Independent Component Analysis of Event-Related Electroencephalography During Speech and Non-Speech Discrimination: : Implications for the Sensorimotor ∆∞ Rhythm in Speech Processing

Background: The functional significance of sensorimotor integration in acoustic speech processing is unclear despite more than three decades of neuroimaging research. Constructivist theories have long speculated that listeners make predictions about articulatory goals functioning to weight sensory analysis toward expected acoustic features (e.g. analysis-by-synthesis; internal models). Direct-realist accounts posit that sensorimotor integration is achieved via a direct match between incoming acoustic cues and articulatory gestures. A method capable of favoring one account over the other requires an ongoing, high-temporal resolution measure of sensorimotor cortical activity prior to and following acoustic input. Although scalp-recorded electroencephalography (EEG) provides a measure of cortical activity on a millisecond time scale, it has low-spatial resolution due to the blurring or mixing of cortical signals on the scalp surface. Recently proposed solutions to the low-spatial resolution of EEG known as blind source separation algorithms (BSS) have made the identification of distinct cortical signals possible. The µ rhythm of the EEG is known to briefly suppress (i.e., decrease in spectral power) over the sensorimotor cortex during the performance, imagination, and observation of biological movements, suggesting that it may provide a sensitive index of sensorimotor integration during speech processing. Neuroimaging studies have traditionally investigated speech perception in two-forced choice designs in which participants discriminate between pairs of speech and nonspeech control stimuli. As such, this classical design was employed in the current dissertation work to address the following specific aims to: 1) isolate independent components with traditional EEG signatures within the dorsal sensorimotor stream network; 2) identify components with features of the sensorimotor µ rhythm and; 3) investigate changes in timefrequency activation of the µ rhythm relative to stimulus type, onset, and discriminability (i.e., perceptual performance). In light of constructivist predictions, it was hypothesized that the µ rhythm would show significant suppression for syllable stimuli prior to and following stimulus onset, with significant differences between correct discrimination trials and those discriminated at chance levels. Methods: The current study employed millisecond temporal resolution EEG to measure ongoing decreases and increases in spectral power (event-related spectral perturbations; ERSPs) prior to, during, and after the onset of acoustic speech and tone-sweep stimuli embedded in white-noise. Sixteen participants were asked to passively listen to or actively identify speech and tone signals in a two-force choice same/different discrimination task. To investigate the role of ERSPs in perceptual identification performance, high signal-to-noise ratios (SNRs) in which speech and tone identification was significantly better than chance (+4dB) and low SNRs in which performance was below chance (-6dB and -18dB) were compared to a baseline of passive noise. Independent component analysis (ICA) of the EEG was used to reduce artifact and source mixing due to volume conduction. Independent components were clustered using measure product methods and cortical source modeling, including spectra, scalp distribution, equivalent current dipole estimation (ECD), and standardized low-resolution tomography (sLORETA). Results: Data analysis revealed six component clusters consistent with a bilateral dorsal-stream sensorimotor network, including component clusters localized to the precentral and postcentral gyrus, cingulate cortex, supplemental motor area, and posterior temporal regions. Timefrequency analysis of the left and right lateralized µ component clusters revealed significant (pFDR\u3c.05) suppression in the traditional beta frequency range (13-30Hz) prior to, during, and following stimulus onset. No significant differences from baseline were found for passive listening conditions. Tone discrimination was different from passive noise in the time period following stimulus onset only. No significant differences were found for correct relative to chance tone stimuli. For both left and right lateralized clusters, early suppression (i.e., prior to stimulus onset) compared to the passive noise baseline was found for the syllable discrimination task only. Significant differences between correct trials and trials identified at chance level were found for the time period following stimulus offset for the syllable discrimination task in left lateralized cluster. Conclusions: As this is the first study to employ BSS methods to isolate components of the EEG during acoustic speech and non-speech discrimination, findings have important implications for the functional role of sensorimotor integration in speech processing. Consistent with expectations, the current study revealed component clusters associated with source models within the sensorimotor dorsal stream network. Beta suppression of the µ component clusters in both the left and right hemispheres is consistent with activity in the precentral gyrus prior to and following acoustic input. As early suppression of the µ was found prior the syllable discrimination task, the present findings favor internal model concepts of speech processing over mechanisms proposed by direct-realists. Significant differences between correct and chance syllable discrimination trials are also consistent with internal model concepts suggesting that sensorimotor integration is related to perceptual performance at the point in time when initial articulatory hypotheses are compared with acoustic input. The relatively inexpensive, noninvasive EEG methodology used in this study may have translational value in the future as a brain computer interface (BCI) approach. As deficits in sensorimotor integration are thought to underlie cognitive-communication impairments in a number of communication disorders, the development of neuromodulatory feedback approaches may provide a novel avenue for augmenting current therapeutic protocols

