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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: O'Hanlon, Erik; Howley, Sarah; Prasad, Sarah; McGrath, Jane; +4 Authors

    AbstractIntroductionImpaired spatial working memory is a core cognitive deficit observed in people with 22q11 Deletion syndrome (22q11DS) and has been suggested as a candidate endophenotype for schizophrenia. However, to date, the neuroanatomical mechanisms describing its structural and functional underpinnings in 22q11DS remain unclear. We quantitatively investigate the cognitive processes and associated neuroanatomy of spatial working memory in people with 22q11DS compared to matched controls. We examine whether there are significant between‐group differences in spatial working memory using task related fMRI, Voxel based morphometry and white matter fiber tractography.Materials and MethodsMultimodal magnetic resonance imaging employing functional, diffusion and volumetric techniques were used to quantitatively assess the cognitive and neuroanatomical features of spatial working memory processes in 22q11DS. Twenty‐six participants with genetically confirmed 22q11DS aged between 9 and 52 years and 26 controls aged between 8 and 46 years, matched for age, gender, and handedness were recruited.ResultsPeople with 22q11DS have significant differences in spatial working memory functioning accompanied by a gray matter volume reduction in the right precuneus. Gray matter volume was significantly correlated with task performance scores in these areas. Tractography revealed extensive differences along fibers between task‐related cortical activations with pronounced differences localized to interhemispheric commissural fibers within the parietal section of the corpus callosum.ConclusionsAbnormal spatial working memory in 22q11DS is associated with aberrant functional activity in conjunction with gray and white matter structural abnormalities. These anomalies in discrete brain regions may increase susceptibility to the development of psychiatric disorders such as schizophrenia. Hum Brain Mapp 37:4689–4705, 2016. © 2016 Wiley Periodicals, Inc.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Human Brain Mappingarrow_drop_down
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Human Brain Mapping
    Article . 2016 . Peer-reviewed
    License: Wiley Online Library User Agreement
    Data sources: Crossref; NARCIS
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Europe PubMed Central
    Other literature type . 2016
    Data sources: PubMed Central
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Human Brain Mappingarrow_drop_down
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Human Brain Mapping
      Article . 2016 . Peer-reviewed
      License: Wiley Online Library User Agreement
      Data sources: Crossref; NARCIS
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Europe PubMed Central
      Other literature type . 2016
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Jagessar, Anwar; Kap, Yolanda; Heijmans, N; van Driel, N; +7 Authors

    Experimental autoimmune encephalomyelitis in the neotropical primate common marmoset (Callithrix jacchus) is a relevant autoimmune animal model of multiple sclerosis. T cells specific for peptide 34 to 56 of myelin/oligodendrocyte glycoprotein (MOG(34-56)) have a central pathogenic role in this model. The aim of this study was to assess the requirement for innate immune stimulation for activation of this core pathogenic autoimmune mechanism. Marmoset monkeys were sensitized against synthetic MOG(34-56) peptide alone or in combination with the nonencephalitogenic peptide MOG(74-96) formulated in incomplete Freund adjuvant, which lacks microbial components. Experimental autoimmune encephalomyelitis development was recorded by monitoring neurological signs, brain magnetic resonance imaging, and longitudinal profiling of cellular and humoral immune parameters. All monkeys developed autoimmune inflammatory/demyelinating central nervous system disease characterized by massive brain and spinal cord demyelinating white matter lesions with activated macrophages and CD3(+) T cells. Immune profiling ex vivo demonstrated the activation of mainly CD3(+)CD4(+)/8(+)CD56(+) T cells against MOG(34-56). Upon ex vivo stimulation, these T cells produced more interleukin 17A compared with TH1 cytokines (e. g. interferon-gamma) and displayed peptide-specific cytolytic activity. These results indicate that the full spectrum of marmoset experimental autoimmune encephalomyelitis can be induced by sensitization against a single MOG peptide in incomplete Freund adjuvant lacking microbial compounds for innate immune activation and by eliciting antigen-specific T-cell cytolytic activity.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Journal of Neuropath...arrow_drop_down
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    NARCIS
    Article . 2010
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Journal of Neuropathology & Experimental Neurology
    Article . 2010 . Peer-reviewed
    Data sources: Crossref
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Journal of Neuropath...arrow_drop_down
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
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      Article . 2010
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Journal of Neuropathology & Experimental Neurology
      Article . 2010 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Radue, E.W.; Barkhof, F.; Kappos, L.; Sprenger, T.; +6 Authors

