Theta EEG neurofeedback promotes early consolidation of real life-like episodic memory.

Theta oscillations are believed to coordinate neuronal activity related to human cognition, especially for memory functions. Theta power during learning and retrieval has been found to correlate with memory performance success. Additionally, up-regulating theta oscillations during a post-encoding epoch crucial for memory consolidation was previously shown to benefit long-term memory for acquired motor sequences, pictures, and object-location associations. However, it remains to be determined whether such effects would be found for more ecological aspects of long-term episodic memory. Therefore, the current study assessed neurofeedback-based theta upregulation effects on movie memory. After viewing a 15-minute silent, narrative movie, participants engaged in neurofeedback-based theta/beta up-regulation, neurofeedback beta/theta up-regulation as an active control condition, or an unrelated passive control task. Memory was tested three times: once immediately after watching the movie (as baseline); 24 hours thereafter; and once again 1 week later. Memory performance 1 week after encoding was significantly enhanced in the theta/beta up-regulation group compared with the other groups. Additionally, changes in neurofeedback theta/beta ratio from baseline EEG recordings correlated with long-term memory gains in retrieving the movie's content. These findings highlight the relationship between post-learning theta oscillations and the consolidation of episodic memory for a naturalistic event.

Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis.

BACKGROUND: Dietary intake of antioxidants such as vitamins C and E protect against oxidative stress, and may also be associated with altered DNA methylation patterns. METHODS: We meta-analysed epigenome-wide association study (EWAS) results from 11,866 participants across eight population-based cohorts to evaluate the association between self-reported dietary and supplemental intake of vitamins C and E with DNA methylation. EWAS were adjusted for age, sex, BMI, caloric intake, blood cell type proportion, smoking status, alcohol consumption, and technical covariates. Significant results of the meta-analysis were subsequently evaluated in gene set enrichment analysis (GSEA) and expression quantitative trait methylation (eQTM) analysis. RESULTS: In meta-analysis, methylation at 4,656 CpG sites was significantly associated with vitamin C intake at FDR ≤ 0.05. The most significant CpG sites associated with vitamin C (at FDR ≤ 0.01) were enriched for pathways associated with systems development and cell signalling in GSEA, and were associated with downstream expression of genes enriched in the immune response in eQTM analysis. Furthermore, methylation at 160 CpG sites was significantly associated with vitamin E intake at FDR ≤ 0.05, but GSEA and eQTM analysis of the top most significant CpG sites associated with vitamin E did not identify significant enrichment of any biological pathways investigated. CONCLUSIONS: We identified significant associations of many CpG sites with vitamin C and E intake, and our results suggest that vitamin C intake may be associated with systems development and the immune response.

The neural representations underlying asymmetric cross-modal prediction of words.

Cross-modal prediction serves a crucial adaptive role in the multisensory world, yet the neural mechanisms underlying this prediction are poorly understood. The present study addressed this important question by combining a novel audiovisual sequence memory task, functional magnetic resonance imaging (fMRI), and multivariate neural representational analyses. Our behavioral results revealed a reliable asymmetric cross-modal predictive effect, with a stronger prediction from visual to auditory (VA) modality than auditory to visual (AV) modality. Mirroring the behavioral pattern, we found the superior parietal lobe (SPL) showed higher pattern similarity for VA than AV pairs, and the strength of the predictive coding in the SPL was positively correlated with the behavioral predictive effect in the VA condition. Representational connectivity analyses further revealed that the SPL mediated the neural pathway from the visual to the auditory cortex in the VA condition but was not involved in the auditory to visual cortex pathway in the AV condition. Direct neural pathways within the unimodal regions were found for the visual-to-visual and auditory-to-auditory predictions. Together, these results provide novel insights into the neural mechanisms underlying cross-modal sequence prediction.

Matrix Gla Protein Levels Are Associated With Arterial Stiffness and Incident Heart Failure With Preserved Ejection Fraction.

