Using Neural Word Embeddings in the Analysis of the Clinical Semantic Verbal Fluency Task

International audienceThe Semantic Verbal Fluency Task is a common neuropsychological assessment for cognitive disorders: patients are prompted to name as many words from a semantic category as possible in a time interval; the count of correctly named concepts is assessed. Patients often organise their retrieval around semantically related clusters. The definition of clusters is usually based on handmade taxonomies and the patient's performance is manually evaluated. In order to overcome limitations of such an approach, we propose a statistical method using distributional semantics. Based on transcribed speech samples from 100 French elderly, 53 diagnosed with Mild Cognitive Impairment and 47 healthy, we used distributional semantic models to cluster words in each sample and compare performance with a taxonomic baseline approach in a realistic classification task. The distributional models outperform the baseline. Comparing different linguistic corpora as basis for the models, our results indicate that models trained on larger corpora perform better

Automatic prediction of autonomy in activities of daily living of older adults

Short-paper15.s.875.00 Purpose: world population is aging and the number of seniors in need of care is expected to surpass the number of young people capable of providing it. It is then quintessential to develop instruments to support doctors at the task of diagnosing and monitoring the health status of seniors 1-3. Methods to assess autonomy and functional abilities of seniors currently rely on rating scales 4. The subjective character of these scales and their dependence on human observations tend to jeopardize the timely diagnosis of deteriorations in cognitive health. We propose a probabilistic model (PM) to objectively classify a person's performance in executive functions into three classes of cognitive status: Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy control (HC); and into different levels of autonomy: good, intermediate or poor. Material & Methods: the proposed PM relies on Naïve Bayes model for classification and takes as input automatically extracted parameters about a person's performance at activities of daily living (event monitoring system, EMS, Fig. 1). To evaluate our approach participants aged 65 or older were recruited within the Dem@care project protocol, at the Memory Center of the Nice university hospital: n=49; 12 AD (5 male), 23 MCI (13) and 14 HC (5). They were asked to carry out a set of instrumental activities of daily living (IADL, e.g., medication preparation; talking on the telephone) in an observation room equipped with everyday objects. Results & Discussion: EMS recognized targeted IADLs with a high precision (e.g., 'prepare medication': 93%, 'talk on the telephone': 89%). The proposed PM achieved average classification accuracy of 73.5 % for cognitive status classes and of 83.7% for autonomy classes. Moreover, the proposed PM displayed a higher accuracy when inputted with EMS data than with human annotations of daily activities. This finding is explained by the stability of EMS recognition which permits to relate subtle deviations from activity norms to characteristic traits of target classes. Conclusion: The proposed framework provides clinicians with diagnostic relevant information to support autonomy assessment in ecological scenarios by decreasing observer biases and facilitating a more timely diagnosis of frailty patterns in senior. Further work will extend the proposed framework to other clinical sites and seek for novel cues about autonomy decline in seniors

Objective measurement of gait parameters in healthy and cognitively impaired elderly using the dual-task paradigm

International audienceObjectives The present study explores the differences in gait parameters in elderly subjects with or without cognitive impairment measured by means of ambulatory actigraphy while performing a single and a dual task.Methods Sixty-nine participants of which 23 individuals were diagnosed with Alzheimer’s disease (AD), 24 with mild cognitive impairment (MCI), and 22 healthy controls performed a single and dual walking task while wearing a wrist-worn accelerometer. Objective measures of gait features such as walking speed, cadence (i.e., number of steps per minute), and step variance (i.e., variance in time between two consecutive steps) were derived andanalyzed.Results While differences in several gait parameters, namely walking speed, were found between MCI and ADpatients, no differences between healthy elderly and MCI patients were found.Conclusion Walking speed seems to be a gait-related feature that differs significantly between MCI and AD patients and thus could be used as an additional measurement in clinical assessment. However, differences in gait may not be salient enough in the early stages of dementia to be detected by actigraphy. More research comparing different methods to measure gait in early stages of dementia under different dual task conditions is necessary