    Objective: We investigated the determinants and clinical correlations of MRI-detected brain volume loss (BVL) among patients with relapsing-remitting multiple sclerosis from the phase 3 trials of fingolimod: FREEDOMS, FREEDOMS II, and TRANSFORMS. Methods: Post hoc analyses were conducted in the intent-to-treat populations from each trial and in a combined dataset of 3,635 patients from the trials and their extensions. The relationship between brain volume changes and demographic, clinical, and MRI parameters was studied in pairwise correlations (Pearson) and in multiple regression models. The relative frequency of confirmed disability progression was evaluated in the combined dataset by strata of concurrent BVL at up to 4 years. Results: Increasing age, disease duration, T2 lesion volume, T1-hypointense lesion volume, and disability were associated with reduced brain volume (p < 0.001, all). The strongest individual baseline predictors of on-study BVL were T2 lesion volume, gadolinium-enhancing lesion count, and T1-hypointense lesion volume (p < 0.01, all). During each study, BVL correlated most strongly with cumulative gadolinium-enhancing lesion count, new/enlarged T2 lesion count (p < 0.001, both), and number of confirmed on-study relapses (p < 0.01). Over 4 years in the combined dataset (mean exposure to study drug, 2.4 years), confirmed disability progression was most frequent in patients with greatest BVL. Conclusions: Rate of BVL in patients during the fingolimod trials correlated with disease severity at baseline and new disease activity on study, and was associated with worsening disability.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2015
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    Neurology
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    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
    Neurology
    Article . 2015 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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      Europe PubMed Central
      Article . 2015
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      Neurology
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      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      image/svg+xml Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao Closed Access logo, derived from PLoS Open Access logo. This version with transparent background. http://commons.wikimedia.org/wiki/File:Closed_Access_logo_transparent.svg Jakob Voss, based on art designer at PLoS, modified by Wikipedia users Nina and Beao
      Neurology
      Article . 2015 . Peer-reviewed
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Suzanne L Franklin; Sophie Schmid; Clemens Bos; Matthias J.P. van Osch;

    PurposeIn this study, the influence of the cardiac cycle on the amount of label produced by a velocity‐selective (VSASL) and acceleration‐selective arterial spin labeling (AccASL) module was investigated.MethodsA short‐PLD sequence was developed where a single VSASL‐ or AccASL‐module was preceded by pCASL labeling to isolate the arterial blood pool. ASL subtraction was performed with label/control images with similar cardiac phase and time‐of‐measurement, followed by retrospective binning in 10 cardiac phase bins. ASL signal variation over the heart cycle was evaluated and tested for significance using a permutation test.ResultsVSASL and AccASL showed significant arterial signal fluctuations over the cardiac cycle of up to ~36% and ~64%, respectively, mainly in areas containing large arteries. pCASL also showed significant signal fluctuations, of up to ~25% in arteries. Raw label/control images confirmed that the observed signal fluctuations were caused by the amount of label produced during the cardiac cycle, rather than inflow‐effects, because the raw images did not all show equal cardiac phase dependence.No significant effects of the cardiac cycle were found on the gray matter ASL‐signal.ConclusionSignificant influence of the cardiac cycle on the generated label was found for spatially nonselective ASL‐sequences. Hence, to become independent of the cardiac cycle, sufficient averages need to be taken. Alternatively, these findings could be highly interesting for the purpose of quantifying pulsatility more distally in the vascular tree.

