51 research outputs found
Inter-expert and intra-expert reliability in sleep spindle scoring
Objectives: To measure the inter-expert and intra-expert agreement in sleep spindle scoring, and to quantify how many experts are needed to build a reliable dataset of sleep spindle scorings.
Methods: The EEG dataset was comprised of 400 randomly selected 115 s segments of stage 2 sleep from 110 sleeping subjects in the general population (57 ± 8, range: 42â72 years). To assess expert agreement, a total of 24 Registered Polysomnographic Technologists (RPSGTs) scored spindles in a subset of the EEG dataset at a single electrode location (C3-M2). Intra-expert and inter-expert agreements were calculated as F_1-scores, Cohenâs kappa (Îș), and intra-class correlation coefficient (ICC).
Results: We found an average intra-expert F_1-score agreement of 72 ± 7% (Îș: 0.66 ± 0.07). The average inter-expert agreement was 61 ± 6% (Îș: 0.52 ± 0.07). Amplitude and frequency of discrete spindles were calculated with higher reliability than the estimation of spindle duration. Reliability of sleep spindle scoring can be improved by using qualitative confidence scores, rather than a dichotomous yes/no scoring system.
Conclusions: We estimate that 2â3 experts are needed to build a spindle scoring dataset with âsubstantialâ reliability (Îș: 0.61â0.8), and 4 or more experts are needed to build a dataset with âalmost perfectâ reliability (Îș: 0.81â1).
Significance: Spindle scoring is a critical part of sleep staging, and spindles are believed to play an important role in development, aging, and diseases of the nervous system
Potent and selective antisense oligonucleotides targeting single-nucleotide polymorphisms in the Huntington disease gene / allele-specific silencing of mutant huntingtin
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG-expansion in the huntingtin gene (HTT) that results in a toxic gain of function in the mutant huntingtin protein (mHTT). Reducing the expression of mHTT is therefore an attractive therapy for HD. However, wild-type HTT protein is essential for development and has critical roles in maintaining neuronal health. Therapies for HD that reduce wild-type HTT may therefore generate unintended negative consequences. We have identified single-nucleotide polymorphism (SNP) targets in the human HD population for the disease-specific targeting of the HTT gene. Using primary cells from patients with HD and the transgenic YAC18 and BACHD mouse lines, we developed antisense oligonucleotide (ASO) molecules that potently and selectively silence mHTT at both exonic and intronic SNP sites. Modification of these ASOs with S-constrained-ethyl (cET) motifs significantly improves potency while maintaining allele selectively in vitro. The developed ASO is potent and selective for mHTT in vivo after delivery to the mouse brain. We demonstrate that potent and selective allele-specific knockdown of the mHTT protein can be achieved at therapeutically relevant SNP sites using ASOs in vitro and in vivo
Sleep spindle alterations in patients with Parkinson's disease
The aim of this study was to identify changes of sleep spindles (SS) in the EEG of patients with Parkinson's disease (PD). Five sleep experts manually identified SS at a central scalp location (C3-A2) in 15 PD and 15 age- and sex-matched control subjects. Each SS was given a confidence score, and by using a group consensus rule, 901 SS were identified and characterized by their (1) duration, (2) oscillation frequency, (3) maximum peak-to-peak amplitude, (4) percent-to-peak amplitude, and (5) density. Between-group comparisons were made for all SS characteristics computed, and significant changes for PD patients vs. control subjects were found for duration, oscillation frequency, maximum peak-to-peak amplitude and density. Specifically, SS density was lower, duration was longer, oscillation frequency slower and maximum peak-to-peak amplitude higher in patients vs. controls. We also computed inter-expert reliability in SS scoring and found a significantly lower reliability in scoring definite SS in patients when compared to controls. How neurodegeneration in PD could influence SS characteristics is discussed. We also note that the SS morphological changes observed here may affect automatic detection of SS in patients with PD or other neurodegenerative disorders (NDDs)
The dementia-associated APOE Δ4 allele is not associated with rapid eye movement sleep behavior disorder
Sleep-spindle detection: crowdsourcing and evaluating performance of experts, non-experts and automated methods
Sleep spindles are discrete, intermittent patterns of brain activity observed in human electroencephalographic data. Increasingly, these oscillations are of biological and clinical interest because of their role in development, learning and neurological disorders. We used an Internet interface to crowdsource spindle identification by human experts and non-experts, and we compared their performance with that of automated detection algorithms in data from middle- to older-aged subjects from the general population. We also refined methods for forming group consensus and evaluating the performance of event detectors in physiological data such as electroencephalographic recordings from polysomnography. Compared to the expert group consensus gold standard, the highest performance was by individual experts and the non-expert group consensus, followed by automated spindle detectors. This analysis showed that crowdsourcing the scoring of sleep data is an efficient method to collect large data sets, even for difficult tasks such as spindle identification. Further refinements to spindle detection algorithms are needed for middle- to older-aged subjects
Common variants in P2RY11 are associated with narcolepsy.
