Comparing aging and fitness effects on brain anatomy

Recent studies suggest that cardiorespiratory fitness (CRF) mitigates the brain’s atrophy typically associated with aging, via a variety of beneficial mechanisms. One could argue that if CRF is generally counteracting the negative effects of aging, the same regions that display the greatest age-related volumetric loss should also show the largest beneficial effects of fitness. To test this hypothesis we examined structural MRI data from 54 healthy older adults (ages 55–87), to determine the overlap, across brain regions, of the profiles of age and fitness effects. Results showed that lower fitness and older age are associated with atrophy in several brain regions, replicating past studies. However, when the profiles of age and fitness effects were compared using a number of statistical approaches, the effects were not entirely overlapping. Interestingly, some of the regions that were most influenced by age were among those not influenced by fitness. Presumably, the age-related atrophy occurring in these regions is due to factors that are more impervious to the beneficial effects of fitness. Possible mechanisms supporting regional heterogeneity may include differential involvement in motor function, the presence of adult neurogenesis, and differential sensitivity to cerebrovascular, neurotrophic and metabolic factors

Dynamics of Alpha Control: Preparatory Suppression of Posterior Alpha Oscillations by Frontal Modulators Revealed with Combined EEG and Event-related Optical Signal

We investigated the dynamics of brain processes facilitating conscious experience of external stimuli. Previously, we proposed that alpha (8–12 Hz) oscillations, which fluctuate with both sustained and directed attention, represent a pulsed inhibition of ongoing sensory brain activity. Here we tested the prediction that inhibitory alpha oscillations in visual cortex are modulated by top–down signals from frontoparietal attention networks. We measured modulations in phase-coherent alpha oscillations from superficial frontal, parietal, and occipital cortices using the event-related optical signal (EROS), a measure of neuronal activity affording high spatiotemporal resolution, along with concurrently recorded EEG, while participants performed a visual target detection task. The pretarget alpha oscillations measured with EEG and EROS from posterior areas were larger for subsequently undetected targets, supporting alpha\u27s inhibitory role. Using EROS, we localized brain correlates of these awareness-related alpha oscillations measured at the scalp to the cuneus and precuneus. Crucially, EROS alpha suppression correlated with posterior EEG alpha power across participants. Sorting the EROS data based on EEG alpha power quartiles to investigate alpha modulators revealed that suppression of posterior alpha was preceded by increased activity in regions of the dorsal attention network and decreased activity in regions of the cingulo-opercular network. Cross-correlations revealed the temporal dynamics of activity within these preparatory networks before posterior alpha modulation. The novel combination of EEG and EROS afforded localization of the sources and correlates of alpha oscillations and their temporal relationships, supporting our proposal that top–down control from attention networks modulates both posterior alpha and awareness of visual stimuli

Estrogenic botanical supplements, health-related quality of life, fatigue, and hormone-related symptoms in breast cancer survivors: a HEAL study report

<p>Abstract</p> <p>Background</p> <p>It remains unclear whether estrogenic botanical supplement (EBS) use influences breast cancer survivors' health-related outcomes.</p> <p>Methods</p> <p>We examined the associations of EBS use with health-related quality of life (HRQOL), with fatigue, and with 15 hormone-related symptoms such as hot flashes and night sweats among 767 breast cancer survivors participating in the Health, Eating, Activity, and Lifestyle (HEAL) Study. HRQOL was measured by the Medical Outcomes Study short form-36 physical and mental component scale summary score. Fatigue was measured by the Revised-Piper Fatigue Scale score.</p> <p>Results</p> <p>Neither overall EBS use nor the number of EBS types used was associated with HRQOL, fatigue, or hormone-related symptoms. However, comparisons of those using each specific type of EBS with non-EBS users revealed the following associations. Soy supplements users were more likely to have a better physical health summary score (odds ratio [OR] = 1.66, 95% confidence interval [CI] = 1.02-2.70). Flaxseed oil users were more likely to have a better mental health summary score (OR = 1.76, 95% CI = 1.05-2.94). Ginseng users were more likely to report severe fatigue and several hormone-related symptoms (all ORs ≥ 1.7 and all 95% CIs exclude 1). Red clover users were less likely to report weight gain, night sweats, and difficulty concentrating (all OR approximately 0.4 and all 95% CIs exclude 1). Alfalfa users were less likely to experience sleep interruption (OR = 0.28, 95% CI = 0.12-0.68). Dehydroepiandrosterone users were less likely to have hot flashes (OR = 0.33, 95% CI = 0.14-0.82).</p> <p>Conclusions</p> <p>Our findings indicate that several specific types of EBS might have important influences on a woman's various aspects of quality of life, but further verification is necessary.</p