    image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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    Europe PubMed Central
    Article . 2019
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    NARCIS
    Article . 2020
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    Magnetic Resonance in Medicine; NARCIS
    Article . 2019 . 2020 . Peer-reviewed
    License: CC BY NC
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/ Europe PubMed Centra...arrow_drop_down
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      Europe PubMed Central
      Article . 2019
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      Article . 2020
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      Magnetic Resonance in Medicine; NARCIS
      Article . 2019 . 2020 . Peer-reviewed
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      image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
      Magnetic Resonance in Medicine
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  • image/svg+xml art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos Open Access logo, converted into svg, designed by PLoS. This version with transparent background. http://commons.wikimedia.org/wiki/File:Open_Access_logo_PLoS_white.svg art designer at PLoS, modified by Wikipedia users Nina, Beao, JakobVoss, and AnonMoos http://www.plos.org/
    Authors: Deckers, C.L.P.; Hekster, Y.A.; Keyser, A.J.M.; Meinardi, H.; +1 Authors

    Summary: Purpose: We reviewed the literature to determine whether an analysis of published data could clarify the relationship between antiepileptic drug (AED) polytherapy and adverse affects (AE). We highlight the problems encountered. Methods: We made a Medline‐search for articles published between 1974 and 1994 reporting the number of AE and doses or serum levels of every AED, per patient or treatment group, and used the PDD/DDD ratio to calculate AED load per patient from doses or the OSL/AToxL ratio to do so from serum levels of individual drugs. The PDD/DDD is the sum of ratios of the actual prescribed daily doses divided by the published average therapeutic dose of each drug. The OSL/AToxL is the sum of each observed serum level divided by its average toxic level. Results: We retrieved 118 trial reports. Most had to be excluded because of incomplete reporting of concomitant medication or AE. The data of the 15 articles selected for further analysis indicate a relationship between drug load and number of AE. We noted no relationship between the number of AEDs administered and AE. In add‐on studies, the difference in neurotoxicity between the active and placebo arm may be obscured if the relative increase in drug load is small, as exemplified by the study of McGuire et al. (35). Conclusions: Articles reporting add‐on trials of new AEDs generally do not provide detailed information about the basic medication to which the new AED is added, which makes calculation of total drug load impossible. Furthermore, often only frequency of AE is reported, not severity or development of tolerance, making it difficult to judge the impact of AE. However, despite the paucity of available information, we present some evidence that toxicity in AED polytherapy may be related to total drug load, rather than to the number of drugs administered. Therefore, the present trend to reject polytherapy for fear of increased toxicity is not warranted, which removes one of the objections to initiating specific research to prove or disprove the value of AED combinations as long as the drug load is appropriate.

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    NARCIS
    Article . 1997
    Data sources: NARCIS
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    Radboud Repository
    Article . 1997
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    Epilepsia
    Article . 1997
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    Epilepsia
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    METIS Research Information System; Epilepsia
    Article . 1997 . Peer-reviewed
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    NARCIS
    Article . 1997
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    Epilepsia
    Article . 1997
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      Article . 1997
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      Article . 1997
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      Article . 1997
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      METIS Research Information System; Epilepsia
      Article . 1997 . Peer-reviewed
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      Article . 1997
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      Epilepsia
      Article . 1997
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    Authors: de Paula, Demetrius Ribeiro; Ziegler, Erik; Abeyasinghe, Pubuditha M.; Das, Tushar K.; +14 Authors

