BT-11 is effective for enhancing cognitive functions in the elderly humans

Roots of Polygala tenuifolia Willdenow have been used in humans for centuries because of its sedative effects. We previously reported that BT-11, extracted from the roots of the plant, improved memory impairments in rats, enhanced memory in normal humans, and inhibited acetylcholinesterase activities in vitro. The present study was a randomized, double-blind, placebo-controlled comparison study to investigate whether BT-11 could enhance memory in the elderly humans. We used the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD) and the Mini-Mental State Examination (MMSE). In the elderly, the total CERAD scores were much more significantly increased in the BT-11-treated group (n = 28) than in the placebo-treated group (n = 25). Especially, the mean scores of word list recognition, constructional recall and praxis, and modified Boston naming test were markedly improved in BT-11-treated group than in placebo-treated group. In conclusion, BT-11 could enhance some cognitive functions including memory in the elderly humans and therefore may be used as nutraceuticals that provide health benefits, including disease prevention and/or treatment.     

Dissociating the effects of semantic grouping and rehearsal strategies on event-related brain potentials

The application of elaborative encoding strategies during learning, such as grouping items on similar semantic categories, increases the likelihood of later recall. Previous studies have suggested that stimuli that encourage semantic grouping strategies had modulating effects on specific ERP components. However, these studies did not differentiate between ERP activation patterns evoked by elaborative working memory strategies like semantic grouping and more simple strategies like rote rehearsal. Identification of neurocognitive correlates underlying successful use of elaborative strategies is important to understand better why certain populations, like children or elderly people, have problems applying such strategies. To compare ERP activation during the application of elaborative versus more simple strategies subjects had to encode either four semantically related or unrelated pictures by respectively applying a semantic category grouping or a simple rehearsal strategy. Another goal was to investigate if maintenance of semantically grouped vs. ungrouped pictures modulated ERP-slow waves differently. At the behavioral level there was only a semantic grouping benefit in terms of faster responding on correct rejections (i.e. when the memory probe stimulus was not part of the memory set). At the neural level, during encoding semantic grouping only had a modest specific modulatory effect on a fronto-central Late Positive Component (LPC), emerging around 650 ms. Other ERP components (i.e. P200, N400 and a second Late Positive Component) that had been earlier related to semantic grouping encoding processes now showed stronger modulation by rehearsal than by semantic grouping. During maintenance semantic grouping had specific modulatory effects on left and right frontal slow wave activity. These results stress the importance of careful control of strategy use when investigating the neural correlates of elaborative encoding.     

Hormonal contraception use alters stress responses and emotional memory

Emotionally arousing material is typically better remembered than neutral material. Since norepinephrine and cortisol interact to modulate emotional memory, sex-related influences on stress responses may be related to sex differences in emotional memory. Two groups of healthy women – one naturally cycling (NC women, n = 42) and one using hormonal contraceptives (HC women, n = 36) – viewed emotionally arousing and neutral images. Immediately after, they were assigned to Cold Pressor Stress (CPS) or a control procedure. One week later, participants received a surprise free recall test. Saliva samples were collected and later assayed for salivary alpha-amylase (biomarker for norepinephrine) and cortisol. Compared to NC women, HC women exhibited significantly blunted stress hormone responses to the images and CPS. Recall of emotional images differed between HC and NC women depending on noradrenergic and cortisol responses. These findings may have important implications for understanding the neurobiology of emotional memory disorders, especially those that disproportionately affect women.     

Association of angiotensin-converting enzyme functional gene I/D polymorphism with amnestic mild cognitive impairment

The relationship between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and serum ACE activity, as well as amnestic mild cognitive impairment (aMCI), was investigated. The study recruited 90 aMCI patients and 90 matched healthy controls. All subjects underwent an extensive assessment of cognitive function. The ACE gene I/D genotype was determined by polymerase chain reaction. Serum ACE activity was measured using a spectrophotometric technique. The scores obtained by the aMCI patients on the neuropsychological tests were significantly lower than those of the control subjects (all p < 0.01). The genotype (χ² = 11.510) and allele (χ² = 6.945) frequencies of the ACE gene were significantly different between the aMCI and the control groups (all p < 0.01). The DD genotype (23%) and D-allele (57%) frequencies in the aMCI patients were higher than those in the controls (16% vs. 43%). ACE genotype was correlated with delayed recall in Auditory Verbal Memory Test, delayed recall in Complex Figure Test, Category Fluency Test, and Symbol Digit Modalities Test in all subjects, in which the carriers of the DD and DI genotypes obtained lower scores than those of the II genotype (p < 0.05). A significant difference in the serum ACE level was observed among the three genotypes (DD > DI > II) in both the aMCI and the control groups (all p < 0.01). D-allele may be a genetic risk factor for the development of aMCI to Alzheimer's disease. A high serum ACE level possibly plays an important role in the incidence of aMCI.     

