Age-Related Changes in Visual Spatial Working Memory Cognits: Frontal-Parietal EEG Coherence During Delay

This study explored changes in scalp electrophysiology across two Working Memory (WM) tasks and two age groups. Continuous electroencephalography (EEG) was recorded from 18 healthy adults (18-34 years) and 12 healthy adolescents (14-17) during the performance of two Oculomotor Delayed Response (ODR) WM tasks; (i.e. eye movements were the metric of motor response). Delay-period, EEG data in the alpha frequency was sampled from anterior and parietal scalp sites to achieve a general measure of frontal and parietal activity, respectively. Frontal-parietal, alpha coherence was calculated for each participant for each ODR-WM task. Coherence significantly decreased in adults moving across the two ODR tasks, whereas, coherence significantly increased in adolescents moving across the two ODR tasks. The effects of task in the adolescent and adult groups were large and medium, respectively. Within the limits of this study, the results provide empirical support that WM development during adolescence include complex, qualitative, change.

Blueberry-induced changes in spatial working memory correlate with changes in hippocampal CREB phosphorylation and brain-derived neurotrophic factor (BDNF) levels

Phytochemical-rich foods have been shown to be effective at reversing age-related deficits in memory in both animals and humans. We show that a supplementation with a blueberry diet (2% w/w) for 12 weeks improves the performance of aged animals in spatial working memory tasks. This improvement emerged within 3 weeks and persisted for the remainder of the testing period. Memory performance correlated well with the activation of cAMP-response element-binding protein (CREB) and increases in both pro- and mature levels of brain-derived neurotrophic factor (BDNF) in the hippocampus. Changes in CREB and BDNF in aged and blueberry-supplemented animals were accompanied by increases in the phosphorylation state of extracellular signal-related kinase (ERK1/2), rather than that of calcium calmodulin kinase (CaMKII and CaMKIV) or protein kinase A. Furthermore, age and blueberry supplementation were linked to changes in the activation state of Akt, mTOR, and the levels of Arc/Arg3.1 in the hippocampus, suggesting that pathways involved in de novo protein synthesis may be involved. Although causal relationships cannot be made among supplementation, behavior, and biochemical parameters, the measurement of anthocyanins and flavanols in the brain following blueberry supplementation may indicate that changes in spatial working memory in aged animals are linked to the effects of flavonoids on the ERK-CREB-BDNF pathway. (c) 2008 Elsevier Inc. All Fights reserved.

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.

Activation of G-protein-coupled receptor 30 is sufficient to enhance spatial recognition memory in ovariectomized rats

In ovariectomized rats, administration of estradiol, or selective estrogen receptor agonists that activate either the alpha or beta isoforms, have been shown to enhance spatial cognition on a variety of learning and memory tasks, including those that capitalize on the preference of rats to seek out novelty. Although the effects of the putative estrogen G-protein-coupled receptor 30 (GPR30) on hippocampus-based tasks have been reported using food-motivated tasks, the effects of activation of GPR30 receptors on tasks that depend on the preference of rats to seek out spatial novelty remain to be determined. Therefore, the aim of the current study was to determine if short-term treatment of ovariectomized rats with G-1, an agonist for GPR30, would mimic the effects on spatial recognition memory observed following short-term estradiol treatment. In Experiment 1, ovariectomized rats treated with a low dose (1mug) of estradiol 48h and 24h prior to the information trial of a Y-maze task exhibited a preference for the arm associated with the novel environment on the retention trial conducted 48h later. In Experiment 2, treatment of ovariectomized rats with G-1 (25mug) 48h and 24h prior to the information trial of a Y-maze task resulted in a greater preference for the arm associated with the novel environment on the retention trial. Collectively, the results indicated that short-term treatment of ovariectomized rats with a GPR30 agonist was sufficient to enhance spatial recognition memory, an effect that also occurred following short-term treatment with a low dose of estradiol.

Tests of the Dynamic Field Theory and the Spatial Precision Hypothesis: Capturing a Qualitative Developmental Transition in Spatial Working Memory

This study tested a dynamic field theory (DFT) of spatial working memory and an associated spatial precision hypothesis (SPH). Between 3 and 6 years of age, there is a qualitative shift in how children use reference axes to remember locations: 3-year-olds’ spatial recall responses are biased toward reference axes after short memory delays, whereas 6-year-olds’ responses are biased away from reference axes. According to the DFT and the SPH, quantitative improvements over development in the precision of excitatory and inhibitory working memory processes lead to this qualitative shift. Simulations of the DFT in Experiment 1 predict that improvements in precision should cause the spatial range of targets attracted toward a reference axis to narrow gradually over development, with repulsion emerging and gradually increasing until responses to most targets show biases away from the axis. Results from Experiment 2 with 3- to 5-year-olds support these predictions. Simulations of the DFT in Experiment 3 quantitatively fit the empirical results and offer insights into the neural processes underlying this developmental change.

