Motor and Linguistic Linking of Space and Time in the Cerebellum

Background: Recent literature documented the presence of spatial-temporal interactions in the human brain. The aim of the present study was to verify whether representation of past and future is also mapped onto spatial representations and whether the cerebellum may be a neural substrate for linking space and time in the linguistic domain. We asked whether processing of the tense of a verb is influenced by the space where response takes place and by the semantics of the verb. Principal Findings: Responses to past tense were facilitated in the left space while responses to future tense were facilitated in the right space. Repetitive transcranial magnetic stimulation (rTMS) of the right cerebellum selectively slowed down responses to future tense of action verbs; rTMS of both cerebellar hemispheres decreased accuracy of responses to past tense in the left space and to future tense in the right space for non-verbs, and to future tense in the right space for state verbs. Conclusions: The results suggest that representation of past and future is mapped onto spatial formats and that motor action could represent the link between spatial and temporal dimensions. Right cerebellar, left motor brain networks could be part of the prospective brain, whose primary function is to use past experiences to anticipate future events. Bot

Implications of non-feasible transformations among icosahedral hh orbitals

The symmetric group $S_6$ that permutes the six five-fold axes of an icosahedron is introduced to go beyond the simple rotations that constitute the icosahedral group $I$. Owing to the correspondence $h\leftrightarrow d$, the calculation of the Coulomb energies for the icosahedral configurations $h^N$ based on the sequence $O(5) \supset S_6 \supset S_5 \supset I$ can be brought to bear on Racah's classic theory for the atomic d shell based on $SO(5) \supset SO_L(3) \supset I$. Among the elements of $S_6$ is the kaleidoscope operator ${\cal K}$ that rotates the weight space of SO(5) by $\pi/2$. Its use explains some puzzling degeneracies in d^3 involving the spectroscopic terms ^2P, ^2F, ^2G and ^2H.Comment: Tentatively scheduled to appear in Physical Preview Letters Apr 5, 99. Revtex, 1 ps figur

Effect of the CXCR4 antagonist plerixafor on endogenous neutrophil dynamics in the bone marrow, lung and spleen

Treatment with the CXCR4 antagonist, plerixafor (AMD3100), has been proposed for clinical use in patients with WHIM (warts, hypogammaglobulinemia, infections and myelokathexis) syndrome and in pulmonary fibrosis. However, there is controversy with respect to the impact of plerixafor on neutrophil dynamics in the lung, which may affect its safety profile. In this study we investigated the kinetics of endogenous neutrophils by direct imaging, using confocal intravital microscopy in mouse bone marrow, spleen and lungs. Neutrophils are observed increasing their velocity and exiting the bone marrow following plerixafor administration, with a concomitant increase in neutrophil numbers in the blood and spleen, while the marginated pool of neutrophils in the lung microvasculature remained unchanged in terms of numbers and cell velocity. Use of autologous radiolabeled neutrophils and SPECT/CT imaging in healthy volunteers showed that plerixafor did not affect GM-CSF-primed neutrophil entrapment or release in the lungs. Taken together these data suggest that plerixafor causes neutrophil mobilization from the bone marrow but does not impact on lung marginated neutrophil dynamics and thus is unlikely to compromise respiratory host defense both in humans and mice.This work was funded by a grant provided to JP by the Lung Foundation Netherlands (5.2.14.058JO), the NIHR Cambridge Biomedical Research Centre and NIHR Imperial Biomedical Research Centre. ERC and CS’ laboratories receive grant support from the Medical Research Council, Wellcome Trust, NIHR, GlaxoSmithKline, MedImmune Ltd., and Bristol-Myers Squibb. CLC is supported by Bloodwise (12033), CRUK (C36195/A1183) and European Research Council (ERC) (337066). CP is supported by Bloodwise (12033). The Facility for Imaging by Light Microscopy (FILM) at Imperial College London is part-supported by funding from the Wellcome Trust (grant 104931/Z/14/Z) and BBSRC (grant BB/L015129/1). KDF is supported by funding from the Wellcome Trust (201356/Z/16/Z). LMC is supported by core funding from Cancer Research UK (A23983 and A17196)

Predicting first-episode psychosis patients who will never relapse over 10 years.