OBJECTIVE: Arterial stiffness is a risk factor for cardiovascular disease, including heart failure with preserved ejection fraction (HFpEF). MGP (matrix Gla protein) is implicated in vascular calcification in animal models, and circulating levels of the uncarboxylated, inactive form of MGP (ucMGP) are associated with cardiovascular disease-related and all-cause mortality in human studies. However, the role of MGP in arterial stiffness is uncertain. Approach and Results: We examined the association of ucMGP levels with vascular calcification, arterial stiffness including carotid-femoral pulse wave velocity (PWV), and incident heart failure in community-dwelling adults from the Framingham Heart Study. To further investigate the link between MGP and arterial stiffness, we compared aortic PWV in age- and sex-matched young (4-month-old) and aged (10-month-old) wild-type and Mgp+/- mice. Among 7066 adults, we observed significant associations between higher levels of ucMGP and measures of arterial stiffness, including higher PWV and pulse pressure. Longitudinal analyses demonstrated an association between higher ucMGP levels and future increases in systolic blood pressure and incident HFpEF. Aortic PWV was increased in older, but not young, female Mgp+/- mice compared with wild-type mice, and this augmentation in PWV was associated with increased aortic elastin fiber fragmentation and collagen accumulation. CONCLUSIONS: This translational study demonstrates an association between ucMGP levels and arterial stiffness and future HFpEF in a large observational study, findings that are substantiated by experimental studies showing that mice with Mgp heterozygosity develop arterial stiffness. Taken together, these complementary study designs suggest a potential role of therapeutically targeting MGP in HFpEF.

Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption.

Coffee and tea are extensively consumed beverages worldwide which have received considerable attention regarding health. Intake of these beverages is consistently linked to, among others, reduced risk of diabetes and liver diseases; however, the mechanisms of action remain elusive. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset. Here we report the results from epigenome-wide association studies (EWAS) on coffee and tea consumption in 15,789 participants of European and African-American ancestries from 15 cohorts. EWAS meta-analysis of coffee consumption reveals 11 CpGs surpassing the epigenome-wide significance threshold (P-value <1.1×10-7), which annotated to the AHRR, F2RL3, FLJ43663, HDAC4, GFI1 and PHGDH genes. Among them, cg14476101 is significantly associated with expression of the PHGDH and risk of fatty liver disease. Knockdown of PHGDH expression in liver cells shows a correlation with expression levels of genes associated with circulating lipids, suggesting a role of PHGDH in hepatic-lipid metabolism. EWAS meta-analysis on tea consumption reveals no significant association, only two CpGs annotated to CACNA1A and PRDM16 genes show suggestive association (P-value <5.0×10-6). These findings indicate that coffee-associated changes in DNA methylation levels may explain the mechanism of action of coffee consumption in conferring risk of diseases.

The Effects of Theta EEG Neurofeedback on the Consolidation of Spatial Memory.

How can the stability of a recently acquired memory be improved? Recent findings regarding the importance of theta frequency EEG activity in the hippocampus suggest that entraining neural activity in that frequency band might increase post-encoding waking replay, reinforcing learning-related plasticity. Our previous studies revealed that upregulating postlearning theta power using EEG neurofeedback (NFB) significantly benefitted procedural and episodic memory performance (both immediate and delayed), and may provide optimal conditions for stabilization of new memories. We have now explored whether memory benefits of theta NFB generalize to delayed spatial memory, an additional hippocampus-dependent process. Participants learned to associate object images with locations on a computer screen. NFB was used to enable participants to selectively increase scalp EEG theta power for 30 minutes. Visuo-spatial memory was tested one week later, with the theta NFB participants compared with 2 control groups (beta-augmentation NFB as an active control group, and an additional passive control group that did not engage in NFB). Theta upregulation was found to improve visuo-spatial memory, as reflected in reduced error distances in location marking and faster reaction time for correct answers by the theta group. This supports the contention that theta upregulation immediately after learning strengthens early consolidation of visuo-spatial memory. This intervention could potentially benefit various memory-challenged populations, as well as healthy individuals.

Cluster Randomized Trial of a Pre/Interconception Health Intervention for Mothers in Pediatric Visits.