A comparative analysis of sensory visual evoked oscillations with visual cognitive event related oscillations in Alzheimer's disease

We compared visual evoked oscillatory responses of subjects with Alzheimer's disease (AD) (n = 22) to healthy elderly controls (n = 19) elicited by simple light stimuli. The visual evoked oscillatory responses in AD subjects without cholinergic treatment (n = 11) show significant differences (df = 2.38, F = 4.957, P = 0.012) from the controls and the AD subjects treated with a cholinesterase inhibitor (n = 11). Higher theta oscillatory responses in untreated AD subjects are seen on the electrode locations over bi-parietal and right occipital regions after simple light stimuli with less, if any, cognitive load. These changes were restricted to the theta frequency range only and are related to location, frequency bands and drug effects. In our previous work we observed that visual event related oscillations elicited after the visual stimuli with a higher cognitive load, i.e. an oddball target, display lower amplitudes: between controls and AD subjects in delta frequency band without a drug effect, over the left and mid-central region. These differences between the visual evoked oscillations and the visual event related oscillations imply that there are at least two different cognitive circuits that are activated upon visual stimuli in AD patients.     

Genotypes and virulence characteristics of Shiga toxin-producing Escherichia coli O104 strains from different origins and sources

Sixty-two Escherichia coli strains carrying the wzx_O104-gene from different sources, origins and time periods were analyzed for their serotypes, virulence genes and compared for genomic similarity by pulsed-field gel-electrophoresis (PFGE). The O104 antigen was present in 55 strains and the structurally and genetically related capsular antigen K9 in five strains. The presence of 49 genes associated with enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC) and enterohemorrhagic E. coli (EHEC) was investigated. Fifty-four strains of serotypes O104:H2 (n = 1), O104:H4 (n = 37), O104:H7 (n = 5) and O104:H21 (n = 11) produced Shiga-toxins (Stx). Among STEC O104, a close association between serotype, virulence gene profile and genomic similarity was found. EAEC virulence genes were only present in STEC O104:H4 strains. EHEC-O157 plasmid-encoded genes were only found in STEC O104:H2, O104:H7 and O104:H21 strains. None of the 62 O104 or K9 strains carried an eae-gene involved in the attaching and effacing phenotype.     

Blood CADPS2ΔExon3 expression is associated with intelligence and memory in healthy adults

Ca²⁺-dependent activator protein for secretion 2 (CADPS2), a secretory granule associate protein, mediates monoamine transmission and neurotrophin release. Both monoamines and neurotrophins play a crucial role in cognition, learning and memory. An aberrant splice variant of CADPS2, CADPS2ΔExon3, was reported to be associated with autism. Therefore, we examined the possible association between the expression of CADPS2/CADPS2ΔExon3 in peripheral blood and brain functions such as intelligence and memory. Quantitative polymerase chain reaction analysis was performed in 271 healthy adults (age range 20-74 years, mean ± SD 43.3 ± 15.3). Data on intelligence quotient (IQ) and memory were obtained by using full versions of the Wechsler Adult Intelligence Scale-Revised (WAIS-R), and the Wechsler Memory Scale-Revised (WMS-R), respectively. CADPS2 expression levels were not significantly associated with any scores/sub-scores of these scales. However, CADPS2ΔExon3 expression was significantly associated with lower IQ (p = 0.022; effect size: η_p² = 0.031), particularly verbal IQ of WAIS-R (p = 0.019; η_p² = 0.032), lower verbal memory (p = 0.026; η_p² = 0.026) and delayed recall (p = 0.042; η_p² = 0.021) of WMS-R. Our results suggest that CADPS2ΔExon3 affects intelligence and memory in the non-clinical population.     

