Novel Television-Based Cognitive Training Improves Working Memory and Executive Function

The main study objective was to investigate the effect of interactive television-based cognitive training on cognitive performance of 119 healthy older adults, aged 60–87 years. Participants were randomly allocated to a cognitive training group or to an active control group in a single-blind controlled two-group design. Before and after training interactive television cognitive performance was assessed on well validated tests of fluid, higher-order ability, and system usability was evaluated. The participants in the cognitive training group completed a television-based cognitive training programme, while the participants in the active control group completed a TV-based programme of personally benefiting activities. Significant improvements were observed in well validated working memory and executive function tasks in the cognitive training but not in the control group. None of the groups showed statistically significant improvement in life satisfaction score. Participants'' reports of “adequate” to “high” system usability testify to the successful development and implementation of the interactive television-based system and compliant cognitive training contents. The study demonstrates that cognitive training delivered by means of an interactive television system can generate genuine cognitive benefits in users and these are measurable using well-validated cognitive tests. Thus, older adults who cannot use or afford a computer can easily use digital interactive television to benefit from advanced software applications designed to train cognition.     

Lifelong Caloric Restriction Increases Working Memory in Mice

Caloric restriction (CR) is argued to positively affect general health, longevity and the normally occurring age-related reduction of cognition. This issue is well examined, but most studies investigated the effect of short-term periods of CR. Herein, 4 weeks old female mice were fed caloric restricted for 4, 20 and especially for 74 weeks. CR mice received 60% of food eaten by their ad libitum (AL) fed littermates, and all age-matched groups were behaviorally analyzed. The motor coordination, which was tested by rotarod/accelerod, decreased age-related, but was not influenced by the different periods of CR. In contrast, the age-related impairment of spontaneous locomotor activity and anxiety, both being evaluated by open field and by elevated plus maze test, was found aggravated by a lifelong CR. Measurement of cognitive performance with morris water maze showed that the working memory decreased age-related in AL mice, while a lifelong CR caused a better cognitive performance and resulted in a significantly better spatial memory upon 74 weeks CR feeding. However, a late-onset CR feeding in 66 weeks old mice did not ameliorate the working memory. Therefore, a lifelong CR seems to be necessary to improve working memory.     

Transfer after Working Memory Updating Training

During the past decade, working memory training has attracted much interest. However, the training outcomes have varied between studies and methodological problems have hampered the interpretation of results. The current study examined transfer after working memory updating training by employing an extensive battery of pre-post cognitive measures with a focus on near transfer. Thirty-one healthy Finnish young adults were randomized into either a working memory training group or an active control group. The working memory training group practiced with three working memory tasks, while the control group trained with three commercial computer games with a low working memory load. The participants trained thrice a week for five weeks, with one training session lasting about 45 minutes. Compared to the control group, the working memory training group showed strongest transfer to an n-back task, followed by working memory updating, which in turn was followed by active working memory capacity. Our results support the view that working memory training produces near transfer effects, and that the degree of transfer depends on the cognitive overlap between the training and transfer measures.     

Cognitive Control in Auditory Working Memory Is Enhanced in Musicians

Musical competence may confer cognitive advantages that extend beyond processing of familiar musical sounds. Behavioural evidence indicates a general enhancement of both working memory and attention in musicians. It is possible that musicians, due to their training, are better able to maintain focus on task-relevant stimuli, a skill which is crucial to working memory. We measured the blood oxygenation-level dependent (BOLD) activation signal in musicians and non-musicians during working memory of musical sounds to determine the relation among performance, musical competence and generally enhanced cognition. All participants easily distinguished the stimuli. We tested the hypothesis that musicians nonetheless would perform better, and that differential brain activity would mainly be present in cortical areas involved in cognitive control such as the lateral prefrontal cortex. The musicians performed better as reflected in reaction times and error rates. Musicians also had larger BOLD responses than non-musicians in neuronal networks that sustain attention and cognitive control, including regions of the lateral prefrontal cortex, lateral parietal cortex, insula, and putamen in the right hemisphere, and bilaterally in the posterior dorsal prefrontal cortex and anterior cingulate gyrus. The relationship between the task performance and the magnitude of the BOLD response was more positive in musicians than in non-musicians, particularly during the most difficult working memory task. The results confirm previous findings that neural activity increases during enhanced working memory performance. The results also suggest that superior working memory task performance in musicians rely on an enhanced ability to exert sustained cognitive control. This cognitive benefit in musicians may be a consequence of focused musical training.     

