Cross-Sectional Associations Between Theta-Beta Ratios and Individual Peak Alpha Frequency Across Adulthood

The ratio of fronto-central theta (4–7 Hz) to beta oscillations (13–30 Hz), known as the theta-beta ratio, is negatively correlated with attentional control, reinforcement learning, executive function, and age. Although theta-beta ratios have been found to decrease with age in adolescents and young adults, theta has been found to increase with age in older adults. Moreover, age-related decrease in individual alpha peak frequency and flattening of the 1/f aperiodic component may artifactually inflate the association between theta-beta ratio and age. These factors lead to an incomplete understanding of how theta-beta ratio varies across the lifespan and the extent to which variation is due to a conflation of aperiodic and periodic activity. We conducted a partially preregistered analysis examining the cross-sectional associations between age and resting canonical fronto-central theta-beta ratio, individual alpha peak frequency, and aperiodic component (n = 268; age 36–84, M = 55.8, SD = 11.0). Age was negatively associated with theta-beta ratios, individual peak alpha frequencies, and the aperiodic exponent. The correlation between theta-beta ratios and age remained after controlling for individual peak alpha frequencies, but was nonsignificant when controlling for the aperiodic exponent. Aperiodic exponent fully mediated the relationship between theta-beta ratio and age, although beta remained significantly associated with age after controlling for theta, individual peak alpha, and aperiodic exponent. Results replicate previous observations and show age-related decreases in theta-beta ratios are not due to age-related decrease in individual peak alpha frequencies but primarily explained by flattening of the aperiodic component with age

Pharmacokinetics and pharmacodynamics of VEGF-neutralizing antibodies

<p>Abstract</p> <p>Background</p> <p>Vascular endothelial growth factor (VEGF) is a potent regulator of angiogenesis, and its role in cancer biology has been widely studied. Many cancer therapies target angiogenesis, with a focus being on VEGF-mediated signaling such as antibodies to VEGF. However, it is difficult to predict the effects of VEGF-neutralizing agents. We have developed a whole-body model of VEGF kinetics and transport under pathological conditions (in the presence of breast tumor). The model includes two major VEGF isoforms VEGF₁₂₁and VEGF₁₆₅, receptors VEGFR1, VEGFR2 and co-receptors Neuropilin-1 and Neuropilin-2. We have added receptors on parenchymal cells (muscle fibers and tumor cells), and incorporated experimental data for the cell surface density of receptors on the endothelial cells, myocytes, and tumor cells. The model is applied to investigate the action of VEGF-neutralizing agents (called "anti-VEGF") in the treatment of cancer.</p> <p>Results</p> <p>Through a sensitivity study, we examine how model parameters influence the level of free VEGF in the tumor, a measure of the response to VEGF-neutralizing drugs. We investigate the effects of systemic properties such as microvascular permeability and lymphatic flow, and of drug characteristics such as the clearance rate and binding affinity. We predict that increasing microvascular permeability in the tumor above 10^-5cm/s elicits the undesired effect of increasing tumor interstitial VEGF concentration beyond even the baseline level. We also examine the impact of the tumor microenvironment, including receptor expression and internalization, as well as VEGF secretion. We find that following anti-VEGF treatment, the concentration of free VEGF in the tumor can vary between 7 and 233 pM, with a dependence on both the density of VEGF receptors and co-receptors and the rate of neuropilin internalization on tumor cells. Finally, we predict that free VEGF in the tumor is reduced following anti-VEGF treatment when VEGF₁₂₁comprises at least 25% of the VEGF secreted by tumor cells.</p> <p>Conclusions</p> <p>This study explores the optimal drug characteristics required for an anti-VEGF agent to have a therapeutic effect and the tumor-specific properties that influence the response to therapy. Our model provides a framework for investigating the use of VEGF-neutralizing drugs for personalized medicine treatment strategies.</p

Periodic and aperiodic contributions to theta‐beta ratios across adulthood

The ratio of fronto-central theta (4–7 Hz) to beta oscillations (13–30 Hz), known as the theta-beta ratio, is negatively correlated with attentional control, reinforcement learning, executive function, and age. Although theta-beta ratios have been found to decrease with age in adolescents and young adults, theta has been found to increase with age in older adults. Moreover, age-related decrease in individual alpha peak frequency and flattening of the 1/f aperiodic component may artifactually inflate the association between theta-beta ratio and age. These factors lead to an incomplete understanding of how theta-beta ratio varies across the lifespan and the extent to which variation is due to a conflation of aperiodic and periodic activity. We conducted a partially preregistered analysis examining the cross-sectional associations between age and resting canonical fronto-central theta-beta ratio, individual alpha peak frequency, and aperiodic component (n = 268; age 36–84, M = 55.8, SD = 11.0). Age was negatively associated with theta-beta ratios, individual peak alpha frequencies, and the aperiodic exponent. The correlation between theta-beta ratios and age remained after controlling for individual peak alpha frequencies, but was nonsignificant when controlling for the aperiodic exponent. Aperiodic exponent fully mediated the relationship between theta-beta ratio and age, although beta remained significantly associated with age after controlling for theta, individual peak alpha, and aperiodic exponent. Results replicate previous observations and show age-related decreases in theta-beta ratios are not due to age-related decrease in individual peak alpha frequencies but primarily explained by flattening of the aperiodic component with age