Emotional and physiological responses to normative and idiographic positive stimuli in bipolar disorder

Background

Few studies have examined differences in emotional responding among distinct types of positive stimuli. This is important to understand both for individuals characterized by extreme positive mood (i.e., bipolar disorder) and healthy adults.

Methods

Using a multi-method within-subjects design, the current study examined physiological, behavioral, and self-reported responses to normative (film) and idiographic (memory) happy stimuli in bipolar (BD; n = 25) and healthy control groups (CTL; n = 23).

Results

For both groups, the happy films were associated with greater self-reported and behavioral displays of positive emotion compared to the happy memory. Furthermore, the BD group displayed greater cardiac vagal tone - a putative marker of positive emotion - across both the film and memory.

Conclusion

Normative stimuli were more potent elicitors of positive emotion compared to idiographic stimuli. The study provided further evidence for cardiac vagal tone as a potential biomarker of extreme positive emotion in BD.     

Brain oscillatory 4–35 Hz EEG responses during an n-back task with complex visual stimuli

Brain oscillatory responses of 4–35 Hz EEG frequencies elicited during performance of a visual n-back task with complex visual stimuli were assessed in 20 adult volunteers. Spectral power changes were assessed separately for target and non-target stimuli in four different memory load conditions (0, 1, 2, and 3-back). The presentation of both target and non-target stimuli elicited long-lasting ∼4–8 Hz power increases, which were more prominent at the beginning of stimulus onset during presentation of target stimuli, as compared to non-target stimuli, in the 0-back memory load condition. ∼8–25 Hz power decreases appeared at stimulus onset. These power decreases were more prominent during the presentation of target stimuli, as compared to non-target stimuli, and their duration increased as a function of memory load between the 0-, 1-, and 2-back, but not the 3-back, memory load conditions. The current results provide further evidence in support of the notion of a complex interplay between both ∼4–8 Hz power increases and ∼8–25 Hz power decreases during cognitive memory task performance.     

Media and memory: The efficacy of video and print materials for promoting patient education about asthma

Objective

We examined the effects of presentation medium on immediate and delayed recall of information and assessed the effect of giving patients take-home materials after initial presentations.

Methods

Primary-care patients received video-based, print-based or no asthma education about asthma symptoms and triggers and then answered knowledge-based questions. Print participants and half the video participants received take-home print materials. A week later, available participants completed the knowledge assessment again.

Results

Participants receiving either intervention outperformed controls on immediate and delayed assessments (p < 0.001). For symptom-related information, immediate performance did not significantly differ between print and video participants. A week later, receiving take-home print predicted better performance (p < 0.05), as did self-reported review among recipients of take-home print (p < 0.01). For content about inhaler usage, although video watchers outperformed print participants immediately after seeing the materials (p < 0.001), a week later these two groups’ performance did not significantly differ. Among participants given take-home materials, review predicted marginally better recall (p = 0.06).

Conclusion

Video and print interventions can promote recall of health-related information. Additionally, reviewable materials, if they are utilized, may improve retention.

Practice implications

When creating educational tools, providers should consider how long information must be retained, its content, and the feasibility of providing tangible supporting materials.     

Interaction between BDNF Val66Met and childhood stressful life events is associated to affective memory bias in men but not women

Recent meta-analyses point towards a pathogenic role of the Val66Met variant of the brain-derived neurotrophic factor (BDNF) in major depressive disorder, specifically in males. We investigated whether BDNF Val66Met shows a male-specific interaction with childhood stressful life events on affective memory bias, a cognitive susceptibility factor for depression. Healthy volunteers (n = 430; 272 females and 158 males) were genotyped for BDNF Val66Met (rs6265) and completed the self-referent encoding task and a childhood stressful life events scale. BDNF Met carriers reporting childhood events tended to recall a lower proportion of positive words compared to Val/Val homozygotes reporting childhood events. Sex-specific analyses revealed that the BDNF genotype × childhood events interaction was significant in male participants and not in female participants. The results suggest that in males, BDNF Val66Met interacts with childhood life events, increasing the cognitive susceptibility markers of depression. In females, this effect may be independent of BDNF Val66Met.     