Working Memory Updating Function Training Influenced Brain Activity

Recent studies demonstrated that working memory could be improved by training. We recruited healthy adult participants and used adaptive running working memory training tasks with a double-blind design, combined with the event-related potentials (ERPs) approach, to explore the influence of updating function training on brain activity. Participants in the training group underwent training for 20 days. Compared with the control group, the training group''s accuracy (ACC) in the two-back working memory task had no significant differences after training, but reaction time (RT) was reduced significantly. Besides, the amplitudes of N160 and P300 increased significantly whereas that of P200 decreased significantly. The results suggest that training could have improved the participants'' capacity on both inhibitory and updating.     

RCT of Working Memory Training in ADHD: Long-Term Near-Transfer Effects

Objective

The aim of the study is to evaluate the long-term near-transfer effects of computerized working memory (WM) training on standard WM tasks in children with Attention-Deficit/Hyperactivity Disorder (ADHD).

Method

Sixty-seven children aged 10–12 years in Vestfold/Telemark counties (Norway) diagnosed with F90.0 Hyperkinetic disorder (ICD-10) were randomly assigned to training or control group. The training group participated in a 25-day training program at school, while the control group received treatment-as-usual. Participants were tested one week before intervention, immediately after and eight months later. Based on a component analysis, six measures of WM were grouped into composites representing Visual, Auditory and Manipulation WM.

Results

The training group had significant long-term differential gains compared to the control group on all outcome measures. Performance gains for the training group were significantly higher in the visual domain than in the auditory domain. The differential gain in Manipulation WM persisted after controlling for an increase in simple storage capacity.

Conclusion

Systematic training resulted in a long-term positive gain in performance on similar tasks, indicating the viability of training interventions for children with ADHD. The results provide evidence for both domain-general and domain-specific models. Far-transfer effects were not investigated in this article.Trial Registration: Controlled-Trials.com ISRCTN19133620     

The Influence of Perceptual Training on Working Memory in Older Adults

Normal aging is associated with a degradation of perceptual abilities and a decline in higher-level cognitive functions, notably working memory. To remediate age-related deficits, cognitive training programs are increasingly being developed. However, it is not yet definitively established if, and by what mechanisms, training ameliorates effects of cognitive aging. Furthermore, a major factor impeding the success of training programs is a frequent failure of training to transfer benefits to untrained abilities. Here, we offer the first evidence of direct transfer-of-benefits from perceptual discrimination training to working memory performance in older adults. Moreover, using electroencephalography to evaluate participants before and after training, we reveal neural evidence of functional plasticity in older adult brains, such that training-induced modifications in early visual processing during stimulus encoding predict working memory accuracy improvements. These findings demonstrate the strength of the perceptual discrimination training approach by offering clear psychophysical evidence of transfer-of-benefit and a neural mechanism underlying cognitive improvement.     

Genetically Determined Measures of Striatal D2 Signaling Predict Prefrontal Activity during Working Memory Performance

Background

Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known.

Methods

Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [¹²³I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [¹²³I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory.

Results

Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [¹²³I]IBZM and of [¹²³I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT.

Conclusions

Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway.     

A Potential Spatial Working Memory Training Task to Improve Both Episodic Memory and Fluid Intelligence