l e t t e r s Growing evidence supports the hypothesis that narcolepsy with cataplexy is an autoimmune disease. We here report genomewide association analyses for narcolepsy with replication and fine mapping across three ethnic groups (3,406 individuals of European ancestry, 2,414 Asians and 302 African Americans). We identify a SNP in the 3âČ untranslated region of P2RY11, the purinergic receptor subtype P2Y 11 gene, which is associated with narcolepsy (rs2305795, combined P = 6.1 Ă 10 â10 , odds ratio = 1.28, 95% CI 1.19-1.39, n = 5689). The diseaseassociated allele is correlated with reduced expression of P2RY11 in CD8 + T lymphocytes (339% reduced, P = 0.003) and natural killer (NK) cells (P = 0.031), but not in other peripheral blood mononuclear cell types. The low expression variant is also associated with reduced P2RY11-mediated resistance to ATP-induced cell death in T lymphocytes (P = 0.0007) and natural killer cells (P = 0.001). These results identify P2RY11 as an important regulator of immune-cell survival, with possible implications in narcolepsy and other autoimmune diseases
Common variants in P2RY11 are associated with narcolepsy.
Growing evidence supports the hypothesis that narcolepsy with cataplexy is an autoimmune disease. We here report genome-wide association analyses for narcolepsy with replication and fine mapping across three ethnic groups (3,406 individuals of European ancestry, 2,414 Asians and 302 African Americans). We identify a SNP in the 3' untranslated region of P2RY11, the purinergic receptor subtype P2Yââ gene, which is associated with narcolepsy (rs2305795, combined P = 6.1 Ă 10â»Âčâ°, odds ratio = 1.28, 95% CI 1.19-1.39, n = 5689). The disease-associated allele is correlated with reduced expression of P2RY11 in CD8(+) T lymphocytes (339% reduced, P = 0.003) and natural killer (NK) cells (P = 0.031), but not in other peripheral blood mononuclear cell types. The low expression variant is also associated with reduced P2RY11-mediated resistance to ATP-induced cell death in T lymphocytes (P = 0.0007) and natural killer cells (P = 0.001). These results identify P2RY11 as an important regulator of immune-cell survival, with possible implications in narcolepsy and other autoimmune diseases.journal articleresearch support, n.i.h., extramuralresearch support, non-u.s. gov'tresearch support, u.s. gov't, p.h.s.2011 Jan2010 12 19importedErratum in : Nat Genet. 2011 Oct;43(10):1040
Sleep Spindles: Breaking the Methodological Wall
In the last decade, sleep spindles have attracted steadily increasing attention. This interest is motivated by the many intriguing relationships between spindles and various diseases (e.g., schizophrenia, Parkinson, Alzheimer, autism, mental retardation), recovery processes (e.g., post brain stroke), and cognitive faculties (e.g., memory consolidation, intelligence, dream recall, sleep preservation). Nonetheless, a methodological wall has impeded the study of sleep spindles. Their investigation rests heavily on our ability to reliably and consistently identify spindle patterns from background EEG activity, a task involving many obstacles, including: a fuzzy definition of spindles, low inter-expert agreement on their scoring, lack of consensus on standard techniques for their automated detection, low reproducibility of observed characteristics and correlates, unavailability of large, standardized, high-quality databases, and inconsistencies in the methods used to evaluate the performance of automated detectors. The primary aims of this research topic were to bring together world-class researchers on a project designed to facilitate exchanges on methodological difficulties encountered in assessing sleep spindles and to promote standardized spindle-related resources. In preparing their contributions, authors were encouraged to use existing â or to propose new â publicly available resources for assessing sleep spindles. To allow fair and accurate comparison of reported results, the authors were also encouraged to validate their tools on a common benchmark. A database containing expert spindle scoring (i.e., the Montreal Archive of Sleep Studies) was made publicly available for that purpose
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