Personality, Sex, and the Neuropsychology of Attention

The influences of sex and personality on attentional style were examined in two neuropsychological studies in which perfor mance and event-related potentials (ERP\u27s) were employed. Pribram and McGuinness1 (1975) conceptions of Activation and Arousal were recast in a lateralized framework in which the former was seen as characteristic of left hemisphere function while the latter was identified more closely with the right hemisphere. Four equal groups of nine subjects were selected on the basis of sex and ex treme extraversion scores (I-E), while controlling for neuroticism, to participate in two lateralized attentional tasks. The first, a vigilance task designed to assess Activation modeled after Dimond and Beaumont (1973), involved responding to infrequent signals from lateralized visual stimuli. The second study, designed to assess Arousal, employed a complex reaction time task used by Heilman and Van Den Abell (1979). Four-way mixed ANOVAs were carried out for both studies on the performance and ERP data. In addition, corre lations were computed between performance and ERP data. A general left hemisphere superiority was observed in the vigilance study according to prediction. Unexpectedly, significant lateral differ ences and changes over time were observed for male and female introverts, but not for extraverts. Such differences are explained by a developmental model and indicate the utility of several models of hemispheric interaction. No between and within group dif ferences in performance were observed on the complex reaction time study, failing to confirm previous findings. On both studies, con sistent sex and I-E differences were observed in the topographical distribution of the ERP\u27s. Interesting sex and I-E differences in the patterns of correlations between ERP and performance data emerged on the vigilance, but not on the complex reaction time study. Results indicate that these groups utilize different brain systems to attend. Questions also arise whether the present para digms tap the Arousal-Activation dimension or a model based on stages of processing

Fast rates in statistical and online learning

The speed with which a learning algorithm converges as it is presented with more data is a central problem in machine learning --- a fast rate of convergence means less data is needed for the same level of performance. The pursuit of fast rates in online and statistical learning has led to the discovery of many conditions in learning theory under which fast learning is possible. We show that most of these conditions are special cases of a single, unifying condition, that comes in two forms: the central condition for 'proper' learning algorithms that always output a hypothesis in the given model, and stochastic mixability for online algorithms that may make predictions outside of the model. We show that under surprisingly weak assumptions both conditions are, in a certain sense, equivalent. The central condition has a re-interpretation in terms of convexity of a set of pseudoprobabilities, linking it to density estimation under misspecification. For bounded losses, we show how the central condition enables a direct proof of fast rates and we prove its equivalence to the Bernstein condition, itself a generalization of the Tsybakov margin condition, both of which have played a central role in obtaining fast rates in statistical learning. Yet, while the Bernstein condition is two-sided, the central condition is one-sided, making it more suitable to deal with unbounded losses. In its stochastic mixability form, our condition generalizes both a stochastic exp-concavity condition identified by Juditsky, Rigollet and Tsybakov and Vovk's notion of mixability. Our unifying conditions thus provide a substantial step towards a characterization of fast rates in statistical learning, similar to how classical mixability characterizes constant regret in the sequential prediction with expert advice setting.Comment: 69 pages, 3 figure

Paradoxical Immune Responses in Non-HIV Cryptococcal Meningitis

The fungus Cryptococcus is a major cause of meningoencephalitis in HIV-infected as well as HIV-uninfected individuals with mortalities in developed countries of 20% and 30%, respectively. In HIV-related disease, defects in T-cell immunity are paramount, whereas there is little understanding of mechanisms of susceptibility in non-HIV related disease, especially that occurring in previously healthy adults. The present description is the first detailed immunological study of non-HIV-infected patients including those with severe central nervous system (s-CNS) disease to 1) identify mechanisms of susceptibility as well as 2) understand mechanisms underlying severe disease. Despite the expectation that, as in HIV, T-cell immunity would be deficient in such patients, cerebrospinal fluid (CSF) immunophenotyping, T-cell activation studies, soluble cytokine mapping and tissue cellular phenotyping demonstrated that patients with s-CNS disease had effective microbiological control, but displayed strong intrathecal expansion and activation of cells of both the innate and adaptive immunity including HLA-DR+ CD4+ and CD8+ cells and NK cells. These expanded CSF T cells were enriched for cryptococcal-antigen specific CD4+ cells and expressed high levels of IFN-gamma as well as a lack of elevated CSF levels of typical T-cell specific Th2 cytokines -- IL-4 and IL-13. This inflammatory response was accompanied by elevated levels of CSF NFL, a marker of axonal damage, consistent with ongoing neurological damage. However, while tissue macrophage recruitment to the site of infection was intact, polarization studies of brain biopsy and autopsy specimens demonstrated an M2 macrophage polarization and poor phagocytosis of fungal cells. These studies thus expand the paradigm for cryptococcal disease susceptibility to include a prominent role for macrophage activation defects and suggest a spectrum of disease whereby severe neurological disease is characterized by immune-mediated host cell damage