Synchronized dynamics of cortical neurons with time-delay feedback

The dynamics of three mutually coupled cortical neurons with time delays in the coupling are explored numerically and analytically. The neurons are coupled in a line, with the middle neuron sending a somewhat stronger projection to the outer neurons than the feedback it receives, to model for instance the relay of a signal from primary to higher cortical areas. For a given coupling architecture, the delays introduce correlations in the time series at the time-scale of the delay. It was found that the middle neuron leads the outer ones by the delay time, while the outer neurons are synchronized with zero lag times. Synchronization is found to be highly dependent on the synaptic time constant, with faster synapses increasing both the degree of synchronization and the firing rate. Analysis shows that presynaptic input during the interspike interval stabilizes the synchronous state, even for arbitrarily weak coupling, and independent of the initial phase. The finding may be of significance to synchronization of large groups of cells in the cortex that are spatially distanced from each other.Comment: 21 pages, 11 figure

Evaluation of a Monitoring System for Event Recognition of Older People

International audiencePopulation aging has been motivating academic research and industry to develop technologies for the improvement of older people's quality of life, medical diagnosis, and support on frailty cases. Most of available research prototypes for older people monitoring focus on fall detection or gait analysis and rely on wearable, environmental, or video sensors. We present an evaluation of a research prototype of a video monitoring system for event recognition of older people. The prototype accuracy is evaluated for the recognition of physical tasks (e.g., Up and Go test) and instrumental activities of daily living (e.g., watching TV, writing a check) of participants of a clinical protocol for Alzheimer's disease study (29 participants). The prototype uses as input a 2D RGB camera, and its performance is compared to the use of a RGB-D camera. The experimentation results show the proposed approach has a competitive performance to the use of a RGB-D camera, even outperforming it on event recognition precision. The use of a 2D-camera is advantageous, as the camera field of view can be much larger and cover an entire room where at least a couple of RGB-D cameras would be necessary

Utilisation de l'analyse automatisée de la parole et des mesures des émotions faciales sur des vidéos pour évaluer les effets des dispositifs de relaxation: une étude pilote

International audienceRapid relaxation installations in order to reduce stress appear more and more in public or work places. However, the effects of such devices on physiological and psychological parameters have not been scientifically tested yet. This pilot study (N=40) evaluates the variations of vocal speech and facial emotions parameters in 3-minute videos of participant recorded just before and after relaxation, on four different groups, three of them using a different rapid (15 minutes) sensorial immersion relaxation devices and a control group using no device. Vocal speech parameters included sound duration, pause mean duration, sound duration ratio, mean vocal frequency (F0), standard deviation of F0, minimum and maximum of F0, jitter and shimmer. Facial emotion analysis included neutral, happy, sad, surprised, angry, disgusted, scared, contempt, valence and arousal. The objective of this study is to evaluate different parameters of the automated vocal and facial emotions analysis that could be of use to evaluate the relaxation effect of different devices and to measure their variations in the different experimental groups. We identified significant parameters that can be of use for evaluating rapid relaxation devices, particularly voice prosody and minimum vocal frequency, and some facial emotion such as happy, sad, the valence and arousal. Those parameters allowed us to discriminate distinct effects of the different devices used: in G1 (control) and G2 (spatialized sounds), we observed a slowdown in voice prosody; in G3 (Be-Breathe) a decrease in minimum vocal frequency and an increase of arousal; while in G4 (3D-video) we found an increase in facial emotion valence (happy increasing and sad decreasing). Other parameters tested were not affected by relaxation.Les installations de relaxation rapide afin de réduire le stress apparaissent de plus en plus dans les lieux publics ou de travail. Cependant, les effets de ces dispositifs sur les paramètres physiologiques et psychologiques n'ont pas encore été testés scientifiquement. Cette étude pilote (N = 40) évalue les variations des paramètres de la parole vocale et des émotions faciales dans des vidéos de 3 minutes de participant enregistrées juste avant et après la relaxation, sur quatre groupes différents, trois d'entre eux utilisant une immersion sensorielle rapide (15 minutes) différente. des appareils de relaxation et un groupe témoin n'utilisant aucun appareil. Les paramètres de la parole vocale comprenaient la durée du son, la durée moyenne de la pause, le rapport de durée du son, la fréquence vocale moyenne (F0), l'écart type de F0, le minimum et le maximum de F0, la gigue et le miroitement. L'analyse des émotions faciales comprenait la neutralité, la joie, la tristesse, la surprise, la colère, le dégoût, la peur, le mépris, la valence et l'excitation. L'objectif de cette étude est d'évaluer différents paramètres de l'analyse automatisée des émotions vocales et faciales qui pourraient être utiles pour évaluer l'effet de relaxation de différents appareils et mesurer leurs variations dans les différents groupes expérimentaux. Nous avons identifié des paramètres significatifs qui peuvent être utiles pour évaluer les dispositifs de relaxation rapide, en particulier la prosodie de la voix et la fréquence vocale minimale, et certaines émotions faciales telles que le bonheur, la tristesse, la valence et l'excitation. Ces paramètres nous ont permis de discriminer des effets distincts des différents appareils utilisés: pour G1 (contrôle) et G2 (sons spatialisés), nous avons observé un ralentissement de la prosodie vocale; dans le groupe G3 (Be-Breathe) une diminution de la fréquence vocale minimale et une augmentation de l'éveil; enfin, pour G4 (vidéo 3D), nous avons trouvé une augmentation de la valence des émotions faciales (augmentation de la joie et diminution de la tristesse). Les autres paramètres testés n'ont pas été affectés par la relaxation

