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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.

SUBMITTER: Stollstorff M

PROVIDER: S-EPMC2888738 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature

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Neural response to working memory load varies by dopamine transporter genotype in children.

Stollstorff Melanie M Foss-Feig Jennifer J Cook Edwin H EH Stein Mark A MA Gaillard William D WD Vaidya Chandan J CJ

NeuroImage 20100104 3

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 resonanc ...[more]

PMID: 20053379

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Project description:BackgroundResearch on the neural bases of cognitive deficits in autism spectrum disorder (ASD) has shown that working memory (WM) difficulties are associated with abnormalities in the prefrontal cortex. However, cognitive load impacts these findings, and no studies have examined the relation between WM load and neural underpinnings in children with ASD. Thus, the current study determined the effects of cognitive load on WM, using a visuo-spatial WM capacity task in children with and without ASD with functional magnetic resonance imaging (fMRI).MethodsWe used fMRI and a 1-back colour matching task (CMT) task with four levels of difficulty to compare the cortical activation patterns associated with WM in children (7-13 years old) with high functioning autism (N = 19) and matched controls (N = 17) across cognitive load.ResultsPerformance on CMT was comparable between groups, with the exception of one difficulty level. Using linear trend analyses, the control group showed increasing activation as a function of difficulty level in frontal and parietal lobes, particularly between the highest difficulty levels, and decreasing activation as a function of difficulty level in the posterior cingulate and medial frontal gyri. In contrast, children with ASD showed increasing activation only in posterior brain regions and decreasing activation in the posterior cingulate and medial frontal gyri, as a function of difficulty level. Significant differences were found in the precuneus, dorsolateral prefrontal cortex and medial premotor cortex, where control children showed greater positive linear relations between cortical activity and task difficulty level, particularly at the highest difficulty levels, but children with ASD did not show these trends.ConclusionsChildren with ASD showed differences in activation in the frontal and parietal lobes-both critical substrates for visuo-spatial WM. Our data suggest that children with ASD rely mainly on posterior brain regions associated with visual and lower level processing, whereas controls showed activity in frontal lobes related to the classic WM network. Findings will help guide future work by localizing areas of vulnerability to developmental disturbances.

Project description:BackgroundVisual working memory (VWM) helps us store visual information to prepare for subsequent behavior. The neuronal mechanisms for sustaining coherent visual information and the mechanisms for limited VWM capacity have remained uncharacterized. Although numerous studies have utilized behavioral accuracy, neural activity, and connectivity to explore the mechanism of VWM retention, little is known about the load-related changes in functional connectivity for hemi-field VWM retention.Methodology/principal findingsIn this study, we recorded electroencephalography (EEG) from 14 normal young adults while they performed a bilateral visual field memory task. Subjects had more rapid and accurate responses to the left visual field (LVF) memory condition. The difference in mean amplitude between the ipsilateral and contralateral event-related potential (ERP) at parietal-occipital electrodes in retention interval period was obtained with six different memory loads. Functional connectivity between 128 scalp regions was measured by EEG phase synchronization in the theta- (4-8 Hz), alpha- (8-12 Hz), beta- (12-32 Hz), and gamma- (32-40 Hz) frequency bands. The resulting matrices were converted to graphs, and mean degree, clustering coefficient and shortest path length was computed as a function of memory load. The results showed that brain networks of theta-, alpha-, beta-, and gamma- frequency bands were load-dependent and visual-field dependent. The networks of theta- and alpha- bands phase synchrony were most predominant in retention period for right visual field (RVF) WM than for LVF WM. Furthermore, only for RVF memory condition, brain network density of theta-band during the retention interval were linked to the delay of behavior reaction time, and the topological property of alpha-band network was negative correlation with behavior accuracy.Conclusions/significanceWe suggest that the differences in theta- and alpha- bands between LVF and RVF conditions in functional connectivity and topological properties during retention period may result in the decline of behavioral performance in RVF task.

Project description:BACKGROUND: The capacity of visual working memory (WM) is substantially limited and only a fraction of what we see is maintained as a temporary trace. The process of binding visual features has been proposed as an adaptive means of minimising information demands on WM. However the neural mechanisms underlying this process, and its modulation by task and load effects, are not well understood. OBJECTIVE: To investigate the neural correlates of feature binding and its modulation by WM load during the sequential phases of encoding, maintenance and retrieval. METHODS AND FINDINGS: 18 young healthy participants performed a visuospatial WM task with independent factors of load and feature conjunction (object identity and position) in an event-related functional MRI study. During stimulus encoding, load-invariant conjunction-related activity was observed in left prefrontal cortex and left hippocampus. During maintenance, greater activity for task demands of feature conjunction versus single features, and for increased load was observed in left-sided regions of the superior occipital cortex, precuneus and superior frontal cortex. Where these effects were expressed in overlapping cortical regions, their combined effect was additive. During retrieval, however, an interaction of load and feature conjunction was observed. This modulation of feature conjunction activity under increased load was expressed through greater deactivation in medial structures identified as part of the default mode network. CONCLUSIONS AND SIGNIFICANCE: The relationship between memory load and feature binding qualitatively differed through each phase of the WM task. Of particular interest was the interaction of these factors observed within regions of the default mode network during retrieval which we interpret as suggesting that at low loads, binding processes may be 'automatic' but at higher loads it becomes a resource-intensive process leading to disengagement of activity in this network. These findings provide new insights into how feature binding operates within the capacity-limited WM system.

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Neural response to working memory load varies by dopamine transporter genotype in children.

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Neural response to working memory load varies by dopamine transporter genotype in children.

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