Cognitive control and discourse comprehension in schizophrenia.

Cognitive deficits across a wide range of domains have been consistently observed in schizophrenia and are linked to poor functional outcome (Green, 1996; Carter, 2006). Language abnormalities are among the most salient and include disorganized speech as well as deficits in comprehension. In this review, we aim to evaluate impairments of language processing in schizophrenia in relation to a domain-general control deficit. We first provide an overview of language comprehension in the healthy human brain, stressing the role of cognitive control processes, especially during discourse comprehension. We then discuss cognitive control deficits in schizophrenia, before turning to evidence suggesting that schizophrenia patients are particularly impaired at processing meaningful discourse as a result of deficits in control functions. We conclude that domain-general control mechanisms are impaired in schizophrenia and that during language comprehension this is most likely to result in difficulties during the processing of discourse-level context, which involves integrating and maintaining multiple levels of meaning. Finally, we predict that language comprehension in schizophrenia patients will be most impaired during discourse processing. We further suggest that discourse comprehension problems in schizophrenia might be mitigated when conflicting information is absent and strong relations amongst individual words are present in the discourse context."There is no "centre of Speech" in the brain any more than there is a faculty of Speech in the mind.The entire brain, more or less, is at work in a man who uses language"William JamesFrom The Principles of Psychology, 1890"The mind in dementia praecox is like an orchestra without a conductor"Kraepelin, 1919

Altered brainstem responses to modafinil in schizophrenia: implications for adjunctive treatment of cognition.

Candidate pro-cognitive drugs for schizophrenia targeting several neurochemical systems have consistently failed to demonstrate robust efficacy. It remains untested whether concurrent antipsychotic medications exert pharmacodynamic interactions that mitigate pro-cognitive action in patients. We used functional MRI (fMRI) in a randomized, double-blind, placebo-controlled within-subject crossover test of single-dose modafinil effects in 27 medicated schizophrenia patients, interrogating brainstem regions where catecholamine systems arise to innervate the cortex, to link cellular and systems-level models of cognitive control. Modafinil effects were evaluated both within this patient group and compared to a healthy subject group. Modafinil modulated activity in the locus coeruleus (LC) and ventral tegmental area (VTA) in the patient group. However, compared to the healthy comparison group, these effects were altered as a function of task demands: the control-independent drug effect on deactivation was relatively attenuated (shallower) in the LC and exaggerated (deeper) in the VTA; in contrast, again compared to the comparison group, the control-related drug effects on positive activation were attenuated in LC, VTA and the cortical cognitive control network. These altered effects in the LC and VTA were significantly and specifically associated with the degree of antagonism of alpha-2 adrenergic and dopamine-2 receptors, respectively, by concurrently prescribed antipsychotics. These sources of evidence suggest interacting effects on catecholamine neurons of chronic antipsychotic treatment, which respectively increase and decrease sustained neuronal activity in LC and VTA. This is the first direct evidence in a clinical population to suggest that antipsychotic medications alter catecholamine neuronal activity to mitigate pro-cognitive drug action on cortical circuits

Surface differential rotation and prominences of the Lupus post T Tauri star RX J1508.6-4423