BA11 FKBP5 expression levels correlate with dendritic spine density in postmortem PTSD and controls

AbstractGenetic variants of the immunophilin FKBP5 have been implicated in susceptibility to post-traumatic stress disorder (PTSD) and other stress-related disorders. We examined the relationship between mushroom, stubby, thin and filopodial spine densities measured with Golgi staining and FKBP5 gene expression in the medial orbitofrontal cortex (BA11) in individuals diagnosed with PTSD and normal controls (n = 8/8). ANCOVA revealed PTSD cases had a significantly elevated density of stubby spines (29%, P < 0.037) and a trend for a reduction in mushroom spine density (25%, p < 0.082). Levels of FKBP5 mRNA were marginally elevated in the PTSD cases (z = 1.94, p = 0.053) and levels correlated inversely with mushroom (Spearman's rho = −0.83, p < 0.001) and overall spine density (rho = −0.75, p < 0.002) and directly with stubby spine density (rho = 0.55, p < 0.027). These data suggest that FKBP5 may participate in a cellular pathway modulating neuronal spine density changes in the brain, and that this pathway may be dysregulated in PTSD

The neural correlates of regulating positive and negative emotions in medication-free major depression

Depressive cognitive schemas play an important role in the emergence and persistence of major depressive disorder (MDD). The current study adapted emotion regulation techniques to reflect elements of cognitive behavioural therapy (CBT) and related psychotherapies to delineate neurocognitive abnormalities associated with modulating the negative cognitive style in MDD. Nineteen non-medicated patients with MDD and 19 matched controls reduced negative or enhanced positive feelings elicited by emotional scenes while undergoing functional magnetic resonance imaging. Although both groups showed significant emotion regulation success as measured by subjective ratings of affect, the controls were significantly better at modulating both negative and positive emotion. Both groups recruited regions of dorsolateral prefrontal cortex and ventrolateral prefrontal cortex (VLPFC) when regulating negative emotions. Only in controls was this accompanied by reduced activity in sensory cortices and amygdala. Similarly, both groups showed enhanced activity in VLPFC and ventral striatum when enhancing positive affect; however, only in controls was ventral striatum activity correlated with regulation efficacy. The results suggest that depression is associated with both a reduced capacity to achieve relief from negative affect despite recruitment of ventral and dorsal prefrontal cortical regions implicated in emotion regulation, coupled with a disconnect between activity in reward-related regions and subjective positive affect

<em>SurfaceSlide</em>: A Multitouch Digital Pathology Platform

Background: Digital pathology provides a digital environment for the management and interpretation of pathological images and associated data. It is becoming increasing popular to use modern computer based tools and applications in pathological education, tissue based research and clinical diagnosis. Uptake of this new technology is stymied by its single user orientation and its prerequisite and cumbersome combination of mouse and keyboard for navigation and annotation.Methodology: In this study we developed SurfaceSlide, a dedicated viewing platform which enables the navigation and annotation of gigapixel digitised pathological images using fingertip touch. SurfaceSlide was developed using the Microsoft Surface, a 30 inch multitouch tabletop computing platform. SurfaceSlide users can perform direct panning and zooming operations on digitised slide images. These images are downloaded onto the Microsoft Surface platform from a remote server on-demand. Users can also draw annotations and key in texts using an on-screen virtual keyboard. We also developed a smart caching protocol which caches the surrounding regions of a field of view in multi-resolutions thus providing a smooth and vivid user experience and reducing the delay for image downloading from the internet. We compared the usability of SurfaceSlide against Aperio ImageScope and PathXL online viewer.Conclusion: SurfaceSlide is intuitive, fast and easy to use. SurfaceSlide represents the most direct, effective and intimate human–digital slide interaction experience. It is expected that SurfaceSlide will significantly enhance digital pathology tools and applications in education and clinical practice

Unique functional abnormalities in youth with combined marijuana use and depression: an fMRI study

