Functional magnetic resonance imaging of impaired sensory prediction in schizophrenia.

IMPORTANCE: Forward models predict the sensory consequences of planned actions and permit discrimination of self- and non-self-elicited sensation; their impairment in schizophrenia is implied by an abnormality in behavioral force-matching and the flawed agency judgments characteristic of positive symptoms, including auditory hallucinations and delusions of control. OBJECTIVE: To assess attenuation of sensory processing by self-action in individuals with schizophrenia and its relation to current symptom severity. DESIGN, SETTING, AND PARTICIPANTS: Functional magnetic resonance imaging data were acquired while medicated individuals with schizophrenia (n = 19) and matched controls (n = 19) performed a factorially designed sensorimotor task in which the occurrence and relative timing of action and sensation were manipulated. The study took place at the neuroimaging research unit at the Institute of Cognitive Neuroscience, University College London, and the Maudsley Hospital. RESULTS: In controls, a region of secondary somatosensory cortex exhibited attenuated activation when sensation and action were synchronous compared with when the former occurred after an unexpected delay or alone. By contrast, reduced attenuation was observed in the schizophrenia group, suggesting that these individuals were unable to predict the sensory consequences of their own actions. Furthermore, failure to attenuate secondary somatosensory cortex processing was predicted by current hallucinatory severity. CONCLUSIONS AND RELEVANCE: Although comparably reduced attenuation has been reported in the verbal domain, this work implies that a more general physiologic deficit underlies positive symptoms of schizophrenia.

Gene function prediction from synthetic lethality networks via ranking on demand.

MOTIVATION: Synthetic lethal interactions represent pairs of genes whose individual mutations are not lethal, while the double mutation of both genes does incur lethality. Several studies have shown a correlation between functional similarity of genes and their distances in networks based on synthetic lethal interactions. However, there is a lack of algorithms for predicting gene function from synthetic lethality interaction networks. RESULTS: In this article, we present a novel technique called kernelROD for gene function prediction from synthetic lethal interaction networks based on kernel machines. We apply our novel algorithm to Gene Ontology functional annotation prediction in yeast. Our experiments show that our method leads to improved gene function prediction compared with state-of-the-art competitors and that combining genetic and congruence networks leads to a further improvement in prediction accuracy.

Neural activity associated with the passive prediction of ambiguity and risk for aversive events.

In economic decision making, outcomes are described in terms of risk (uncertain outcomes with certain probabilities) and ambiguity (uncertain outcomes with uncertain probabilities). Humans are more averse to ambiguity than to risk, with a distinct neural system suggested as mediating this effect. However, there has been no clear disambiguation of activity related to decisions themselves from perceptual processing of ambiguity. In a functional magnetic resonance imaging (fMRI) experiment, we contrasted ambiguity, defined as a lack of information about outcome probabilities, to risk, where outcome probabilities are known, or ignorance, where outcomes are completely unknown and unknowable. We modified previously learned pavlovian CS+ stimuli such that they became an ambiguous cue and contrasted evoked brain activity both with an unmodified predictive CS+ (risky cue), and a cue that conveyed no information about outcome probabilities (ignorance cue). Compared with risk, ambiguous cues elicited activity in posterior inferior frontal gyrus and posterior parietal cortex during outcome anticipation. Furthermore, a similar set of regions was activated when ambiguous cues were compared with ignorance cues. Thus, regions previously shown to be engaged by decisions about ambiguous rewarding outcomes are also engaged by ambiguous outcome prediction in the context of aversive outcomes. Moreover, activation in these regions was seen even when no actual decision is made. Our findings suggest that these regions subserve a general function of contextual analysis when search for hidden information during outcome anticipation is both necessary and meaningful.

The MHP36 line of murine neural stem cells expresses functional CXCR1 chemokine receptors that initiate chemotaxis in vitro.

Chemokines help to establish cerebral inflammation after ischemia, which comprises a major component of secondary brain injury. The CXCR4 chemokine receptor system induces neural stem cell migration, and hence has been implicated in brain repair. We show that CXCR1 and interleukin-8 also stimulate chemotaxis in murine neural stem cells from the MHP36 cell line. The presence of CXCR1 was confirmed by reverse transcriptase PCR and immunohistochemistry. Interleukin-8 evoked intracellular calcium currents, upregulated doublecortin (a protein expressed by migrating neuroblasts), and elicited positive chemotaxis in vitro. Therefore, effectors of the early innate immune response may also influence brain repair mechanisms.

Deficits in sensory prediction are related to delusional ideation in healthy individuals.

Motor control strongly relies on neural processes that predict the sensory consequences of self-generated actions. Previous research has demonstrated deficits in such sensory-predictive processes in schizophrenic patients and these low-level deficits are thought to contribute to the emergence of delusions of control. Here, we examined the extent to which individual differences in sensory prediction are associated with a tendency towards delusional ideation in healthy participants. We used a force-matching task to quantify sensory-predictive processes, and administered questionnaires to assess schizotypy and delusion-like thinking. Individuals with higher levels of delusional ideation showed more accurate force matching suggesting that such thinking is associated with a reduced tendency to predict and attenuate the sensory consequences of self-generated actions. These results suggest that deficits in sensory prediction in schizophrenia are not simply consequences of the deluded state and are not related to neuroleptic medication. Rather they appear to be stable, trait-like characteristics of an individual, a finding that has important implications for our understanding of the neurocognitive basis of delusions.

Large eddy simulations for fan-OGV broadband noise prediction

The work in this paper forms part of a project on the use of large eddy simulation (LES) for broadband rotor-stator interaction noise prediction. Here we focus on LES of the flow field near a fan blade trailing edge. The first part of the paper aims to evaluate LES suitability for predicting the near-field velocity field for a blunt NACA-0012 airfoil at moderate Reynolds numbers (2× 10 5 and 4× 10 5). Preliminary computations of turbulent mean and root-mean-square velocities, as well as energy spectra at the trailing edge, are compared with those from a recent experiment.1 The second part of the paper describes preliminary progress on an LES calculation of the fan wakes on a fan rig. 2 The CFD code uses a mixed element unstructured mesh with a median dual control volume. A wall-adapting local eddy-viscosity sub-grid scale model is employed. A very small amount of numerical dissipation is added in the numerical scheme to keep the compressible solver stable. Further results for the fan turbulentmean and RMS velocity, and especially the aeroacoustics field will be presented at a later stage. Copyright © 2008 by Qinling LI, Nigel Peake & Mark Savill.

Rotor - Stator broadband noise prediction

In this paper a semi analytic model for rotor - stator broadband noise is presented. The work can be split into two sections. The first examines the distortion of the rotor wake in mean swirling flow, downstream of the fan. Previous work by Cooper and Peake4 is extended to include dissipative effects. In the second section we consider the interaction of this gust with the downstream stator row. We examine the way in which an unsteady pressure field is generated by the interaction of this wake flow with the stator blades and obtain estimates for the radiated noise. A new method is presented to extend the well known LINSUB code to the third dimension to capture the effect of the spanwise wavenumber and stator lean and sweep. Copyright © 2008 by Adrian Lloyd and Nigel Peake.