Eye-to-face Gaze in Stuttered Versus Fluent Speech

The present study investigated the effects of viewing audio-visual presentations of stuttered relative to fluent speech samples on the ocular reactions of participants. Ten adults, 5 males and 5 females, aged 18-55 who had a negative history of any speech, language and hearing disorders participated in the study. Participants were shown three 30 second audio-visual recordings of stuttered speech, and three 30 second audio-visual recordings of fluent speech, with a three second break (black screen) between the presentation of each video. All three individuals who stutter were rated as ‘severe’ (SSI-3, Riley, 1994), exhibiting high levels of struggle filled with overt stuttering behaviors such as repetitions, prolongations and silent postural fixations on speech sounds, in addition to tension-filled secondary behaviors such as head jerks, lip protrusion, and facial grimaces. During stuttered and fluent conditions, ocular behaviors of the viewers including pupillary movement, fixation time, eye-blink, and relative changes in pupil diameter were recorded using the Arrington ViewPoint Eye-Tracker infrared camera and the system’s data analysis software (e.g., Wong & Cronin-Colomb & Neargarder, 2005) via a 2.8GHz Dell Optiplex GX270 computer. For all ocular measures except fixation time, there were significant (p\u3c.05) differences for stuttered relative to fluent speech. There was an increase in the number of pupillary movements, blinks, and relative change in pupil diameter and a decrease in time fixated when viewing stuttered relative to fluent speech samples. While not significant, participants fixated or directed their attention for less time during stuttered than fluent conditions, indicating decreased attention overall during stuttered speech samples. Increases in eye-blink data and pupil-dilation data were also significant. Because both eye-blink, as a measure of the startle reflex, and pupil-dilation are resistant to voluntary control or are completely under the control of the autonomic nervous system, significant increases in both for stuttered relative to fluent speech indicate a visceral reaction to stuttering

Editorial:Developing research potential in the primary and community-nursing workforce

the impact of a community of practic

The Bromodomain and Extra-Terminal Protein Inhibitor OTX015 Suppresses T Helper Cell Proliferation and Differentiation

BACKGROUND: Dynamic epigenetic alterations accompanying CD4+ T helper cell differentiation have been implicated in multiple autoimmune diseases. The bromodomain and extra-terminal (BET) proteins are epigenetic regulators that recognize and bind to acetylated histones in chromatin and are targets for pharmacological inhibition. In this study we tested a new BET inhibitor under clinical development, OTX015, to interrogate its effects on key CD4+ T cell subsets associated with autoimmunity. METHODS: Naïve and memory murine and human CD4+ T cells were isolated and differentiated into populations characterized by the expression of interferon (IFN)-γ and interleukin (IL)-17. Cultured cells were then exposed to varying concentrations of OTX015 in vitro, and its impact on cytokine expression was quantified by flow cytometry. In parallel, the expression of the transcription factors TBX21 and RORC was quantified by PCR. A previously studied BET inhibitor JQ1 was used as a pharmacological control. RESULTS: OTX015 suppressed both murine and human CD4+ T cell proliferation. Its impact on cytokine expression varied in murine and human naïve and memory subsets. OTX015 was similarly effective as JQ1 in the suppression of cytokines and T helper cell proliferation. Higher concentrations of OTX015 also had a greater impact on the viability of murine versus human cells. IL-17 and IFN-γ expression was not altered in murine memory CD4+ T cells, whereas in human memory CD4+ T cells, OTX015 inhibited IL-17, but not IFN-γ. Across all human T cell subsets OTX015 suppressed IL-17 more effectively than IFN-γ. CONCLUSION: Our studies demonstrate that OTX015 has anti-inflammatory effects by suppressing murine and human CD4+ T cell proliferation and subset-dependent proinflammatory cytokine expression, including the selective suppression of IL-17 in human memory CD4+ T cells

Physical and Genetic Structure of the Maize Genome Reflects Its Complex Evolutionary History