Prior research has shown a relationship between early onset marijuana (MJ) use and depression; however, this relationship is complex and poorly understood. Here, we utilized passive music listening and fMRI to examine functional brain activation to a rewarding stimulus in 75 participants [healthy controls (HC), patients with major depressive disorder (MDD), frequent MJ users, and the combination of MDD and MJ (MDD?+?MJ)]. For each participant, a preferred and neutral piece of instrumental music was determined (utilizing ratings on a standardized scale), and each completed two 6-min fMRI scans of a passive music listening task. Data underwent pre-processing and 61 participants were carried forward for analysis (17 HC, 15 MDD, 15MJ, 14 MDD + MJ). Two statistical analyses were performed using SPM8, an analysis of covariance with two factors (group x music type) and a whole brain, multiple regression analysis incorporating two predictors of interest [MJ use in past 28 days; and Beck Depression Inventory (BDI) score]. We identified a significant group x music type interaction. Post hoc comparisons showed that the preferred music had significantly greater activation in the MDD + MJ group in areas including the right middle and inferior frontal gyri extending into the claustrum and putamen and the anterior cingulate. No significant differences were identified in MDD, MJ, or HC groups. Multiple regression analysis showed that activation in medial frontal cortex was positively correlated with amount of MJ use, and activation in areas including the insula was negatively correlated with BDI score. Results showed modulation in brain activation during passive music listening specific to MDD, frequent MJ users. This supports the suggestion that frequent MJ use, when combined with MDD, is associated with changes in neurocircuitry involved in reward processing in ways that are absent with either frequent MJ use or MDD alone. This could help inform clinical recommendations for youth with MDD

Multiplex meta-analysis of RNA expression to identify genes with variants associated with immune dysfunction

ObjectiveWe demonstrate a genome-wide method for the integration of many studies of gene expression of phenotypically similar disease processes, a method of multiplex meta-analysis. We use immune dysfunction as an example disease process.DesignWe use a heterogeneous collection of datasets across human and mice samples from a range of tissues and different forms of immunodeficiency. We developed a method integrating Tibshirani's modified t-test (SAM) is used to interrogate differential expression within a study and Fisher's method for omnibus meta-analysis to identify differentially expressed genes across studies. The ability of this overall gene expression profile to prioritize disease associated genes is evaluated by comparing against the results of a recent genome wide association study for common variable immunodeficiency (CVID).ResultsOur approach is able to prioritize genes associated with immunodeficiency in general (area under the ROC curve = 0.713) and CVID in particular (area under the ROC curve = 0.643).ConclusionsThis approach may be used to investigate a larger range of failures of the immune system. Our method may be extended to other disease processes, using RNA levels to prioritize genes likely to contain disease associated DNA variants

Pretreatment, Psychological, and Behavioral Predictors of Weight Outcomes Among Lifestyle Intervention Participants in the Diabetes Prevention Program (DPP)

OBJECTIVE To identify the most important pretreatment characteristics and changes in psychological and behavioral factors that predict weight outcomes in the Diabetes Prevention Program (DPP). RESEARCH DESIGN AND METHODS Approximately 25% of DPP lifestyle intervention participants (n = 274) completed questionnaires to assess weight history and psychological and behavioral factors at baseline and 6 months after completion of the 16-session core curriculum. The change in variables from baseline to 6 months was assessed with t tests. Multivariate models using hierarchical logistic regression assessed the association of weight outcomes at end of study with each demographic, weight loss history, psychological, and behavioral factor. RESULTS At end of study, 40.5% had achieved the DPP 7% weight loss goal. Several baseline measures (older age, race, older age when first overweight, fewer self-implemented weight loss attempts, greater exercise self-efficacy, greater dietary restraint, fewer fat-related dietary behaviors, more sedentary activity level) were independent predictors of successful end-of-study weight loss with the DPP lifestyle program. The DPP core curriculum resulted in significant improvements in many psychological and behavioral targets. Changes in low-fat diet self-efficacy and dietary restraint skills predicted better long-term weight loss, and the association of low-fat diet self-efficacy with weight outcomes was explained by dietary behaviors. CONCLUSIONS Health care providers who translate the DPP lifestyle intervention should be aware of pretreatment characteristics that may hamper or enhance weight loss, consider prioritizing strategies to improve low-fat diet self-efficacy and dietary restraint skills, and examine whether taking these actions improves weight loss outcomes