    AbstractIntroductionIndependent component analysis (ICA) has been extensively used for reducing task‐free BOLD fMRI recordings into spatial maps and their associated time‐courses. The spatially identified independent components can be considered as intrinsic connectivity networks (ICNs) of non‐contiguous regions. To date, the spatial patterns of the networks have been analyzed with techniques developed for volumetric data.ObjectiveHere, we detail a graph building technique that allows these ICNs to be analyzed with graph theory.MethodsFirst, ICA was performed at the single‐subject level in 15 healthy volunteers using a 3T MRI scanner. The identification of nine networks was performed by a multiple‐template matching procedure and a subsequent component classification based on the network “neuronal” properties. Second, for each of the identified networks, the nodes were defined as 1,015 anatomically parcellated regions. Third, between‐node functional connectivity was established by building edge weights for each networks. Group‐level graph analysis was finally performed for each network and compared to the classical network.ResultsNetwork graph comparison between the classically constructed network and the nine networks showed significant differences in the auditory and visual medial networks with regard to the average degree and the number of edges, while the visual lateral network showed a significant difference in the small‐worldness.ConclusionsThis novel approach permits us to take advantage of the well‐recognized power of ICA in BOLD signal decomposition and, at the same time, to make use of well‐established graph measures to evaluate connectivity differences. Moreover, by providing a graph for each separate network, it can offer the possibility to extract graph measures in a specific way for each network. This increased specificity could be relevant for studying pathological brain activity or altered states of consciousness as induced by anesthesia or sleep, where specific networks are known to be altered in different strength.

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    Europe PubMed Central
    Article . 2017
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    Other literature type . 2017
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    Brain and Behavior
    Article . 2017 . Peer-reviewed
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      Article . 2017
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      Scholarship@Western
      Other literature type . 2017
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      Brain and Behavior
      Article . 2017 . Peer-reviewed
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    Authors: Fahrenfort, Johannes Jacobus; Grubert, Anna; Olivers, Christian N. L.; Eimer, Martin;

    Abstract The primary electrophysiological marker of feature-based selection is the N2pc, a lateralized posterior negativity emerging around 180-200 ms. As it relies on hemispheric differences, its ability to discriminate the locus of focal attention is severely limited. Here we demonstrate that multivariate analyses of raw EEG data provide a much more fine-grained spatial profile of feature-based target selection. When training a pattern classifier to determine target position from EEG, we were able to decode target positions on the vertical midline, which cannot be achieved using standard N2pc methodology. Next, we used a forward encoding model to construct a channel tuning function that describes the continuous relationship between target position and multivariate EEG in an eight-position display. This model can spatially discriminate individual target positions in these displays and is fully invertible, enabling us to construct hypothetical topographic activation maps for target positions that were never used. When tested against the real pattern of neural activity obtained from a different group of subjects, the constructed maps from the forward model turned out statistically indistinguishable, thus providing independent validation of our model. Our findings demonstrate the power of multivariate EEG analysis to track feature-based target selection with high spatial and temporal precision. Significance Statement Feature-based attentional selection enables observers to find objects in their visual field. The spatiotemporal profile of this process is difficult to assess with standard electrophysiological methods, which rely on activity differences between cerebral hemispheres. We demonstrate that multivariate analyses of EEG data can track target selection across the visual field with high temporal and spatial resolution. Using a forward model, we were able to capture the continuous relationship between target position and EEG measurements, allowing us to reconstruct the distribution of cortical activity for target locations that were never shown during the experiment. Our findings demonstrate the existence of a temporally and spatially precise EEG signal that can be used to study the neural basis of feature-based attentional selection.

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    bioRxiv
    Preprint . 2016
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    Scientific Reports
    Article . 2017
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    Article . 2018
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      Europe PubMed Central
      Article . 2018
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    Authors: Witte, Annemieke M; Riem, Madelon M E; van der Knaap, N; de Moor, Marleen H M; +2 Authors

    Contains fulltext : 247709.pdf (Publisher’s version ) (Open Access) In a randomized double-blind within-subject control study we investigated the effects of oxytocin and vasopressin administration on neural reactivity to infant cry sounds in 70 first-time fathers in the first year of fatherhood. Additionally, we examined whether effects of oxytocin and vasopressin administration on neural reactivity were moderated by fathers’ early childhood experiences. Neural reactivity to infant cry sounds (versus control sounds) was measured using functional magnetic resonance imaging (fMRI). Furthermore, participants reported on their childhood experiences of parental harsh discipline and parental love withdrawal. Whole brain analyses revealed no significant effect of vasopressin or oxytocin administration on neural activation in response to infant cry sounds. Region of interest analyses showed decreased amygdala activation in both the oxytocin condition and the vasopressin condition as compared to placebo. We found no moderating effects of fathers’ early childhood experiences. Our findings suggest that oxytocin administration may decrease feelings of anxiety or aversion to a crying infant. Whether decreased amygdala activation after vasopressin administration might be explained by contextual factors (e.g., absence of high levels of threat, unfamiliarity of the infant) or represents an affiliative response to infant distress warrants further investigation. Findings of the present study showed that oxytocin and vasopressin are important hormones implicated in neural models of infant cry perception in fatherhood. 12 p.