One current challenge in cognitive training is to create a training regime that benefits multiple cognitive domains, including episodic memory, without relying on a large battery of tasks, which can be time-consuming and difficult to learn. By giving careful consideration to the neural correlates underlying episodic and working memory, we devised a computerized working memory training task in which neurologically healthy participants were required to monitor and detect repetitions in two streams of spatial information (spatial location and scene identity) presented simultaneously (i.e. a dual n-back paradigm). Participants’ episodic memory abilities were assessed before and after training using two object and scene recognition memory tasks incorporating memory confidence judgments. Furthermore, to determine the generalizability of the effects of training, we also assessed fluid intelligence using a matrix reasoning task. By examining the difference between pre- and post-training performance (i.e. gain scores), we found that the trainers, compared to non-trainers, exhibited a significant improvement in fluid intelligence after 20 days. Interestingly, pre-training fluid intelligence performance, but not training task improvement, was a significant predictor of post-training fluid intelligence improvement, with lower pre-training fluid intelligence associated with greater post-training gain. Crucially, trainers who improved the most on the training task also showed an improvement in recognition memory as captured by d-prime scores and estimates of recollection and familiarity memory. Training task improvement was a significant predictor of gains in recognition and familiarity memory performance, with greater training improvement leading to more marked gains. In contrast, lower pre-training recollection memory scores, and not training task improvement, led to greater recollection memory performance after training. Our findings demonstrate that practice on a single working memory task can potentially improve aspects of both episodic memory and fluid intelligence, and that an extensive training regime with multiple tasks may not be necessary.     

水迷宫实验中三种品系小鼠学习记忆能力的比较

目的探讨三种品系小鼠在Morris水迷宫实验中的学习记忆能力差异,为与改善学习记忆能力相关新药研究的实验动物选择提供参考。方法选用C57BL/6小鼠、昆明种小鼠和ICR小鼠,进行定位航行实验(5d)、空间搜索实验(1d)和工作记忆实验(4d),考察其学习记忆能力。结果定位航行实验从第3天起C57BL/6小鼠的潜伏期明显小于昆明种小鼠和ICR小鼠(P0.01);空间搜索实验C57BL/6小鼠穿过原平台位置的次数、在原平台象限游程比率和时间比率均明显多于昆明种小鼠和ICR小鼠(P0.05);动物每天工作记忆实验的潜伏期随测试次数增加而缩短,C57BL/6小鼠缩短的较昆明种小鼠和ICR小鼠稍多。结论C57BL/6小鼠的空间参考记忆能力与工作记忆能力均优于昆明种小鼠和ICR小鼠,且非空间因素对其学习记忆能力的评价干扰较小,可作为优先选择的水迷宫实验动物。     

Dual N-Back Working Memory Training in Healthy Adults: A Randomized Comparison to Processing Speed Training

Enhancing cognitive ability is an attractive concept, particularly for middle-aged adults interested in maintaining cognitive functioning and preventing age-related declines. Computerized working memory training has been investigated as a safe method of cognitive enhancement in younger and older adults, although few studies have considered the potential impact of working memory training on middle-aged adults. This study investigated dual n-back working memory training in healthy adults aged 30–60. Fifty-seven adults completed measures of working memory, processing speed, and fluid intelligence before and after a 5-week web-based dual n-back or active control (processing speed) training program. Results: Repeated measures multivariate analysis of variance failed to identify improvements across the three cognitive composites, working memory, processing speed, and fluid intelligence, after training. Follow-up Bayesian analyses supported null findings for training effects for each individual composite. Findings suggest that dual n-back working memory training may not benefit working memory or fluid intelligence in healthy adults. Further investigation is necessary to clarify if other forms of working memory training may be beneficial, and what factors impact training-related benefits, should they occur, in this population.     

蛋白质组学方法分析多T迷宫训练后的小鼠空间记忆蛋白

应用双向凝胶电泳结合质谱鉴定和数据库检索,分析比较C57BL/6J小鼠在多T迷宫(MTM)训练和记忆测试组与未训练组海马蛋白表达的差异,探讨与MTM空间记忆相关的蛋白质.C57BL/6J小鼠经MTM训练后,可对相应的空间线索保持记忆能力,其海马蛋白质表达存在明显差异,14个蛋白质与MTM空间记忆形成显著相关.其中,6个蛋白点表达显著上调,8个蛋白点表达水平显著降低.这些蛋白按功能可分为6类: 细胞骨架相关蛋白,物质运输相关蛋白,蛋白合成相关蛋白,能量和物质代谢相关蛋白,信号转导相关蛋白,通道蛋白. 这些空间记忆形成相关蛋白的研究深化了对空间记忆机制的认识,为研究和治疗认知相关疾病提供了新靶标.     

