Cortico-cerebellar functional connectivity and sequencing of movements in schizophrenia

<p>Abstract</p> <p>Background</p> <p>Abnormal execution of several movements in a sequence is a frequent finding in schizophrenia. Successful performance of such motor acts requires correct integration of cortico-subcortical processes, particularly those related to cerebellar functions. Abnormal connectivity between cortical and cerebellar regions with resulting cognitive dysmetria has been proposed as the core dysfunction behind many signs and symptoms of schizophrenia. The aim of the present study was to assess if these proposed abnormalities in connectivity are a unifying feature of schizophrenia, or, rather, reflect a specific symptom domain of a heterogeneous disease. We predicted that abnormal functional connectivity between the motor cortex and cerebellum would be linked with abnormal performance of movement sequencing.</p> <p>Methods</p> <p>We examined 24 schizophrenia patients (SCH) and 24 age-, sex-, and handedness-matched healthy controls (HC) using fMRI during a modified finger-tapping task. The ability to perform movement sequencing was tested using the Neurological Evaluation Scale (NES). The subjects were categorized into two groups, with (SQ+) and without (SQ-) movement sequencing abnormalities, according to the NES-SQ score. The effects of diagnosis and movement sequencing abnormalities on the functional connectivity parameters between the motor cortex and cerebellum (MC-CRBL) and the supplementary motor cortex and cerebellum (SMA-CRBL) activated during the motor task were analyzed.</p> <p>Results</p> <p>We found no effect of diagnosis on the functional connectivity measures. There was, however, a significant effect on the SQ group: SQ + patients showed a lower level of MC-CRBL connectivity than SQ- patients and healthy controls. Moreover, the level of MC-CRBL and SMA-CRBL negatively correlated with the magnitude of NES-SQ abnormalities, but with no other NES domain.</p> <p>Conclusions</p> <p>Abnormal cortico-cerebellar functional connectivity during the execution of a motor task is linked with movement sequencing abnormalities in schizophrenia, but not with the diagnosis of schizophrenia per se. It seems that specific patterns of inter-regional connectivity are linked with corresponding signs and symptoms of clinically heterogeneous conditions such as schizophrenia.</p

Structural Correlates of Taste and Smell Loss in Encephalitis Disseminata

BACKGROUND: Olfactory dysfunction in MS patients is reported in the literature. MRI of the olfactory bulb (OB) is discussed as a promising new testing method for measuring olfactory function (OF). Aim of this study was to explore reasons for and optimize the detection of olfactory dysfunction in MS patients with MRI. MATERIALS AND METHODS: OB and olfactory brain volume was assessed within 34 MS patients by manual segmentation. Olfactory function was tested using the Threshold-Discrimination-Identification-Test (TDI), gustatory function was tested using Taste Strips (TST). RESULTS: 41% of the MS patients displayed olfactory dysfunction (8% of the control group), 16% displayed gustatory dysfunction (5% of the control group). There was a correlation between the OB volume and the number and volume of MS lesions in the olfactory brain. Olfactory brain volume correlated with the volume of lesions in the olfactory brain and the EDSS score. The TST score correlated with the number and volume of lesions in the olfactory brain. CONCLUSION: The correlation between a higher number and volume of MS lesions with a decreased OB and olfactory brain volume could help to explain olfactory dysfunction

Intra-Individual Variability in Alzheimer's Disease and Cognitive Aging: Definitions, Context, and Effect Sizes

To explore different definitions of intra-individual variability (IIV) to summarize performance on commonly utilized cognitive tests (Mini Mental State Exam; Clock Drawing Test); compare them and their potential to differentiate clinically-defined populations; and to examine their utility in predicting clinical change in individuals from the Alzheimer's Disease Neuroimaging Initiative (ADNI).) were computed for each of these definitions in 500 simulated replicates using scores on the Mini Mental State Exam and Clock Drawing Test. IIV was computed based on test items separately (‘within test’ IIV) and the two tests together (‘across test’ IIV). The best performing definition was then used to compute IIV for a third test, the Alzheimer's Disease Assessment Scale-Cognitive, and the simulations and effect sizes were again computed. All effect size estimates based on simulated data were compared to those computed based on the total scores in the observed data. Association between total score and IIV summaries of the tests and the Clinician's Dementia Rating were estimated to test the utility of IIV in predicting clinically meaningful changes in the cohorts over 12- and 24-month intervals.ES estimates differed substantially depending on the definition of IIV and the test(s) on which IIV was based. IIV (coefficient of variation) summaries of MMSE and Clock-Drawing performed similarly to their total scores, the ADAS total performed better than its IIV summary.IIV can be computed within (items) or across (totals) items on commonly-utilized cognitive tests, and may provide a useful additional summary measure of neuropsychological test performance

A systematic review and meta-analysis of neurological soft signs in relatives of people with schizophrenia

<p>Abstract</p> <p>Background</p> <p>Neurological soft signs are subtle but observable impairments in motor and sensory functions that are not localized to a specific area of the brain. Neurological soft signs are common in schizophrenia. It has been established that soft signs meet two of five criteria for an endophenotype, namely: association with the illness, and state independence. This review investigated whether soft signs met a further criterion for an endophenotype, namely familial association. It was hypothesized that if familial association were present then neurological soft signs would be: (a) more common in first-degree relatives of people with schizophrenia than in controls; and (b) more common in people with schizophrenia than in their first-degree relatives.</p> <p>Method</p> <p>A systematic search identified potentially eligible studies in the EMBASE (1980-2011), OVID - MEDLINE (1950-2011) and PsycINFO (1806-2011) databases. Studies were included if they carried out a three-way comparison of levels of soft signs between people with schizophrenia, their first-degree relatives, and normal controls. Data were extracted independently by two reviewers and cross-checked by double entry.</p> <p>Results</p> <p>After screening 8678 abstracts, seven studies with 1553 participants were identified. Neurological soft signs were significantly more common in first-degree relatives of people with schizophrenia than in controls (pooled standardised mean difference (SMD) 1.24, 95% confidence interval (c.i) 0.59-1.89). Neurological soft signs were also significantly more common in people with schizophrenia than in their first-degree relatives (SMD 0.92, 95% c.i 0.64-1.20). Sensitivity analyses examining the effects of age and group blinding did not significantly alter the main findings.</p> <p>Conclusions</p> <p>Both hypotheses were confirmed, suggesting that the distribution of neurological soft signs in people with schizophrenia and their first-degree relatives is consistent with the endophenotype criterion of familial association.</p