We present in this paper a spectroscopic monitoring of the Lupus post T Tauri star RX J1508.6-4423 carried out at two closely separated epochs (1998 May 06 and 10) with the UCL Echelle Spectrograph on the 3.9-m Anglo-Australian Telescope. Applying least-squares convolution and maximum entropy image reconstruction techniques to our sets of spectra, we demonstrate that this star features on its surface a large cool polar cap with several appendages extending to lower latitudes, as well as one spot close to the equator. The images reconstructed at both epochs are in good overall agreement, except for a photospheric shear that we interpret in terms of latitudinal differential rotation. Given the spot distribution at the epoch of our observations, differential rotation could only be investigated between latitudes 15° and 60°. We find in particular that the observed differential rotation is compatible with a solar-like law (i.e., with rotation rate decreasing towards high latitudes proportionally to sin 2l, where l denotes the latitude) in this particular latitude range. Assuming that such a law can be extrapolated to all latitudes, we find that the equator of RX J1508.6-4423 does one more rotational cycle than the pole every 50 ±10 d, implying a photospheric shear 2 to 3 times stronger than that of the Sun. We also discover that the Hα emission profile of RX J1508.6-4423 is most of the time double-peaked and strongly modulated with the rotation period of the star. We interpret this rotationally modulated emission as being caused by a dense and complex prominence system, the circumstellar distribution of which is obtained through maximum entropy Doppler tomography. These maps show in particular that prominences form a complete and inhomogeneous ring around the star, precisely at the corotation radius. We use the total Hα and Hβ emission flux to estimate that the mass of the whole prominence system is about 10 20g. From our observation that the whole cloud system surrounding the star is regenerated in less than 4 d, we conclude that the braking time-scale of RX J1508.6-4423 is shorter than 1 Gyr, and that prominence expulsion is thus likely to contribute significantly to the rotational spindown of young low-mass stars

Model selection and prediction of outcomes in recent onset schizophrenia patients who undergo cognitive training.

Predicting treatment outcomes in psychiatric populations remains a challenge, but is increasingly important in the pursuit of personalized medicine. Patients with schizophrenia have deficits in cognition, and targeted cognitive training (TCT) of auditory processing and working memory has been shown to improve some of these impairments; but little is known about the baseline patient characteristics predictive of cognitive improvement. Here we use a model selection and regression approach called least absolute shrinkage and selection operator (LASSO) to examine predictors of cognitive improvement in response to TCT for patients with recent onset schizophrenia. Forty-three individuals with recent onset schizophrenia randomized to undergo TCT were assessed at baseline on measures of cognition, symptoms, functioning, illness duration, and demographic variables. We carried out 10-fold cross-validation of LASSO for model selection and regression. We followed up on these results using linear models for statistical inference. No individual variable was found to correlate with improvement in global cognition using a Pearson correlation approach, and a linear model including all variables was also found not to be significant. However, the LASSO model identified baseline global cognition, education, and gender in a model predictive of improvement on global cognition following TCT. These findings offer guidelines for personalized approaches to cognitive training for patients with schizophrenia

A rapid survey method for native blue mud shrimp (Upogebia pugettensis) and its associated parasitic isopod, Orthione griffenis, in Alsea Bay, Oregon and alternative applications of this methodology

Declines or extinctions of the native intertidal estuary blue mud shrimp, Upogebia pugettensis, have been observed or are suspected in all of its populations over the species’ range. These declines are associated with the introduced Asian bopyrid isopod parasite, Orthione griffenis, which effectively castrates females. Baseline estimates of population abundances and distributions to measure overall change over their entire species ranges however, are lacking due, in part, to the massive efforts they require. We partially tested a simple rapid method for estimating total numbers and the structures of U. pugettensis and O. griffenis populations in Alsea Bay, Oregon that can be applied to many more populations and may more times per population than was previously possible. Additionally, portions of this novel methodology were used to develop middle school math and science curriculum using guidelines from the Oregon Department of Education's common core state standards. The curriculum will be a valuable addition to the STEM (Science, Technology, Engineering, and Mathematics) initiative, which seeks to develop analytical and problem solving skills of students in these target disciplines through project-based learning

A History of Trauma is Associated with Aggression, Depression, Non-Suicidal Self-Injury Behavior, and Suicide Ideation in First-Episode Psychosis.

