The role of cognitive control in memory retrieval applications to schizotypy and schizophrenia

Individuals with schizophrenia have memory impairments. The experiments in this thesis were designed to determine whether these impairments arise from failures of cognitive control operations. Specifically, these experiments examined whether differences in target and non-target left-parietal old/new effects – a proposed neural correlate of strategic control over recollection - are predicted by schizotypy and/or schizophrenia symptomology. Correlations between schizotypy measures or symptom scores and how well people exercise control over retrieval of relevant information would point to one locus for memory problems associated with schizophrenia

Subgenual Cingulum Microstructure Supports Control of Emotional Conflict

This is the final version of the article. Available from Oxford University Press via the DOI in this record.Major depressive disorder (MDD) is associated with specific difficulties in attentional disengagement from negatively valenced material. Diffusion MRI studies have demonstrated altered white matter microstructure in the subgenual cingulum bundle (CB) in individuals with MDD, though the functional significance of these alterations has not been examined formally. This study explored whether individual differences in selective attention to negatively valenced stimuli are related to interindividual differences in subgenual CB microstructure. Forty-six individuals (21 with remitted MDD, 25 never depressed) completed an emotional Stroop task, using happy and angry distractor faces overlaid by pleasant or unpleasant target words and a control gender-based Stroop task. CBs were reconstructed in 38 individuals using diffusion-weighted imaging and tractography, and mean fractional anisotropy (FA) computed for the subgenual, retrosplenial, and parahippocampal subdivisions. No significant correlations were found between FA and performance in the control gender-based Stroop task in any CB region. However, the degree of interference produced by angry face distractors on time to identify pleasant words (emotional conflict) correlated selectively with FA in the subgenual CB (r= -0.53;P= 0.01). Higher FA was associated with reduced interference, irrespective of a diagnosis of MDD, suggesting that subgenual CB microstructure is functionally relevant for regulating attentional bias toward negative interpersonal stimuli.P.A.K. was funded by the Higher Education Funding Council for Wales (HEFCW) and an Academy of Medical Sciences and Wellcome Trust Starter Grant (AJ17102004). M.M. received an EPSRC Doctoral Training Grant. This work was also supported by a Marie Curie fellowship to Marcel Meyer and received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 267171. D.K.J. was funded by HEFCW and received grants from the MS Society, a Wellcome Trust New Investigator Award, a Wellcome Trust Multi User Equipment Grant and Medical Research Council, and Wellcome Trust project grants. A.N.D. was supported by the Wellcome Trust PhD schemes. N.L. was funded by HEFCW. A.D.L. was funded by HEFCW. He also received grants from the ESRC, Wellcome Trust, and NISCHR. Funding to pay the Open Access publication charges for this article was provided by The Wellcome Trust

The regulation of cytokine networks in hippocampal CA1 differentiates extinction from those required for the maintenance of contextual fear memory after recall

We investigated the distinctiveness of gene regulatory networks in CA1 associated with the extinction of contextual fear memory (CFM) after recall using Affymetrix GeneChip Rat Genome 230 2.0 Arrays. These data were compared to previously published retrieval and reconsolidation-attributed, and consolidation datasets. A stringent dual normalization and pareto-scaled orthogonal partial least-square discriminant multivariate analysis together with a jack-knifing-based cross-validation approach was used on all datasets to reduce false positives. Consolidation, retrieval and extinction were correlated with distinct patterns of gene expression 2 hours later. Extinction-related gene expression was most distinct from the profile accompanying consolidation. A highly specific feature was the discrete regulation of neuroimmunological gene expression associated with retrieval and extinction. Immunity–associated genes of the tyrosine kinase receptor TGFβ and PDGF, and TNF families’ characterized extinction. Cytokines and proinflammatory interleukins of the IL-1 and IL-6 families were enriched with the no-extinction retrieval condition. We used comparative genomics to predict transcription factor binding sites in proximal promoter regions of the retrieval-regulated genes. Retrieval that does not lead to extinction was associated with NF-κB-mediated gene expression. We confirmed differential NF-κBp65 expression, and activity in all of a representative sample of our candidate genes in the no-extinction condition. The differential regulation of cytokine networks after the acquisition and retrieval of CFM identifies the important contribution that neuroimmune signalling plays in normal hippocampal function. Further, targeting cytokine signalling upon retrieval offers a therapeutic strategy to promote extinction mechanisms in human disorders characterised by dysregulation of associative memory

Subgenual cingulum microstructure supports control of emotional conflict

Major depressive disorder (MDD) is associated with specific difficulties in attentional disengagement from negatively valenced material. Diffusion MRI studies have demonstrated altered white matter microstructure in the subgenual cingulum bundle (CB) in individuals with MDD, though the functional significance of these alterations has not been examined formally. This study explored whether individual differences in selective attention to negatively valenced stimuli are related to interindividual differences in subgenual CB microstructure. Forty-six individuals (21 with remitted MDD, 25 never depressed) completed an emotional Stroop task, using happy and angry distractor faces overlaid by pleasant or unpleasant target words and a control gender-based Stroop task. CBs were reconstructed in 38 individuals using diffusion-weighted imaging and tractography, and mean fractional anisotropy (FA) computed for the subgenual, retrosplenial, and parahippocampal subdivisions. No significant correlations were found between FA and performance in the control gender-based Stroop task in any CB region. However, the degree of interference produced by angry face distractors on time to identify pleasant words (emotional conflict) correlated selectively with FA in the subgenual CB (r = −0.53; P = 0.01). Higher FA was associated with reduced interference, irrespective of a diagnosis of MDD, suggesting that subgenual CB microstructure is functionally relevant for regulating attentional bias toward negative interpersonal stimul