Maize (Zea mays L.) is one of the most important cereal crops and a model for the study of genetics, evolution, and domestication. To better understand maize genome organization and to build a framework for genome sequencing, we constructed a sequence-ready fingerprinted contig-based physical map that covers 93.5% of the genome, of which 86.1% is aligned to the genetic map. The fingerprinted contig map contains 25,908 genic markers that enabled us to align nearly 73% of the anchored maize genome to the rice genome. The distribution pattern of expressed sequence tags correlates to that of recombination. In collinear regions, 1 kb in rice corresponds to an average of 3.2 kb in maize, yet maize has a 6-fold genome size expansion. This can be explained by the fact that most rice regions correspond to two regions in maize as a result of its recent polyploid origin. Inversions account for the majority of chromosome structural variations during subsequent maize diploidization. We also find clear evidence of ancient genome duplication predating the divergence of the progenitors of maize and rice. Reconstructing the paleoethnobotany of the maize genome indicates that the progenitors of modern maize contained ten chromosomes

Conserved Role of unc-79 in Ethanol Responses in Lightweight Mutant Mice

The mechanisms by which ethanol and inhaled anesthetics influence the nervous system are poorly understood. Here we describe the positional cloning and characterization of a new mouse mutation isolated in an N-ethyl-N-nitrosourea (ENU) forward mutagenesis screen for animals with enhanced locomotor activity. This allele, Lightweight (Lwt), disrupts the homolog of the Caenorhabditis elegans (C. elegans) unc-79 gene. While Lwt/Lwt homozygotes are perinatal lethal, Lightweight heterozygotes are dramatically hypersensitive to acute ethanol exposure. Experiments in C. elegans demonstrate a conserved hypersensitivity to ethanol in unc-79 mutants and extend this observation to the related unc-80 mutant and nca-1;nca-2 double mutants. Lightweight heterozygotes also exhibit an altered response to the anesthetic isoflurane, reminiscent of unc-79 invertebrate mutant phenotypes. Consistent with our initial mapping results, Lightweight heterozygotes are mildly hyperactive when exposed to a novel environment and are smaller than wild-type animals. In addition, Lightweight heterozygotes exhibit increased food consumption yet have a leaner body composition. Interestingly, Lightweight heterozygotes voluntarily consume more ethanol than wild-type littermates. The acute hypersensitivity to and increased voluntary consumption of ethanol observed in Lightweight heterozygous mice in combination with the observed hypersensitivity to ethanol in C. elegans unc-79, unc-80, and nca-1;nca-2 double mutants suggests a novel conserved pathway that might influence alcohol-related behaviors in humans

2007, Physical and genetic structure of the maize genome reflects its complex evolutionary history, PLoS

Maize (Zea mays L.) is one of the most important cereal crops and a model for the study of genetics, evolution, and domestication. To better understand maize genome organization and to build a framework for genome sequencing, we constructed a sequence-ready fingerprinted contig-based physical map that covers 93.5% of the genome, of which 86.1% is aligned to the genetic map. The fingerprinted contig map contains 25,908 genic markers that enabled us to align nearly 73% of the anchored maize genome to the rice genome. The distribution pattern of expressed sequence tags correlates to that of recombination. In collinear regions, 1 kb in rice corresponds to an average of 3.2 kb in maize, yet maize has a 6-fold genome size expansion. This can be explained by the fact that most rice regions correspond to two regions in maize as a result of its recent polyploid origin. Inversions account for the majority of chromosome structural variations during subsequent maize diploidization. We also find clear evidence of ancient genome duplication predating the divergence of the progenitors of maize and rice. Reconstructing the paleoethnobotany of the maize genome indicates that the progenitors of modern maize contained ten chromosomes. Citation: Wei F, Coe E, Nelson W, Bharti AK, Engler F, et al. (2007) Physical and genetic structure of the maize genome reflects its complex evolutionary history. PLoS Genet 3(7): e123

Synthase-selected sorting approach identifies a beta-lactone synthase in a nudibranch symbiotic bacterium

