Effect of the COMT Val158Met genotype on lateral prefrontal activations in young children

Low executive function (EF) during early childhood is a major risk factor for developmental delay, academic failure, and social withdrawal. Susceptible genes may affect the molecular and biological mechanisms underpinning EF. More specifically, genes associated with the regulation of prefrontal dopamine may modulate the response of prefrontal neurons during executive control. Several studies with adults and older children have shown that variants of the catechol‐O‐methyltransferase (COMT) gene are associated with behavioral performance and prefrontal activations in EF tasks. However, the effect of the COMT genotype on prefrontal activations during EF tasks on young children is still unknown. The present study examined whether a common functional polymorphism (Val158Met) in the COMT gene was associated with prefrontal activations and cognitive shifting in 3‐ to 6‐year‐old children. The study revealed that, compared with children with at least one Met allele (Met/Met and Met/Val), children who were Val homozygous (i) were more able to flexibly switch rules in cognitive shifting tasks and (ii) exhibited increased activations in lateral prefrontal regions during these tasks. This is the first evidence that demonstrates the relationship between a gene polymorphism and prefrontal activations in young children. It also indicates that COMT Val homozygosity may be advantageous for cognitive shifting and prefrontal functions, at least during early childhood, and children who possess this variant may have a lower risk of developing future cognitive and social development issues.     

COMT基因Val158Met多态性与抑郁的关系

抑郁的发生具有重要的遗传学基础。COMT基因Val158Met多态性是抑郁的重要候选基因位点。目前有关COMT基因Val158Met多态性与抑郁关系的研究主要采用单基因设计、单基因-环境设计以及多基因-环境设计。有资料显示负性情绪偏向及其相关脑区可能在COMT基因Val158Met多态性与抑郁间起中介作用, 但具体机制仍有待探究。未来研究可以进一步考察被试的种族、年龄和性别等因素对COMT基因Val158Met多态性与抑郁关系的调节作用, 并通过采用多基因-环境设计, 综合运用积极与消极环境指标等措施深入考察负性情绪偏向和相关脑区在COMT基因Val158Met多态性与抑郁间的作用及其机制。     

BIS and BAS correlates with psychophysiological and cortical response systems during aversive and appetitive emotional stimuli processing

The present research intended first to confirm psychophysiological and cortical responses to valence- and arousal-manipulated stimuli and second to show how the BIS and BAS (Behavioural Inhibition and Activation System) personality characteristics correlated with these psychophysiological and cortical responses. Multiple measures were recorded, such as psychophysiological (skin conductance response, heart rate, and electromyography) and ERPs (event-related potentials) responses, during viewing IAPS figures, that varied in terms of pleasantness (appetitive vs. aversive) and arousing power (high vs. low intensity). Autonomic variables and two ERP positive deflections (P3 and LPP ERP effects) were found to be modulated by valence and arousal rating, with an increased response for high arousing and negative or positive stimuli in comparison with low arousing and neutral stimuli. Moreover, high BAS subjects were more responsive to positive than negative emotions, whereas high BIS subjects responded in greater measure to negative and arousing emotions. Findings were discussed in light of biphasic model of emotion comprehension.     

Association of Catechol-O-Methyltransferase Polymorphism (Val108/158Met) With Parkinson's Disease: A Meta-Analysis

Parkinson's disease (PD) is a common neurodegenerative disease, the risk factors of which are gaining more attentions. Among all these risk factors, catechol-o-methyltransferase (COMT) has been widely studied, and believed to be associated with PD. However, the relationship between COMT polymorphism and PD has not been confirmed hitherto. Therefore, a meta-analysis was performed to evaluate the effect of COMT polymorphism on PD patients. A total of 24 study subjects comprising 3,807 patients with PD and 3,942 unrelated healthy controls were recruited in this meta-analysis. Heterogeneity testing and sensitivity analysis were conducted with Review Manager 5.0 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) and Stata software (StataCorp, College Station, TX), together with publication bias by funnel plot method and modified Egger's linear regression test. No evidences of publication bias and heterogeneity were detected. In the 24 studies, the estimated odds ratios (OR) in PD patients are 0.98 for the Met allele (95% confidence interval [0.92, 1.05]) under a fixed-effects model. The authors also conducted a stratified analysis according to geographic region among Europe, Asia, and North America, the ORs for the Met allele are 0.92, 1.02, and 1.10, respectively. According to the results of the meta-analysis, a conclusion could be drawn that polymorphism of Val108/158Met are not associated with the risk of PD. However, more convincing studies are warranted to have a solid conclusion supported.     

