title: Neural response to working memory load varies by dopamine transporter genotype in children.
abstract: Inheriting two (10/10) relative to one (9/10) copy of the 10-repeat allele of the dopamine transporter genotype (DAT1) is associated with Attention Deficit Hyperactivity Disorder, a childhood disorder marked by poor executive function. We examined whether functional anatomy underlying working memory, a component process of executive function, differed by DAT1 in 7-12 year-old typically developing children. 10/10 and 9/10 carriers performed a verbal n-back task in two functional magnetic resonance imaging (fMRI) runs varying in working memory load, high (2-back vs. 1-back) and low (1-back vs. 0-back). Performance accuracy was superior in 9/10 than 10/10 carriers in the high but not low load runs. Examination of each run separately revealed that frontal-striatal-parietal regions were more activated in 9/10 than 10/10 carriers in the high load run; the groups did not differ in the low load run. Examination of load effects revealed a DAT1xLoad interaction in the right hemisphere in the caudate, our a priori region of interest. Exploratory analysis at a more liberal threshold revealed this interaction in other basal ganglia regions (putamen, and substantial nigra/subthalamic nuclei - SN/STN) and in medial parietal cortex (left precuneus). The striatal and parietal regions were more activated in 9/10 carriers under high than low load, and DAT1 differences (9/10>10/10) were evident only under high load. In contrast, SN/STN tended to be more activated in 10/10 carriers under low than high load and DAT1 differences (10/10>9/10) were evident only under low load. Thus, 10-repeat homozygosity of DAT1 was associated with reduced performance and a lack of increased basal ganglia involvement under higher working memory demands.
authors.affiliation: Department of Psychology, Georgetown University, Washington, DC, USA.
authors.forename: Melanie
authors.initials: M
authors.lastname: Stollstorff
authors.forename: Jennifer
authors.initials: J
authors.lastname: Foss-Feig
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Cook
authors.forename: Mark A
authors.initials: MA
authors.lastname: Stein
authors.forename: William D
authors.initials: WD
authors.lastname: Gaillard
authors.forename: Chandan J
authors.initials: CJ
authors.lastname: Vaidya
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D001931:Brain Mapping; D002648:Child; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008570:Memory, Short-Term / Q000502:physiology*; D011110:Polymorphism, Genetic; D011930:Reaction Time; D020080:Tandem Repeat Sequences / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human