Detection of activities of daily living impairment in Alzheimer's disease and mild cognitive impairment using information and communication technology

International audienceBackground: One of the key clinical features of Alzheimer's disease (AD) is impairment in daily functioning. Patients with mild cognitive impairment (MCI) also commonly have mild problems performing complex tasks. Information and communication technology (ICT), particularly techniques involving imaging and video processing, is of interest in order to improve assessment. The overall aim of this study is to demonstrate that it is possible using a video monitoring system to obtain a quantifiable assessment of instrumental activities of daily living (IADLs) in AD and in MCI. Methods: The aim of the study is to propose a daily activity scenario (DAS) score that detects functional impairment using ICTs in AD and MCI compared with normal control group (NC). Sixty-four participants over 65 years old were included: 16 AD matched with 10 NC for protocol 1 (P1) and 19 MCI matched with 19 NC for protocol 2 (P2). Each participant was asked to undertake a set of daily tasks in the setting of a "smart home" equipped with two video cameras and everyday objects for use in activities of daily living (8 IADLs for P1 and 11 for P2, plus 4 temporal execution constraints). The DAS score was then computed from quantitative and qualitative parameters collected from video recordings. Results: In P1, the DAS score differentiated AD (DASAD,P1 = 0.47, 95% confidence interval [CI] 0.38-0.56) from NC (DASNC,P1 = 0.71, 95% CI 0.68-0.74). In P2, the DAS score differentiated MCI (DASMCI,P2 = 0.11, 95% CI 0.05-0.16) and NC (DASNC,P2 = 0.36, 95% CI 0.26-0.45). Conclusion: In conclusion, this study outlines the interest of a novel tool coming from the ICT world for the assessment of functional impairment in AD and MCI. The derived DAS scores provide a pragmatic, ecological, objective measurement which may improve the prediction of future dementia, be used as an outcome measurement in clinical trials and lead to earlier therapeutic intervention

Role of Abl Kinase and the Wave2 Signaling Complex in HIV-1 Entry at a Post-Hemifusion Step

Entry of human immunodeficiency virus type 1 (HIV-1) commences with binding of the envelope glycoprotein (Env) to the receptor CD4, and one of two coreceptors, CXCR4 or CCR5. Env-mediated signaling through coreceptor results in Gαq-mediated Rac activation and actin cytoskeleton rearrangements necessary for fusion. Guanine nucleotide exchange factors (GEFs) activate Rac and regulate its downstream protein effectors. In this study we show that Env-induced Rac activation is mediated by the Rac GEF Tiam-1, which associates with the adaptor protein IRSp53 to link Rac to the Wave2 complex. Rac and the tyrosine kinase Abl then activate the Wave2 complex and promote Arp2/3-dependent actin polymerization. Env-mediated cell-cell fusion, virus-cell fusion and HIV-1 infection are dependent on Tiam-1, Abl, IRSp53, Wave2, and Arp3 as shown by attenuation of fusion and infection in cells expressing siRNA targeted to these signaling components. HIV-1 Env-dependent cell-cell fusion, virus-cell fusion and infection were also inhibited by Abl kinase inhibitors, imatinib, nilotinib, and dasatinib. Treatment of cells with Abl kinase inhibitors did not affect cell viability or surface expression of CD4 and CCR5. Similar results with inhibitors and siRNAs were obtained when Env-dependent cell-cell fusion, virus-cell fusion or infection was measured, and when cell lines or primary cells were the target. Using membrane curving agents and fluorescence microscopy, we showed that inhibition of Abl kinase activity arrests fusion at the hemifusion (lipid mixing) step, suggesting a role for Abl-mediated actin remodeling in pore formation and expansion. These results suggest a potential utility of Abl kinase inhibitors to treat HIV-1 infected patients