OBJECTIVE: Recognizing that pediatric primary care focuses on family health and is an important location of contact for women of childbearing age, this project assessed the effectiveness of a pre/interconception women's health intervention delivered during pediatric primary care using a cluster randomized trial. METHODS: Pediatric clinicians were randomized to a screening and brief educational intervention group or usual care comparison group. Intervention group clinicians received training on pre/interconception care, including recommended counseling and referral resources for needs identified. Women presenting to primary care with their child ≤12 months were enrolled and assigned to the group corresponding to the assignment of their child's clinician. Mothers seen by clinicians in the intervention group completed a pre/interconception health screening tool and discussed results with their child's clinician during the visit. These mothers were compared to mothers seen by comparison group clinicians who did not receive the screening tool or clinician discussion. All enrolled mothers (Intervention and Comparison) received written preconception health information and a 90-day supply of multivitamins. Primary outcomes at 6 and 12 months post enrollment included contraception use, pregnancy, and access to and use of preventive health care. Secondary outcomes included daily folic acid supplementation, smoking, and substance use. RESULTS: A total of 415 women were enrolled and those who had at least 1 follow-up assessment were included in the analysis (n = 383). There was no significant effect of the intervention on contraceptive use, pregnancy incidence, or use of preventive care. Assignment to the intervention increased the odds of daily folic acid use (odds ratio 1.82, 95% confidence interval 1.25, 2.63) during follow-up. Intervention mothers were less likely to smoke at 6, but not 12 months. CONCLUSIONS: Pediatric visits are an opportune location for addressing maternal health and this intervention demonstrated feasibility and improved outcomes for some but not all outcomes. Attention to maternal health needs in pediatric visits during infancy may be important for maintaining positive pre/interconception health behaviors.

Has Self-reported Marijuana Use Changed in Patients Undergoing Total Joint Arthroplasty After the Legalization of Marijuana?

BACKGROUND: Marijuana use has become more accessible since its recent legalization in several states. However, its use in a total joint arthroplasty population to our knowledge has not been reported, and the implications of its use in this setting remain unclear. QUESTIONS/PURPOSES: We report (1) the self-reported use of marijuana in patients undergoing total joint arthroplasty both before and after its legalization; and (2) clinical and demographic factors associated with marijuana use in patients undergoing total joint arthroplasty. METHODS: One thousand records of patients undergoing primary total joint arthroplasty (500 consecutive before and 500 consecutive after the legalization of the commercial sale of marijuana in Colorado) were included for analysis. Preoperative medical history and physicals were retrospectively reviewed for self-reported and reasons (medicinal versus recreational) for use. Additionally, patient records were used to determine insurance type, age, gender, smoking status, history of substance abuse, preoperative narcotic use, alcohol intake, and the type of arthroplasty performed. RESULTS: Self-reported use after legalization dramatically increased from 1% (four of 500) to 11% (55 of 500) (odds ratio [OR], 15.3 [95% confidence interval, 5.5-42.6]; p < 0.001) after legalization. For those reporting use after legalization, 46% (25 of 55) of patients reported recreational use, 26% (14 of 55) medicinal use, 27% (15 of 55) did not report a reason for use, and 2% (one of 55) reported both recreational and medicinal use. Factors associated with use included younger age (with a 10-year mean difference between the groups [p < 0.001]), male gender (36 of 59 users [61%] versus 411 of 941 nonusers [44%]; OR, 2.02; p < 0.01), current smokers (22 of 59 users [37%] versus 54 of 941 [6%] nonusers; OR, 0.09; p < 0.01), a history of substance abuse (eight of 59 users [14%] versus 18 of 941 nonusers [2%]; OR, 8.04; p < 0.001), insurance type (Medicaid only, 28 of 59 [48%] users versus 56 of 941 [6%] nonusers; OR, 20.45; p < 0.01), and preoperative narcotic use (eight of 59 users [14%] versus 17 of 941 nonusers [2%]; OR, 2.4; p < 0.001). We did not find differences with regard to alcohol use, amount of alcohol consumption, or insurance types other than Medicaid. CONCLUSIONS: These results suggest the legalization of marijuana has led to either more users or more patients who are willing to report its use given the lack of legal ramifications. Despite these findings, the evidence to date precludes the use of marijuana postoperatively in patients undergoing total joint arthroplasty. Further investigation, ideally in a prospective randomized manner, should focus on opioid consumption, nausea, sleep patterns, and outcomes in patients using marijuana who are undergoing total joint arthroplasty before recommendations can be made for its use. LEVEL OF EVIDENCE: Level III, therapeutic study.

Enhancing early consolidation of human episodic memory by theta EEG neurofeedback.

