Surface electromyographic control of a novel phonemic interface for speech synthesis

Many individuals with minimal movement capabilities use AAC to communicate. These individuals require both an interface with which to construct a message (e.g., a grid of letters) and an input modality with which to select targets. This study evaluated the interaction of two such systems: (a) an input modality using surface electromyography (sEMG) of spared facial musculature, and (b) an onscreen interface from which users select phonemic targets. These systems were evaluated in two experiments: (a) participants without motor impairments used the systems during a series of eight training sessions, and (b) one individual who uses AAC used the systems for two sessions. Both the phonemic interface and the electromyographic cursor show promise for future AAC applications.F31 DC014872 - NIDCD NIH HHS; R01 DC002852 - NIDCD NIH HHS; R01 DC007683 - NIDCD NIH HHS; T90 DA032484 - NIDA NIH HHShttps://www.ncbi.nlm.nih.gov/pubmed/?term=Surface+electromyographic+control+of+a+novel+phonemic+interface+for+speech+synthesishttps://www.ncbi.nlm.nih.gov/pubmed/?term=Surface+electromyographic+control+of+a+novel+phonemic+interface+for+speech+synthesisPublished versio

Down syndrome and Alzheimer\u27s disease: A scoping review of functional performance and fall risk

INTRODUCTION: Alzheimer\u27s disease (AD) occurs in aging adults with Down syndrome (DS) at a higher prevalence and an earlier age than in typical aging adults. As with the general aging adult population, there is an urgent need to understand the preclinical and early phases of AD progression in the adult population with DS. The aim of this scoping review was to synthesize the current state of the evidence and identify gaps in the literature regarding functional activity performance and falls and their significance to disease staging (i.e., mild, moderate, and severe defined staging criteria) in relation to Alzheimer\u27s disease and related dementias (ADRD) in adults with DS. METHODS: This scoping review included six electronic databases (e.g., PsycInfo, Academic Search Complete, CINAHL, COCHRANE Library, MEDLINE, and PubMed). Eligible studies included participants with DS ≥25 years of age, studies with functional measures and/or outcomes (e.g., activities of daily living, balance, gait, motor control, speech, behavior, and cognition; falls; and fall risks), and studies that investigated AD pathology and implications. RESULTS: Fourteen eligible studies were included and categorized through a thematic analysis into the following themes: (1) physical activity and motor coordination (PAMC), (2) cognition, (3) behavior, and (4) sleep. The studies indicated how functional activity performance and engagement may contribute to early identification of those at risk of cognitive decline and AD development and/or progression. DISCUSSION: There is a need to expand the research regarding ADRD pathology relative to functional outcomes in adults with DS. Functional measures related to disease staging and cognitive impairment are essential to understanding how AD progression is characterized within real-world settings. This scoping review identified the need for additional mixed-methods research to examine the use of assessment and intervention related to function and its detection of cognitive decline and AD progression

Elevated iron concentration in putamen and cortical speech motor network in developmental stuttering

Theoretical accounts of developmental stuttering implicate dysfunctional cortico-striatal-thalamo-cortical motor loops through the putamen. However, the analysis of conventional MRI brain scans in individuals who stutter has failed to yield strong support for this theory in terms of reliable differences in the structure or function of the basal ganglia. Here, we performed quantitative mapping of brain tissue, which can be used to measure iron content alongside markers sensitive to myelin and thereby offers particular sensitivity to the measurement of iron-rich structures such as the basal ganglia. Analysis of these quantitative maps in 41 men and women who stutter and 32 individuals who are typically fluent revealed significant group differences in maps of R2∗, indicative of higher iron content in individuals who stutter in the left putamen and in left hemisphere cortical regions important for speech motor control. Higher iron levels in brain tissue in individuals who stutter could reflect elevated dopamine levels or lysosomal dysfunction, both of which are implicated in stuttering. This study represents the first use of these quantitative measures in developmental stuttering and provides new evidence of microstructural differences in the basal ganglia and connected frontal cortical regions

LaDIVA: A neurocomputational model providing laryngeal motor control for speech acquisition and production