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    Authors: Dzyubachyk, O.; Khmelinskii, A.; Plenge, E.; Kok, P.; +8 Authors

    In small animal imaging studies, when the locations of the micro-structures of interest are unknown a priori, there is a simultaneous need for full-body coverage and high resolution. In MRI, additional requirements to image contrast and acquisition time will often make it impossible to acquire such images directly. Recently, a resolution enhancing post-processing technique called super-resolution reconstruction (SRR) has been demonstrated to improve visualization and localization of micro-structures in small animal MRI by combining multiple low-resolution acquisitions. However, when the field-of-view is large relative to the desired voxel size, solving the SRR problem becomes very expensive, in terms of both memory requirements and computation time. In this paper we introduce a novel local approach to SRR that aims to overcome the computational problems and allow researchers to efficiently explore both global and local characteristics in whole-body small animal MRI. The method integrates state-of-the-art image processing techniques from the areas of articulated atlas-based segmentation, planar reformation, and SRR. A proof-of-concept is provided with two case studies involving CT, BLI, and MRI data of bone and kidney tumors in a mouse model. We show that local SRR-MRI is a computationally efficient complementary imaging modality for the precise characterization of tumor metastases, and that the method provides a feasible high-resolution alternative to conventional MRI. ImPhys/Imaging Physics Applied Sciences

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    Europe PubMed Central
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    Authors: Buijsen, Ronald; Sellier, C; Severijnen, Lies-anne; Oulad-Abdelghani, M; +5 Authors