The association between trauma and psychosis outcomes is well-established, and yet the impact of trauma on comorbid clinical symptoms-such as aggression, non-suicidal self-injury behavior (NSSIB), suicide ideation, and suicide behavior-for those with psychosis is unclear. To effectively treat those with first-episode psychosis (FEP) and a history of trauma, we need to understand the impact of trauma on their whole presentation. FEP participants were recruited from an Early Psychosis Program (N = 187, ages 12-35, 72.2% male). Clinicians gathered history of trauma, aggression, and suicide data, and rated current symptom severity and functioning. Data was coded using clinician rated measures, self-report measures, and retrospective clinical chart review. Regression analyses examined whether trauma was associated with a history of aggression, suicidal ideation, suicide behavior, NSSIB, symptoms, and functioning. Trauma was associated with aggression, aggression severity and type of aggression (aggression towards others). Trauma was also associated with depression severity, suicide ideation, most severe suicide ideation, and NSSIB. Trauma was not associated with suicide behavior, severity of suicide behavior or psychosocial functioning. Integrating trauma treatment into FEP care could reduce rates of depression, aggression, suicide ideation, and NSSIB for those with a history of trauma. To reduce suicide attempt occurrence and improve functioning, more research is needed

Proactive and reactive cognitive control and dorsolateral prefrontal cortex dysfunction in first episode schizophrenia.

Cognitive control deficits have been consistently documented in patients with schizophrenia. Recent work in cognitive neuroscience has hypothesized a distinction between two theoretically separable modes of cognitive control-reactive and proactive. However, it remains unclear the extent to which these processes are uniquely associated with dysfunctional neural recruitment in individuals with schizophrenia. This functional magnetic resonance imaging (fMRI) study utilized the color word Stroop task and AX Continuous Performance Task (AX-CPT) to tap reactive and proactive control processes, respectively, in a sample of 54 healthy controls and 43 patients with first episode schizophrenia. Healthy controls demonstrated robust dorsolateral prefrontal, anterior cingulate, and parietal cortex activity on both tasks. In contrast, patients with schizophrenia did not show any significant activation during proactive control, while showing activation similar to control subjects during reactive control. Critically, an interaction analysis showed that the degree to which prefrontal activity was reduced in patients versus controls depended on the type of control process engaged. Controls showed increased dorsolateral prefrontal cortex (DLPFC) and parietal activity in the proactive compared to the reactive control task, whereas patients with schizophrenia did not demonstrate this increase. Additionally, patients' DLPFC activity and performance during proactive control was associated with disorganization symptoms, while no reactive control measures showed this association. Proactive control processes and concomitant dysfunctional recruitment of DLPFC represent robust features of schizophrenia that are also directly associated with symptoms of disorganization

Preliminary evidence of increased striatal dopamine in a nonhuman primate model of maternal immune activation.

Women exposed to a variety of viral and bacterial infections during pregnancy have an increased risk of giving birth to a child with autism, schizophrenia or other neurodevelopmental disorders. Preclinical maternal immune activation (MIA) models are powerful translational tools to investigate mechanisms underlying epidemiological links between infection during pregnancy and offspring neurodevelopmental disorders. Our previous studies documenting the emergence of aberrant behavior in rhesus monkey offspring born to MIA-treated dams extends the rodent MIA model into a species more closely related to humans. Here we present novel neuroimaging data from these animals to further explore the translational potential of the nonhuman primate MIA model. Nine male MIA-treated offspring and 4 controls from our original cohort underwent in vivo positron emission tomography (PET) scanning at approximately 3.5-years of age using [18F] fluoro-l-m-tyrosine (FMT) to measure presynaptic dopamine levels in the striatum, which are consistently elevated in individuals with schizophrenia. Analysis of [18F]FMT signal in the striatum of these nonhuman primates showed that MIA animals had significantly higher [18F]FMT index of influx compared to control animals. In spite of the modest sample size, this group difference reflects a large effect size (Cohen's d = 0.998). Nonhuman primates born to MIA-treated dams exhibited increased striatal dopamine in late adolescence-a hallmark molecular biomarker of schizophrenia. These results validate the MIA model in a species more closely related to humans and open up new avenues for understanding the neurodevelopmental biology of schizophrenia and other neurodevelopmental disorders associated with prenatal immune challenge