Consolidation of newly formed memories is readily disrupted, but can it be enhanced? Given the prominent role of hippocampal theta oscillations in memory formation and retrieval, we hypothesized that upregulating theta power during early stages of consolidation might benefit memory stability and persistence. We used EEG neurofeedback to enable participants to selectively increase theta power in their EEG spectra following episodic memory encoding, while other participants engaged in low beta-focused neurofeedback or passively viewed a neutral nature movie. Free recall assessments immediately following the interventions, 24h later and 7d later all indicated benefit to memory of theta neurofeedback, relative to low beta neurofeedback or passive movie-viewing control conditions. The degree of benefit to memory was correlated with the extent of theta power modulation, but not with other spectral changes. Theta enhancement may provide optimal conditions for stabilization of new hippocampus-dependent memories.

Theta EEG neurofeedback benefits early consolidation of motor sequence learning.

Procedural learning is subject to consolidation processes believed to depend on the modulation of functional connections involved in representing the acquired skill. While sleep provides the most commonly studied framework for such consolidation processes, posttraining modulation of oscillatory brain activity may also impact on plasticity processes. Under the hypothesis that consolidation of motor learning is associated with theta band activity, we used EEG neurofeedback (NFB) to enable participants to selectively increase either theta or beta power in their EEG spectra following the acquisition phase of motor sequence learning. We tested performance on a motor task before and after training, right after the NFB session to assess immediate NFB effects, 1 day after NFB to assess interaction between NFB effects and overnight sleep-dependent stabilization, and 1 week after the initial session, to assess the effects of NFB on long-term stabilization of motor training. We also explored the extent of the influence of single-electrode NFB on EEG recorded across the scalp. Results revealed a significantly greater improvement in performance immediately after NFB in the theta group than in the beta group. This effect continued for testing up to 1 week following training. Across participants, post-NFB improvement correlated positively with theta/beta ratio change achieved during NFB. Additionally, NFB was found to cause widespread band-power modulation beyond the electrode used for feedback. Thus, upregulating postlearning theta power may yield contributions to the immediate performance and subsequent consolidation of an acquired motor skill.

Parietal lesion effects on cued recall following pair associate learning.

We investigated the involvement of the posterior parietal cortex in episodic memory in a lesion-effects study of cued recall following pair-associate learning. Groups of patients who had experienced first-incident stroke, generally in middle cerebral artery territory, and exhibited damage that included lateral posterior parietal regions, were tested within an early post-stroke time window. In three experiments, patients and matched healthy comparison groups executed repeated study and cued recall test blocks of pairs of words (Experiment 1), pairs of object pictures (Experiment 2), or pairs of object pictures and environmental sounds (Experiment 3). Patients' brain CT scans were subjected to quantitative analysis of lesion volumes. Behavioral and lesion data were used to compute correlations between area lesion extent and memory deficits, and to conduct voxel-based lesion-symptom mapping. These analyses implicated lateral ventral parietal cortex, especially the angular gyrus, in cued recall deficits, most pronouncedly in the cross-modal picture-sound pairs task, though significant parietal lesion effects were also found in the unimodal word pairs and picture pairs tasks. In contrast to an earlier study in which comparable parietal lesions did not cause deficits in item recognition, these results indicate that lateral posterior parietal areas make a substantive contribution to demanding forms of recollective retrieval as represented by cued recall, especially for complex associative representations.

High plasma folate is negatively associated with leukocyte telomere length in Framingham Offspring cohort.

PURPOSE: Shortening of telomeres, the protective structures at the ends of eukaryotic chromosomes, is associated with age-related pathologies. Telomere length is influenced by DNA integrity and DNA and histone methylation. Folate plays a role in providing precursors for nucleotides and methyl groups for methylation reactions and has the potential to influence telomere length. METHOD: We determined the association between leukocyte telomere length and long-term plasma folate status (mean of 4 years) in Framingham Offspring Study (n = 1,044, females = 52.1 %, mean age 59 years) using data from samples collected before and after folic acid fortification. Leukocyte telomere length was determined by Southern analysis and fasting plasma folate concentration using microbiological assay. RESULTS: There was no significant positive association between long-term plasma folate and leukocyte telomere length among the Framingham Offspring Study participants perhaps due to their adequate folate status. While the leukocyte telomere length in the second quintile of plasma folate was longer than that in the first quintile, the difference was not statistically significant. The leukocyte telomere length of the individuals in the fifth quintile of plasma folate was shorter than that of those in the second quintile by 180 bp (P < 0.01). There was a linear decrease in leukocyte telomere length with higher plasma folate concentrations in the upper four quintiles of plasma folate (P for trend = 0.001). Multivitamin use was associated with shorter telomeres in this cohort (P = 0.015). CONCLUSIONS: High plasma folate status possibly resulting from high folic acid intake may interfere with the role of folate in maintaining telomere integrity.