Cell Free DNA of Tumor Origin Induces a 'Metastatic' Expression Profile in HT-29 Cancer Cell Line

BACKGROUND: Epithelial cells in malignant conditions release DNA into the extracellular compartment. Cell free DNA of tumor origin may act as a ligand of DNA sensing mechanisms and mediate changes in epithelial-stromal interactions. AIMS: To evaluate and compare the potential autocrine and paracrine regulatory effect of normal and malignant epithelial cell-related DNA on TLR9 and STING mediated pathways in HT-29 human colorectal adenocarcinoma cells and normal fibroblasts. MATERIALS AND METHODS: DNA isolated from normal and tumorous colonic epithelia of fresh frozen surgically removed tissue samples was used for 24 and 6 hour treatment of HT-29 colon carcinoma and HDF-alpha fibroblast cells. Whole genome mRNA expression analysis and qRT-PCR was performed for the elements/members of TLR9 signaling pathway. Immunocytochemistry was performed for epithelial markers (i.e. CK20 and E-cadherin), DNA methyltransferase 3a (DNMT3a) and NFkappaB (for treated HDFalpha cells). RESULTS: Administration of tumor derived DNA on HT29 cells resulted in significant (p/=1, p/=1, p</=0.05), including increased expression of key adaptor molecules of TLR9 pathway (e.g. MYD88, IRAK2, NFkappaB, IL8, IL-1beta), STING pathway (ADAR, IRF7, CXCL10, CASP1) and the FGF2 gene. CONCLUSIONS: DNA from tumorous colon epithelium, but not from the normal epithelial cells acts as a pro-metastatic factor to HT-29 cells through the overexpression of pro-metastatic genes through TLR9/MYD88 independent pathway. In contrast, DNA derived from healthy colonic epithelium induced TLR9 and STING signaling pathway in normal fibroblasts

VEGFR2 promotes central endothelial activation and the spread of pain in inflammatory arthritis

Chronic pain can develop in response to conditions such as inflammatory arthritis. The central mechanisms underlying the development and maintenance of chronic pain in humans are not well elucidated although there is evidence for a role of microglia and astrocytes. However in pre-clinical models of pain, including models of inflammatory arthritis, there is a wealth of evidence indicating roles for pathological glial reactivity within the CNS. In the spinal dorsal horn of rats with painful inflammatory arthritis we found both a significant increase in CD11b+ microglia-like cells and GFAP+ astrocytes associated with blood vessels, and the number of activated blood vessels expressing the adhesion molecule ICAM-1, indicating potential glio-vascular activation. Using pharmacological interventions targeting VEGFR2 in arthritic rats, to inhibit endothelial cell activation, the number of dorsal horn ICAM-1+ blood vessels, CD11b+ microglia and the development of secondary mechanical allodynia, an indicator of central sensitization, were all prevented. Targeting endothelial VEGFR2 by inducible Tie2-specific VEGFR2 knock-out also prevented secondary allodynia in mice and glio-vascular activation in the dorsal horn in response to inflammatory arthritis. Inhibition of VEGFR2 in vitro significantly blocked ICAM-1-dependent monocyte adhesion to brain microvascular endothelial cells, when stimulated with inflammatory mediators TNFa and VEGF-A165a. Taken together our findings suggest that a novel VEGFR2-mediated spinal cord gliovascular mechanism may promote peripheral CD11b+ circulating cell transmigration into the CNS parenchyma and contribute to the development of chronic pain in inflammatory arthritis. We hypothesise that preventing this glio-vascular activation and circulating cell translocation into the spinal cord could be a new therapeutic strategy for pain caused by rheumatoid arthritis