COMT基因Val158Met多态性与同伴关系对青少年抑郁的影响

以1048名汉族青少年为被试,采用问卷法和基因分型技术,综合运用传统回归分析和新兴的再参数化回归分析,考察COMT基因Val158Met多态性与同伴关系对青少年抑郁的交互作用模式及其性别差异。结果发现,COMT基因与同伴接纳和同伴拒绝交互预测青少年抑郁,具体表现为,在低同伴接纳或高同伴拒绝环境中,携带ValVal基因型的青少年抑郁水平高于Met等位基因携带者;在高同伴接纳或低同伴拒绝环境中,携带ValVal基因型的青少年抑郁水平低于Met等位基因携带者。此外,COMT基因与同伴接纳和同伴拒绝的交互作用与男生抑郁的关联更加密切。结果显示,COMT基因与同伴关系的交互效应为不同易感性模型提供了证据,而且该基因×环境交互效应存在性别差异。     

Cognitive control and the COMT Val158Met polymorphism: genetic modulation of videogame training and transfer to task-switching efficiency

The study investigated whether successful transfer of game-based cognitive improvements to untrained tasks might be modulated by preexisting neuro-developmental factors, such as genetic variability related to the catechol-O-methyltransferase (COMT)—an enzyme responsible for the degradation of dopamine. The COMT Val¹⁵⁸Met genotype may differentially affect cognitive stability and flexibility, and we hypothesized that Val/Val homozygous individuals (who possess low prefrontal dopamine levels) show more pronounced cognitive flexibility than Met/-carriers (who possess high prefrontal dopamine levels). We trained participants, genotyped for the COMT Val¹⁵⁸Met polymorphism on playing “Half-Life 2”, a first-person shooter game which has been shown to improve cognitive flexibility. Pre-training (baseline) and post-training measures of cognitive flexibility were acquired by means of a task-switching paradigm. As expected, Val/Val homozygous individuals showed larger beneficial transfer effects than Met/-carriers. Our findings support the idea that genetic predisposition modulates transfer effects and that playing first-person shooter games promotes cognitive flexibility in individuals with a suitable genetic predisposition.     

Differential prefrontal-temporal neural correlates of semantic processing in children

This study used functional magnetic resonance imaging (fMRI) to examine brain-behavior correlations in a group of 16 children (9- to 12-year-olds). Activation was measured during a semantic judgment task presented in either the visual or auditory modality that required the individual to determine whether a final word was related in meaning to one of two previous words (e.g., found-tank-lost). The main finding was that higher performers (i.e., accuracy) were associated with more activation in posterior representational systems including the inferior and middle temporal gyri, whereas lower performers were associated with more activation in anterior regions including the inferior and middle frontal gyri. This pattern of results was interpreted as reflecting an elaborated semantic representational system in temporal areas for the high accuracy performers that allowed them to efficiently and accurately make meaning based judgments. The low accuracy performers may have an inaccurate or weakly interconnected semantic system that results in greater use of frontal areas in a feature selection process.     

Transfer of conditioned appetitive stimuli to conditioned aversive excitatory and inhibitory stimuli

The transfer of Pavlovian appetitive stimuli to Pavlovian aversive stimuli was examined in three experiments. In Experiment 1, rats received appetitive (Ap) conditioning designed to establish a flashing-light stimulus as either a CS+, CSo, or CS? for food, or to maintain it as a novel stimulus for US-alone subjects. Then, the stimulus was employed as a signal for weak shock in conditioned-emotional-response (CER) training. Both acquisition and extinction results showed that the ApCS+ facilitated and the ApCS? retarded aversive excitatory conditioning relative to the ApCSo and US-alone controls. Experiment 2 replicated the findings of Experiment 1 with both a moderate and a severe shock in CER training. In Experiment 3, different groups received the same appetitive conditioning as before, but to a flashing-light stimulus which was then employed as a signal for no shock in CER training. The ApCS? facilitated and the ApCS+ retarded aversive inhibitory conditioning relative to ApCSo and US-alone controls. Collectively, these findings establish that, in Pavlovian conditioning, transfer of an appetitive CS to an aversive excitor or inhibitor is facilitated by maintaining the initial conditioning contingency.     

An analysis of aversive stimuli in classroom demand contexts

Although recent research has identified numerous variables that can affect behavior maintained by negative reinforcement, questions remain concerning the potential aspects of the demand context that evoke problem behavior. To date, few studies have examined these questions within general education classrooms. The current study assessed the influence of social and task-difficulty variables on problem behavior maintained by negative reinforcement. Teachers in general education classrooms implemented three analyses to determine the influence of these variables on the problem behavior of 4 boys. Results are discussed in terms of response covariation within the demand context.     

