Phenolic acid intake, delivered via moderate champagne wine consumption, improves spatial working memory via the modulation of hippocampal and cortical protein expression/activation.

Aims: While much data exist for the effects of flavonoid-rich foods on spatial memory in rodents, there are no such data for foods/beverages predominantly containing hydroxycinnamates and phenolic acids. To address this, we investigated the effects of moderate Champagne wine intake, which is rich in these components, on spatial memory and related mechanisms relative to the alcohol- and energy-matched controls. Results: In contrast to the isocaloric and alcohol-matched controls, supplementation with Champagne wine (1.78 ml/kg BW, alcohol 12.5% vol.) for 6 weeks led to an improvement in spatial working memory in aged rodents. Targeted protein arrays indicated that these behavioral effects were paralleled by the differential expression of a number of hippocampal and cortical proteins (relative to the isocaloric control group), including those involved in signal transduction, neuroplasticity, apoptosis, and cell cycle regulation. Western immunoblotting confirmed the differential modulation of brain-derived neurotrophic factor, cAMP response-element-binding protein (CREB), p38, dystrophin, 2',3'-cyclic-nucleotide 3'-phosphodiesterase, mammalian target of rapamycin (mTOR), and Bcl-xL in response to Champagne supplementation compared to the control drink, and the modulation of mTOR, Bcl-xL, and CREB in response to alcohol supplementation. Innovation: Our data suggest that smaller phenolics such as gallic acid, protocatechuic acid, tyrosol, caftaric acid, and caffeic acid, in addition to flavonoids, are capable of exerting improvements in spatial memory via the modulation in hippocampal signaling and protein expression. Conclusion: Changes in spatial working memory induced by the Champagne supplementation are linked to the effects of absorbed phenolics on cytoskeletal proteins, neurotrophin expression, and the effects of alcohol on the regulation of apoptotic events in the hippocampus and cortex. Antioxid. Redox Signal. 00, 000-000.

An investigation of working memory effects on oral grammatical accuracy and fluency in producing questions in English

This article addresses the question of how far working memory may affect second language (L2) learners' improvement in spoken language during a period of immersion. Research is presented testing the hypothesis that individual differences in working memory (WM) capacity are associated with individual variation in improvements in oral production of questions in English. Thirty-two Chinese adult speakers of English were tested, before and after a year's postgraduate study in the United Kingdom, to measure grammatical accuracy and fluency using a question elicitation task, and to measure WM using a battery of first language (L1) and L2 WM tests. Story recall in L1 (Mandarin) was significantly associated with individuals' improvement in oral grammatical measures (p < .05). However, there was no significant mean improvement across the cohort in grammatical accuracy, although there was for fluency. The findings suggest that WM may aid certain aspects of individuals' L2 oral proficiency during academic immersion through postgraduate study. They also indicate that academic immersion in itself can lead to improvements in oral proficiency, independent of WM capacity, but there is no general guarantee of significant grammatical change. Further research to clarify the opportunities for input and interaction available in academic immersion settings is called for.

The role of working memory in the processing of reflexives

We report results from two eye-movement experiments that examined how differences in working memory (WM) capacity affect readers' application of structural constraints on reflexive anaphor resolution during sentence comprehension. We examined whether binding Principle A, a syntactic constraint on the interpretation of reflexives, is reducible to a memory friendly “recency” strategy, and whether WM capacity influences the degree to which readers create anaphoric dependencies ruled out by binding theory. Our results indicate that low and high WM span readers applied Principle A early during processing. However, contrary to previous findings, low span readers also showed immediate intrusion effects of a linearly closer but structurally inaccessible competitor antecedent. We interpret these findings as indicating that although the relative prominence of potential antecedents in WM can affect online anaphor resolution, Principle A is not reducible to a processing or linear distance based “least effort” constraint.

Causal evidence for a privileged working memory state in early visual cortex

Emerging evidence suggests that items held in working memory(WM)might not all be in the same representational state. One item might be privileged over others, making it more accessible and thereby recalled with greater precision. Here, using transcranial magnetic stimulation (TMS), we provide causal evidence in human participants that items inWMare differentially susceptible to disruptive TMS, depending on their state, determined either by task relevance or serial position. Across two experiments, we applied TMS to area MT during the WM retention of two motion directions. In Experiment 1, we used an “incidental cue” to bring one of the two targets into a privileged state. In Experiment 2, we presented the targets sequentially so that the last item was in a privileged state by virtue of recency. In both experiments, recall precision of motion direction was differentially affected by TMS, depending on the state of the memory target at the time of disruption. Privileged items were recalled with less precision, whereas nonprivileged items were recalled with higher precision. Thus, only the privileged item was susceptible to disruptive TMS over MT�. By contrast, precision of the nonprivileged item improved either directly because of facilitation by TMS or indirectly through reduced interference from the privileged item. Our results provide a unique line of evidence, as revealed by TMS over a posterior sensory brain region, for at least two different states of item representation in WM.