Does this ring a bell? Music-cued retrieval of semantic knowledge and metamemory judgments.

Failed knowledge recall attempts are sometimes accompanied by a strong feeling of imminent success, giving rise to a "tip-of-the-tongue" (TOT) experience. Similar to successful retrieval (i.e., the Know state, K), a TOT commences with strong cue familiarity but involves only partial retrieval of related information. We sought to characterize the cognitive processes and temporal dynamics of these retrieval states and to extend the applicability of previous findings about TOT to the auditory modality. Participants heard 3-sec initial segments of popular songs and were asked to recall their names. EEG was recorded while participants indicated their retrieval state via button press. Stimulus-locked analyses revealed a significant early left fronto-central difference between TOT and K, at 300-550 msec postcue onset. Post hoc analysis revealed that, in this time window, TOT also differed from DK (Don't Know) responses, which themselves were similar to the K responses. This finding indicates that neural processes, which may reflect strategy selection, ease of semantic processing, familiarity-related processes, or conflict monitoring, are indicative of the fate of our knowledge judgments long before we actually execute them.

Dietary factors and incident atrial fibrillation: the Framingham Heart Study.

BACKGROUND: There have been conflicting reported associations between dietary factors and incident atrial fibrillation (AF). OBJECTIVE: We evaluated associations between consumption of alcohol, caffeine, fiber, and polyunsaturated fatty acids (PUFAs) and incident AF in the Framingham Heart Study. DESIGN: Participants without AF (n = 4526; 9640 examinations; mean age: 62 y; 56% women) from the original and offspring cohorts completed food-frequency questionnaires and were followed prospectively for 4 y. We examined the associations between dietary exposures and AF with Cox proportional hazards regression. RESULTS: A total of 296 individuals developed AF (177 men, 119 women). In multivariable analyses, there were no significant associations between examined dietary exposures and AF risk. Hazard ratios (HRs) for increasing quartiles of dietary factors were as follows: for alcohol, 0.73 (95% CI: 0.5, 1.05), 0.85 (95% CI: 0.61, 1.18), and 1.12 (95% CI: 0.83, 1.51) (P for trend = 0.48); for caffeine, 0.84 (95% CI: 0.62, 1.15), 0.87 (95% CI: 0.64, 1.2), and 0.98 (95% CI: 0.7, 1.39) (P for trend = 0.84); for total fiber, 0.86 (95% CI: 0.61, 1.2), 0.64 (95% CI: 0.44, 0.92), and 0.81 (95% CI: 0.54, 1.2) (P for trend = 0.16); and for n-3 (omega-3) PUFAs, 1.11 (95% CI: 0.81, 1.54), 0.92 (95% CI: 0.65, 1.29), and 1.18 (95% CI: 0.85, 1.64) (P for trend = 0.57; quartile 1 was the reference group). In exploratory analyses, consumption of >4 servings of dark fish/wk (5 cases and 21 individuals at risk) was significantly associated with AF risk compared with the consumption of <1 serving of dark fish/wk (HR: 6.53; 95% CI: 2.65, 16.06; P < 0.0001). CONCLUSIONS: Consumption of alcohol, caffeine, fiber, and fish-derived PUFAs was not significantly associated with AF risk. The observed adverse association between the consumption of dark fish and AF merits further investigation. Our findings suggest that the dietary exposures examined convey limited attributable risk of AF in the general population.

Common genetic variants associate with serum phosphorus concentration.

