关键词: 注意网络, 功能磁共振成像, 影像遗传学, 多巴胺系统, 元分析

Abstract: Dopamine (DA) is one of the major neurotransmitters in central nervous system and acts as a powerful modulator of different aspects of cognitive brain functions. Numerous studies have revealed the important role of DA on attention networks. However, current imaging genetics studies only focus on the effect of one single gene of the dopaminergic system on local brain regions (mostly prefrontal cortex) but ignore the whole brain analysis and comparison between different genes. To advance our understanding of DA on attention, we conducted a meta-analysis to examine modulatory effects of three typical dopamine genes on whole brain attention networks. A literature search was first performed on imaging genetics studies on modulation of DA in attention tasks through PubMed. Keywords included but not limited to functional magnetic resonance imaging (fMRI), and candidate dopaminergic system genes targeting the presynaptic, the postsynaptic neurons, or the synaptic cleft, such as the dopamine transporter gene (DAT), the catechol-O-methyltransferase gene (COMT) or the dopamine receptor gene (DRD). Reference lists were checked by hand and a total of forty-four papers were gathered and applied to our meta-analysis. We extracted the coordinates of peak voxels where genetic modulatory effect on attention was reported in the papers and then projected them onto a brain template in Caret to visualize the distribution of the modulatory effects of genes. Effect sizes were calculated using Cohen’s d to quantify the magnitude of activation difference between subjects with separate genotypes on each attention task. Random-effects model was chosen for the meta-analysis and effect sizes on effective modulation of dopaminergic system genes in different brain regions were calculated with Comprehensive Meta-Analysis program (CMA). To comparing difference across attention networks and dopaminergic genes, the Q-test of homogeneity was used to test for variations in effect size. Our results showed that the integrated effect sizes on effective modulation of dopaminergic system genes were all above .8 (Cohen’s d) in ventral attention network (VAN), including ventral prefrontal cortex (VLPFC), orbitofrontal gyrus (OFG), and superior temporal gyrus (STG), and also in dorsal attention network (DAN), consisting of dorsolateral prefrontal cortex (DLPFC), superior parietal lobule (SPL) and frontal eye field (FEF). The VAN presented a significantly higher effect size in comparison to the DAN (Qb = 4.94, p < .05). In addition, variation test of effect sizes for dopaminergic system genes showed that COMT gene exhibited a significantly higher effect size than that of DAT gene (Qb = 77.04, p < .001) and DRD gene (Qb = 186.35, p < .001). Our study suggests the important role of dopaminergic system genes in regulating attention networks in the whole brain. As DAN enables the selection of sensory stimuli based on internal goals and VAN detects salient and relevant stimuli in the environment, the observed stronger modulatory effect of dopaminergic system genes in VAN than in DAN suggests that bottom-up attention, comparing with top-down attention, received more modulation from genes than environment. Our study invites broader and deeper studies on the relationship among genes, brain, and attentional behaviors at the network level in the future.

Key words: attention networks, MRI, imaging genetics, dopaminergic system, meta-analysis