Many voice disorders are the result of intricate neural and/or biomechanical impairments that are poorly understood. The limited knowledge of their etiological and pathophysiological mechanisms hampers effective clinical management. Behavioral studies have been used concurrently with computational models to better understand typical and pathological laryngeal motor control. Thus far, however, a unified computational framework that quantitatively integrates physiologically relevant models of phonation with the neural control of speech has not been developed. Here, we introduce LaDIVA, a novel neurocomputational model with physiologically based laryngeal motor control. We combined the DIVA model (an established neural network model of speech motor control) with the extended body-cover model (a physics-based vocal fold model). The resulting integrated model, LaDIVA, was validated by comparing its model simulations with behavioral responses to perturbations of auditory vocal fundamental frequency (fo) feedback in adults with typical speech. LaDIVA demonstrated capability to simulate different modes of laryngeal motor control, ranging from short-term (i.e., reflexive) and long-term (i.e., adaptive) auditory feedback paradigms, to generating prosodic contours in speech. Simulations showed that LaDIVA’s laryngeal motor control displays properties of motor equivalence, i.e., LaDIVA could robustly generate compensatory responses to reflexive vocal fo perturbations with varying initial laryngeal muscle activation levels leading to the same output. The model can also generate prosodic contours for studying laryngeal motor control in running speech. LaDIVA can expand the understanding of the physiology of human phonation to enable, for the first time, the investigation of causal effects of neural motor control in the fine structure of the vocal signal.Fil: Weerathunge, Hasini R.. Boston University; Estados UnidosFil: Alzamendi, Gabriel Alejandro. Universidad Nacional de Entre Ríos. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Investigación y Desarrollo en Bioingeniería y Bioinformática; ArgentinaFil: Cler, Gabriel J.. University of Washington; Estados UnidosFil: Guenther, Frank H.. Boston University; Estados UnidosFil: Stepp, Cara E.. Boston University; Estados UnidosFil: Zañartu, Matías. Universidad Técnica Federico Santa María; Chil

Speaking to a metronome reduces kinematic variability in typical speakers and people who stutter.

Background: Several studies indicate that people who stutter show greater variability in speech movements than people who do not stutter, even when the speech produced is perceptibly fluent. Speaking to the beat of a metronome reliably increases fluency in people who stutter, regardless of the severity of stuttering.Objectives: Here, we aimed to test whether metronome-timed speech reduces articulatory variability.Method: We analysed vocal tract MRI data from 24 people who stutter and 16 controls. Participants repeated sentences with and without a metronome. Midsagittal images of the vocal tract from lips to larynx were reconstructed at 33.3 frames per second. Any utterances containing dysfluencies or non-speech movements (e.g. swallowing) were excluded. For each participant, we measured the variability of movements (coefficient of variation) from the alveolar, palatal and velar regions of the vocal tract.Results: People who stutter had more variability than control speakers when speaking without a metronome, which was then reduced to the same level as controls when speaking with the metronome. The velar region contained more variability than the alveolar and palatal regions, which were similar.Conclusions: These results demonstrate that kinematic variability during perceptibly fluent speech is increased in people who stutter compared with controls when repeating naturalistic sentences without any alteration or disruption to the speech. This extends our previous findings of greater variability in the movements of people who stutter when producing perceptibly fluent nonwords compared with controls. These results also show, that in addition to increasing fluency in people who stutter, metronome-timed speech also reduces articulatory variability to the same level as that seen in control speakers

Functional organisation for verb generation in children with developmental language disorder