17 beta-Estradiol replacement in young, adult and middle-aged female ovariectomized rats promotes improvement of spatial reference memory and an antidepressant effect and alters monoamines and BDNF levels in memory- and depression-related brain areas

Clinical and experimental evidence suggest that estrogens have a major impact on cognition, presenting neurotrophic and neuroprotective actions in regions involved in such function. In opposite, some studies indicate that certain hormone therapy regimens may provoke detrimental effects over female cognitive and neurological function. Therefore, we decided to investigate how estrogen treatment would influence cognition and depression in different ages. For that matter, this study assessed the effects of chronic 17 beta-estradiol treatment over cognition and depressive-like behaviors of young (3 months old), adult (7 months old) and middle-aged (12 months old) reproductive female Wistar rats. These functions were also correlated with alterations in the serotonergic system, as well as hippocampal BDNF. 17 beta-Estradiol treatment did not influence animals' locomotor activity and exploratory behavior, but it was able to improve the performance of adult and middle-aged rats in the Morris water maze, the latter being more responsive to the treatment. Young and adult rats displayed decreased immobility time in the forced swimming test, suggesting an effect of 17 beta-estradiol also over such depressive-like behavior. This same test revealed increased swimming behavior, triggered by serotonergic pathway, in adult rats. Neurochemical evaluations indicated that 17 beta-estradiol treatment was able to increase serotonin turnover rate in the hippocampus of adult rats. Interestingly, estrogen treatment increased BDNF levels from animals of all ages. These findings support the notion that the beneficial effects of 17 beta-estradiol over spatial reference memory and depressive-like behavior are evident only when hormone therapy occurs at early ages and early stages of hormonal decline. (C) 2011 Elsevier B.V. All rights reserved.

Time-dependent hierarchical organization of spatial working memory: a transcranial magnetic stimulation study

The performance of memory-guided saccades with two different delays (3 and 30 s of memorization) was studied in seven healthy subjects. Double-pulse transcranial magnetic stimulation (dTMS) with an interstimulus interval of 100 ms was applied over the right dorsolateral prefrontal cortex (DLPFC) early (1 s after target presentation) and late (28 s after target presentation). Early stimulation significantly increased in both delays the percentage of error in amplitude (PEA) of contralateral memory-guided saccades compared to the control experiment without stimulation. dTMS applied late in the delay had no significant effect on PEA. Furthermore, we found a significantly smaller effect of early stimulation in the long-delay paradigm. These results suggest a time-dependent hierarchical organization of the spatial working memory with a functional dominance of DLPFC during the early memorization, independent from the memorization delay. For a long memorization delay, however, working memory seems to have an additional, DLPFC-independent component.

A virtual environment for the assessment and the rehabilitation of the visuo-constructional ability in dementia patients

This study proposes a VE that offers a reliable diagnosis of the stage of cognitive decline in dementia patients and assists the delay of this decline in terms of the visuo-constructional ability. The proposed VE, in the case of the assessment, presents a visuo-constructional completion task, which requires spatial perception, motor memory and the perception of the target object. In the case of the rehabilitation the VE uses sound as audio-feedback that, with the aid of the music perception, tends to develop an enhancement in the visuo-construction ability of the dementia patients that can be generalized even outside of the VE. The study examined 30 subjects that were normal controls (N), 30 patients suffering from memory disorders (Age-Associated Memory Impairment--AAMI) and 30 suffering from Alzheimer's Disease (AD). The results showed that there is a significant correlation between the performance in the visuo-constructional task and the dementia diagnosis. It also seems that the visuo-constructional ability of the (AD) patients can be statistically improved by the audio experience in the VE. The empirical results of this study offer an alternative diagnosis and treatment of dementia patients and could share some light in the brain sub-systems that are responsible for the visuo-constructional ability. Further studies are required in order to investigate the nature of this phenomenon more.

