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RAB2A Polymorphism impacts prefrontal morphology, functional connectivity, and working memory.

ABSTRACT: Calbindin-containing ?-aminobutyric acid (GABA)ergic interneurons in the prefrontal cortex (PFC) have been found to play an important role in working memory (WM) and their malfunctions have been linked to psychiatric disorders. A recent genome-wide association and expression-SNP study indicated that the RAB2A gene was associated with the density of prefrontal calbindin-positive neurons, suggesting this gene may have a broader influence on prefrontal structure and function. Using multimodal MRI and behavioral tasks, the current study investigated the effect of RAB2A on prefrontal morphology, resting-state functional connectivity, and WM performance in a large sample of healthy Han Chinese subjects. Results showed that the RAB2A AGCAAA haplotype was associated with improved WM accuracy, increased cortical thickness in the left inferior frontal gyrus, and decreased functional connectivity between the left inferior frontal gyrus and the left dorsolateral PFC. Our findings provide consistent evidence supporting the effect of RAB2A on the structure and function of the PFC and related cognitive functions. These results should provide new insights into the neural mechanisms underlying the GABAergic genes' role in WM as well as its dysfunction.

SUBMITTER: Li J

PROVIDER: S-EPMC6869184 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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RAB2A Polymorphism impacts prefrontal morphology, functional connectivity, and working memory.

Li Jin J Liu Bing B Chen Chuansheng C Cui Yue Y Shang Liqing L Zhang Yun Y Wang Chao C Zhang Xiaolong X He Qinghua Q Zhang Wen W Bi Wenwei W Jiang Tianzi T

Human brain mapping 20150807 11

Calbindin-containing γ-aminobutyric acid (GABA)ergic interneurons in the prefrontal cortex (PFC) have been found to play an important role in working memory (WM) and their malfunctions have been linked to psychiatric disorders. A recent genome-wide association and expression-SNP study indicated that the RAB2A gene was associated with the density of prefrontal calbindin-positive neurons, suggesting this gene may have a broader influence on prefrontal structure and function. Using multimodal MRI a ...[more]

PMID: 26249043

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Project description:Background: Normal aging is associated with working memory decline. A decrease in working memory performance is associated with age-related changes in functional activation patterns in the dorsolateral prefrontal cortex (DLPFC). Cognitive training can improve cognitive performance in healthy older adults. We implemented a cognitive training study to assess determinants of generalization of training gains to untrained tasks, a key indicator for the effectiveness of cognitive training. We aimed to investigate the association of resting-state functional connectivity (FC) of DLPFC with working memory performance improvement and cognitive gains after the training. Method: A sample of 60 healthy older adults (mean age: 68 years) underwent a 4-week neuropsychological training, entailing a working memory task. Baseline resting-state functional MRI (rs-fMRI) images were acquired in order to investigate the FC of DLPFC. To evaluate training effects, participants underwent a neuropsychological assessment before and after the training. A second follow-up assessment was applied 12 weeks after the training. We used cognitive scores of digit span backward and visual block span backward tasks representing working memory function. The training group was divided into subjects who had and who did not have training gains, which was defined as a higher improvement in working memory tasks than the control group (N = 19). Results: A high FC of DLPFC of the right hemisphere was significantly associated with training gains and performance improvement in the visuospatial task. The maintenance of cognitive gains was restricted to the time period directly after the training. The training group showed performance improvement in the digit span backward task. Conclusion: Functional activation patterns of the DLPFC were associated with the degree of working memory training gains and visuospatial performance improvement. Although improvement through cognitive training and acquisition of training gains are possible in aging, they remain limited.

Dataset Information

RAB2A Polymorphism impacts prefrontal morphology, functional connectivity, and working memory.

Publications

RAB2A Polymorphism impacts prefrontal morphology, functional connectivity, and working memory.

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