and clinical populations. This variant has also been associated with ADHD, a disorder that is characterised by disturbed dopamine function as well as problems with response inhibition. In the present study we used fMRI to investigate the role of dopaminergic genetic variation on executive functioning by comparing how activation associated with successful and unsuccessful inhibitions differs based on DAT1-genotype and ADHD-diagnosis in adolescents performing a go/nogo task. The results identify regional specificity concerning which functional differences can be attributed to the possession of the high risk DAT1 genotype, the clinical condition or an interaction between the two. During response inhibition, individuals with two copies of the 10-repeat allele showed increased activation in frontal, medial, and parietal regions, which may indicate that inhibition is more effortful for this group. Conversely, this group displayed a reduced error response in the parahippocampal gyrus, suggestive of reduced learning from errors. There were also a number of frontal, parietal, medial and occipital regions, where the relationship between genotype and fMRI-activation differed between the ADHD group and the typically developing adolescents. Finally, the ADHD group displayed decreased activation in parietal and (pre)frontal regions during response inhibition, and in frontal and medial brain regions on error trials.
Original languageEnglish
Pages (from-to)1641 - 1650
Number of pages10
JournalNeuropsychologia
Volume49
Issue number7
DOIs
Publication statusPublished - 2011
Externally publishedYes

Cite this

Braet, Wouter ; Johnson, Katherine ; Tobin, Claire ; Acheson, Ruth ; McDonnell, Caroline ; Hawi, Ziarih ; Barry, Edwina ; Mulligan, Aisling ; Gill, Michael ; Bellgrove, Mark ; Robertson, Ian ; Garavan, Hugh. / fMRI activation during response inhibition and error processing: the role of the DAT1 gene in typically developing adolescents and those diagnosed with ADHD. In: Neuropsychologia. 2011 ; Vol. 49, No. 7. pp. 1641 - 1650.
@article{4c8ab795a4a0415399ff896505893907,
title = "fMRI activation during response inhibition and error processing: the role of the DAT1 gene in typically developing adolescents and those diagnosed with ADHD",
abstract = "The DAT1 gene codes for the dopamine transporter, which clears dopamine from the synaptic cleft, and a variant of this gene has previously been associated with compromised response inhibition in both healthy and clinical populations. This variant has also been associated with ADHD, a disorder that is characterised by disturbed dopamine function as well as problems with response inhibition. In the present study we used fMRI to investigate the role of dopaminergic genetic variation on executive functioning by comparing how activation associated with successful and unsuccessful inhibitions differs based on DAT1-genotype and ADHD-diagnosis in adolescents performing a go/nogo task. The results identify regional specificity concerning which functional differences can be attributed to the possession of the high risk DAT1 genotype, the clinical condition or an interaction between the two. During response inhibition, individuals with two copies of the 10-repeat allele showed increased activation in frontal, medial, and parietal regions, which may indicate that inhibition is more effortful for this group. Conversely, this group displayed a reduced error response in the parahippocampal gyrus, suggestive of reduced learning from errors. There were also a number of frontal, parietal, medial and occipital regions, where the relationship between genotype and fMRI-activation differed between the ADHD group and the typically developing adolescents. Finally, the ADHD group displayed decreased activation in parietal and (pre)frontal regions during response inhibition, and in frontal and medial brain regions on error trials.",
author = "Wouter Braet and Katherine Johnson and Claire Tobin and Ruth Acheson and Caroline McDonnell and Ziarih Hawi and Edwina Barry and Aisling Mulligan and Michael Gill and Mark Bellgrove and Ian Robertson and Hugh Garavan",
year = "2011",
doi = "10.1016/j.neuropsychologia.2011.01.001",
language = "English",
volume = "49",
pages = "1641 -- 1650",
journal = "Neuropsychologia",
issn = "0028-3932",
publisher = "Elsevier",
number = "7",

}

fMRI activation during response inhibition and error processing: the role of the DAT1 gene in typically developing adolescents and those diagnosed with ADHD. / Braet, Wouter; Johnson, Katherine; Tobin, Claire; Acheson, Ruth; McDonnell, Caroline; Hawi, Ziarih; Barry, Edwina; Mulligan, Aisling; Gill, Michael; Bellgrove, Mark; Robertson, Ian; Garavan, Hugh.