Functional organization of spatial and nonspatial working memory processing within the human lateral frontal cortex

The present study used functional magnetic resonance imaging to demonstrate that performance of visual spatial and visual nonspatial working memory tasks involve the same regions of the lateral prefrontal cortex when all factors unrelated to the type of stimulus material are appropriately controlled. These results provide evidence that spatial and nonspatial working memory may not be mediated, respectively, by mid-dorsolateral and mid-ventrolateral regions of the frontal lobe, as widely assumed, and support the alternative notion that specific regions of the lateral prefrontal cortex make identical executive functional contributions to both spatial and nonspatial working memory.

Electroconvulsive shock and lidocaine reveal rapid consolidation of spatial working memory in the water maze.

Head trauma leading to concussion and electroconvulsive shock (ECS) in humans causes amnesia for events that occurred shortly before the injury (retrograde amnesia). The present experiment investigated the amnesic effect of lidocaine and ECS in 25 rats trained on a working memory version of the Morris water task. Each day, the escape platform was moved to a new location; learning was evidenced by a decrease in the latency to find the platform from the first to the second trial. "Consolidation" of this newly encoded spatial engram was disrupted by bilateral inactivation of the dorsal hippocampus with 1 microliter of 4% lidocaine applied as soon as possible after the first trial. When trial 2 was given after recovery from the lidocaine (30 min after the injection), a normal decrease in latency indicated that the new engram was not disrupted. When trial 2 was given under the influence of lidocaine (5 min after injection), absence of latency decrease demonstrated both the success of the inactivation and the importance of hippocampus for the task. To examine the role of events immediately after learning, ECS (30 or 100 mA, 50 Hz, 1.2 sec) was applied 0 sec to 45 sec after a single escape to the new platform location. A 2-h delay between ECS and trial 2 allowed the effects of ECS to dissipate. ECS applied 45 sec or 30 sec after trial 1 caused no retrograde amnesia: escape latencies on trial 2 were the same as in control rats. However, ECS applied 0 sec or 15 sec after trial 1 induced clear retrograde amnesia: escape latencies on trial 2 were no shorter than on trial 1. It is concluded that the consolidation of a newly formed memory for spatial location can only be disrupted by ECS within 30 sec after learning.

Increased dopamine turnover in the prefrontal cortex impairs spatial working memory performance in rats and monkeys.

The selective activation of the prefrontal cortical dopamine system by mild stress can be mimicked by anxiogenic beta-carbolines such as FG7142. To investigate the functional relevance of elevated levels of dopamine turnover in the prefrontal cortex, the current study examined the effects of FG7142 on the performance of spatial working memory tasks in the rat and monkey. FG7142 selectively increased prefrontal cortical dopamine turnover in rats and significantly impaired performance on spatial working memory tasks in both rats and monkeys. Spatial discrimination, a task with similar motor and motivational demands (rats), or delayed response performance following zero-second delays (monkeys) was unaffected by FG7142. Further, biochemical analysis in rats revealed a significant positive correlation between dopamine turnover in the prefrontal cortex and cognitive impairment on the delayed alternation task. The cognitive deficits in both rats and monkeys were prevented by pretreatment with the benzodiazepine receptor antagonist, RO15-1788, which blocked the increase in dopamine turnover and by the dopamine receptor antagonists, haloperidol, clozapine, and SCH23390. These findings indicate that excessive dopamine activity in the prefrontal cortex is detrimental to cognitive functions mediated by the prefrontal cortex.

Distinct neural correlates of visual long-term memory for spatial location and object identity: a positron emission tomography study in humans.

The purpose of the present study was to investigate by using positron emission tomography (PET) whether the cortical pathways that are involved in visual perception of spatial location and object identity are also differentially implicated in retrieval of these types of information from episodic long-term memory. Subjects studied a set of displays consisting of three unique representational line drawings arranged in different spatial configurations. Later, while undergoing PET scanning, subjects' memory for spatial location and identity of the objects in the displays was tested and compared to a perceptual baseline task involving the same displays. In comparison to the baseline task, each of the memory tasks activated both the dorsal and the ventral pathways in the right hemisphere but not to an equal extent. There was also activation of the right prefrontal cortex. When PET scans of the memory tasks were compared to each other, areas of activation were very circumscribed and restricted to the right hemisphere: For retrieval of object identity, the area was in the inferior temporal cortex in the region of the fusiform gyrus (area 37), whereas for retrieval of spatial location, it was in the inferior parietal lobule in the region of the supramarginal gyrus (area 40). Thus, our study shows that distinct neural pathways are activated during retrieval of information about spatial location and object identity from long-term memory.

