329 research outputs found
A hierarchy of linguistic predictions during natural language comprehension
Understanding spoken language requires transforming ambiguous acoustic streams into a hierarchy of representations, from phonemes to meaning. It has been suggested that the brain uses prediction to guide the interpretation of incoming input. However, the role of prediction in language processing remains disputed, with disagreement about both the ubiquity and representational nature of predictions. Here, we address both issues by analyzing brain recordings of participants listening to audiobooks, and using a deep neural network (GPT-2) to precisely quantify contextual predictions. First, we establish that brain responses to words are modulated by ubiquitous predictions. Next, we disentangle model-based predictions into distinct dimensions, revealing dissociable neural signatures of predictions about syntactic category (parts of speech), phonemes, and semantics. Finally, we show that high-level (word) predictions inform low-level (phoneme) predictions, supporting hierarchical predictive processing. Together, these results underscore the ubiquity of prediction in language processing, showing that the brain spontaneously predicts upcoming language at multiple levels of abstraction
Gene-Environment Interactions for Parkinson's Disease.
OBJECTIVE: Parkinson's disease (PD) is a neurodegenerative disorder with complex etiology. Multiple genetic and environmental factors have been associated with PD, but most PD risk remains unexplained. The aim of this study was to test for statistical interactions between PD-related genetic and environmental exposures in the 23andMe, Inc. research dataset. METHODS: Using a validated PD polygenic risk score and common PD-associated variants in the GBA gene, we explored interactions between genetic susceptibility factors and 7 lifestyle and environmental factors: body mass index (BMI), type 2 diabetes (T2D), tobacco use, caffeine consumption, pesticide exposure, head injury, and physical activity (PA). RESULTS: We observed that T2D, as well as higher BMI, caffeine consumption, and tobacco use, were associated with lower odds of PD, whereas head injury, pesticide exposure, GBA carrier status, and PD polygenic risk score were associated with higher odds. No significant association was observed between PA and PD. In interaction analyses, we found statistical evidence for an interaction between polygenic risk of PD and the following environmental/lifestyle factors: T2D (p = 6.502 × 10-8 ), PA (p = 8.745 × 10-5 ), BMI (p = 4.314 × 10-4 ), and tobacco use (p = 2.236 × 10-3 ). Although BMI and tobacco use were associated with lower odds of PD regardless of the extent of individual genetic liability, the direction of the relationship between odds of PD and T2D, as well as PD and PA, varied depending on polygenic risk score. INTERPRETATION: We provide preliminary evidence that associations between some environmental and lifestyle factors and PD may be modified by genotype. ANN NEUROL 2024
Sociology and postcolonialism: another 'missing' revolution?
Sociology is usually represented as having emerged alongside European modernity. The latter is frequently understood as sociology's special object with sociology itself a distinctively modern form of explanation. The period of sociology's disciplinary formation was also the heyday of European colonialism, yet the colonial relationship did not figure in the development of sociological understandings. While the recent emergence of postcolonialism appears to have initiated a reconsideration of understandings of modernity, with the development of theories of multiple modernities, I suggest that this engagement is more an attempt at recuperating the transformative aspect of postcolonialism than engaging with its critiques. In setting out the challenge of postcolonialism to dominant sociological accounts, I also address `missing feminist/queer revolutions', suggesting that by engaging with postcolonialism there is the potential to transform sociological understandings by opening up a dialogue beyond the simple pluralism of identity claims
The Parkinson's phenome-traits associated with Parkinson's disease in a broadly phenotyped cohort
In order to systematically describe the Parkinson's disease phenome, we performed a series of 832 cross-sectional case-control analyses in a large database. Responses to 832 online survey-based phenotypes including diseases, medications, and environmental exposures were analyzed in 23andMe research participants. For each phenotype, survey respondents were used to construct a cohort of Parkinson's disease cases and age-matched and sex-matched controls, and an association test was performed using logistic regression. Cohorts included a median of 3899 Parkinson's disease cases and 49,808 controls, all of European ancestry. Highly correlated phenotypes were removed and the novelty of each significant association was systematically assessed (assigned to one of four categories: known, likely, unclear, or novel). Parkinson's disease diagnosis was associated with 122 phenotypes. We replicated 27 known associations and found 23 associations with a strong a priori link to a known association. We discovered 42 associations that have not previously been reported. Migraine, obsessive-compulsive disorder, and seasonal allergies were associated with Parkinson's disease and tend to occur decades before the typical age of diagnosis for Parkinson's disease. The phenotypes that currently comprise the Parkinson's disease phenome have mostly been explored in relatively small purpose-built studies. Using a single large dataset, we have successfully reproduced many of these established associations and have extended the Parkinson's disease phenome by discovering novel associations. Our work paves the way for studies of these associated phenotypes that explore shared molecular mechanisms with Parkinson's disease, infer causal relationships, and improve our ability to identify individuals at high-risk of Parkinson's disease
Multi-ancestry genome-wide association meta-analysis of Parkinson's disease.