Flexibility of representational states in working memory

The relationship between working memory (WM) and attention is a highly interdependent one, with evidence that attention determines the state in which items in WM are retained. Through focusing of attention, an item might be held in a more prioritized state, commonly termed as the focus of attention (FOA). The remaining items, although still retrievable, are considered to be in a different representational state. One means to bring an item into the FOA is to use retrospective cues (‘retro-cues’) which direct attention to one of the objects retained in WM. Alternatively, an item can enter a privileged state once attention is directed towards it through bottom-up influences (e.g. recency effect) or by performing an action on one of the retained items (‘incidental’ cueing). In all these cases, the item in the FOA is recalled with better accuracy compared to the other items in WM. Far less is known about the nature of the other items in WM and whether they can be flexibly manipulated in and out of the FOA. We present data from three types of experiments as well as transcranial magnetic stimulation to early visual cortex to manipulate the item inside FOA. Taken together, our results suggest that the context in which items are retained in WM matters. When an item remains behaviourally relevant, despite not being inside the FOA, re-focusing attention upon it can increase its recall precision. This suggests that a non-FOA item can be held in a state in which it can be later retrieved. However, if an item is rendered behaviourally unimportant because it is very unlikely to be probed, it cannot be brought back into the FOA, nor recalled with high precision. Under such conditions, some information appears to be irretrievably lost from WM. These findings, obtained from several different methods, demonstrate quite considerable flexibility with which items in WM can be represented depending upon context. They have important consequences for emerging state-dependent models of WM.

The development of time-based prospective memory in childhood: the role of working memory updating

This large-scale study examined the development of time-based prospective memory (PM) across childhood and the roles that working memory updating and time monitoring play in driving age effects in PM performance. One hundred and ninety-seven children aged 5 to 14 years completed a time-based PM task where working memory updating load was manipulated within individuals using a dual task design. Results revealed age-related increases in PM performance across childhood. Working memory updating load had a negative impact on PM performance and monitoring behavior in older children, but this effect was smaller in younger children. Moreover, the frequency as well as the pattern of time monitoring predicted children’s PM performance. Our interpretation of these results is that processes involved in children’s PM may show a qualitative shift over development from simple, nonstrategic monitoring behavior to more strategic monitoring based on internal temporal models that rely specifically on working memory updating resources. We discuss this interpretation with regard to possible trade-off effects in younger children as well as alternative accounts.

Carotenoids but not flavonoids are associated with improvements in spatial working memory in younger adults in a flavonoid-rich v. -poor fruit and vegetable intervention study

Findings from animal studies suggest that components of fruit and vegetables (F&V) may protect against, and even reverse, age-related decline(1,2) in aspects of cognitive functioning such as spatial working memory (SWM). Human subjects in vivo and in vitro studies indicate that anti-inflammatory, anti-oxidant and cell-signalling properties of flavonoids and carotenoids, non-nutrient components of F&V, may underpin this protective effect(3–5). The Flavonoid University of Reading Study (FLAVURS), designed to explore the dose-response relationship between dietary F&V flavonoids and CVD, enabled the investigation of such an association with SWM. FLAVURS is an 18-week parallel three-arm randomised controlled dietary intervention trial with four time points, measured at 6-weekly intervals from baseline. Low F&V consumers at risk of CVD aged 26–70 years were randomly assigned to high flavonoid (HF), low flavonoid (LF) or control group. F&V intake increased by two daily 80 g portions every 6 weeks, with either HF or LF F&V, in addition to each participant's habitual diet, while controls maintained their habitual diet. At each visit, participants completed a cognitive test battery with SWM as the primary outcome. The HF group showed significantly higher levels of urinary flavonoids than LF or controls at 12 weeks (P<0.001) as expected, but surprisingly only higher levels than LF at 18 weeks (P<0.01). The LF group showed higher levels of plasma carotenoids than the other groups at 18 weeks (P<0.001). No group differences were found for SWM overall, however, age-group sub-analyses (26–50 and 51–70 years of age) showed differences from 0 to 18 weeks for younger adults, with LF improving significantly more than the other two groups on SWM (P<0.05). As nutritional absorption is known to decrease with age, separate stepwise regressions were performed on the two age groups irrespective of dietary group, with urinary flavonoids and plasma carotenoids as predictors. For younger adults, improved SWM performance from 0 to 18 weeks was associated with higher carotenoid levels, β=0.28, t(55)=2.10, P<0.05, accounting for 7.5% of the variance, R2=0.075, F(1,54)=4.41, P=0.040. For older adults, no between-group SWM differences were found. Findings suggest that F&V-based flavonoids and carotenoids may provide benefits for cognitive function, and that carotenoids in particular may improve cognitive performance in SWM. Given that these benefits were restricted to younger adults, future work is needed to test the reliability of this finding, as well as determine the mechanisms by which age-dependent differences in F&V responsiveness occur.