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer

We performed a multistage genome-wide association study (GWAS) including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT; per-allele odds ratio [OR] = 0.79; 95% confidence interval [CI] = 0.74–0.84; P = 3.0×10−12), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2; OR = 1.46; 95% CI = 1.30–1.65; P = 1.1×10−10), rs9581943 at 13q12.2 (PDX1; OR = 1.15; 95% CI = 1.10–1.20; P = 2.4×10−9), and rs16986825 at 22q12.1 (ZNRF3; OR = 1.18; 95% CI = 1.12–1.25; P = 1.2×10−8). An independent signal was identified in exon 2 of TERT at the established region 5p15.33 (rs2736098; OR = 0.80; 95% CI = 0.76–0.85; P = 9.8×10−14). We also identified a locus at 8q24.21 (rs1561927; P = 1.3×10−7) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study has identified multiple new susceptibility alleles for pancreatic cancer worthy of follow-up studies

Stimulus-induced changes in 1/f-like background activity in EEG

Research into the nature of 1/f-like, nonoscillatory electrophysiological activity has grown exponentially in recent years in cognitive neuroscience. The shape of this activity has been linked to the balance between excitatory and inhibitory neural circuits, which is thought to be important for information processing. However, to date, it is not known whether the presentation of a stimulus induces changes in the parameters of 1/f activity in scalp recordings, separable from event-related potentials (ERPs). Here, we analyzed event-related broadband changes in human EEG both before and after removing ERPs to demonstrate their confounding effect, and to establish whether there are genuine stimulus-induced changes in 1/f. Using data from a passive and an active auditory task (n = 23, 61% female), we found that the shape of the post-event spectra between 2 and 25 Hz differed significantly from the pre-event spectra even after removing the frequency-content of ERPs. Further, a significant portion of this difference could be accounted for by a rotational shift in 1/f activity, manifesting as an increase in low and a decrease in high frequencies. Importantly, the magnitude of this rotational shift was related to the attentional demands of the task. This change in 1/f is consistent with increased inhibition following stimulus onset, and likely reflects a disruption of ongoing excitatory activity proportional to processing demands. Finally, these findings contradict the central assumption of baseline normalization strategies in time-frequency analyses, namely, that background EEG activity is stationary across time. As such, they have far-reaching consequences relevant for several subfields of neuroscience

Stimulus-induced changes in 1/f-like background activity in EEG

Research into the nature of 1/f-like, non-oscillatory electrophysiological activity has grown exponentially in recent years in cognitive neuroscience. The shape of this activity has been linked to the balance between excitatory and inhibitory neural circuits, which is thought to be important for information processing. However, to date, it is not known whether the presentation of a stimulus induces changes in the parameters of 1/f activity, which are separable from the emergence of event-related potentials (ERPs). Here, we analyze event-related broadband changes in scalp-recorded EEG both before and after removing ERPs to demonstrate their confounding effect, and to establish whether there are genuine stimulus-induced changes in 1/f. Using data from a passive and an active auditory task (n=23), we found that the shape of the post-event spectra differed significantly from the pre-event spectra even after removing the frequency-content of ERPs. Further, a significant portion of this difference could be accounted for by a rotational shift in 1/f activity, manifesting as an increase in low and a decrease in high frequencies. Importantly, the magnitude of this rotational shift was related to the attentional demands of the task. This change in 1/f is consistent with increased inhibition following the onset of a stimulus, and likely reflects a disruption of ongoing excitatory activity proportional to processing demands. Finally, these findings contradict the central assumption of baseline normalization strategies in time-frequency analyses, namely that background EEG activity is stationary across time. As such, they have far-reaching consequences that cut across several subfields of neuroscience

The impact of 1/f activity and baseline correction on the results and interpretation of time-frequency analyses of EEG/MEG data: A cautionary tale

Typically, time-frequency analysis (TFA) of electrophysiological data is aimed at isolating narrowband signals (oscillatory activity) from broadband non-oscillatory (1/f) activity, so that changes in oscillatory activity resulting from experimental manipulations can be assessed. A widely used method to do this is to convert the data to the decibel (dB) scale through baseline division and log transformation. This procedure assumes that, for each frequency, sources of power (i.e., oscillations and 1/f activity) scale by the same factor relative to the baseline (multiplicative model). This assumption may be incorrect when signal and noise are independent contributors to the power spectrum (additive model). Using resting-state EEG data from 80 participants, we found that the level of 1/f activity and alpha power are not positively correlated within participants, in line with the additive but not the multiplicative model. Then, to assess the effects of dB conversion on data that violate the multiplicativity assumption, we simulated a mixed design study with one between-subject (noise level, i.e., level of 1/f activity) and one within-subject (signal amplitude, i.e., amplitude of oscillatory activity added onto the background 1/f activity) factor. The effect size of the noise level × signal amplitude interaction was examined as a function of noise difference between groups, following dB conversion. Findings revealed that dB conversion led to the over- or under-estimation of the true interaction effect when groups differing in 1/f levels were compared, and it also led to the emergence of illusory interactions when none were present. This is because signal amplitude was systematically underestimated in the noisier compared to the less noisy group. Hence, we recommend testing whether the level of 1/f activity differs across groups or conditions and using multiple baseline correction strategies to validate results if it does. Such a situation may be particularly common in aging, developmental, or clinical studies