Phosphorus is an essential mineral that maintains cellular energy and mineralizes the skeleton. Because complex actions of ion transporters and regulatory hormones regulate serum phosphorus concentrations, genetic variation may determine interindividual variation in phosphorus metabolism. Here, we report a comprehensive genome-wide association study of serum phosphorus concentration. We evaluated 16,264 participants of European ancestry from the Cardiovascular Heath Study, Atherosclerosis Risk in Communities Study, Framingham Offspring Study, and the Rotterdam Study. We excluded participants with an estimated GFR <45 ml/min per 1.73 m(2) to focus on phosphorus metabolism under normal conditions. We imputed genotypes to approximately 2.5 million single-nucleotide polymorphisms in the HapMap and combined study-specific findings using meta-analysis. We tested top polymorphisms from discovery cohorts in a 5444-person replication sample. Polymorphisms in seven loci with minor allele frequencies 0.08 to 0.49 associate with serum phosphorus concentration (P = 3.5 x 10(-16) to 3.6 x 10(-7)). Three loci were near genes encoding the kidney-specific type IIa sodium phosphate co-transporter (SLC34A1), the calcium-sensing receptor (CASR), and fibroblast growth factor 23 (FGF23), proteins that contribute to phosphorus metabolism. We also identified genes encoding phosphatases, kinases, and phosphodiesterases that have yet-undetermined roles in phosphorus homeostasis. In the replication sample, five of seven top polymorphisms associate with serum phosphorous concentrations (P < 0.05 for each). In conclusion, common genetic variants associate with serum phosphorus in the general population. Further study of the loci identified in this study may help elucidate mechanisms of phosphorus regulation.

Watching the components of photosynthetic bacterial membranes and their in situ organisation by atomic force microscopy.

The atomic force microscope has developed into a powerful tool in structural biology allowing information to be acquired at submolecular resolution on the protruding structures of membrane proteins. It is now a complementary technique to X-ray crystallography and electron microscopy for structure determination of individual membrane proteins after extraction, purification and reconstitution into lipid bilayers. Moving on from the structures of individual components of biological membranes, atomic force microscopy has recently been demonstrated to be a unique tool to identify in situ the individual components of multi-protein assemblies and to study the supramolecular architecture of these components allowing the efficient performance of a complex biological function. Here, recent atomic force microscopy studies of native membranes of different photosynthetic bacteria with different polypeptide contents are reviewed. Technology, advantages, feasibilities, restrictions and limits of atomic force microscopy for the acquisition of highly resolved images of up to 10 A lateral resolution under native conditions are discussed. From a biological point of view, the new insights contributed by the images are analysed and discussed in the context of the strongly debated organisation of the interconnected network of membrane-associated chlorophyll-protein complexes composing the photosynthetic apparatus in different species of purple bacteria.

Magnetoencephalographic study of the cortical activity elicited by human voice.

In an attempt to identify voice-specific neural activities in auditory cortex in humans, we recorded cortical magnetic responses. Volunteers were instructed to listen to vocal and instrumental sounds matched in fundamental-frequency, duration, temporal envelope and average root mean square power. The stimuli were sounds produced by four singers and four musical instruments at each of two fundamental frequencies: 220 Hz (musical note A3) and 261.9 Hz (C3). Two components of the evoked responses were analyzed, one at approximately 100 ms (N1m) and the other 400 ms after the stimulus onset (sustained field, SF). The source locations of equivalent current dipoles for both components were estimated around the Heschl's gyrus in both hemispheres. Compared with the instrumental sound, the source strength of the SF component for the voice was significantly larger.

Neural sensitivity to human voices: ERP evidence of task and attentional influences.

In an earlier study, we found that human voices evoked a positive event-related potential (ERP) peaking at approximately 320 ms after stimulus onset, distinctive from those elicited by instrumental tones. Here we show that though similar in latency to the Novelty P3, this Voice-Sensitive Response (VSR) differs in antecedent conditions and scalp distribution. Furthermore, when participants were not attending to stimuli, the response to voices was undistinguished from other harmonic stimuli (strings, winds, and brass). During a task requiring attending to a feature other than timbre, voices were not distinguished from voicelike stimuli (strings), but were distinguished from other harmonic stimuli. We suggest that the component elicited by voices and similar sounds reflects the allocation of attention on the basis of stimulus significance (as opposed to novelty), and propose an explanation of the task and attentional factors that contribute to the effect.