Working memory, reading ability and the effects of distance and typicality on anaphor resolution in children

We investigated the time course of anaphor resolution in children and whether this is modulated by individual differences in working memory and reading skill. The eye movements of 30 children (10-11 years) were monitored as they read short paragraphs in which (i) the semantic typicality of an antecedent and (ii) its distance in relation to an anaphor, were orthogonally manipulated. Children showed effects of distance and typicality on the anaphor itself, and also on the word to the right of the anaphor, suggesting that anaphoric processing begins immediately but continues after the eyes have left the anaphor. Furthermore, children showed no evidence of resolving anaphors in the most difficult condition (distant atypical antecedent), suggesting that anaphoric processing that is demanding may not occur online in children of this age. Finally, working memory capacity and reading comprehension skill affect the magnitude and time course of typicality and distance effects during anaphoric processing.

Relationship between verbal working memory and the SCAN-C in children with specific language impairment

Purpose: An ongoing concern with the evaluation of auditory processing disorders is the extent that assessment instruments are influenced by higher order cognitive functions. This study examined the relationship between verbal working memory and performance on the Test for Auditory Processing Disorders in Children--Revised (SCAN-C; Keith, 2000b) in children with specific language impairment (SLI) and typically developing (TD) children.

Method: Sixteen children with SLI and 16 TD children ages 8/4 to 11 years participated in the study. The children were presented with the SCAN-C and tests measuring verbal working memory.

Results: Initial comparisons revealed that the SLI group obtained significantly lower scores than the TD group on the SCAN-C. However, after controlling for verbal working memory, significant differences between the 2 groups were no longer observed. Correlational analyses revealed that the composite score from the SCAN-C was related to all tests assessing verbal working memory.

Conclusions: Performance on the SCAN-C may be related to working memory functioning. As a consequence, it is unclear whether difficulty on this task should be viewed as a problem with auditory processing or a problem with verbal working memory.

Can improving working memory prevent academic difficulties? a school based randomised controlled trial

Background: Low academic achievement is common and is associated with adverse outcomes such as grade repetition, behavioural disorders and unemployment. The ability to accurately identify these children and intervene before they experience academic failure would be a major advance over the current ‘wait to fail’ model. Recent research suggests that a possible modifiable factor for low academic achievement is working memory, the ability to temporarily store and manipulate information in a ‘mental workspace’. Children with working memory difficulties are at high risk of academic failure. It has recently been demonstrated that working memory can be improved with adaptive training tasks that encourage improvements in working memory capacity. Our trial will determine whether the intervention is efficacious as a selective prevention strategy for young children at risk of academic difficulties and is cost-effective.

Methods/Design: This randomised controlled trial aims to recruit 440 children with low working memory after a school-based screening of 2880 children in Grade one. We will approach caregivers of all children from 48 participating primary schools in metropolitan Melbourne for consent. Children with low working memory will be randomised to usual care or the intervention. The intervention will consist of 25 computerised working memory training sessions, which take approximately 35 minutes each to complete. Follow-up of children will be conducted at 6, 12 and 24 months post-randomisation through child face-to-face assessment, parent and teacher surveys and data from government authorities. The primary outcome is academic achievement at 12 and 24 months, and other outcomes include child behaviour, attention, health-related quality of life, working memory, and health and educational service
utilisation.

Discussion: A successful start to formal learning in school sets the stage for future academic, psychological and economic well-being. If this preventive intervention can be shown to be efficacious, then we will have the potential to prevent academic underachievement in large numbers of at-risk children, to offer a ready-to-use intervention to the Australian school system and to build international research partnerships along the health education interface, in order to carry our further studies of effectiveness and generalisability.

Malondialdehyde plasma concentration correlates with declarative and working memory in patients with recurrent depressive disorder

Oxidative stress has been implicated in the cognitive decline, especially in memory impairment. The purpose of this study was to determine the concentration of malondialdehyde (MDA) in patients with recurrent depressive disorders (rDD) and to define relationship between plasma levels of MDA and the cognitive performance. The study comprised 46 patients meeting criteria for rDD. Cognitive function assessment was based on: The Trail Making Test , The Stroop Test, Verbal Fluency Test and Auditory-Verbal Learning Test. The severity of depression symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Statistically significant differences were found in the intensity of depression symptoms, measured by the HDRS on therapy onset versus the examination results after 8 weeks of treatment (P < 0.001). Considering the 8-week pharmacotherapy period, rDD patients presented better outcomes in cognitive function tests. There was no statistically significant correlation between plasma MDA levels, and the age, disease duration, number of previous depressive episodes and the results in HDRS applied on admission and on discharge. Elevated levels of MDA adversely affected the efficiency of visual-spatial and auditory-verbal working memory, short-term declarative memory and the delayed recall declarative memory. 1. Higher concentration of plasma MDA in rDD patients is associated with the severity of depressive symptoms, both at the beginning of antidepressants pharmacotherapy, and after 8 weeks of its duration. 2. Elevated levels of plasma MDA are related to the impairment of visual-spatial and auditory-verbal working memory and short-term and delayed declarative memory.