[Background] Nudibranchs comprise a group of > 6000 marine soft-bodied mollusk species known to use secondary metabolites (natural products) for chemical defense. The full diversity of these metabolites and whether symbiotic microbes are responsible for their synthesis remains unexplored. Another issue in searching for undiscovered natural products is that computational analysis of genomes of uncultured microbes can result in detection of novel biosynthetic gene clusters; however, their in vivo functionality is not guaranteed which limits further exploration of their pharmaceutical or industrial potential. To overcome these challenges, we used a fluorescent pantetheine probe, which produces a fluorescent CoA-analog employed in biosynthesis of secondary metabolites, to label and capture bacterial symbionts actively producing these compounds in the mantle of the nudibranch Doriopsilla fulva.[Results] We recovered the genome of Candidatus Doriopsillibacter californiensis from the Ca. Tethybacterales order, an uncultured lineage of sponge symbionts not found in nudibranchs previously. It forms part of the core skin microbiome of D. fulva and is nearly absent in its internal organs. We showed that crude extracts of D. fulva contained secondary metabolites that were consistent with the presence of a beta-lactone encoded in Ca. D. californiensis genome. Beta-lactones represent an underexplored group of secondary metabolites with pharmaceutical potential that have not been reported in nudibranchs previously.[Conclusions] Altogether, this study shows how probe-based, targeted sorting approaches can capture bacterial symbionts producing secondary metabolites in vivo.The work (proposal: 10.46936/10.25585/60000940) conducted by the U.S. Department of Energy Joint Genome Institute (https://ror.org/04xm1d337), a DOE Office of Science User Facility, is supported by the Office of Science of the U.S. Department of Energy operated under Contract No. DE-AC02-05CH11231. RS, MB, JL, and TW are supported by NIH grant R01AI168993. The John Templeton Foundation (grant nos. 51250 and 60973) supported TT and SVD, and the Gordon and Betty Moore Foundation grants (GBMF7617 and GBMF9340) supported SVD. MD is supported by the Generalitat Valenciana program GenT grant number CDEIGENT/2021/008. SPE is supported by a FPU grant from the Spanish Ministry of Universities (Reference: FPU20/05756).Peer reviewe

Modes of Gene Duplication Contribute Differently to Genetic Novelty and Redundancy, but Show Parallels across Divergent Angiosperms

BACKGROUND: Both single gene and whole genome duplications (WGD) have recurred in angiosperm evolution. However, the evolutionary effects of different modes of gene duplication, especially regarding their contributions to genetic novelty or redundancy, have been inadequately explored. RESULTS: In Arabidopsis thaliana and Oryza sativa (rice), species that deeply sample botanical diversity and for which expression data are available from a wide range of tissues and physiological conditions, we have compared expression divergence between genes duplicated by six different mechanisms (WGD, tandem, proximal, DNA based transposed, retrotransposed and dispersed), and between positional orthologs. Both neo-functionalization and genetic redundancy appear to contribute to retention of duplicate genes. Genes resulting from WGD and tandem duplications diverge slowest in both coding sequences and gene expression, and contribute most to genetic redundancy, while other duplication modes contribute more to evolutionary novelty. WGD duplicates may more frequently be retained due to dosage amplification, while inferred transposon mediated gene duplications tend to reduce gene expression levels. The extent of expression divergence between duplicates is discernibly related to duplication modes, different WGD events, amino acid divergence, and putatively neutral divergence (time), but the contribution of each factor is heterogeneous among duplication modes. Gene loss may retard inter-species expression divergence. Members of different gene families may have non-random patterns of origin that are similar in Arabidopsis and rice, suggesting the action of pan-taxon principles of molecular evolution. CONCLUSION: Gene duplication modes differ in contribution to genetic novelty and redundancy, but show some parallels in taxa separated by hundreds of millions of years of evolution

The James Webb Space Telescope Mission: Optical Telescope Element Design, Development, and Performance

The James Webb Space Telescope (JWST) is a large, infrared space telescope that has recently started its science program which will enable breakthroughs in astrophysics and planetary science. Notably, JWST will provide the very first observations of the earliest luminous objects in the Universe and start a new era of exoplanet atmospheric characterization. This transformative science is enabled by a 6.6 m telescope that is passively cooled with a 5-layer sunshield. The primary mirror is comprised of 18 controllable, low areal density hexagonal segments, that were aligned and phased relative to each other in orbit using innovative image-based wavefront sensing and control algorithms. This revolutionary telescope took more than two decades to develop with a widely distributed team across engineering disciplines. We present an overview of the telescope requirements, architecture, development, superb on-orbit performance, and lessons learned. JWST successfully demonstrates a segmented aperture space telescope and establishes a path to building even larger space telescopes.Comment: accepted by PASP for JWST Overview Special Issue; 34 pages, 25 figure