Electrographic correlates of lateral asymmetry in the processing of verbal and nonverbal auditory stimuli

A veraged evoked potentials (AEP) to verbal (digits) and nonverbal (clicks) auditory stimuli were recorded from left and right temporal leads in ten right-handed Ss. With dichotic presentation, there was no significant difference in accuracy of report of the clicks heard in each ear, but significantly more digits were identified correctly from the right ear than from the left. Dichotic verbal stimuli elicited AEP whose early components were of greater amplitude, and whose later components were of shorter latency, from the left hemisphere than from the right. No consistent latency or amplitude differences were observed between AEP from the left and right hemispheres when clicks were presented dichotically.     

A time of change: Behavioral and neural correlates of adolescent sensitivity to appetitive and aversive environmental cues

Adolescence is a developmental period that entails substantial changes in affective and incentive-seeking behavior relative to both childhood and adulthood, including a heightened propensity to engage in risky behaviors and experience persistent negative and labile mood states. This review discusses the emotional and incentive-driven behavioral changes in adolescents and their associated neural mechanisms, focusing on the dynamic interactions between the amygdala, ventral striatum, and prefrontal cortex. Common behavioral changes during adolescence may be associated with a heightened responsiveness to incentives and emotional cues while the capacity to effectively engage in cognitive and emotion regulation is still relatively immature. We highlight empirical work in humans and animals that addresses the interactions between these neural systems in adolescents relative to children and adults, and propose a neurobiological model that may account for the nonlinear changes in adolescent behavior. Finally, we discuss other influences that may contribute to exaggerated reward and emotion processing associated with adolescence, including hormonal fluctuations and the role of the social environment.     

Differential prefrontal–temporal neural correlates of semantic processing in children

This study used functional magnetic resonance imaging (fMRI) to examine brain–behavior correlations in a group of 16 children (9- to 12-year-olds). Activation was measured during a semantic judgment task presented in either the visual or auditory modality that required the individual to determine whether a final word was related in meaning to one of two previous words (e.g., found–tank–lost). The main finding was that higher performers (i.e., accuracy) were associated with more activation in posterior representational systems including the inferior and middle temporal gyri, whereas lower performers were associated with more activation in anterior regions including the inferior and middle frontal gyri. This pattern of results was interpreted as reflecting an elaborated semantic representational system in temporal areas for the high accuracy performers that allowed them to efficiently and accurately make meaning based judgments. The low accuracy performers may have an inaccurate or weakly interconnected semantic system that results in greater use of frontal areas in a feature selection process.     

The COMT Val/Met polymorphism is associated with reading‐related skills and consistent patterns of functional neural activation

In both children and adults there is large variability in reading skill, with approximately 5–10% of individuals characterized as having reading disability; these individuals struggle to learn to read despite adequate intelligence and opportunity. Although it is well established that a substantial portion of this variability is attributed to the genetic differences between individuals, specifics of the connections between reading and the genome are not understood. This article presents data that suggest that variation in the COMT gene, which has previously been associated with variation in higher‐order cognition, is associated with reading and reading‐related skills, at the level of both brain and behavior. In particular, we found that the COMT Val/Met polymorphism at rs4680, which results in the substitution of the ancestral Valine (Val) by Methionine (Met), was associated with better performance on a number of critical reading measures and with patterns of functional neural activation that have been linked to better readers. We argue that this polymorphism, known for its broad effects on cognition, may modulate (likely through frontal lobe function) reading skill.     

The levels of perceptual processing and the neural correlates of increasing subjective visibility

According to the levels-of-processing hypothesis, transitions from unconscious to conscious perception may depend on stimulus processing level, with more gradual changes for low-level stimuli and more dichotomous changes for high-level stimuli. In an event-related fMRI study we explored this hypothesis using a visual backward masking procedure. Task requirements manipulated level of processing. Participants reported the magnitude of the target digit in the high-level task, its color in the low-level task, and rated subjective visibility of stimuli using the Perceptual Awareness Scale. Intermediate stimulus visibility was reported more frequently in the low-level task, confirming prior behavioral results. Visible targets recruited insulo-fronto-parietal regions in both tasks. Task effects were observed in visual areas, with higher activity in the low-level task across all visibility levels. Thus, the influence of level of processing on conscious perception may be mediated by attentional modulation of activity in regions representing features of consciously experienced stimuli.