Functional neuroanatomy supporting judgments of when events occurred

The neural substrates of memory for when events occurred are not well described. One reason for this is that the paradigms used to date have permitted isolation of only some of the relevant memory processes. In this experiment, functional magnetic resonance imaging was used to identify for the first time brain regions that support two distinct bases upon which “when” judgments can be made. Seventeen human participants (6 male) completed a continuous recognition memory task where the interval between presentation and re-presentation of words varied between 5 and 25 intervening words (the lag). The task on each trial was to distinguish repeated words from those presented for the first time, and to indicate the lag for repeated words. The inferior parietal lobe showed greater activation for shorter lag judgments, regardless of judgment accuracy. The lingual gyrus, by contrast, was more active for correct than for incorrect lag judgments, regardless of the interval between first and second item presentations. Both of these regions have been linked in previous work to the process of recollection, and the findings described here represent a novel neural dissociation across regions that deploy mnemonic information in fundamentally different ways to support judgments about when events occurred

Phyllosticta citricarpa and sister species of global importance to Citrus.

Several Phyllosticta species are known as pathogens of Citrus spp., and are responsible for various disease symptoms including leaf and fruit spots. One of the most important species is P. citricarpa, which causes a foliar and fruit disease called citrus black spot. The Phyllosticta species occurring on citrus can most effectively be distinguished from P. citricarpa by means of multilocus DNA sequence data. Recent studies also demonstrated P. citricarpa to be heterothallic, and reported successful mating in the laboratory. Since the domestication of citrus, different clones of P. citricarpa have escaped Asia to other continents via trade routes, with obvious disease management consequences. This pathogen profile represents a comprehensive literature review of this pathogen and allied taxa associated with citrus, focusing on identification, distribution, genomics, epidemiology and disease management. This review also considers the knowledge emerging from seven genomes of Phyllosticta spp., demonstrating unknown aspects of these species, including their mating behaviour.TaxonomyPhyllosticta citricarpa (McAlpine) Aa, 1973. Kingdom Fungi, Phylum Ascomycota, Class Dothideomycetes, Order Botryosphaeriales, Family Phyllostictaceae, Genus Phyllosticta, Species citricarpa.Host rangeConfirmed on more than 12 Citrus species, Phyllosticta citricarpa has only been found on plant species in the Rutaceae.Disease symptomsP. citricarpa causes diverse symptoms such as hard spot, virulent spot, false melanose and freckle spot on fruit, and necrotic lesions on leaves and twigs.Useful websitesDOE Joint Genome Institute MycoCosm portals for the Phyllosticta capitalensis (https://genome.jgi.doe.gov/Phycap1), P. citriasiana (https://genome.jgi.doe.gov/Phycit1), P. citribraziliensis (https://genome.jgi.doe.gov/Phcit1), P. citrichinaensis (https://genome.jgi.doe.gov/Phcitr1), P. citricarpa (https://genome.jgi.doe.gov/Phycitr1, https://genome.jgi.doe.gov/Phycpc1), P. paracitricarpa (https://genome.jgi.doe.gov/Phy27169) genomes. All available Phyllosticta genomes on MycoCosm can be viewed at https://genome.jgi.doe.gov/Phyllosticta

Search for right-handed W bosons in top quark decay

We present a measurement of the fraction f+ of right-handed W bosons produced in top quark decays, based on a candidate sample of $t\bar{t}$ events in the lepton+jets decay mode. These data correspond to an integrated luminosity of 230pb^-1, collected by the DO detector at the Fermilab Tevatron $p\bar{p}$ Collider at sqrt(s)=1.96 TeV. We use a constrained fit to reconstruct the kinematics of the $t\bar{t}$ and decay products, which allows for the measurement of the leptonic decay angle $\theta^*$ for each event. By comparing the $\cos\theta^*$ distribution from the data with those for the expected background and signal for various values of f+, we find f+=0.00+-0.13(stat)+-0.07(syst). This measurement is consistent with the standard model prediction of f+=3.6x10^-4.Comment: Submitted to Physical Review D Rapid Communications 7 pages, 3 figure

A search for W bb and W Higgs production in ppbar collisions at sqrt(s)=1.96 TeV

We present a search for W b \bar{b} production in p \bar{p} collisions at sqrt{s}=1.96 TeV in events containing one electron, an imbalance in transverse momentum, and two b-tagged jets. Using 174 pb-1 of integrated luminosity accumulated by the D0 experiment at the Fermilab Tevatron collider, and the standard-model description of such events, we set a 95% C.L. upper limit on W b \bar{b}$production of 6.6 pb for b quarks with transverse momenta p_T^b > 20 GeV and b \bar{b} separation in pseudorapidity-azimuth space Delta R_bb > 0.75. Restricting the search to optimized b \bar{b} mass intervals provides upper limits on$WH$production of 9.0$-$12.2 pb, for Higgs-boson masses of 105$-$135 GeV.Comment: 7 pages, 4 figures, 1 table, submitted to Physical Review Letter