Purpose: This study examines the efficacy of perceptual training for improving typical listeners' identification of vowels produced by individuals with dysarthria. We examined whether training on a ...subset of vowels can generalize to (a) untrained vowels and (b) other speakers with similar overall intelligibility. Method: Sixty naive listeners completed a pretest/posttest perceptual learning task. In the pretraining test and posttraining test, participants identified nine American English monophthongs produced by two speakers with dysarthria secondary to amyotrophic lateral sclerosis (ALS). In the 20-min training task, a two-alternative forced choice (2AFC) task with feedback trained listeners on a subset of the vowels and speakers presented in the pretraining test. Results: Vowel identification accuracy improved overall as a function of training. However, patterns of generalization between speakers and vowel types were not symmetric. Specifically, listeners generalized training from front vowels to back vowels but not vice versa. Likewise, listeners generalized from one speaker to another but not in the opposite direction. Examination of confusion matrices for the pretraining and posttraining revealed complex patterns of vowel-specific improvement. Conclusions: This study demonstrates that listeners benefit from a very simple training paradigm targeting vowels. Additionally, error patterns revealed that vowels are both resistant to and responsive to perceptual learning. Implications for future research and clinical training paradigms are discussed.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
Mitochondrial dysfunction is a feature of neurodegenerative diseases, including Alzheimer's disease (AD). Changes in the mitochondrial DNA copy number (mtDNAcn) and increased mitochondrial DNA ...mutation burden have both been associated with neurodegenerative diseases and cognitive decline. This study aims to systematically identify which common brain pathologies in the aged human brain are associated with mitochondrial recalibrations and to disentangle the relationship between these pathologies, mtDNAcn, mtDNA heteroplasmy, aging, neuronal loss, and cognitive function.
Whole-genome sequencing data from n = 1361 human brain samples from 5 different regions were used to quantify mtDNAcn as well as heteroplasmic mtDNA point mutations and small indels. Brain samples were assessed for 10 common pathologies. Annual cognitive test results were used to assess cognitive function proximal to death. For a subset of samples, neuronal proportions were estimated from RNA-seq profiles, and mass spectrometry was used to quantify the mitochondrial protein content of the tissue.
mtDNAcn was 7-14% lower in AD relative to control participants. When accounting for all 10 common neuropathologies, only tau was significantly associated with lower mtDNAcn in the dorsolateral prefrontal cortex. In the posterior cingulate cortex, TDP-43 pathology demonstrated a distinct association with mtDNAcn. No changes were observed in the cerebellum, which is affected late by pathologies. Neither age nor gender was associated with mtDNAcn in the studied brain regions when adjusting for pathologies. Mitochondrial content and mtDNAcn independently explained variance in cognitive function unaccounted by pathologies, implicating complex mitochondrial recalibrations in cognitive decline. In contrast, mtDNA heteroplasmy levels increased by 1.5% per year of life in the cortical regions, but displayed no association with any of the pathologies or cognitive function.
We studied mtDNA quantity and quality in relation to mixed pathologies of aging and showed that tau and not amyloid-β is primarily associated with reduced mtDNAcn. In the posterior cingulate cortex, the association of TDP-43 with low mtDNAcn points to a vulnerability of this region in limbic-predominant age-related TDP-43 encephalopathy. While we found low mtDNAcn in brain regions affected by pathologies, the absence of associations with mtDNA heteroplasmy burden indicates that mtDNA point mutations and small indels are unlikely to be involved in the pathogenesis of late-onset neurodegenerative diseases.
Purpose: We present a tripartite view of intelligibility in which the contributions of both the speaker and listener, as well as their joint effort during interaction, are considered. While ...considerable research has examined communicative interactions in situ, there is a critical gap in current knowledge on how speech intelligibility unfolds during such interactions. Here, we argue that research examining speech intelligibility in communicative interactions may provide important groundwork for advancement in clinical interventions for individuals with dysarthria. Method: First, we describe the view and argue for its consideration as a powerful way of thinking about speech intelligibility. We then briefly situate the view in the relevant literature on speech intelligibility and existing theoretical frameworks. We then identify suitable methodological paradigms for studying joint contributions to intelligibility and, lastly, discuss the clinical application and potential impact of this tripartite view. Conclusions: Speech communication occurs through interaction; however, in the laboratory and clinic, emphasis is usually placed on individual speakers and listeners. We have proposed that it is critical to consider how the joint contributions of speakers and listeners affect speech intelligibility in communicative interaction. This conceptualization is well aligned with the International Classification of Functioning, Disability and Health, and the findings from such an approach will allow us to better understand how to maximize available resources to enhance speech intelligibility.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
In this study, we examined the utility of vowel intelligibility testing for assessing the impact of dysarthria on speech characteristics in people with amyotrophic lateral sclerosis (ALS). We tested ...the sensitivity and specificity of overall vowel identification, as well as that of vowel-specific identification, to dysarthria presence and severity. We additionally examined the relationship between vowel intelligibility and sentence intelligibility.