BACKGROUND: Although relapse in psychosis is common, a small proportion of patients will not relapse in the long term. We examined the proportion and predictors of patients who never relapsed in the 10 years following complete resolution of positive symptoms from their first psychotic episode. METHOD: Patients who previously enrolled in a 12-month randomized controlled trial on medication discontinuation and relapse following first-episode psychosis (FEP) were followed up after 10 years. Relapse of positive symptoms was operationalized as a change from a Clinical Global Impression scale positive score of <3 for at least 3 consecutive months to a score of ⩾3 (mild or more severe). Baseline predictors included basic demographics, premorbid functioning, symptoms, functioning, and neurocognitive functioning. RESULTS: Out of 178 first-episode patients, 37 (21%) never relapsed during the 10-year period. Univariate predictors (p ⩽ 0.1) of patients who never relapsed included a duration of untreated psychosis (DUP) ⩽30 days, diagnosed with non-schizophrenia spectrum disorders, having less severe negative symptoms, and performing better in logical memory immediate recall and verbal fluency tests. A multivariate logistic regression analysis further suggested that the absence of any relapsing episodes was significantly related to better short-term verbal memory, shorter DUP, and non-schizophrenia spectrum disorders. CONCLUSIONS: Treatment delay and neurocognitive function are potentially modifiable predictors of good long-term prognosis in FEP. These predictors are informative as they can be incorporated into an optimum risk prediction model in the future, which would help with clinical decision making regarding maintenance treatment in FEP

Frequency of Peripheral CD8+ T Cells Expressing Chemo-Attractant Receptors CCR1, 4 and 5 Increases in NPC Patients with EBV Clearance upon Radiotherapy

Radiotherapy (RT) is the standard-of-care for Epstein–Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC), where the post-RT clearance of plasma EBV DNA is prognostic. Currently, it is not known whether the post-RT clearance of plasma EBV DNA is related to the presence of circulating T-cell subsets. Blood samples from NPC patients were used to assess the frequency of T-cell subsets relating to differentiation, co-signaling and chemotaxis. Patients with undetectable versus detectable plasma EBV DNA levels post-RT were categorized as clearers vs. non-clearers. Clearers had a lower frequency of PD1+CD8+ T cells as well as CXCR3+CD8+ T cells during RT compared to non-clearers. Clearers exclusively showed a temporal increase in chemo-attractant receptors CCR1, 4 and/or 5, expressing CD8+ T cells upon RT. The increase in CCR-expressing CD8+ T cells was accompanied by a drop in naïve CD8+ T cells and an increase in OX40+CD8+ T cells. Upon stratifying these patients based on clinical outcome, the dynamics of CCR-expressing CD8+ T cells were in concordance with the non-recurrence of NPC. In a second cohort, non-recurrence associated with higher quantities of circulating CCL14 and CCL15. Collectively, our findings relate plasma EBV DNA clearance post-RT to T-cell chemotaxis, which requires validation in larger cohorts.</p

Quantitative High-Speed Laryngoscopic Analysis of Vocal Fold Vibration in Fatigued Voice of Young Karaoke Singers

Summary: Purpose. The present study aimed to determine whether there were physiological differences in the vocal fold vibration between nonfatigued and fatigued voices using high-speed laryngoscopic imaging and quantitative analysis. Methods. Twenty participants aged from 18 to 23 years (mean, 21.2 years; standard deviation, 1.3 years) with normal voice were recruited to participate in an extended singing task. Vocal fatigue was induced using a singing task. Highspeed laryngoscopic image recordings of /i/ phonation were taken before and after the singing task. The laryngoscopic images were semiautomatically analyzed with the quantitative high-speed video processing program to extract indices related to the anteroposterior dimension (length), transverse dimension (width), and the speed of opening and closing. Results. Significant reduction in the glottal length-to-width ratio index was found after vocal fatigue. Physiologically, this indicated either a significantly shorter (anteroposteriorly) or a wider (transversely) glottis after vocal fatigue. Conclusion. The high-speed imaging technique using quantitative analysis has the potential for early identification of vocally fatigued voice