Assessment of predictive models for chlorophyll-a concentration of a tropical lake

<p>Abstract</p> <p>Background</p> <p>This study assesses four predictive ecological models; Fuzzy Logic (FL), Recurrent Artificial Neural Network (RANN), Hybrid Evolutionary Algorithm (HEA) and multiple linear regressions (MLR) to forecast chlorophyll- a concentration using limnological data from 2001 through 2004 of unstratified shallow, oligotrophic to mesotrophic tropical Putrajaya Lake (Malaysia). Performances of the models are assessed using Root Mean Square Error (RMSE), correlation coefficient (r), and Area under the Receiving Operating Characteristic (ROC) curve (AUC). Chlorophyll-a have been used to estimate algal biomass in aquatic ecosystem as it is common in most algae. Algal biomass indicates of the trophic status of a water body. Chlorophyll- a therefore, is an effective indicator for monitoring eutrophication which is a common problem of lakes and reservoirs all over the world. Assessments of these predictive models are necessary towards developing a reliable algorithm to estimate chlorophyll- a concentration for eutrophication management of tropical lakes.</p> <p>Results</p> <p>Same data set was used for models development and the data was divided into two sets; training and testing to avoid biasness in results. FL and RANN models were developed using parameters selected through sensitivity analysis. The selected variables were water temperature, pH, dissolved oxygen, ammonia nitrogen, nitrate nitrogen and Secchi depth. Dissolved oxygen, selected through stepwise procedure, was used to develop the MLR model. HEA model used parameters selected using genetic algorithm (GA). The selected parameters were pH, Secchi depth, dissolved oxygen and nitrate nitrogen. RMSE, r, and AUC values for MLR model were (4.60, 0.5, and 0.76), FL model were (4.49, 0.6, and 0.84), RANN model were (4.28, 0.7, and 0.79) and HEA model were (4.27, 0.7, and 0.82) respectively. Performance inconsistencies between four models in terms of performance criteria in this study resulted from the methodology used in measuring the performance. RMSE is based on the level of error of prediction whereas AUC is based on binary classification task.</p> <p>Conclusions</p> <p>Overall, HEA produced the best performance in terms of RMSE, r, and AUC values. This was followed by FL, RANN, and MLR.</p

Roles for the Conserved Spc105p/Kre28p Complex in Kinetochore-Microtubule Binding and the Spindle Assembly Checkpoint

Kinetochores attach sister chromatids to microtubules of the mitotic spindle and orchestrate chromosome disjunction at anaphase. Although S. cerevisiae has the simplest known kinetochores, they nonetheless contain approximately 70 subunits that assemble on centromeric DNA in a hierarchical manner. Developing an accurate picture of the DNA-binding, linker and microtubule-binding layers of kinetochores, including the functions of individual proteins in these layers, is a key challenge in the field of yeast chromosome segregation. Moreover, comparison of orthologous proteins in yeast and humans promises to extend insight obtained from the study of simple fungal kinetochores to complex animal cell kinetochores.We show that S. cerevisiae Spc105p forms a heterotrimeric complex with Kre28p, the likely orthologue of the metazoan kinetochore protein Zwint-1. Through systematic analysis of interdependencies among kinetochore complexes, focused on Spc105p/Kre28p, we develop a comprehensive picture of the assembly hierarchy of budding yeast kinetochores. We find Spc105p/Kre28p to comprise the third linker complex that, along with the Ndc80 and MIND linker complexes, is responsible for bridging between centromeric heterochromatin and kinetochore MAPs and motors. Like the Ndc80 complex, Spc105p/Kre28p is also essential for kinetochore binding by components of the spindle assembly checkpoint. Moreover, these functions are conserved in human cells.Spc105p/Kre28p is the last of the core linker complexes to be analyzed in yeast and we show it to be required for kinetochore binding by a discrete subset of kMAPs (Bim1p, Bik1p, Slk19p) and motors (Cin8p, Kar3p), all of which are nonessential. Strikingly, dissociation of these proteins from kinetochores prevents bipolar attachment, even though the Ndc80 and DASH complexes, the two best-studied kMAPs, are still present. The failure of Spc105 deficient kinetochores to bind correctly to spindle microtubules and to recruit checkpoint proteins in yeast and human cells explains the observed severity of missegregation phenotypes

A pedestrian approach to the invariant Gibbs measures for the 2-d defocusing nonlinear Schrödinger equations

42 pagesInternational audienceWe consider the defocusing nonlinear Schr\"odinger equations on the two-dimensional compact Riemannian manifold without boundary or a bounded domain in $\R^2$. Our aim is to give a pedagogic and self-contained presentation on the Wick renormalization in terms of the Hermite polynomials and the Laguerre polynomials and construct the Gibbs measures corresponding to the Wick ordered Hamiltonian. Then, we construct global-in-time solutions with initial data distributed according to the Gibbs measure and show that the law of the random solutions, at any time, is again given by the Gibbs measure