Different types of avoidance behavior in rats produce dissociable post-training changes in sleep

Avoidance learning affects post-training sleep, and post-training sleep deprivation impairs performance. However, not all rats learn to make avoidance responses, and some rats fail to escape; a definitive behavior of learned helplessness, a model of depression. This study investigated the changes in sleep associated with different behaviors adopted following avoidance training. Rats (n = 53) were trained for 100 trials over 2 days (50 trials/day), followed by 23-24 h of post-training polysomnography, then re-tested (25 trials). At re-test, rats were categorized into: 1) Active Avoiders (AA; n = 22), 2), Non-learning (NL; n = 21), or 3) Escape Failures (EF; n = 10). AA rats increased avoidances over days, whereas the NL and EF groups did not. EF rats increased escape failures over days, whereas the NL and AA rats did not. EF rats had increased rapid eye movement (REM) sleep in the first 4 h on training day 1. They also had increased non-REM sleep in the first 4 h and last 4 h on both training days. AA rats had increased REM sleep 13-20 h post-training. The type of behavioral strategy adopted throughout training is associated with a unique pattern of changes in post-training sleep. Training-dependent changes in post-acquisition sleep may reflect distinct processes involved in the consolidation of these different memory traces.     

Effects of bromazepam in frontal theta activity on the performance of a sensorimotor integration task: A quantitative electroencephalography study

Our objective is to verify the modulatory effects of bromazepam on EEG theta absolute power when subjects were submitted to a visuomotor task (i.e., car driver task). Sample was composed of 14 students (9 males and 5 females), right handed, with ages varying between 23 and 42 years (mean = 32.5 ± 9.5), absence of mental or physical impairments, no psychoactive or psychotropic substance use and no neuromuscular disorders (screened by a clinical examination). The results showed an interaction between condition and electrodes (p = 0.034) in favor of F8 electrode compared with F7 in both experimental conditions (t-test; p = 0.001). Additionally, main effects were observed for condition (p = 0.001), period (p = 0.001) and electrodes (p = 0.031) in favor of F4 electrode compared with F3. In conclusion, Br 6 mg of bromazepam may interfere in sensorimotor processes in the task performance in an unpredictable scenario allowing that certain visuospatial factors were predominant. Therefore, the results may reflect that bromazepam effects influence the performance of the involved areas because of the acquisition and integration of sensory stimuli processes until the development of a motor behavior based on the same stimuli.     

Urine formaldehyde level is inversely correlated to mini mental state examination scores in senile dementia

It is widely known that exogenous formaldehyde exposure induces human cognitive impairment and animal memory loss; and recent studies show that formaldehyde at pathological levels induces Aβ deposition and misfolding of tau protein to form globular amyloid-like aggregates. Endogenous formaldehyde may be a marker for progressive senile dementia.The aim of this study was to investigate the correlation of endogenous formaldehyde in urine of senile dementia and mini mental state examination (MMSE) scores.Formaldehyde level was analyzed by high-performance liquid chromatography (with fluorescence detection) in human urine from dementia patients (n = 141), patients with hypertension (n = 33) or diabetes (n = 16) and healthy individuals (n = 38), autopsy hippocampus samples from Alzheimer's disease (AD) patients and brains of three types of AD animal model: namely, senescence accelerated mice (SAMP8), APP-transgenic mice and APP/PS1-transgenic mice.In a double-blind study, there was marked elevation of urine formaldehyde levels in patients (n = 91) with dementia, and a slight increase in patients (n = 50) with mild cognitive impairment. Urine formaldehyde level was inversely correlated with mini mental state examination scores (Rs = −0.441, p < 0.0001). Furthermore, formaldehyde levels were significantly increased in the autopsy hippocampus from Alzheimer's patients (n = 4). In SAMP8 brains the formaldehyde level was significantly increased, suggesting that the endogenous formaldehyde is related to aging in mice. The brain formaldehyde level in APP/PS1-transgenic (n = 8) mice at age of 3 months and APP-transgenic (n = 8) mice at age of 6 months was increased (0.56 ± 0.02 mM), respectively, as compared with their respective age-matched controls, when these two types of AD-like animals, respectively, started to form Aβ deposits and memory loss obviously. According to the level of formaldehyde in the brain of the transgenic mice, we treated normal mice with formaldehyde (0.5 mM, intraperitoneal administration) and observed the memory loss of the animal in Morris water maze trial.Cognitive impairments for the senile dementia are probably related to endogenous formaldehyde levels; and the mini mental state examination scores referred to the evaluation of urine formaldehyde level in dementia patients may be used as a non-invasive method for the investigation and diagnosis of senile dementia.     

