A supramodal representation of the body surface

The ability to accurately localize both tactile and painful sensations on the body is one of the most important functions of the somatosensory system. Most accounts of localization refer to the systematic spatial relation between skin receptors and cortical neurons. The topographic organization of somatosensory neurons in the brain provides a map of the sensory surface. However, systematic distortions in perceptual localization tasks suggest that localizing a somatosensory stimulus involves more than simply identifying specific active neural populations within a somatotopic map. Thus, perceptual localization may depend on both afferent inputs and other unknown factors. In four experiments, we investigated whether localization biases vary according to the specific skin regions and subset of afferent fibers stimulated. We represented localization errors as a ‘perceptual map’ of skin locations. We compared the perceptual maps of stimuli that activate Aβ (innocuous touch), Aδ (pinprick pain), and C fibers (non-painful heat) on both the hairy and glabrous skin of the left hand. Perceptual maps exhibited systematic distortions that strongly depended on the skin region stimulated. We found systematic distal and radial (i.e., towards the thumb) biases in localization of touch, pain, and heat on the hand dorsum. A less consistent proximal bias was found on the palm. These distortions were independent of the population of afferent fibers stimulated, and also independent of the response modality used to report localization. We argue that these biases are likely to have a central origin, and result from a supramodal representation of the body surface

Stimulating somatosensory psychophysics: a double-blind, sham-controlled study of the neurobiological mechanisms of tDCS

In this study, the influence of tDCS on vibrotactile adaptation is investigated. Double-blind tDCS (Anodal/Sham) of 1 mA was delivered for 600 s to electrodes positioned in a somatosensory/contralateral orbit montage. Stimulation was applied between blocks of the implemented amplitude discrimination tasks. Amplitude discrimination thresholds were significantly degraded during adaptation trials, compared to those achieved at baseline but tDCS failed to modify task performance. Using Bayesian statistics, this finding was revealed to constitute substantial evidence for the null hypothesis. The failure of DC stimulation to alter performance is discussed in the context of several factors that may have confounded the induction of changes in cortical plasticity

Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction

The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.Peer reviewe

Pupillary dilation responses as a midlife indicator of risk for Alzheimer's disease: association with Alzheimer's disease polygenic risk

Locus coeruleus (LC) tau accumulation begins early. Targeting LC (dys)function might improve early identification for Alzheimer's disease (AD) risk. Pupillary responses during cognitive tasks are driven by the LC and index cognitive effort. Despite equivalent task performance, adults with mild cognitive impairment have greater pupil dilation/effort during digit span than cognitively normal (CN) individuals. We hypothesized that AD polygenic risk scores (AD-PRSs) would be associated with pupillary responses in middle-aged CN adults. Pupillary responses during digit span tasks were heritable (h2 = 0.30-0.36) in 1119 men aged 56-66 years. In a CN subset-all with comparable span capacities (n = 539)-higher AD-PRSs were associated with greater pupil dilation/effort in a high (9-digit) cognitive load condition (Cohen's d = 0.36 for upper vs. lower quartile of AD-PRS distribution). Results held up after controlling for APOE genotype. Results support pupillary response-and by inference, LC dysfunction-as a genetically mediated biomarker of early mild cognitive impairment/AD risk. In combination with other biomarkers, task-evoked pupillary responses may provide additional information for early screening of genetically at-risk individuals even before cognitive declines

Association of glucose homeostasis measures with heart rate variability among Hispanic/Latino adults without diabetes: the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

Abstract Background Reduced heart rate variability (HRV), a measure of cardiac autonomic function, is associated with an increased risk of cardiovascular disease (CVD) and mortality. Glucose homeostasis measures are associated with reduced cardiac autonomic function among those with diabetes, but inconsistent associations have been reported among those without diabetes. This study aimed to examine the association of glucose homeostasis measures with cardiac autonomic function among diverse Hispanic/Latino adults without diabetes. Methods The Hispanic community Health Study/Study of Latinos (HCHS/SOL; 2008–2011) used two-stage area probability sampling of households to enroll 16,415 self-identified Hispanics/Latinos aged 18–74 years from four USA communities. Resting, standard 12-lead electrocardiogram recordings were used to estimate the following ultrashort-term measures of HRV: RR interval (RR), standard deviation of all normal to normal RR (SDNN) and root mean square of successive differences in RR intervals (RMSSD). Multivariable regression analysis was used to estimate associations between glucose homeostasis measures with HRV using data from 11,994 adults without diabetes (mean age 39 years; 52 % women). Results Higher fasting glucose was associated with lower RR, SDNN, and RMSSD. Fasting insulin and the homeostasis model assessment of insulin resistance was negatively associated with RR, SDNN, and RMSSD, and the association was stronger among men compared with women. RMSSD was, on average, 26 % lower in men with higher fasting insulin and 29 % lower in men with lower insulin resistance; for women, the corresponding estimates were smaller at 4 and 9 %, respectively. Higher glycated hemoglobin was associated with lower RR, SDNN, and RMSSD in those with abdominal adiposity, defined by sex-specific cut-points for waist circumference, after adjusting for demographics and medication use. There were no associations between glycated hemoglobin and HRV measures among those without abdominal adiposity. Conclusions Impairment in glucose homeostasis was associated with lower HRV in Hispanic/Latino adults without diabetes, most prominently in men and individuals with abdominal adiposity. These results suggest that reduced cardiac autonomic function is associated with metabolic impairments before onset of overt diabetes in certain subgroups, offering clues for the pathophysiologic processes involved as well as opportunity for identification of those at high risk before autonomic control is manifestly impaired

The Impact of Genes and Environment on Brain Ageing in Males Aged 51 to 72 Years

Magnetic resonance imaging data are being used in statistical models to predicted brain ageing (PBA) and as biomarkers for neurodegenerative diseases such as Alzheimer’s Disease. Despite their increasing application, the genetic and environmental etiology of global PBA indices is unknown. Likewise, the degree to which genetic influences in PBA are longitudinally stable and how PBA changes over time are also unknown. We analyzed data from 734 men from the Vietnam Era Twin Study of Aging with repeated MRI assessments between the ages 51–72 years. Biometrical genetic analyses “twin models” revealed significant and highly correlated estimates of additive genetic heritability ranging from 59 to 75%. Multivariate longitudinal modeling revealed that covariation between PBA at different timepoints could be explained by a single latent factor with 73% heritability. Our results suggest that genetic influences on PBA are detectable in midlife or earlier, are longitudinally very stable, and are largely explained by common genetic influences

The Impact of Genes and Environment on Brain Ageing in Males Aged 51 to 72 Years.

Magnetic resonance imaging data are being used in statistical models to predicted brain ageing (PBA) and as biomarkers for neurodegenerative diseases such as Alzheimer's Disease. Despite their increasing application, the genetic and environmental etiology of global PBA indices is unknown. Likewise, the degree to which genetic influences in PBA are longitudinally stable and how PBA changes over time are also unknown. We analyzed data from 734 men from the Vietnam Era Twin Study of Aging with repeated MRI assessments between the ages 51-72 years. Biometrical genetic analyses "twin models" revealed significant and highly correlated estimates of additive genetic heritability ranging from 59 to 75%. Multivariate longitudinal modeling revealed that covariation between PBA at different timepoints could be explained by a single latent factor with 73% heritability. Our results suggest that genetic influences on PBA are detectable in midlife or earlier, are longitudinally very stable, and are largely explained by common genetic influences