Twenty-three people with ALS and 22 age- and sex-matched control speakers produced sentences from the Speech Intelligibility Test (SIT), as well as 10 American English monophthongs in /h/-vowel-/d/ words for the vowel intelligibility test (VIT). Data for SIT and VIT scores came from 135 listeners. Diagnostic accuracy of VIT measures was evaluated using the area under the curve of receiver operator characteristics. We then examined differences between control speakers, speakers with mild dysarthria, and speakers with severe dysarthria in their relationship between SIT and VIT scores.
The results suggest that the overall vowel intelligibility score showed high sensitivity and specificity in differentiating between speakers with and without dysarthria, even those with milder symptoms. In addition, single-vowel identification scores showed at least acceptable group differentiation between the mild and severe dysarthria groups, though fewer single vowels were acceptable discriminators between the control group and the group with mild dysarthria. Identification accuracy of /ɪ/ in particular showed excellent discrimination across all groups. Examination of the relationship between SIT and VIT scores suggests a severity-specific relationship. Speakers with SIT scores above 70% generally had higher SIT than VIT scores, whereas speakers with SIT below 70% generally had higher VIT than SIT scores.
Vowel intelligibility testing can detect speech impairments in speakers with mild dysarthria and residual articulatory function in speakers with severe dysarthria. Vowel intelligibility testing may, therefore, be a useful addition to intelligibility testing for individuals with dysarthria.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
IMPORTANCE: Genetic studies of Alzheimer disease have focused on the clinical or pathologic diagnosis as the primary outcome, but little is known about the genetic basis of the preclinical phase of ...the disease. OBJECTIVE: To examine the underlying genetic basis for brain amyloidosis in the preclinical phase of Alzheimer disease. DESIGN, SETTING, AND PARTICIPANTS: In the first stage of this genetic association study, a meta-analysis was conducted using genetic and imaging data acquired from 6 multicenter cohort studies of healthy older individuals between 1994 and 2019: the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease Study, the Berkeley Aging Cohort Study, the Wisconsin Registry for Alzheimer’s Prevention, the Biomarkers of Cognitive Decline Among Normal Individuals cohort, the Baltimore Longitudinal Study of Aging, and the Alzheimer Disease Neuroimaging Initiative, which included Alzheimer disease and mild cognitive impairment. The second stage was designed to validate genetic observations using pathologic and clinical data from the Religious Orders Study and Rush Memory and Aging Project. Participants older than 50 years with amyloid positron emission tomographic (PET) imaging data and DNA from the 6 cohorts were included. The largest cohort, the Anti-Amyloid Treatment in Asymptomatic Alzheimer Disease Study (n = 3154), was the PET screening cohort used for a secondary prevention trial designed to slow cognitive decline associated with brain amyloidosis. Six smaller, longitudinal cohort studies (n = 1160) provided additional amyloid PET imaging data with existing genetic data. The present study was conducted from March 29, 2019, to February 19, 2020. MAIN OUTCOMES AND MEASURES: A genome-wide association study of PET imaging amyloid levels. RESULTS: From the 4314 analyzed participants (age, 52-96 years; 2478 participants 57% were women), a novel locus for amyloidosis was noted within RBFOX1 (β = 0.61, P = 3 × 10−9) in addition to APOE. The RBFOX1 protein localized around plaques, and reduced expression of RBFOX1 was correlated with higher amyloid-β burden (β = −0.008, P = .002) and worse cognition (β = 0.007, P = .006) during life in the Religious Orders Study and Rush Memory and Aging Project cohort. CONCLUSIONS AND RELEVANCE: RBFOX1 encodes a neuronal RNA-binding protein known to be expressed in neuronal tissues and may play a role in neuronal development. The findings of this study suggest that RBFOX1 is a novel locus that may be involved in the pathogenesis of Alzheimer disease.
Alzheimer’s disease (AD) has been associated with cardiovascular and cerebrovascular risk factors (CVRFs) during middle age and later and is frequently accompanied by cerebrovascular pathology at ...death. An interaction between CVRFs and genetic variants might explain the pathogenesis. Genome-wide, gene by CVRF interaction analyses for AD, in 6568 patients and 8101 controls identified
FMNL2
(
p
= 6.6 × 10
–7
). A significant increase in
FMNL2
expression was observed in the brains of patients with brain infarcts and AD pathology and was associated with amyloid and phosphorylated tau deposition. FMNL2 was also prominent in astroglia in AD among those with cerebrovascular pathology. Amyloid toxicity in zebrafish increased
fmnl2a
expression in astroglia with detachment of astroglial end feet from blood vessels. Knockdown of
fmnl2a
prevented gliovascular remodeling, reduced microglial activity and enhanced amyloidosis. APP/PS1dE9 AD mice also displayed increased
Fmnl2
expression and reduced the gliovascular contacts independent of the gliotic response. Based on this work, we propose that FMNL2 regulates pathology-dependent plasticity of the blood–brain-barrier by controlling gliovascular interactions and stimulating the clearance of extracellular aggregates. Therefore, in AD cerebrovascular risk factors promote cerebrovascular pathology which in turn, interacts with
FMNL2
altering the normal astroglial-vascular mechanisms underlying the clearance of amyloid and tau increasing their deposition in brain.
