Frontal theta band oscillations predict error correction and posterror slowing in typing

Performance errors are associated with robust behavioral and electroencephalography (EEG) effects. However, there is a debate about the nature of the relationship between these effects and implicit versus explicit error awareness. Our aim was to study the relationship between error related electrophysiological effects, such as spectral perturbations in fronto-medial theta band oscillations (FMT), and error awareness in typing. Typing has an advantage as an experimental paradigm in that detected errors are quickly and habitually signaled by the participant using backspace, allowing separation of detected from undetected errors without interruption in behavior. Typing is thought to be controlled hierarchically via inner and outer loops, which rely on different sources for error detection. Touch-typist participants were asked to copy-type 100 sentences as EEG was recorded in the absence of visual feedback. Continuous EEG data were analyzed using independent component analysis (ICA). Time-frequency and ERP analyses were applied to emergent independent components. The results show that single-trial FMT parameters and error related negativity (ERN) amplitude predict overt, adaptive posterror actions such as error correction via backspace; and, posterror slowing, reflecting implicit error awareness. In addition, we found that those uncorrected errors which were slowed down the most were also the ones associated with a high level of FMT activity. Our results as a whole show that FMT are related to neural mechanisms involved in explicit awareness of errors, and input from inner loop is sufficient for error correction in typing. (PsycINFO Database Record (c) 2017 APA, all rights reserved

T-cell hyperactivation and paralysis in severe COVID-19 infection revealed by single-cell analysis

Severe COVID-19 patients show various immunological abnormalities including T-cell reduction and cytokine release syndrome, which can be fatal and is a major concern of the pandemic. However, it is poorly understood how T-cell dysregulation can contribute to the pathogenesis of severe COVID-19. Here we show single cell-level mechanisms for T-cell dysregulation in severe COVID-19, demonstratingnewpathogenetic mechanisms ofT-cell activation and differentiation underlying severe COVID-19. By in silico sorting CD4+ T-cells from a single cell RNA-seq dataset, we found that CD4+ T-cells were highly activated and showed unique differentiation pathways in the lung of severe COVID-19 patients. Notably, those T-cells in severe COVID-19 patients highly expressed immunoregulatory receptors and CD25, whilst repressing the expression of FOXP3. Furthermore, we show that CD25+ hyperactivated T-cells differentiate into multiple helper T-cell lineages, showing multifaceted effector T-cells with Th1 and Th2 characteristics. Lastly, we show that CD25-expressing hyperactivated T-cells produce the protease Furin, which facilitates the viral entry of SARS-CoV-2. Collectively, CD4+T-cells from severe COVID-19 patients are hyperactivated and FOXP3-mediated negative feedback mechanisms are impaired in the lung, which may promote immunopathology. Therefore, our study proposes a new model of T-cell hyperactivation and paralysis that drives immunopathology in severe COVID-19

Brief homogeneous TCR signals instruct common iNKT progenitors whose effector diversification is characterized by subsequent cytokine signaling.

Innate-like T cell populations expressing conserved TCRs play critical roles in immunity through diverse developmentally acquired effector functions. Focusing on the prototypical lineage of invariant natural killer T (iNKT) cells, we sought to dissect the mechanisms and timing of fate decisions and functional effector differentiation. Utilizing induced expression of the semi-invariant NKT cell TCR on double positive thymocytes, an initially highly synchronous wave of iNKT cell development was triggered by brief homogeneous TCR signaling. After reaching a uniform progenitor state characterized by IL-4 production potential and proliferation, effector subsets emerged simultaneously, but then diverged toward different fates. While NKT17 specification was quickly completed, NKT1 cells slowly differentiated and expanded. NKT2 cells resembled maturing progenitors, which gradually diminished in numbers. Thus, iNKT subset diversification occurs in dividing progenitor cells without acute TCR input but utilizes multiple active cytokine signaling pathways. These data imply a two-step model of iNKT effector differentiation