RESUMEN
Hearing-in-noise perception is a challenging task that is critical to human function, but how the brain accomplishes it is not well understood. A candidate mechanism proposes that the neural representation of an attended auditory stream is enhanced relative to background sound via a combination of bottom-up and top-down mechanisms. To date, few studies have compared neural representation and its task-related enhancement across frequency bands that carry different auditory information, such as a sound's amplitude envelope (i.e., syllabic rate or rhythm; 1-9 Hz), and the fundamental frequency of periodic stimuli (i.e., pitch; >40 Hz). Furthermore, hearing-in-noise in the real world is frequently both messier and richer than the majority of tasks used in its study. In the present study, we use continuous sound excerpts that simultaneously offer predictive, visual, and spatial cues to help listeners separate the target from four acoustically similar simultaneously presented sound streams. We show that while both lower and higher frequency information about the entire sound stream is represented in the brain's response, the to-be-attended sound stream is strongly enhanced only in the slower, lower frequency sound representations. These results are consistent with the hypothesis that attended sound representations are strengthened progressively at higher level, later processing stages, and that the interaction of multiple brain systems can aid in this process. Our findings contribute to our understanding of auditory stream separation in difficult, naturalistic listening conditions and demonstrate that pitch and envelope information can be decoded from single-channel EEG data.
RESUMEN
Osteoporosis is a common disease diagnosed primarily by measurement of bone mineral density (BMD). We undertook a genome-wide association study (GWAS) in 142,487 individuals from the UK Biobank to identify loci associated with BMD as estimated by quantitative ultrasound of the heel. We identified 307 conditionally independent single-nucleotide polymorphisms (SNPs) that attained genome-wide significance at 203 loci, explaining approximately 12% of the phenotypic variance. These included 153 previously unreported loci, and several rare variants with large effect sizes. To investigate the underlying mechanisms, we undertook (1) bioinformatic, functional genomic annotation and human osteoblast expression studies; (2) gene-function prediction; (3) skeletal phenotyping of 120 knockout mice with deletions of genes adjacent to lead independent SNPs; and (4) analysis of gene expression in mouse osteoblasts, osteocytes and osteoclasts. The results implicate GPC6 as a novel determinant of BMD, and also identify abnormal skeletal phenotypes in knockout mice associated with a further 100 prioritized genes.