In: Neuropsychologia, Vol. 49, No. 7, 2011, p. 1641 - 1650.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - fMRI activation during response inhibition and error processing: the role of the DAT1 gene in typically developing adolescents and those diagnosed with ADHD

AU - Braet, Wouter

AU - Johnson, Katherine

AU - Tobin, Claire

AU - Acheson, Ruth

AU - McDonnell, Caroline

AU - Hawi, Ziarih

AU - Barry, Edwina

AU - Mulligan, Aisling

AU - Gill, Michael

AU - Bellgrove, Mark

AU - Robertson, Ian

AU - Garavan, Hugh

PY - 2011

Y1 - 2011

N2 - The DAT1 gene codes for the dopamine transporter, which clears dopamine from the synaptic cleft, and a variant of this gene has previously been associated with compromised response inhibition in both healthy and clinical populations. This variant has also been associated with ADHD, a disorder that is characterised by disturbed dopamine function as well as problems with response inhibition. In the present study we used fMRI to investigate the role of dopaminergic genetic variation on executive functioning by comparing how activation associated with successful and unsuccessful inhibitions differs based on DAT1-genotype and ADHD-diagnosis in adolescents performing a go/nogo task. The results identify regional specificity concerning which functional differences can be attributed to the possession of the high risk DAT1 genotype, the clinical condition or an interaction between the two. During response inhibition, individuals with two copies of the 10-repeat allele showed increased activation in frontal, medial, and parietal regions, which may indicate that inhibition is more effortful for this group. Conversely, this group displayed a reduced error response in the parahippocampal gyrus, suggestive of reduced learning from errors. There were also a number of frontal, parietal, medial and occipital regions, where the relationship between genotype and fMRI-activation differed between the ADHD group and the typically developing adolescents. Finally, the ADHD group displayed decreased activation in parietal and (pre)frontal regions during response inhibition, and in frontal and medial brain regions on error trials.

AB - The DAT1 gene codes for the dopamine transporter, which clears dopamine from the synaptic cleft, and a variant of this gene has previously been associated with compromised response inhibition in both healthy and clinical populations. This variant has also been associated with ADHD, a disorder that is characterised by disturbed dopamine function as well as problems with response inhibition. In the present study we used fMRI to investigate the role of dopaminergic genetic variation on executive functioning by comparing how activation associated with successful and unsuccessful inhibitions differs based on DAT1-genotype and ADHD-diagnosis in adolescents performing a go/nogo task. The results identify regional specificity concerning which functional differences can be attributed to the possession of the high risk DAT1 genotype, the clinical condition or an interaction between the two. During response inhibition, individuals with two copies of the 10-repeat allele showed increased activation in frontal, medial, and parietal regions, which may indicate that inhibition is more effortful for this group. Conversely, this group displayed a reduced error response in the parahippocampal gyrus, suggestive of reduced learning from errors. There were also a number of frontal, parietal, medial and occipital regions, where the relationship between genotype and fMRI-activation differed between the ADHD group and the typically developing adolescents. Finally, the ADHD group displayed decreased activation in parietal and (pre)frontal regions during response inhibition, and in frontal and medial brain regions on error trials.

UR - http://www.sciencedirect.com/science/article/pii/S0028393211000030

U2 - 10.1016/j.neuropsychologia.2011.01.001

DO - 10.1016/j.neuropsychologia.2011.01.001

M3 - Article

VL - 49

SP - 1641

EP - 1650

JO - Neuropsychologia

JF - Neuropsychologia

SN - 0028-3932

IS - 7

ER -