Respiratory pattern in awake rats: Effects of motor activity and of alerting stimuli

Our aim was to assess the impact of motor activity and of arousing stimuli on respiratory rate in the awake rats. The study was performed in male adult Sprague-Dawley (SD, n = 5) and Hooded Wistar (HW, n = 5) rats instrumented for ECG telemetry. Respiratory rate was recorded using whole-body plethysmograph, with a piezoelectric sensor attached for the simultaneous assessment of motor activity. All motor activity was found to be associated with an immediate increase in respiratory rate that remained elevated for the whole duration of movement; this was reflected by: i) bimodal distribution of respiratory intervals (modes for slow peak: 336 ± 19 and 532 ± 80 ms for HW and SD, p < 0.05; modes for fast peak 128 ± 6 and 132 ± 7 ms for HW and SD, NS); and ii) a tight correlation between total movement time and total time of tachypnoea, with an R² ranging 0.96-0.99 (n = 10, p < 0001). The extent of motor-related tachypnoea was significantly correlated with the intensity of associated movement. Mild alerting stimuli produced stereotyped tachypnoeic responses, without affecting heart rate: tapping the chamber raised respiratory rate from 117 ± 7 to 430 ± 15 cpm; sudden side move — from 134 ± 13 to 487 ± 16 cpm, and turning on lights — from 136 ± 12 to 507 ± 14 cpm (n = 10; p < 0.01 for all; no inter-strain differences). We conclude that: i) sniffing is an integral part of the generalized arousal response and does not depend on the modality of sensory stimuli; ii) tachypnoea is a sensitive index of arousal; and iii) respiratory rate is tightly correlated with motor activity.     

Investigation of Van Gogh-like 2 mRNA regulation and localisation in response to nociception in the brain of adult common carp (Cyprinus carpio)

The Van Gogh-like 2 (vangl2) gene is typically associated with planar cell polarity pathways, which is essential for correct orientation of epithelial cells during development. The encoded protein of this gene is a transmembrane protein and is highly conserved through evolution. Van Gogh-like 2 was selected for further study on the basis of consistent regulation after a nociceptive stimulus in adult common carp and rainbow trout in a microarray study. An in situ hybridisation was conducted in the brain of mature common carp (Cyprinus carpio), 1.5 and 3 h after a nociceptive stimulus comprising of an acetic acid injection to the lips of the fish and compared with a saline-injected control. The vangl2 gene was expressed in all brain regions, and particularly intensely in neurons of the telencephalon and in ependymal cells. In the cerebellum, a greater number (P = 0.018) of Purkinje cells expressed vangl2 after nociception (n = 7) compared with controls (n = 5). This regulation opens the possibility that vangl2 is involved in nociceptive processing in the adult fish brain and may be a novel target for central nociception in vertebrates.     

The rs2030324 SNP of brain-derived neurotrophic factor (BDNF) is associated with visual cognitive processing in multiple sclerosis

Purpose: To investigate the associations between the rs2030324 SNP of brain-derived neurotrophic factor (BDNF) and neuropsychological (NP) test measures in multiple sclerosis (MS) patients. Background: BDNF regulates the survival of neuronal and non-neuronal cells and plays a critical role in neurochemical processes underlying learning and memory. Methods: A total of 209 MS patients (161 females; 48 males) underwent brain MRI and genotyping for BDNF rs2030324. The NP testing (n = 108) assessed processing speed, working memory, new learning and executive control. The MRI measurements included T1 and T2 lesion volume, whole brain, white and gray matter volumes, magnetization transfer imaging and regional subcortical brain volumes. Results: The T/T rs2030324 genotype group performed poorly on the Brief Visuospatial Memory Test-Revised (p = 0.031) and the Symbol Digit Modalities Test (p = 0.045) compared to the C/C genotype group. Because these NP tests both involve visual processing, the relationship with the volume of the thalamus was assessed. The BDNF rs2030324 genotype was associated with the volume of the left thalamus (p = 0.036). There were no significant associations with whole brain lesional and atrophy MRI measures. Conclusions: The C allele of BDNF rs2030324 is associated with protection against visual cognitive processing deficits via mechanisms that appear associated with the volume of the thalamus.     