Although over 90 independent risk variants have been identified for Parkinson's disease using genome-wide association studies, most studies have been performed in just one population at a time. Here we performed a large-scale multi-ancestry meta-analysis of Parkinson's disease with 49,049 cases, 18,785 proxy cases and 2,458,063 controls including individuals of European, East Asian, Latin American and African ancestry. In a meta-analysis, we identified 78 independent genome-wide significant loci, including 12 potentially novel loci (MTF2, PIK3CA, ADD1, SYBU, IRS2, USP8, PIGL, FASN, MYLK2, USP25, EP300 and PPP6R2) and fine-mapped 6 putative causal variants at 6 known PD loci. By combining our results with publicly available eQTL data, we identified 25 putative risk genes in these novel loci whose expression is associated with PD risk. This work lays the groundwork for future efforts aimed at identifying PD loci in non-European populations
The Parkinson's Disease Mendelian Randomization Research Portal
Background
Mendelian randomization is a method for exploring observational associations to find evidence of causality.
Objective
To apply Mendelian randomization between risk factors/phenotypic traits (exposures) and PD in a large, unbiased manner, and to create a public resource for research.
Methods
We used two‐sample Mendelian randomization in which the summary statistics relating to single‐nucleotide polymorphisms from 5,839 genome‐wide association studies of exposures were used to assess causal relationships with PD. We selected the highest‐quality exposure genome‐wide association studies for this report (n = 401). For the disease outcome, summary statistics from the largest published PD genome‐wide association studies were used. For each exposure, the causal effect on PD was assessed using the inverse variance weighted method, followed by a range of sensitivity analyses. We used a false discovery rate of 5% from the inverse variance weighted analysis to prioritize exposures of interest.
Results
We observed evidence for causal associations between 12 exposures and risk of PD. Of these, nine were effects related to increasing adiposity and decreasing risk of PD. The remaining top three exposures that affected PD risk were tea drinking, time spent watching television, and forced vital capacity, but these may have been biased and were less convincing. Other exposures at nominal statistical significance included inverse effects of smoking and alcohol.
Conclusions
We present a new platform which offers Mendelian randomization analyses for a total of 5,839 genome‐wide association studies versus the largest PD genome‐wide association studies available (https://pdgenetics.shinyapps.io/MRportal/). Alongside, we report further evidence to support a causal role for adiposity on lowering the risk of P
On the verge of Umdeutung in Minnesota: Van Vleck and the correspondence principle (Part One)
In October 1924, the Physical Review, a relatively minor journal at the time,
published a remarkable two-part paper by John H. Van Vleck, working in virtual
isolation at the University of Minnesota. Van Vleck combined advanced
techniques of classical mechanics with Bohr's correspondence principle and
Einstein's quantum theory of radiation to find quantum analogues of classical
expressions for the emission, absorption, and dispersion of radiation. For
modern readers Van Vleck's paper is much easier to follow than the famous paper
by Kramers and Heisenberg on dispersion theory, which covers similar terrain
and is widely credited to have led directly to Heisenberg's "Umdeutung" paper.
This makes Van Vleck's paper extremely valuable for the reconstruction of the
genesis of matrix mechanics. It also makes it tempting to ask why Van Vleck did
not take the next step and develop matrix mechanics himself.Comment: 82 page
Author Correction: Discovery of 42 genome-wide significant loci associated with dyslexia
Correction to: Nature Genetics https://doi.org/10.1038/s41588-022-01192-y. Published online 20 October 2022.
In the version of this article originally published, a paragraph was omitted in the Methods section, reading “Genomic control. Top SNPs are reported from the more conservative GWAS results adjusted for genomic control (Fig. 1, Extended Data Figs. 1–4, and Supplementary Tables 1, 2, 9 and 10), whereas downstream analyses (including gene-set analysis, enrichment and heritability partitioning, genetic correlations, polygenic prediction, candidate gene replication) are based on GWAS results without genomic control.” The paragraph has now been included in the HTML and PDF versions of the article
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