Resting EEG periodic and aperiodic components predict cognitive decline over 10 years

Measures of intrinsic brain function at rest show promise as predictors of cognitive decline in humans, including EEG metrics such as individual alpha peak frequency (IAPF) and the aperiodic exponent, reflecting the strongest frequency of alpha oscillations and the relative balance of excitatory:inhibitory neural activity, respectively. Both IAPF and the aperiodic exponent decrease with age and have been associated with worse executive function and working memory. However, few studies have jointly examined their associations with cognitive function, and none have examined their association with longitudinal cognitive decline rather than cross-sectional impairment. In a preregistered secondary analysis of data from the longitudinal Midlife in the United States (MIDUS) study, we tested whether IAPF and aperiodic exponent measured at rest predict cognitive function (N = 235; age at EEG recording M = 55.10, SD = 10.71) over 10 years. The IAPF and the aperiodic exponent interacted to predict decline in overall cognitive ability, even after controlling for age, sex, education, and lag between data collection timepoints. Post-hoc tests showed that “mismatched” IAPF and aperiodic exponents (e.g., higher exponent with lower IAPF) predicted greater cognitive decline compared to “matching” IAPF and aperiodic exponents (e.g., higher exponent with higher IAPF; lower IAPF with lower aperiodic exponent). These effects were largely driven by measures of executive function. Our findings provide the first evidence that IAPF and the aperiodic exponent are joint predictors of cognitive decline from midlife into old age and thus may offer a useful clinical tool for predicting cognitive risk in aging

Purpose in life as a resilience factor for brain health: diffusion MRI findings from the Midlife in the U.S. study

IntroductionA greater sense of purpose in life is associated with several health benefits relevant for active aging, but the mechanisms remain unclear. We evaluated if purpose in life was associated with indices of brain health.MethodsWe examined data from the Midlife in the United States (MIDUS) Neuroscience Project. Diffusion weighted magnetic resonance imaging data (n=138; mean age 65.2 years, age range 48-95; 80 females; 37 black, indigenous, and people of color) were used to estimate microstructural indices of brain health such as axonal density, and axonal orientation. The seven-item purpose in life scale was used. Permutation analysis of linear models was used to examine associations between purpose in life scores and the diffusion metrics in white matter and in the bilateral hippocampus, adjusting for age, sex, education, and race.Results and discussionGreater sense of purpose in life was associated with brain microstructural features consistent with better brain health. Positive associations were found in both white matter and the right hippocampus, where multiple convergent associations were detected. The hippocampus is a brain structure involved in learning and memory that is vulnerable to stress but retains the capacity to grow and adapt through old age. Our findings suggest pathways through which an enhanced sense of purpose in life may contribute to better brain health and promote healthy aging. Since purpose in life is known to decline with age, interventions and policy changes that facilitate a greater sense of purpose may extend and improve the brain health of individuals and thus improve public health

Dangling Conversations:Reflections on the Process of Creating Digital Stories During a Workshop with People with Early Stage Dementia

Care and compassion are key features of the NHS Constitution. Recent reports have identified a lack of compassion in the care and treatment of older people. Nurses draw on aesthetic knowledge, developed through engagement with the experience of others, when providing compassionate care. Patient Voices reflective digital stories are used in healthcare education to facilitate student engagement with the patient experience. Digital stories were made with seven people with early-stage dementia as part of a learning package for student nurses. In this paper the authors reflect on their experience and observations from facilitating the 4-day digital story-making workshop. Social theories of dementia provide a theoretical framework for understanding these reflections. Despite considerable challenges in developing a story, and anxiety about using the technology, reading and speaking, all participants engaged in creating their own digital stories. Positive changes in the participants' interactions were observed. These improvements appeared to be the product of the person-centred facilitation and the creative process which supported self-expression and a sense of identity. Nurses working in this way could facilitate ability of the person with dementia to participate in their care, and improve their sense of well-being by supporting self-expression.Digital stories provide a creative way for people to tell their stories using an amalgamation of voice, image and music, and can be used to engage nurses with others' experiences in the classroom setting.\ud Seven people with early-stage dementia and one carer participated in making their own stories during a digital storytelling workshop.\ud These participants experienced particular and varied challenges relating to telling a story and engaging with the technical process of digital storytelling. They were supported in overcoming these challenges through person-centred relationships with facilitators, allowing them to negotiate the help required.\ud During the workshop a number of positive changes were observed in the participants: increased confidence, improved speech, a sense of purpose and increased connection

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead