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Abstract Background In older adults, the extent to which performing a cognitive task when standing diminishes postural control is predictive of future falls and cognitive decline. The neurophysiology of such “dual-tasking” and its effect on postural control (i.e., dual-task cost) in older adults are poorly understood. The purpose of this study was to use electroencephalography (EEG) to examine the effects of dual-tasking when standing on brain activity in older adults. We hypothesized that compared to single-task “quiet” standing, dual-task standing would decrease alpha power, which has been linked to decreased motor inhibition, as well as increase the ratio of theta to beta power, which has been linked to increased attentional control. Methods Thirty older adults without overt disease completed four separate visits. Postural sway together with EEG (32-channels) were recorded during trials of standing with and without a concurrent verbalized serial subtraction dual-task. Postural control was measured by average sway area, velocity, and path length. EEG metrics included absolute alpha-, theta-, and beta-band powers as well as theta/beta power ratio, within six demarcated regions-of-interest: the left and right anterior, central, and posterior regions of the brain. Results Most EEG metrics demonstrated moderate-to-high between-day test–retest reliability (intra-class correlation coefficients > 0.70). Compared with quiet standing, dual-tasking decreased alpha-band power particularly in the central regions bilaterally (p = 0.002) and increased theta/beta power ratio in the anterior regions bilaterally (p

PurposePrevious studies have linked gait variability to resting-state functional connectivity between the dorsal attention network (DAN) and the default network (DN) in the brain. The purpose of this study was to examine the effects of a novel transcranial direct current stimulation (tDCS) paradigm designed to simultaneously facilitate the excitability of the DAN and suppress the excitability of the DN (i.e., DAN+/DN-tDCS) on gait variability and other gait characteristics in young healthy adults.MethodsIn this double-blinded randomized and sham-controlled study, 48 healthy adults aged 22 ± 2 years received one 20-min session of DAN+/DN-tDCS (n = 24) or no stimulation (the Sham group, n = 24). Immediately before and after stimulation, participants completed a gait assessment under three conditions: walking at self-selected speed (i.e., normal walking), walking as fast as possible (i.e., fast walking), and walking while counting backward (i.e., dual-task walking). Primary outcomes included gait stride time variability and gait stride length variability in normal walking conditions. Secondary outcomes include gait stride time and length variability in fast and dual-task conditions, and other gait metrics derived from the three walking conditions.ResultsCompared to the Sham group, DAN+/DN-tDCS reduced stride length variability in normal and fast walking conditions, double-limb support time variability in fast and dual-task walking conditions, and step width variability in fast walking conditions. In contrast, DAN+/DN-tDCS did not alter average gait speed or the average value of any other gait metrics as compared to the sham group.ConclusionIn healthy young adults, a single exposure to tDCS designed to simultaneously modulate DAN and DN excitability reduced gait variability, yet did not alter gait speed or other average gait metrics, when tested just after stimulation. These results suggest that gait variability may be uniquely regulated by these spatially-distinct yet functionally-connected cortical networks. These results warrant additional research on the short- and longer-term effects of this type of network-based tDCS on the cortical control of walking in younger and older populations.

IntroductionTranscranial direct current stimulation (tDCS) targeting the left dorsolateral prefrontal cortex (dlPFC) improves dual task walking in older adults, when tested just after stimulation. The acute effects of tDCS on the cortical physiology of walking, however, remains unknown.MethodsIn a previous study, older adults with slow gait and executive dysfunction completed a dual task walking assessment before and after 20 min of tDCS targeting the left dlPFC or sham stimulation. In a subset of seven participants per group, functional near-infrared spectroscopy (fNIRS) was used to quantify left and right prefrontal recruitment defined as the oxygenated hemoglobin response to usual and dual task walking (ΔHbO2), as well as the absolute change in this metric from usual to dual task conditions (i.e., ΔHbO2cost). Paired t-tests examined pre- to post-stimulation differences in each fNIRS metric within each group.ResultsThe tDCS group exhibited pre- to post-stimulation reduction in left prefrontal ΔHbO2cost (p = 0.03). This mitigation of dual task “cost” to prefrontal recruitment was induced primarily by a reduction in left prefrontal ΔHbO2 specifically within the dual task condition (p = 0.001), an effect that was observed in all seven participants within this group. Sham stimulation did not influence ΔHbO2cost or ΔHbO2 in either walking condition (p > 0.35), and neither tDCS nor sham substantially influenced right prefrontal recruitment (p > 0.16).DiscussionThis preliminary fNIRS data suggests that tDCS over the left dlPFC may modulate prefrontal recruitment, as reflected by a relative reduction in the oxygen consumption of this brain region in response to dual task walking.

