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.     

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。     

Stressful life events, perceived stress, and 12-month course of geriatric depression: direct effects and moderation by the 5-HTTLPR and COMT Val158Met polymorphisms

Although the relation between stressful life events (SLEs) and risk of major depressive disorder is well established, important questions remain about the effects of stress on the course of geriatric depression. Our objectives were (1) to examine how baseline stress and change in stress is associated with course of geriatric depression and (2) to test whether polymorphisms of serotonin transporter (5-HTTLPR) and catechol-O-methyltransferase (COMT Val158Met) genes moderate this relation. Two-hundred and sixteen depressed subjects aged 60 years or older were categorized by remission status (Montgomery-Asberg depression rating scale≤6) at 6 and 12 months. At 6 months, greater baseline numbers of self-reported negative and total SLEs and greater baseline perceived stress severity were associated with lower odds of remission. At 12 months, only baseline perceived stress predicted remission. When we examined change in stress, 12-month decrease in negative SLEs and level of perceived stress were associated with improved odds of 12-month remission. When genotype data were included, COMT Val158Met genotype did not influence these relations. However, when compared with 5-HTTLPR L/L homozygotes, S allele carriers with greater baseline numbers of negative SLEs and with greater decrease in negative SLEs were more likely to remit at 12 months. This study demonstrates that baseline SLEs and perceived stress severity may influence the 12-month course of geriatric depression. Moreover, changes in these stress measures over time correlate with depression outcomes. 5-HTTLPR S carriers appear to be more susceptible to both the effects of enduring stress and the benefit of interval stress reduction.     

Mindfulness meditation practice and executive functioning: Breaking down the benefit

This paper focuses on evidence for mindfulness meditation-related benefits to executive functioning, processes important for much of human volitional behaviour. Miyake et al. (2000) have shown that executive functions can be fractionated into three distinct domains including inhibition, working memory updating, and mental set shifting. Considering these separable domains, it is important to determine whether the effects of mindfulness can generalize to all three sub-functions or are specific to certain domains. To address this, the current review applied Miyake et al.’s (2000) fractionated model of executive functioning to the mindfulness literature. Empirical studies assessing the benefits of mindfulness to measures tapping the inhibition, updating, and shifting components of executive functioning were examined. Results suggest a relatively specific as opposed to general benefit resulting from mindfulness, with consistent inhibitory improvement, but more variable advantages to the updating and shifting domains. Recommendations surrounding application of mindfulness practice and future research are discussed.     

Common and specific cognitive deficits in schizophrenia: relationships to function

The goals of the present study were to assess the interrelationships among tasks from the MATRICS and CNTRACS batteries, to determine the degree to which tasks from each battery capture unique variance in cognitive dysfunction in schizophrenia, and to determine the ability of tasks from each battery to predict functional outcome. Subjects were 104 schizophrenia patients and 132 healthy control subjects recruited as part of the CNTRACS initiative. All subjects completed four CNTRACS tasks and two tasks from the MATRICS battery: Brief Assessment of Cognition in Schizophrenia Symbol Coding and the Hopkins Verbal Learning Test. Functional outcome was also assessed in the schizophrenia subjects. In both the patient and control groups, we found significant intercorrelations between all higher order cognitive tasks (episodic memory, goal maintenance, processing speed, verbal learning) but minimal relationships with the visual task. For almost all tasks, scores were significantly related to measures of functional outcome, with higher associations between CNTRACS tasks and performance-based measures of function and between one of the MATRICS tasks and self-reported functioning, relative to the other functioning measures. After regressing out variance shared by other tasks, we continued to observe group differences in performance among task residuals, particularly for measures of episodic memory from both batteries, although these residuals did not correlate as robustly with functional outcome as raw test scores. These findings suggest that there exists both shared and specific variance across cognitive tasks related to cognitive and functional impairments in schizophrenia and that measures derived from cognitive neuroscience can predict functional capacity and status in schizophrenia.     

Risk-factor research and prevention programs for anxiety disorders: a translational research framework

The aim of the present essay is to discuss the interconnection between risk-factor research and prevention program development for panic-spectrum psychopathology. We argue that prevention of panic-spectrum psychopathology specifically, and anxiety disorders more generally, is likely to be best advanced through active, systematic translation of basic, risk-factor research. After operationalizing key terminology, we present some exemplar risk-factor candidates for panic-spectrum psychopathology, summarize research related to their role as risk-factors for panic problems, and link this discussion to risk-factor nomenclature. We then present a translational framework for extrapolating extant knowledge on these and other potential risk-factors for panic-spectrum psychopathology with respect to the development of preventative interventions. The proposed translational framework is intended to describe a forward-feeding process by which risk-factor research could be used by clinical researchers to inform prevention programs; and reciprocally, how such prevention knowledge could be most effectively utilized to drive new, clinically focused risk-factor research.     