Working Memory Training in Post-Secondary Students with ADHD: A Randomized Controlled Study

Objectives

To determine whether standard-length computerized training enhances working memory (WM), transfers to other cognitive domains and shows sustained effects, when controlling for motivation, engagement, and expectancy.

Methods

97 post-secondary students (59.8% female) aged 18–35 years with Attention-Deficit/Hyperactivity Disorder, were randomized into standard-length adaptive Cogmed WM training (CWMT; 45-min/session), a shortened-length adaptive version of CWMT (15 min/session) that controlled for motivation, engagement and expectancy of change, or into a no training group (waitlist-control group). All three groups received weekly telephone calls from trained coaches, who supervised the CWMT and were independent from the research team. All were evaluated before and 3 weeks post-training; those in the two CWMT groups were also assessed 3 months post-training. Untrained outcome measures of WM included the WAIS-IV Digit Span (auditory-verbal WM), CANTAB Spatial Span (visual-spatial WM) and WRAML Finger Windows (visual-spatial WM). Transfer-of-training effects included measures of short-term memory, cognitive speed, math and reading fluency, complex reasoning, and ADHD symptoms.

Results

Performance on 5/7 criterion measures indicated that shortened-length CWMT conferred as much benefit on WM performance as did standard-length training, with both CWMT groups improving more than the waitlist-control group. Only 2 of these findings remained robust after correcting for multiple comparisons. Follow-up analyses revealed that post-training improvements on WM performance were maintained for at least three months. There was no evidence of any transfer effects but the standard-length group showed improvement in task-specific strategy use.

Conclusions

This study failed to find robust evidence of benefits of standard-length CWMT for improving WM in college students with ADHD and the overall pattern of findings raise questions about the specificity of training effects.

Trial Registration

ClinicalTrials.gov NCT01657721     

Impact of Working Memory Load on Cognitive Control in Trait Anxiety: An ERP Study

Whether trait anxiety is associated with a general impairment of cognitive control is a matter of debate. This study investigated whether and how experimentally manipulated working memory (WM) load modulates the relation between trait anxiety and cognitive control. This question was investigated using a dual-task design in combination with event-related potentials. Participants were required to remember either one (low WM load) or six letters (high WM load) while performing a flanker task. Our results showed that a high WM load disrupted participants'' ability to overcome distractor interference and this effect was exacerbated for the high trait-anxious (HTA) group. This exacerbation was reflected by larger interference effects (i.e., incongruent minus congruent) on reaction times (RTs) and N2 amplitudes for the HTA group than for the low trait-anxious group under high WM load. The two groups, however, did not differ in their ability to inhibit task-irrelevant distractors under low WM load, as indicated by both RTs and N2 amplitudes. These findings underscore the significance of WM-related cognitive demand in contributing to the presence (or absence) of a general cognitive control deficit in trait anxiety. Furthermore, our findings show that when limited WM resources are depleted by high WM load, HTA individuals exhibit less efficient recruitments of cognitive control required for the inhibition of distractors, therefore resulting in a greater degree of response conflict.     

Estimating Premorbid Cognitive Abilities in Low-Educated Populations

Objective

To develop an informant-based instrument that would provide a valid estimate of premorbid cognitive abilities in low-educated populations.

Methods

A questionnaire was drafted by focusing on the premorbid period with a 10-year time frame. The initial pool of items was submitted to classical test theory and a factorial analysis. The resulting instrument, named the Premorbid Cognitive Abilities Scale (PCAS), is composed of questions addressing educational attainment, major lifetime occupation, reading abilities, reading habits, writing abilities, calculation abilities, use of widely available technology, and the ability to search for specific information. The validation sample was composed of 132 older Brazilian adults from the following three demographically matched groups: normal cognitive aging (n = 72), mild cognitive impairment (n = 33), and mild dementia (n = 27). The scores of a reading test and a neuropsychological battery were adopted as construct criteria. Post-mortem inter-informant reliability was tested in a sub-study with two relatives from each deceased individual.

