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Resting-state striato-frontal functional connectivity is sensitive to DAT1 genotype and predicts executive function.

ABSTRACT: Individual differences in striatal dopamine (DA) signaling have been associated both with individual differences in executive function in healthy individuals and with risk for psychiatric disorders defined by executive dysfunction. We used resting-state functional connectivity in 50 healthy adults to examine whether a polymorphism of the dopamine transporter gene (DAT1), which regulates striatal DA function, affects striatal functional connectivity in healthy adults, and whether that connectivity predicts executive function. We found that 9/10 heterozygotes, who are believed to have higher striatal DA signaling, demonstrated stronger connectivity between dorsal caudate (DC) and insular, dorsal anterior cingulate, and dorsolateral prefrontal regions, as well as between ventral striatum and ventrolateral prefrontal cortex, than 10/10 homozygotes. Across subjects, stronger DC-seeded connectivity predicted superior N-back working memory performance, while stronger ventral striatum-seeded connectivity predicted reduced impulsivity in everyday life. Further, mediation analysis suggested that connectivity strength mediated relationships between DAT1 genotype and behavior. These findings suggest that resting-state striato-frontal connectivity may be an endophenotype for executive function in healthy individuals.

SUBMITTER: Gordon EM

PROVIDER: S-EPMC4351426 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Resting-state striato-frontal functional connectivity is sensitive to DAT1 genotype and predicts executive function.

Gordon Evan M EM Devaney Joseph M JM Bean Stephanie S Vaidya Chandan J CJ

Cerebral cortex (New York, N.Y. : 1991) 20130822 2

Individual differences in striatal dopamine (DA) signaling have been associated both with individual differences in executive function in healthy individuals and with risk for psychiatric disorders defined by executive dysfunction. We used resting-state functional connectivity in 50 healthy adults to examine whether a polymorphism of the dopamine transporter gene (DAT1), which regulates striatal DA function, affects striatal functional connectivity in healthy adults, and whether that connectivit ...[more]

PMID: 23968837

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Project description:Background and purposeEpilepsy is considered a disorder of neural networks. The aims of this study were to assess functional connectivity within resting-state networks and functional network connectivity across resting-state networks by use of resting-state fMRI in children with frontal lobe epilepsy and to relate changes in resting-state networks with neuropsychological function.Materials and methodsFifteen patients with frontal lobe epilepsy and normal MR imaging and 14 healthy control subjects were recruited. Spatial independent component analysis was used to identify the resting-state networks, including frontal, attention, default mode network, sensorimotor, visual, and auditory networks. The Z-maps of resting-state networks were compared between patients and control subjects. The relation between abnormal connectivity and neuropsychological function was assessed. Correlations from all pair-wise combinations of independent components were performed for each group and compared between groups.ResultsThe frontal network was the only network that showed reduced connectivity in patients relative to control subjects. The remaining 5 networks demonstrated both reduced and increased functional connectivity within resting-state networks in patients. There was a weak association between connectivity in frontal network and executive function (P = .029) and a significant association between sensorimotor network and fine motor function (P = .004). Control subjects had 79 pair-wise independent components that showed significant temporal coherence across all resting-state networks except for default mode network-auditory network. Patients had 66 pairs of independent components that showed significant temporal coherence across all resting-state networks. Group comparison showed reduced functional network connectivity between default mode network-attention, frontal-sensorimotor, and frontal-visual networks and increased functional network connectivity between frontal-attention, default mode network-sensorimotor, and frontal-visual networks in patients relative to control subjects.ConclusionsWe found abnormal functional connectivity within and across resting-state networks in children with frontal lobe epilepsy. Impairment in functional connectivity was associated with impaired neuropsychological function.

Dataset Information

Resting-state striato-frontal functional connectivity is sensitive to DAT1 genotype and predicts executive function.

Publications

Resting-state striato-frontal functional connectivity is sensitive to DAT1 genotype and predicts executive function.

Similar Datasets

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