Methodology for identifying specific psychological deficits: introduction to the special section

A long-standing problem in psychopathology research is establishing that patterns of differences between groups reflects differences of underlying constructs and not artifacts of research design, measurement, or analysis. This introduction provides a context for 4 articles that consider several controversial issues regarding this problem and presents a précis. Although these articles focus on schizophrenia, it is noted how the issues are of more general relevance to psychopathology researchers.     

The contribution of executive control to semantic cognition: Convergent evidence from semantic aphasia and executive dysfunction

Semantic cognition, as described by the controlled semantic cognition (CSC) framework (Rogers et al., 2015 , Neuropsychologia, 76, 220), involves two key components: activation of coherent, generalizable concepts within a heteromodal ‘hub’ in combination with modality‐specific features (spokes), and a constraining mechanism that manipulates and gates this knowledge to generate time‐ and task‐appropriate behaviour. Executive–semantic goal representations, largely supported by executive regions such as frontal and parietal cortex, are thought to allow the generation of non‐dominant aspects of knowledge when these are appropriate for the task or context. Semantic aphasia (SA) patients have executive–semantic deficits, and these are correlated with general executive impairment. If the CSC proposal is correct, patients with executive impairment should not only exhibit impaired semantic cognition, but should also show characteristics that align with those observed in SA. This possibility remains largely untested, as patients selected on the basis that they show executive impairment (i.e., with ‘dysexecutive syndrome’) have not been extensively tested on tasks tapping semantic control and have not been previously compared with SA cases. We explored conceptual processing in 12 patients showing symptoms consistent with dysexecutive syndrome (DYS) and 24 SA patients, using a range of multimodal semantic assessments which manipulated control demands. Patients with executive impairments, despite not being selected to show semantic impairments, nevertheless showed parallel patterns to SA cases. They showed strong effects of distractor strength, cues and miscues, and probe–target distance, plus minimal effects of word frequency on comprehension (unlike semantic dementia patients with degradation of conceptual knowledge). This supports a component process account of semantic cognition in which retrieval is shaped by control processes, and confirms that deficits in SA patients reflect difficulty controlling semantic retrieval.     

Modes of executive control in sequence learning: from stimulus-based to plan-based control

The authors argue that human sequential learning is often but not always characterized by a shift from stimulus- to plan-based action control. To diagnose this shift, they manipulated the frequency of 1st-order transitions in a repeated manual left-right sequence, assuming that performance is sensitive to frequency-induced biases under stimulus- but not plan-based control. Indeed, frequency biases tended to disappear with practice, but only for explicit learners. This tendency was facilitated by visual-verbal target stimuli, response-contingent sounds, and intentional instructions and hampered by auditory (but not visual) noise. Findings are interpreted within an event-coding model of action control, which holds that plans for sequences of discrete actions are coded phonetically, integrating order and relative timing. The model distinguishes between plan acquisition, linked to explicit knowledge, and plan execution, linked to the action control mode.     

Gaining control: training executive function and far transfer of the ability to resolve interference

Functional brain-imaging data document overlapping sites of activation in prefrontal cortex across memory tasks, suggesting that these tasks may share common executive components. We leveraged this evidence to develop a training regimen and a set of transfer tasks to examine the trainability of a putative executive-control process: interference resolution. Eight days of training on high-interference versions of three different working memory tasks increased the efficiency with which proactive interference was resolved on those particular tasks. Moreover, an improved ability to resolve interference was also transferred to different working memory, semantic memory, and episodic memory tasks, a demonstration of far-transfer effects from process-specific training. Participants trained with noninterference versions of the tasks did not exhibit transfer. We infer that the transfer we demonstrated resulted from increased efficiency of the interference-resolution process. Therefore, this aspect of executive control is plastic and adaptive, and can be improved by training.     