Developmental language disorder (DLD) is characterised by difficulties in learning one's native language for no apparent reason. These language difficulties occur in 7% of children and are known to limit future academic and social achievement. Our understanding of the brain abnormalities associated with DLD is limited. Here, we used a simple four-minute verb generation task (children saw a picture of an object and were instructed to say an action that goes with that object) to test children between the ages of 10–15 years (DLD N = 50, typically developing N = 67). We also tested 26 children with poor language ability who did not meet our criteria for DLD. Contrary to our registered predictions, we found that children with DLD did not have (i) reduced activity in language relevant regions such as the left inferior frontal cortex; (ii) dysfunctional striatal activity during overt production; or (iii) a reduction in left-lateralised activity in frontal cortex. Indeed, performance of this simple language task evoked activity in children with DLD in the same regions and to a similar level as in typically developing children. Consistent with previous reports, we found sub-threshold group differences in the left inferior frontal gyrus and caudate nuclei, but only when analysis was limited to a subsample of the DLD group (N = 14) who had the poorest performance on the task. Additionally, we used a two-factor model to capture variation in all children studied (N = 143) on a range of neuropsychological tests and found that these language and verbal memory factors correlated with activity in different brain regions. Our findings indicate a lack of support for some neurological models of atypical language learning, such as the procedural deficit hypothesis or the atypical lateralization hypothesis, at least when using simple language tasks that children can perform. These results also emphasise the importance of controlling for and monitoring task performance.</p

PloS one

Collagen 6A3 (Col6a3), a component of extracellular matrix, is often up-regulated in tumours and is believed to play a pro-oncogenic role. However the mechanisms of its tumorigenic activity are poorly understood. We show here that Col6a3 is highly expressed in densely growing mouse embryonic fibroblasts (MEFs). In MEFs where the TAF4 subunit of general transcription factor IID (TFIID) has been inactivated, elevated Col6a3 expression prevents contact inhibition promoting their 3 dimensional growth as foci and fibrospheres. Analyses of gene expression in densely growing Taf4(-/-) MEFs revealed repression of the Hippo pathway and activation of Wnt signalling. The Hippo activator Kibra/Wwc1 is repressed under dense conditions in Taf4(-/-) MEFs, leading to nuclear accumulation of the proliferation factor YAP1 in the cells forming 3D foci. At the same time, Wnt9a is activated and the Sfrp2 antagonist of Wnt signalling is repressed. Surprisingly, treatment of Taf4(-/-) MEFs with all-trans retinoic acid (ATRA) restores contact inhibition suppressing 3D growth. ATRA represses Col6a3 expression independently of TAF4 expression and Col6a3 silencing is sufficient to restore contact inhibition in Taf4(-/-) MEFs and to suppress 3D growth by reactivating Kibra expression to induce Hippo signalling and by inducing Sfrp2 expression to antagonize Wnt signalling. All together, these results reveal a critical role for Col6a3 in regulating both Hippo and Wnt signalling to promote 3D growth, and show that the TFIID subunit TAF4 is essential to restrain the growth promoting properties of Col6a3. Our data provide new insight into the role of extra cellular matrix components in regulating cell growth

The YEATS domain of Taf14 in Saccharomyces cerevisiae has a negative impact on cell growth

The role of a highly conserved YEATS protein motif is explored in the context of the Taf14 protein of Saccharomyces cerevisiae. In S. cerevisiae, Taf14 is a protein physically associated with many critical multisubunit complexes including the general transcription factors TFIID and TFIIF, the chromatin remodeling complexes SWI/SNF, Ino80 and RSC, Mediator and the histone modification enzyme NuA3. Taf14 is a member of the YEATS superfamily, conserved from bacteria to eukaryotes and thought to have a transcription stimulatory activity. However, besides its ubiquitous presence and its links with transcription, little is known about Taf14’s role in the nucleus. We use structure–function and mutational analysis to study the function of Taf14 and its well conserved N-terminal YEATS domain. We show here that the YEATS domain is not necessary for Taf14’s association with these transcription and chromatin remodeling complexes, and that its presence in these complexes is dependent only on its C-terminal domain. Our results also indicate that Taf14’s YEATS domain is not necessary for complementing the synthetic lethality between TAF14 and the general transcription factor TFIIS (encoded by DST1). Furthermore, we present evidence that the YEATS domain of Taf14 has a negative impact on cell growth: its absence enables cells to grow better than wild-type cells under stress conditions, like the microtubule destabilizing drug benomyl. Moreover, cells expressing solely the YEATS domain grow worser than cells expressing any other Taf14 construct tested, including the deletion mutant. Thus, this highly conserved domain should be considered part of a negative regulatory loop in cell growth