Editorial: Insights in Neurocognitive Aging and Behavior: 2021

In recent years, exceptional scientific achievements have led to major advancements in the fast-growing field of neurocognitive aging and behavior. In this inaugural collection, Insights in Neurocognitive Aging and Behavior: 2021, we sought to highlight the latest advancements and challenges for the current state of knowledge and future directions in aging neuroscience in the neurocognitive arena. Here we outline the contributions and implications for future research of the 15 papers in this topic collection across four important research areas: (1) novel approaches to identifying and tracking brain aging and impending cognitive decline; (2) neurocognitive markers of risks for Alzheimer’s disease (AD) and its progression; (3) lifestyle contributions to cognitive aging and AD; and (4) the status and future of neurocognitive and brain aging theory

The Relation Between White Matter Microstructure and Network Complexity: Implications for Processing Efficiency

Brain structure has been proposed to facilitate as well as constrain functional interactions within brain networks. Simulation models suggest that integrity of white matter (WM) microstructure should be positively related to the complexity of BOLD signal – a measure of network interactions. Using 121 young adults from the Human Connectome Project, we empirically tested whether greater WM integrity would be associated with greater complexity of the BOLD signal during rest via multiscale entropy. Multiscale entropy measures the lack of predictability within a given time series across varying time scales, thus being able to estimate fluctuating signal dynamics within brain networks. Using multivariate analysis techniques (Partial Least Squares), we found that greater WM integrity was associated with greater network complexity at fast time scales, but less network complexity at slower time scales. These findings implicate two separate pathways through which WM integrity affects brain function in the prefrontal cortex – an executive-prefrontal pathway and a perceptuo-occipital pathway. In two additional samples, the main patterns of WM and network complexity were replicated. These findings support simulation models of WM integrity and network complexity and provide new insights into brain structure-function relationships

Structural Complexity is Negatively Associated with Brain Activity: A Novel Multimodal Test of Compensation Theories of Aging

Fractal dimensionality (FD) measures the complexity within the folds and ridges of cortical and subcortical structures. We tested the degree that FD might provide a new perspective on the atrophy-compensation hypothesis: age or disease-related atrophy causes a compensatory neural response in the form of increased brain activity in prefrontal cortex (PFC) to maintain cognition. Brain structural and functional data were collected from 63 middle-aged and older adults and 18 young-adult controls. Two distinct patterns of FD were found that separated cortical from subcortical structures. Subcortical FD was more strongly negatively correlated with age than cortical FD and cortical FD was negatively associated with brain activity during memory retrieval in medial and lateral parietal cortices uniquely in middle-aged and older adults. Multivariate analyses revealed that the lower FD/higher brain activity pattern was associated with poorer cognition—patterns not present in young adults, consistent with compensation. Bayesian analyses provide further evidence against the modal interpretation of the atrophy-compensation hypothesis in the PFC—a key principle found in some neurocognitive theories of aging

Human exposure to per- and polyfluoroalkyl substances (PFAS) via the consumption of fish leads to exceedance of safety thresholds

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Effect of a self-determination theory-based communication skills training program on physiotherapists' psychological support for their patients with chronic low back pain: a randomized controlled trial

Objective: To examine the effects of communication skills training on physiotherapists' supportive behavior during clinical practice. Design: Randomized trial. Setting: Hospital outpatient physiotherapy clinics. Participants: Physiotherapists (N=24) and patients (N=24) with chronic low back pain. Interventions: Two hospital clinics were randomly assigned to the intervention arm. Physiotherapists (n=12) received 8 hours of communication skills training focused on supporting patients' psychological needs. Physiotherapists (n=12) from 2 other hospital clinics formed a waitlist control arm. Main Outcome Measures: Verbal communication between each physiotherapist and a patient was recorded on an audiotape, and independent, blinded raters used the Health Care Climate Questionnaire to assess physiotherapists' needs-supportive behavior (primary outcome). Results: Independent raters' Health Care Climate Questionnaire scores favored the intervention arm (Cohen's d=2.27; P<.01). Conclusions: Compared with controls, independent ratings demonstrated that physiotherapists who completed the Communication style and exercise compliance in physiotherapy training were found to provide greater support for patients' needs in a single assessed session. Long-term maintenance of this needs-supportive behavior should be examined

Mindcontrol: a web application for brain segmentation quality control

Tissue classification plays a crucial role in the investigation of normal neural development, brain-behavior relationships, and the disease mechanisms of many psychiatric and neurological illnesses. Ensuring the accuracy of tissue classification is important for quality research and, in particular, the translation of imaging biomarkers to clinical practice. Assessment with the human eye is vital to correct various errors inherent to all currently available segmentation algorithms. Manual quality assurance becomes methodologically difficult at a large scale - a problem of increasing importance as the number of data sets is on the rise. To make this process more efficient, we have developed Mindcontrol, an open-source web application for the collaborative quality control of neuroimaging processing outputs. The Mindcontrol platform consists of a dashboard to organize data, descriptive visualizations to explore the data, an imaging viewer, and an in-browser annotation and editing toolbox for data curation and quality control. Mindcontrol is flexible and can be configured for the outputs of any software package in any data organization structure. Example configurations for three large, open-source datasets are presented: the 1000 Functional Connectomes Project (FCP), the Consortium for Reliability and Reproducibility (CoRR), and the Autism Brain Imaging Data Exchange (ABIDE) Collection. These demo applications link descriptive quality control metrics, regional brain volumes, and thickness scalars to a 3D imaging viewer and editing module, resulting in an easy-to-implement quality control protocol that can be scaled for any size and complexity of study