Delayed sodium pyruvate treatment improves working memory following experimental traumatic brain injury

Prior work indicates that cerebral glycolysis is impaired following traumatic brain injury (TBI) and that pyruvate treatment acutely after TBI can improve cerebral metabolism and is neuroprotective. Since extracellular levels of glucose decrease during periods of increased cognitive demand and exogenous glucose improves cognitive performance, we hypothesized that pyruvate treatment prior to testing could ameliorate cognitive deficits in rats with TBI. Based on pre-surgical spatial alternation performance in a 4-arm plus-maze, adult male rats were randomized to receive either sham injury or unilateral (left) cortical contusion injury (CCI). On days 4, 9 and 14 after surgery animals received an intraperitoneal injection of either vehicle (Sham-Veh, n = 6; CCI-Veh, n = 7) or 1000 mg/kg of sodium pyruvate (CCI-SP, n = 7). One hour after each injection rats were retested for spatial alternation performance. Animals in the CCI-SP group showed no significant working memory deficits in the spatial alternation task compared to Sham-Veh controls. The percent four/five alternation scores for CCI-Veh rats were significantly decreased from Sham-Veh scores on days 4 and 9 (p < 0.01) and from CCI-SP scores on days 4, 9 and 14 (p < 0.05). Measures of cortical contusion volume, regional cerebral metabolic rates of glucose and regional cytochrome oxidase activity at day 15 post-injury did not differ between CCI-SP and CCI-Veh groups. These results show that spatial alternation testing can reliably detect temporal deficits and recovery of working memory after TBI and that delayed pyruvate treatment can ameliorate TBI-induced cognitive impairments.     

The effects of aging on lifetime of auditory sensory memory in humans

The amplitude change of cortical responses to repeated stimulation with respect to different interstimulus intervals (ISIs) is considered as an index of sensory memory. To determine the effect of aging on lifetime of auditory sensory memory, N100m responses were recorded in young, middle-aged, and elderly healthy volunteers (n = 15 for each group). Trains of 5 successive tones were presented with an inter-train interval of 10 s. In separate sessions, the within-train ISIs were 0.5, 1, 2, 4, and 8 s. The amplitude ratio between N100m responses to the first and fifth stimuli (S5/S1 N100m ratio) within each ISI condition was obtained to reflect the recovery cycle profile. The recovery function time constant (τ) was smaller in the elderly (1.06 ± 0.26 s, p < 0.001) and middle-aged (1.70 ± 0.25 s, p = 0.009) groups compared with the young group (2.77 ± 0.25 s). In conclusion, the present study suggests an aging-related decrease in lifetime of auditory sensory memory.     

Dissociating the effects of semantic grouping and rehearsal strategies on event-related brain potentials

The application of elaborative encoding strategies during learning, such as grouping items on similar semantic categories, increases the likelihood of later recall. Previous studies have suggested that stimuli that encourage semantic grouping strategies had modulating effects on specific ERP components. However, these studies did not differentiate between ERP activation patterns evoked by elaborative working memory strategies like semantic grouping and more simple strategies like rote rehearsal. Identification of neurocognitive correlates underlying successful use of elaborative strategies is important to understand better why certain populations, like children or elderly people, have problems applying such strategies. To compare ERP activation during the application of elaborative versus more simple strategies subjects had to encode either four semantically related or unrelated pictures by respectively applying a semantic category grouping or a simple rehearsal strategy. Another goal was to investigate if maintenance of semantically grouped vs. ungrouped pictures modulated ERP-slow waves differently. At the behavioral level there was only a semantic grouping benefit in terms of faster responding on correct rejections (i.e. when the memory probe stimulus was not part of the memory set). At the neural level, during encoding semantic grouping only had a modest specific modulatory effect on a fronto-central Late Positive Component (LPC), emerging around 650 ms. Other ERP components (i.e. P200, N400 and a second Late Positive Component) that had been earlier related to semantic grouping encoding processes now showed stronger modulation by rehearsal than by semantic grouping. During maintenance semantic grouping had specific modulatory effects on left and right frontal slow wave activity. These results stress the importance of careful control of strategy use when investigating the neural correlates of elaborative encoding.