Threat-evoked anxiety disrupts spatial working memory performance:an attentional account

It is proposed that threat-evoked anxiety and spatial Working Memory (WM) rely on a common visuospatial attention mechanism. A prediction of this hypothesis is that spatial but not verbal WM should be disrupted in conditions of threat anxiety. Participants performed verbal and spatial n-back WM tasks in the presence or absence of threat of shock (shocks were not delivered). The presence of anxiety was assessed via heart rate recordings and self-report. Both measures clearly distinguished between WM blocks associated with threat of shock (Threat) and blocks, in which threat was absent (Safety). Performance on the spatial WM task was impaired in Threat relative to Safety. Furthermore, the more anxiety participants reported and the higher their heart rate in Threat compared to Safety, the more impaired was their spatial WM performance. This effect was not observed for verbal WM. The results indicate selective disruption of spatial WM performance by threat-evoked anxiety, interpreted in terms of more overlap in visuospatial attention between anxiety and spatial WM vs. anxiety and verbal WM.

Counteractive effects of antenatal glucocorticoid treatment on D1 receptor modulation of spatial working memory

RATIONALE: Antenatal exposure to the glucocorticoid dexamethasone dramatically increases the number of mesencephalic dopaminergic neurons in rat offspring. However, the consequences of this expansion in midbrain dopamine (DA) neurons for behavioural processes in adulthood are poorly understood, including working memory that depends on DA transmission in the prefrontal cortex (PFC). OBJECTIVES: We therefore investigated the influence of antenatal glucocorticoid treatment (AGT) on the modulation of spatial working memory by a D1 receptor agonist and on D1 receptor binding and DA content in the PFC and striatum. METHODS: Pregnant rats received AGT on gestational days 16-19 by adding dexamethasone to their drinking water. Male offspring reared to adulthood were trained on a delayed alternation spatial working memory task and administered the partial D1 agonist SKF38393 (0.3-3 mg/kg) by systemic injection. In separate groups of control and AGT animals, D1 receptor binding and DA content were measured post-mortem in the PFC and striatum. RESULTS: SKF38393 impaired spatial working memory performance in control rats but had no effect in AGT rats. D1 binding was significantly reduced in the anterior cingulate cortex, prelimbic cortex, dorsal striatum and ventral pallidum of AGT rats compared with control animals. However, AGT had no significant effect on brain monoamine levels. CONCLUSIONS: These findings demonstrate that D1 receptors in corticostriatal circuitry down-regulate in response to AGT. This compensatory effect in D1 receptors may result from increased DA-ergic tone in AGT rats and underlie the resilience of these animals to the disruptive effects of D1 receptor activation on spatial working memory.

Distraction by task-irrelevant stimuli: the effects of endogenous spatial attention and visual working memory load

Salient stimuli, like sudden changes in the environment or emotional stimuli, generate a priority signal that captures attention even if they are task-irrelevant. However, to achieve goal-driven behavior, we need to ignore them and to avoid being distracted. It is generally agreed that top-down factors can help us to filter out distractors. A fundamental question is how and at which stage of processing the rejection of distractors is achieved. Two circumstances under which the allocation of attention to distractors is supposed to be prevented are represented by the case in which distractors occur at an unattended location (as determined by the deployment of endogenous spatial attention) and when the amount of visual working memory resources is reduced by an ongoing task. The present thesis is focused on the impact of these factors on three sources of distraction, namely auditory and visual onsets (Experiments 1 and 2, respectively) and pleasant scenes (Experiment 3). In the first two studies we recorded neural correlates of distractor processing (i.e., Event-Related Potentials), whereas in the last study we used interference effects on behavior (i.e., a slowing down of response times on a simultaneous task) to index distraction. Endogenous spatial attention reduced distraction by auditory stimuli and eliminated distraction by visual onsets. Differently, visual working memory load only affected the processing of visual onsets. Emotional interference persisted even when scenes occurred always at unattended locations and when visual working memory was loaded. Altogether, these findings indicate that the ability to detect the location of salient task-irrelevant sounds and identify the affective significance of natural scenes is preserved even when the amount of visual working memory resources is reduced by an ongoing task and when endogenous attention is elsewhere directed. However, these results also indicate that the processing of auditory and visual distractors is not entirely automatic.