    Fragile X-associated Tremor/Ataxia syndrome (FXTAS), a late-onset monogenetic neurodegenerative disorder, is caused by a CGG-repeat expansion (55-200) in the 5′ UTR of the fragile-X mental retardation 1 gene (FMR1) on the X-chromosome [1]. The prevalence of the FMR1 premutation (PM) is about 1:855 in males and 1:291 in females [2]. Approximately 45.5% of male and 16.5% of female PM carriers older than 50 years will develop signs of FXTAS [3]. In addition to the core features of tremor and gait ataxia, unexplained medical co-morbidities have been reported, including thyroid disease, cardiac arrhythmias, hypertension, migraine, impotence, and neuropathy [4]. PM carriers have increased levels of FMR1 mRNA (2 to 8 fold in leucocytes) and normal to slightly reduced FMR1 protein (FMRP) levels [5]. The current hypothesis is that FXTAS is caused by an RNA gain-of-function mechanism. Ubiquitin-positive intranuclear inclusions, are found in both brain and non-central nervous system (CNS) organs of patients with FXTAS [6,7]. So far, it is not clear whether these inclusions are protective or toxic. Recently, it has been hypothesized that repeat-associated non-AUG (RAN) translation plays a role in disease process and inclusion formation. Todd et al. [8] demonstrated that through initiation at a near-ATG codon located in the 5′UTR of the FMR1 gene a polyGlycine-containing protein, FMRpolyG, is expressed. This protein accumulates in ubiquitin-positive inclusions in Drosophila, cell culture, mouse disease models and brain from FXTAS patients. To investigate the link between FMRpolyG expression and the co-morbid medical problems associated with the PM we have developed two novel mouse monoclonal antibodies against polyGlycine; 8FM and 9FM (for epitopes and specificity see Additional file 1: Figure S1), and performed immunostaining in CNS as well as in non-CNS organs of FXTAS patient J.L. (case 6 in [7]; other cases not available). To establish antibody specificity, we performed immunostaining with both antibodies on brain sections from FXTAS patient J.L., healthy non-demented controls (n = 3) and a patient with Parkinson disease, Alzheimer disease, or C9FTD. In hippocampus and cerebellum from FXTAS patient J.L. we identified FMRpolyG-positive inclusions with both 8FM (1:10) and 9FM (1:10) antibody (Figure 1a-b, Additional file 2: Figure S2a-b), as was described previously [8]. None of the controls showed FMRpolyG-positive inclusions (data not shown). Next, we studied the immunolocalization of FMRpolyG protein in heart, kidney, adrenal gland and thyroid in patient J.L. with 8FM (1:10) and 9FM (1:10), compared to post mortem non-CNS somatic organ tissues from 3 healthy controls. We also examined tissues for FMRP (mouse T1A; 1:200) expression and ubiquitin-positive inclusions (DAKO, ZO458; 1:200). Consistent with our previous report [7], ubiquitin-positive intranuclear inclusions were identified along with a normal distribution of FMRP (data not shown). Intranuclear FMRpolyG-positive inclusions could be detected in all organs examined (Figure 1c-h, Additional file 2: Figure S2c-h). No control tissues showed any FMRpolyG-positive inclusions (data not shown). Colocalization of ubiquitin- and FMRpolyG-positive inclusions was visualized and quantified by immunofluorescent double staining using antibodies against ubiquitin and FMRpolyG (8FM) (Figure 2a-f). For hippocampus, cerebellum and the non-CNS organs most inclusions are positive for both FMRpolyG and ubiquitin, although some rare inclusions positive for only one of the proteins could also be detected (Figure 2g, n = 100 inclusions). In conclusion, using two novel antibodies the present report not only confirms the existence of FMRpolyG-positive aggregates in CNS tissue from a FXTAS individual but also demonstrates for the first time the presence of FMRpolyG-positive intranuclear inclusions in post mortem non-CNS material of a PM carrier with FXTAS. Furthermore, colocalization of FMRpolyG and ubiquitin is found in the vast majority of inclusions. The presence of FMRpolyG-positive intranuclear inclusions in heart, kidney, adrenal gland and thyroid is consistent with the unexplained medical co-morbidities reported in some patients with FXTAS, including thyroid disease, cardiac arrhythmias, hypertension, migraine, impotence, and neuropathy. We hypothesize that the underlying pathological mechanisms of the medical co-morbidities in systemic tissues share common features (protein toxic gain-of-function) with CNS pathology of patients with FXTAS. Our report suggests that in addition to elevated levels of FMR1 mRNA containing an expanded CGG repeat, and ubiquitin-positive inclusions, FMRpolyG expression might also play a role in a toxic gain-of-function mechanism in medical co-morbidities in FXTAS (RNA versus FMRpolyG toxic gain-of-function). Interestingly, a very recent report suggests that RAN translation products in C9FTD/ALS, toxic dipeptide repeat proteins (poly-(glycine-arginine) and poly-(proline-arginine)), are toxic in Drosophila [9]. Further research is needed to understand how FMRpolyG may elicit toxicity in both CNS and non-CNS organs and its precise role in co-morbidities in PM carriers. Importantly, if FMRpolyG production is important for cellular toxicity this will open new avenues for therapeutic intervention studies for FXTAS by developing drugs that block this aberrant translation. Figure 1 9FM FMRpolyG-positive intranuclear inclusions in hippocampus, cerebellum and non-CNS tissues of a FXTAS patient. FMRpolyG-positive (9FM) intranuclear inclusions in a hippocampus, b cerebellum, c glomeruli and d distal tubule of the kidney, e zona glomerulosa ... Figure 2 Colocalization of FMRpolyG (8FM) and ubiquitin in intranuclear inclusions in hippocampus, cerebellum and of non-CNS tissues of a FXTAS patient. Staining for ubiquitin (green), FMRpolyG (8FM; red) and DAPI (blue). Colocalization of ubiquitin and FMRpolyG ...

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      This Research product is the result of merged Research products in OpenAIRE.

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