Results

All items presented good discriminative power, with corrected item-total correlation varying from 0.35 to 0.74. The summed score of the instrument presented high correlation coefficients with global cognitive function (r = 0.73) and reading skills (r = 0.82). Cronbach''s alpha was 0.90, showing optimal internal consistency without redundancy. The scores did not decrease across the progressive levels of cognitive impairment, suggesting that the goal of evaluating the premorbid state was achieved. The intraclass correlation coefficient was 0.96, indicating excellent inter-informant reliability.

Conclusion

The instrument developed in this study has shown good properties and can be used as a valid estimate of premorbid cognitive abilities in low-educated populations. The applicability of the PCAS, both as an estimate of premorbid intelligence and cognitive reserve, is discussed.     

T-maze Forced Alternation and Left-right Discrimination Tasks for Assessing Working and Reference Memory in Mice

Forced alternation and left-right discrimination tasks using the T-maze have been widely used to assess working and reference memory, respectively, in rodents. In our laboratory, we evaluated the two types of memory in more than 30 strains of genetically engineered mice using the automated version of this apparatus. Here, we present the modified T-maze apparatus operated by a computer with a video-tracking system and our protocols in a movie format. The T-maze apparatus consists of runways partitioned off by sliding doors that can automatically open downward, each with a start box, a T-shaped alley, two boxes with automatic pellet dispensers at one side of the box, and two L-shaped alleys. Each L-shaped alley is connected to the start box so that mice can return to the start box, which excludes the effects of experimenter handling on mouse behavior. This apparatus also has an advantage that in vivo microdialysis, in vivo electrophysiology, and optogenetics techniques can be performed during T-maze performance because the doors are designed to go down into the floor. In this movie article, we describe T-maze tasks using the automated apparatus and the T-maze performance of α-CaMKII+/- mice, which are reported to show working memory deficits in the eight-arm radial maze task. Our data indicated that α-CaMKII+/- mice showed a working memory deficit, but no impairment of reference memory, and are consistent with previous findings using the eight-arm radial maze task, which supports the validity of our protocol. In addition, our data indicate that mutants tended to exhibit reversal learning deficits, suggesting that α-CaMKII deficiency causes reduced behavioral flexibility. Thus, the T-maze test using the modified automatic apparatus is useful for assessing working and reference memory and behavioral flexibility in mice.     

Variability of Prefrontal Neuronal Discharges before and after Training in a Working Memory Task

Variability of neural discharges can be revealing about the computations and network properties of neuronal populations during the performance of cognitive tasks. We sought to quantify neuronal variability in the prefrontal cortex of naïve monkeys that were only required to fixate, and to examine how this measure was altered by learning and execution of a working memory task. We therefore performed analysis of a large database of recordings in the same animals, using the same stimuli, before and after training. Our results indicate that the Fano Factor, a measure of variability, differs across neurons depending on their functional properties both before and after learning. Fano Factor generally decreased after learning the task. Variability was modulated by task events and displayed lowest values during the stimulus presentation. Nonetheless, the decrease in variability after training was present even prior to the presentation of any stimuli, in the fixation period. The greatest decreases were observed comparing populations of neurons that exhibited elevated firing rate during the trial events. Our results offer insights on how properties of the prefrontal network are affected by performance of a cognitive task.     

Inattentional Blindness and Individual Differences in Cognitive Abilities

People sometimes fail to notice salient unexpected objects when their attention is otherwise occupied, a phenomenon known as inattentional blindness. To explore individual differences in inattentional blindness, we employed both static and dynamic tasks that either presented the unexpected object away from the focus of attention (spatial) or near the focus of attention (central). We hypothesized that noticing in central tasks might be driven by the availability of cognitive resources like working memory, and that noticing in spatial tasks might be driven by the limits on spatial attention like attention breadth. However, none of the cognitive measures predicted noticing in the dynamic central task or in either the static or dynamic spatial task. Only in the central static task did working memory capacity predict noticing, and that relationship was fairly weak. Furthermore, whether or not participants noticed an unexpected object in a static task was only weakly associated with their odds of noticing an unexpected object in a dynamic task. Taken together, our results are largely consistent with the notion that noticing unexpected objects is driven more by stochastic processes common to all people than by stable individual differences in cognitive abilities.