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.
authors.affiliation: School of Psychology and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin 2, Ireland. Wouter.braet@gmail.com
authors.forename: Wouter
authors.initials: W
authors.lastname: Braet
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Johnson
authors.forename: Claire T
authors.initials: CT
authors.lastname: Tobin
authors.forename: Ruth
authors.initials: R
authors.lastname: Acheson
authors.forename: Caroline
authors.initials: C
authors.lastname: McDonnell
authors.forename: Ziarah
authors.initials: Z
authors.lastname: Hawi
authors.forename: Edwina
authors.initials: E
authors.lastname: Barry
authors.forename: Aisling
authors.initials: A
authors.lastname: Mulligan
authors.forename: Michael
authors.initials: M
authors.lastname: Gill
authors.forename: Mark A
authors.initials: MA
authors.lastname: Bellgrove
authors.forename: Ian H
authors.initials: IH
authors.lastname: Robertson
authors.forename: Hugh
authors.initials: H
authors.lastname: Garavan
mesh_terms: D000293:Adolescent; D001288:Attention / Q000502:physiology; D001289:Attention Deficit Disorder with Hyperactivity / Q000235:genetics* / Q000523:psychology*; D001921:Brain / Q000033:anatomy & histology / Q000502:physiology; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology; D004247:DNA / Q000235:genetics; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human; D004247:DNA