Aging and strategic retrieval in a cued-recall test: the role of executive functions and fluid intelligence

Cued-recall in episodic memory was investigated in relation to low and high cognitive support at retrieval, executive function level and fluid intelligence level in 81 healthy adults divided first into two age groups (young and elderly adults). The first analyses showed that age-related differences were greater when a low cognitive support was provided to recall the words. An individual index of loss of performance when the number of cues was decreased was then calculated. Hierarchical regression analysis revealed that the executive functions measure (perseverative errors on the Wisconsin Card Sorting Test) was a better candidate than the fluid intelligence measure (Cattell's culture fair test) to account for the age-related variance of the size of performance loss. These findings suggest that age differences in implementing strategic retrieval may be mainly due to a decline in executive functions.     

Assessing the executive function deficits of patients with Parkinson's disease: utility of the Tower of London-Drexel

The aim of the study was to investigate the utility of the Tower of London-Drexel (TOLDX) in assessing the executive deficits associated with Parkinson's disease (PD). We sought to determine whether the TOLDX would differentiate between (a) patients with PD and healthy control participants (HCP), (b) demented and nondemented patients, and (c) depressed and nondepressed patients. A new TOLDX score, stimulus bound, was introduced to assess utilization behaviors. Furthermore, the convergent and divergent validity of the TOLDX was examined. The TOLDX total move, rule and time violation, and stimulus-bound scores of patients with PD significantly differed from the HCP. Demented and nondemented patients also differed significantly in their TOLDX performance, with the stimulus-bound score being the most significantly differentiating score. However, the depressed and nondepressed patients did not differ in their TOLDX performance. Support was found for the convergent and divergent validity of the TOLDX. The clinical and theoretical implications of the findings are discussed.     

To a young basic scientist, about to embark on a program of translational research

From recent commentaries about the role of basic behavior scientists in translational research, I distill some advice to young investigators who seek to apply their basic science training to translational studies. Among the challenges are (a) devising use-inspired research programs that complement, and are not redundant with, existing efforts in basic and applied behavior analysis; and (b) making tactical decisions, such as the selection of methods and collaborators, based on the research topic rather than, necessarily, the existing traditions in behavioral research. Finally, it must be recognized that although use-inspired basic research has the potential to attract support to basic laboratories and contribute to "saving the world," neither of these outcomes is guaranteed. I discuss the relative risks for basic scientists who proceed with use-inspired basic research rather than ignore such translational questions.     

Task-switching costs, Stroop-costs, and executive control: a correlational study.

Three correlational studies investigated the relationship between the time costs associated with Stroop stimuli (Stroop-costs) with the time costs associated with task-switching (switch-costs) obtained from colour-word stimuli and digit stimuli. In all studies, large and significant positive correlations were found between different measures of switch-costs. However, only small (and sometimes non-significant) correlations were obtained between the different measures of Stroop-costs and between measures of Stroop-costs and measures of switch-costs. The results are taken as evidence for the existence of some common or shared specialized mechanisms involved in task-switching, which are different from those used to overcome Stroop interference.     

A research strategy for investigating group differences in a cognitive construct: Application to ageing and executive processes

A strategy involving five distinct phases is proposed as a means of obtaining the most informative evidence about group differences in a particular aspect of cognitive functioning. Perhaps because the phases require different types of analytical methods, most prior research has focused on only a few of the proposed phases. This is unfortunate because each phase provides valuable information about the nature of the relevant construct, and its role in group differences in cognition. The strategy is illustrated with research on adult age differences in executive processes.     

Relation of perinatal risk and early parenting to executive control at the transition to school

Executive control (EC) develops rapidly during the preschool years and is central to academic achievement and functional outcome. Although children with perinatal adversity are at known risk for EC impairments, little is known about the underlying nature of these impairments or the mechanisms that contribute to their development over time. Drawing on a cohort of 110 high‐risk children born very preterm (VPT; < 33 weeks / < 1500 g) and 113 healthy full‐term children, this study examined the implications of perinatal adversity and early parenting for children's EC as they transitioned to formal schooling. Parent supportive presence, intrusiveness, and parent–child synchrony were observed during a series of problem‐solving tasks at ages 2 and 4 years. At age 6, children completed a comprehensive battery of EC tasks. Academic outcomes were assessed at age 9. The VPT group showed global EC impairments at age 6, although the unitary factor that best characterized the structure of EC was the same in both groups. High‐risk dyads were characterized by more intrusive and less synchronous parent–child interactions in early childhood, which in turn predicted poorer child EC at age 6. EC partially mediated the relation of risk status to poorer academic achievement at age 9. Findings demonstrate the cumulative effects of perinatal adversity on children's EC in the crucial transition to schooling. They also highlight the importance of the parent–child relationship as a target for intervention efforts to help mitigate these effects.