Queries for the presence of cardiovascular and cerebrovascular risk factors are typically assessed through self-report. However, the reliability and validity of self-reported cardiovascular and ...cerebrovascular risk factors remain inconsistent in aging research.
To determine the reliability and validity of the most frequently self-reported vascular risk factors: hypertension, diabetes, and heart disease.
1,870 individuals aged 65 years or older among African Americans, Caribbean Hispanics, and white non-Hispanic individuals were recruited as part of a community study of aging and dementia. We assessed the reliability, validity, sensitivity, specificity, and percent agreement of self-reported hypertension, diabetes, and heart disease, in comparison with direct measures of blood pressure, hemoglobin A1c (HbA1c), and medication use. The analyses were subsequently stratified by age, sex, education, and ethnic group.
Reliability of self-reported hypertension, diabetes, and heart disease was excellent. Agreement between self-reports and clinical measures was moderate for hypertension (kappa: 0.58), good for diabetes (kappa: 0.76-0.79), and moderate for heart disease (kappa: 0.45) differing slightly by age, sex, education, and ethnic group. Sensitivity and specificity for hypertension was 88.6% -78.1%, for diabetes was 87.7% -92.0% (HbA1c ≥6.5%) or 92.7% -92.8% (HbA1c ≥7%), and for heart disease was 85.8% -75.5%. Percent agreement of self-reported was 87.0% for hypertension, 91.6% -92.6% for diabetes, and 77.4% for heart disease.
Ascertainment of self-reported histories of hypertension, diabetes, and heart disease are reliable and valid compared to direct measurements or medication use.
Brushlands support a diverse suite of bird species, including species of conservation concern in the western Great Lakes region of central North America. Information on how to effectively manage ...lowland brushlands for birds and associations between breeding birds and local‐scale vegetation structure and composition is lacking. We surveyed lowland brushlands from 2016–2018 in Minnesota, USA, to assess bird‐habitat associations using avian point‐count surveys and fixed‐radius vegetation plots. We used Poisson regression models to assess the associations between breeding bird species richness, total abundance, and abundance of frequently detected species (using counts as an index for abundance) to woody stem density and height, patchiness of woody stem density, variation of woody stem height, and number of woody plant species. Sedge wrens (Cistothorus stellaris), the most abundant species, were negatively associated with multiple woody plant metrics and positively associated with patchiness. Common yellowthroats (Geothlypis trichas) were the second‐most abundant species and associated with low‐stature woody plants (<1 m based on average heights in study sites). Bird species richness, alder flycatchers (Empidonax alnorum), chestnut‐sided warblers (Setophaga pensylvanica), swamp sparrows (Melospiza georgiana), veeries (Catharus fuscescens), and yellow warblers (Setophaga petechia) increased with woody vegetation height. Chestnut‐sided warbler and Nashville warbler (Leiothlypis ruficapilla) abundances also increased with woody stem density. We suggest that managing lowland brushlands to promote diverse woody plant structure, including tall shrubs and areas with patchy, open herbaceous cover, by implementing temporally and spatially variable disturbance regimes, may benefit bird species that rely on lowland brushlands with a range of vegetation structure requirements.
Lowland brushlands are disturbance‐dependent and provide breeding habitat for diverse avian communities. Bird‐habitat associations vary considerably within lowland brushlands, indicating that a diversity of woody vegetation structure (density and height) may be required to support diverse bird communities with small area requirements in these systems. It may be possible to focus management to benefit species of conservation concern in lowland brushlands.
Based on Habermas' Theory of Communicative Action, this paper critiques the transparency and legitimacy of participatory scenario planning, considering a case study of scenario development for the ...livestock industry within Scotland. The paper considers the extent to which the case study approximates the conditions for ‘ideal speech situations’ and how these conditions could be applied more widely in participatory scenario planning. The authors explore the rationale for participatory scenario planning within the science–policy interface with critical reference to the corporate context in which scenario planning has evolved. The aim is to optimise the potential for its use in the context of socio-technical and environmental governance. Researcher co-reflections on the case study are mapped within a matrix of indices representing conditions for ideal speech situations. Further analytical categories highlight the extent to which ideal speech was approximated. Although many of the constraints on achieving ideal speech situations reflect intransigent, practical logistics of organising participatory exercises, our novel approach enables the systematic identification of some important issues and provides a conceptual framework for understanding how they interrelate that may prove useful to practitioners and theorists alike.
•We focus on scenario planning as a participatory process.•We build a critique based on Habermas' concept of ‘ideal speech’.•Through a case study we explore legitimacy in participatory scenario planning.•We consider the context of socio-technical problems in the public sphere.•We differentiate between scenario planning in the corporate and public sphere.
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