Vocal markers from sustained phonation in Huntington's Disease

Disease-modifying treatments are currently assessed in neurodegenerative diseases. Huntington's Disease represents a unique opportunity to design automatic sub-clinical markers, even in premanifest gene carriers. We investigated phonatory impairments as potential clinical markers and propose them for both diagnosis and gene carriers follow-up. We used two sets of features: Phonatory features and Modulation Power Spectrum Features. We found that phonation is not sufficient for the identification of sub-clinical disorders of premanifest gene carriers. According to our regression results, Phonatory features are suitable for the predictions of clinical performance in Huntington's Disease.Comment: To appear at INTERSPEECH 2020. 1 pages of supplementary material appear only in the arxiv version. Code to replicate https://github.com/bootphon/sustained-phonation-feature

A comparison study on patient-psychologist voice diarization

International audienceConversations between a clinician and a patient, in natural conditions, are valuable sources of information for medical follow-up. The automatic analysis of these dialogues could help extract new language markers and speed up the clinicians' reports. Yet, it is not clear which model is the most efficient to detect and identify the speaker turns, especially for individuals with speech disorders. Here, we proposed a split of the data that allows conducting a comparative evaluation of different diarization methods. We designed and trained end-to-end neural network architectures to directly tackle this task from the raw signal and evaluate each approach under the same metric. We also studied the effect of fine-tuning models to find the best performance. Experimental results are reported on naturalistic clinical conversations between Psychologists and Interviewees, at different stages of Huntington's disease, displaying a large panel of speech disorders. We found out that our best end-to-end model achieved 19.5% IER on the test set, compared to 23.6% achieved by the finetuning of the X-vector architecture. Finally, we observed that we could extract clinical markers directly from the automatic systems, highlighting the clinical relevance of our methods

Vocal markers from sustained phonation in Huntington's Disease

To appear at INTERSPEECH 2020. 1 pages of supplementary material appear only in the arxiv version. Code to replicate https://github.com/bootphon/sustained-phonation-featuresInternational audienceDisease-modifying treatments are currently assessed in neurodegenerative diseases. Huntington's Disease represents a unique opportunity to design automatic sub-clinical markers, even in premanifest gene carriers. We investigated phonatory impairments as potential clinical markers and propose them for both diagnosis and gene carriers follow-up. We used two sets of features: Phonatory features and Modulation Power Spectrum Features. We found that phonation is not sufficient for the identification of sub-clinical disorders of premanifest gene carriers. According to our regression results, Phonatory features are suitable for the predictions of clinical performance in Huntington's Disease

Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition)

In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. For example, a key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process versus those that measure fl ux through the autophagy pathway (i.e., the complete process including the amount and rate of cargo sequestered and degraded). In particular, a block in macroautophagy that results in autophagosome accumulation must be differentiated from stimuli that increase autophagic activity, defi ned as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (inmost higher eukaryotes and some protists such as Dictyostelium ) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the fi eld understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. It is worth emphasizing here that lysosomal digestion is a stage of autophagy and evaluating its competence is a crucial part of the evaluation of autophagic flux, or complete autophagy. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. Along these lines, because of the potential for pleiotropic effects due to blocking autophagy through genetic manipulation it is imperative to delete or knock down more than one autophagy-related gene. In addition, some individual Atg proteins, or groups of proteins, are involved in other cellular pathways so not all Atg proteins can be used as a specific marker for an autophagic process. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field

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Fat mass localization alters fuel oxidation during exercise in normal weight women