Freezing of gait (FOG) is a debilitating motor phenomenon that is common among individuals with advanced Parkinson’s disease. Objective and sensitive measures are needed to better quantify FOG. The present work addresses this need by leveraging wearable devices and machine-learning methods to develop and evaluate automated detection of FOG and quantification of its severity. Seventy-one subjects with FOG completed a FOG-provoking test while wearing three wearable sensors (lower back and each ankle). Subjects were videotaped before (OFF state) and after (ON state) they took their antiparkinsonian medications. Annotations of the videos provided the “ground-truth” for FOG detection. A leave-one-patient-out validation process with a training set of 57 subjects resulted in 84.1% sensitivity, 83.4% specificity, and 85.0% accuracy for FOG detection. Similar results were seen in an independent test set (data from 14 other subjects). Two derived outcomes, percent time frozen and number of FOG episodes, were associated with self-report of FOG. Both derived-metrics were higher in the OFF state than in the ON state and in the most challenging level of the FOG-provoking test, compared to the least challenging level. These results suggest that this automated machine-learning approach can objectively assess FOG and that its outcomes are responsive to therapeutic interventions.

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p < 8 X 10-10) pQTLs in 38 (43%) of blood proteins tested. Most pQTL SNPs were novel with low overlap to eQTL SNPs. The pQTL SNPs explained >10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10-392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group.

The study examined the association of childhood and current economic hardship with anthropometric indices in Hispanic/Latino adults, using data from the HCHS/SOL Socio-cultural ancillary study (N = 5,084), a community-based study of Hispanic/Latinos living in four urban areas (Bronx, NY, Chicago, IL, Miami, FL, and San Diego, CA). Childhood economic hardship was defined as having experienced a period of time when one's family had trouble paying for basic needs (e.g., food, housing), and when this economic hardship occurred: between 0-12, 13-18 years old, or throughout both of those times. Current economic hardship was defined as experiencing trouble paying for basic needs during the past 12 months. Anthropometry included height, body mass index (BMI), waist circumference (WC), and percentage body fat (%BF). Complex survey linear regression models were used to test the associations of childhood economic hardship with adult anthropometric indices, adjusting for potential confounders (e.g., age, sex, Hispanic background). Childhood economic hardship varied by Hispanic background, place of birth, and adult socio-economic status. Childhood economic hardship during both periods, childhood and adolescence, was associated with shorter height. Childhood economic hardship was associated with greater adiposity among US born individuals only. Current economic hardship was significantly associated with all three measures of adiposity (BMI, WC, %BF). These findings suggest that previous periods of childhood economic hardship appear to influence adult height more than adiposity, whereas current economic hardship may be a better determinant of adult adiposity in Hispanics.

White blood cell (WBC) count is a common clinical measure from complete blood count assays, and it varies widely among healthy individuals. Total WBC count and its constituent subtypes have been shown to be moderately heritable, with the heritability estimates varying across cell types. We studied 19,509 subjects from seven cohorts in a discovery analysis, and 11,823 subjects from ten cohorts for replication analyses, to determine genetic factors influencing variability within the normal hematological range for total WBC count and five WBC subtype measures. Cohort specific data was supplied by the CHARGE, HeamGen, and INGI consortia, as well as independent collaborative studies. We identified and replicated ten associations with total WBC count and five WBC subtypes at seven different genomic loci (total WBC count-6p21 in the HLA region, 17q21 near ORMDL3, and CSF3; neutrophil count-17q21; basophil count- 3p21 near RPN1 and C3orf27; lymphocyte count-6p21, 19p13 at EPS15L1; monocyte count-2q31 at ITGA4, 3q21, 8q24 an intergenic region, 9q31 near EDG2), including three previously reported associations and seven novel associations. To investigate functional relationships among variants contributing to variability in the six WBC traits, we utilized gene expression- and pathways-based analyses. We implemented gene-clustering algorithms to evaluate functional connectivity among implicated loci and showed functional relationships across cell types. Gene expression data from whole blood was utilized to show that significant biological consequences can be extracted from our genome-wide analyses, with effect estimates for significant loci from the meta-analyses being highly corellated with the proximal gene expression. In addition, collaborative efforts between the groups contributing to this study and related studies conducted by the COGENT and RIKEN groups allowed for the examination of effect homogeneity for genome-wide significant associations across populations of diverse ancestral backgrounds.