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.     

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.     

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.     

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.     

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.     

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.     

Reduced specificity of autobiographical memory and depression: the role of executive control

It has been widely established that depressed mood states and clinical depression, as well as a range of other psychiatric disorders, are associated with a relative difficulty in accessing specific autobiographical information in response to emotion-related cue words on an Autobiographical Memory Test (AMT; J. M. G. Williams & K. Broadbent, 1986). In 8 studies the authors examined the extent to which this relationship is a function of impaired executive control associated with these mood states and clinical disorders. Studies 1-4 demonstrated that performance on the AMT is associated with performance on measures of executive control, independent of depressed mood. Furthermore, Study 1 showed that executive control (as measured by verbal fluency) mediated the relationship between both depressed mood and a clinical diagnosis of eating disorder and AMT performance. Using a stratified sample in Study 5, the authors confirmed the positive association between depressed mood and impaired performance on the AMT. Studies 6-8 involved experimental manipulations of the parameters of the AMT designed to further indicate that reduced executive control is to a significant extent driving the relationship between depressed mood and AMT performance. The potential role of executive control in accounting for other aspects of the AMT literature is discussed.     

Harming and failing to benefit: a reply to purves

Philosophical Studies - A prominent objection to the counterfactual comparative account of harm is that it classifies as harmful some events that are, intuitively, mere failures to benefit. In an...     

Space Fortress game training and executive control in older adults: a pilot intervention

We investigated the feasibility of using the Space Fortress (SF) game, a complex video game originally developed to study complex skill acquisition in young adults, to improve executive control processes in cognitively healthy older adults. The study protocol consisted of 36 one-hour game play sessions over 3 months with cognitive evaluations before and after, and a follow-up evaluation at 6 months. Sixty participants were randomized to one of three conditions: Emphasis Change (EC)--elders were instructed to concentrate on playing the entire game but place particular emphasis on a specific aspect of game play in each particular game; Active Control (AC)--game play with standard instructions; Passive Control (PC)--evaluation sessions without game play. Primary outcome measures were obtained from five tasks, presumably tapping executive control processes. A total of 54 older adults completed the study protocol. One measure of executive control, WAIS-III letter-number sequencing, showed improvement in performance from pre- to post-evaluations in the EC condition, but not in the other two conditions. These initial findings are modest but encouraging. Future SF interventions need to carefully consider increasing the duration and or the intensity of the intervention by providing at-home game training, reducing the motor demands of the game, and selecting appropriate outcome measures.     

Practice-related optimization and transfer of executive functions: a general review and a specific realization of their mechanisms in dual tasks

Improvements in performing demanding and complex task situations are typically related to the optimization of executive functions and efficient behavioral control. The present study systematizes and reviews the optimization of different executive function types: Shifting, Inhibition, Updating, and Dual tasking. In particular, we focus on optimisations of these functions with training and on transfer effects of related training skills to non-trained situations. The aim of the study’s empirical part (see also Appendix) was to investigate the specific mechanisms of executive functions in the context of Dual tasking, leading to improved dual-task performance after practice. More specifically, we tested the Efficient Task Instantiation (ETI) model that includes specific assumptions regarding practice-related improvements of executive task coordination skills: Dual-task performance is improved with practice because of an efficient and conjoint instantiation of sets of relevant task information in working memory at the onset of a dual task. According to our knowledge, the ETI model is one of the first that allows illustrating the contribution of cognitive mechanisms underlying practice-related improvements in performing dual tasks and the impact of task coordination skills on this performance.     

Task feedback effects on conflict monitoring and executive control: relationship to subclinical measures of depression

Emerging evidence suggests that depression is associated with executive dysfunction, particularly after committing errors or receiving negative performance feedback. To test this hypothesis, 57 participants performed two executive tasks known to elicit errors (the Simon and Stroop Tasks) during positive or negative performance feedback. Participants with elevated depressive symptoms (Beck Depression Inventory scores >or= 13) were characterized by impaired posterror and postconflict performance adjustments, especially during emotionally negative task-related feedback. Additionally, for both tasks, depressive symptoms were inversely related to postconflict reaction time adjustments following negative, but not positive, feedback. These findings suggest that subclinical depression is associated with impairments in behavioral adjustments after internal (perceived failure) and external feedback about deficient task performance.