International audiencePurpose: Abdominal and lower body fat mass tissues exhibit particular metabolic profiles at rest and during exercise. However, data are missing in normal weight women during exercise. The purpose of this study was to investigate the effect of low (LA/LB) and high (HA/LB) abdominal to lower body (A/LB) fat mass ratio on metabolic and hormonal responses during exercise in premenopausal normal weight women. Methods: After preliminary testing ((V) over dotO(2max) and body composition assessment), substrate oxidation (RER, lipid, and carbohydrate oxidation rates), metabolic response (glycerol, free fatty acids, and glucose), and hormonal response (insulin, growth hormone, atrial natriuretic peptide, adrenaline, and noradrenaline) were determined during exercise (45 min at 65% of (V) over dotO(2max)) in 21 premenopausal normal weight women (10 HA/LB women vs 11 LA/LB women). Results: Waist circumference was significantly higher in HA/LB women compared with LA/LB women (P < 0.01). No difference in other anthropometric characteristics, (V) over dotO(2max), and resting blood values was observed between the two groups. LA/LB subjects exhibited greater lipid oxidation rates compared with HA/LB women during exercise (P < 0.01). This occurred with lower plasma insulin (P < 0.05) and glucose (P < 0.05) concentrations and higher plasma free fatty acids (P < 0.05), glycerol (P < 0.05), growth hormone (P < 0.05), and atrial natriuretic peptide levels (P G 0.01) during exercise in the LA/LB group compared with the HA/LB group. Conclusions: The present study demonstrated that LA/LB women exhibited an increase in whole-body lipid mobilization and use during exercise compared with HA/LB counterparts. This greater reliance on lipid as fuel metabolism during exercise could be explained by substrate availability and metabolic and hormonal responses. It appeared that LA/LB women exhibited greater metabolic flexibility during an exercise bout of 45 min at 65% of (V) over dotO(2max) on cycle ergometer

The specific role of the striatum in interval timing: The Huntington’s disease model

International audienceTime processing over intervals of hundreds of milliseconds to minutes, also known as interval timing, is associated with the striatum. Huntington's disease patients (HD) with striatal degeneration have impaired interval timing, but the extent and specificity of these deficits remain unclear. Are they specific to the temporal domain, or do they extend to the spatial domain too? Do they extend to both the perception and production of interval timing? Do they appear before motor symptoms in Huntington's disease (Pre-HD)? We addressed these issues by assessing both temporal abilities (in the seconds range) and spatial abilities (in the cm range) in 20 Pre-HD, 25 HD patients, and 25 healthy Controls, in discrimination, bisection and production paradigms. In addition, all participants completed a questionnaire assessing temporal and spatial disorientation in daily life, and the gene carriers (i.e., HD and Pre-HD participants) underwent structural brain MRI. Overall, HD patients were more impaired in the temporal than in the spatial domain in the behavioral tasks, and expressed a greater disorientation in the temporal domain in the daily life questionnaire. In contrast, Pre-HD participants showed no sign of a specific temporal deficit. Furthermore, MRI analyses indicated that performances in the temporal discrimination task were associated with a larger striatal grey matter volume in the striatum in gene carriers. Altogether, behavioral, brain imaging and questionnaire data support the hypothesis that the striatum is a specific component of interval timing processes. Evaluations of temporal disorientation and interval timing processing could be used as clinical tools for HD patients

A comparison study on patient-psychologist voice diarization

International audienceConversations between a clinician and a patient, in natural conditions, are valuable sources of information for medical follow-up. The automatic analysis of these dialogues could help extract new language markers and speed up the clinicians' reports. Yet, it is not clear which model is the most efficient to detect and identify the speaker turns, especially for individuals with speech disorders. Here, we proposed a split of the data that allows conducting a comparative evaluation of different diarization methods. We designed and trained end-to-end neural network architectures to directly tackle this task from the raw signal and evaluate each approach under the same metric. We also studied the effect of fine-tuning models to find the best performance. Experimental results are reported on naturalistic clinical conversations between Psychologists and Interviewees, at different stages of Huntington's disease, displaying a large panel of speech disorders. We found out that our best end-to-end model achieved 19.5% IER on the test set, compared to 23.6% achieved by the finetuning of the X-vector architecture. Finally, we observed that we could extract clinical markers directly from the automatic systems, highlighting the clinical relevance of our methods