Young Adults with a Parent with Dementia Show Early Abnormalities in Brain Activity and Brain Volume in the Hippocampus: A Matched Case-Control Study

Having a parent with Alzheimer’s disease (AD) and related dementias confers a risk for developing these types of neurocognitive disorders in old age, but the mechanisms underlying this risk are understudied. Although the hippocampus is often one of the earliest brain regions to undergo change in the AD process, we do not know how early in the lifespan such changes might occur or whether they differ early in the lifespan as a function of family history of AD. Using a rare sample, young adults with a parent with late-onset dementia, we investigated whether brain abnormalities could already be detected compared with a matched sample. Moreover, we employed simple yet novel techniques to characterize resting brain activity (mean and standard deviation) and brain volume in the hippocampus. Young adults with a parent with dementia showed greater resting mean activity and smaller volumes in the left hippocampus compared to young adults without a parent with dementia. Having a parent with AD or a related dementia was associated with early aberrations in brain function and structure. This early hippocampal dysfunction may be due to aberrant neural firing, which may increase the risk for a diagnosis of dementia in old age

Ribosomal oxygenases are structurally conserved from prokaryotes to humans

2-Oxoglutarate (2OG)-dependent oxygenases have important roles in the regulation of gene expression via demethylation of N-methylated chromatin components1,2 and in the hydroxylation of transcription factors3 and splicing factor proteins4. Recently, 2OG-dependent oxygenases that catalyse hydroxylation of transfer RNA5,6,7 and ribosomal proteins8 have been shown to be important in translation relating to cellular growth, TH17-cell differentiation and translational accuracy9,10,11,12. The finding that ribosomal oxygenases (ROXs) occur in organisms ranging from prokaryotes to humans8 raises questions as to their structural and evolutionary relationships. In Escherichia coli, YcfD catalyses arginine hydroxylation in the ribosomal protein L16; in humans, MYC-induced nuclear antigen (MINA53; also known as MINA) and nucleolar protein 66 (NO66) catalyse histidine hydroxylation in the ribosomal proteins RPL27A and RPL8, respectively. The functional assignments of ROXs open therapeutic possibilities via either ROX inhibition or targeting of differentially modified ribosomes. Despite differences in the residue and protein selectivities of prokaryotic and eukaryotic ROXs, comparison of the crystal structures of E. coli YcfD and Rhodothermus marinus YcfD with those of human MINA53 and NO66 reveals highly conserved folds and novel dimerization modes defining a new structural subfamily of 2OG-dependent oxygenases. ROX structures with and without their substrates support their functional assignments as hydroxylases but not demethylases, and reveal how the subfamily has evolved to catalyse the hydroxylation of different residue side chains of ribosomal proteins. Comparison of ROX crystal structures with those of other JmjC-domain-containing hydroxylases, including the hypoxia-inducible factor asparaginyl hydroxylase FIH and histone Nε-methyl lysine demethylases, identifies branch points in 2OG-dependent oxygenase evolution and distinguishes between JmjC-containing hydroxylases and demethylases catalysing modifications of translational and transcriptional machinery. The structures reveal that new protein hydroxylation activities can evolve by changing the coordination position from which the iron-bound substrate-oxidizing species reacts. This coordination flexibility has probably contributed to the evolution of the wide range of reactions catalysed by oxygenases

Clinician-facilitated physical activity intervention versus pulmonary rehabilitation for improving physical activity in COPD: a feasibility study

Pulmonary rehabilitation (PR) may not suit all individuals with chronic obstructive pulmonary disease (COPD) and may not result in increased physical activity. Higher levels of physical activity are associated with reduced mortality and morbidity. The aim of this study was to assess the feasibility of conducting a trial to investigate the effectiveness of a clinician-facilitated physical activity intervention (PAI) versus PR in improving physical activity in patients with COPD referred to PR. In this randomised controlled mixed methods feasibility study, all patients referred to PR who were eligible and willing were assessed at baseline and then randomised to the PAI or to PR. The assessments were repeated post-intervention and at 3-month follow-up. The main outcome was step count measured by Actigraph. Semi-structured interviews were conducted post-intervention. The N = 50 patients; mean (SD) age, 64.1(8.6) years, 24M were recruited and randomised; N = 23 (PAI) and n = 26 (PR): one patient was excluded from the analysis as that person did not meet the GOLD diagnostic criteria. Key feasibility criteria were met; recruitment was 11%, dropouts in PAI were 26% (n = 6) and 50% (n = 13/26) PR. Participants in both groups experienced a range of health benefits from their respective programmes. The PAI appears to be effective in increasing step counts in people with COPD: mean change (standard deviation) [confidence interval] for the PAI group was 972.0(3230.3)[–1080.3 to 3024.4], n = 12 and 4.3(662.7)[-440.9 to 449.5], n = 11 for the PR group. The PAI met all domains of fidelity. This study provides key information to inform a future-randomised controlled trial in physical activity