Assessing neural tuning for object perception in schizophrenia and bipolar disorder with multivariate pattern analysis of fMRI data.

IntroductionDeficits in visual perception are well-established in schizophrenia and are linked to abnormal activity in the lateral occipital complex (LOC). Related deficits may exist in bipolar disorder. LOC contains neurons tuned to object features. It is unknown whether neural tuning in LOC or other visual areas is abnormal in patients, contributing to abnormal perception during visual tasks. This study used multivariate pattern analysis (MVPA) to investigate perceptual tuning for objects in schizophrenia and bipolar disorder.MethodsFifty schizophrenia participants, 51 bipolar disorder participants, and 47 matched healthy controls completed five functional magnetic resonance imaging (fMRI) runs of a perceptual task in which they viewed pictures of four different objects and an outdoor scene. We performed classification analyses designed to assess the distinctiveness of activity corresponding to perception of each stimulus in LOC (a functionally localized region of interest). We also performed similar classification analyses throughout the brain using a searchlight technique. We compared classification accuracy and patterns of classification errors across groups.ResultsStimulus classification accuracy was significantly above chance in all groups in LOC and throughout visual cortex. Classification errors were mostly within-category confusions (e.g., misclassifying one chair as another chair). There were no group differences in classification accuracy or patterns of confusion.ConclusionsThe results show for the first time MVPA can be used successfully to classify individual perceptual stimuli in schizophrenia and bipolar disorder. However, the results do not provide evidence of abnormal neural tuning in schizophrenia and bipolar disorder

Disorder-induced Majorana metal in interacting non-Abelian anyon systems

We demonstrate that a thermal metal of Majorana fermions forms in a two-dimensional system of interacting non-Abelian (Ising) anyons in the presence of moderate disorder. This bulk metallic phase arises in the $\nu=5/2$ quantum Hall state when disorder pins the anyonic quasiparticles. More generally, it naturally occurs for various proposed systems supporting Majorana fermion zero modes when disorder induces the random pinning of a finite density of vortices. This includes all two-dimensional topological superconductors in so-called symmetry class D. A distinct experimental signature of the thermal metal phase is the presence of bulk heat transport down to zero temperature.Comment: 4 pages, 6 figure

Spectroscopy, Interactions and Level Splittings in Au Nanoparticles

We have measured the electronic energy spectra of nm-scale Au particles using a new tunneling spectroscopy configuration. The particle diameters ranged from 5nm to 9nm, and at low energies the spectrum is discrete, as expected by the electron-in-a-box model. The density of tunneling resonances increases rapidly with energy, and at higher energies the resonances overlap forming broad resonances. Near the Thouless energy, the broad resonances merge into a continuum. The tunneling resonances display Zeeman splitting in a magnetic field. Surprisingly, the g-factors (~0.3) of energy levels in Au nano-particles are much smaller than the g-factor (2.1) in bulk gold

The Role of CD 133+ Cells in a Recurrent Embryonal Tumor with Abundant Neuropil and True Rosettes ( ETANTR )

Embryonal tumor with abundant neuropil and true rosettes ( ETANTR ) is a recently described embryonal neoplasm of the central nervous system, consisting of a well‐circumscribed embryonal tumor of infancy with mixed features of ependymoblastoma (multilayer ependymoblastic rosettes and pseudorosettes) and neuroblastoma (neuroblastic rosettes) in the presence of neuropil‐like islands. We present the case of a young child with a very aggressive tumor that rapidly recurred after gross total resection, chemotherapy and radiation. Prominent vascular sclerosis and circumscribed tumor led to the diagnosis of malignant astroblastoma; however, rapid recurrence and progression of this large tumor after gross total resection prompted review of the original pathology. ETANTR is histologically distinct with focal glial fibrillary acid protein ( GFAP ) and synaptophysin expression in the presence of neuronal and ependymoblastic rosettes with focal neuropil islands. These architectural features, combined with unique chromosome 19q13.42 amplification, confirmed the diagnosis. In this report, we describe tumor stem cell ( TSC ) marker CD 133, CD 15 and nestin alterations in ETANTR before and after chemotherapy. We found that TSC marker CD 133 was richly expressed after chemotherapy in recurrent ETANTR , while CD 15 is depleted compared with that expressed in the original tumor, suggesting that CD 133+ cells likely survived initial treatment, further contributing to formation of the recurrent tumor.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/102077/1/bpa12079.pd

African Ancestry and Its Correlation to Type 2 Diabetes in African Americans: A Genetic Admixture Analysis in Three U.S. Population Cohorts

The risk of type 2 diabetes is approximately 2-fold higher in African Americans than in European Americans even after adjusting for known environmental risk factors, including socioeconomic status (SES), suggesting that genetic factors may explain some of this population difference in disease risk. However, relatively few genetic studies have examined this hypothesis in a large sample of African Americans with and without diabetes. Therefore, we performed an admixture analysis using 2,189 ancestry-informative markers in 7,021 African Americans (2,373 with type 2 diabetes and 4,648 without) from the Atherosclerosis Risk in Communities Study, the Jackson Heart Study, and the Multiethnic Cohort to 1) determine the association of type 2 diabetes and its related quantitative traits with African ancestry controlling for measures of SES and 2) identify genetic loci for type 2 diabetes through a genome-wide admixture mapping scan. The median percentage of African ancestry of diabetic participants was slightly greater than that of non-diabetic participants (study-adjusted difference = 1.6%, P<0.001). The odds ratio for diabetes comparing participants in the highest vs. lowest tertile of African ancestry was 1.33 (95% confidence interval 1.13–1.55), after adjustment for age, sex, study, body mass index (BMI), and SES. Admixture scans identified two potential loci for diabetes at 12p13.31 (LOD = 4.0) and 13q14.3 (Z score = 4.5, P = 6.6×10−6). In conclusion, genetic ancestry has a significant association with type 2 diabetes above and beyond its association with non-genetic risk factors for type 2 diabetes in African Americans, but no single gene with a major effect is sufficient to explain a large portion of the observed population difference in risk of diabetes. There undoubtedly is a complex interplay among specific genetic loci and non-genetic factors, which may both be associated with overall admixture, leading to the observed ethnic differences in diabetes risk

Bistability in the Tunnelling Current through a Ring of NN Coupled Quantum Dots

We study bistability in the electron transport through a ring of N coupled quantum dots with two orbitals in each dot. One orbital is localized (called b orbital) and coupling of the b orbitals in any two dots is negligible; the other is delocalized in the plane of the ring (called d orbital), due to coupling of the d orbitals in the neighboring dots, as described by a tight-binding model. The d orbitals thereby form a band with finite width. The b and d orbitals are connected to the source and drain electrodes with a voltage bias V, allowing the electron tunnelling. Tunnelling current is calculated by using a nonequilibrium Green function method recently developed to treat nanostructures with multiple energy levels. We find a bistable effect in the tunnelling current as a function of bias V, when the size N>50; this effect scales with the size N and becomes sizable at N~100. The temperature effect on bistability is also discussed. In comparison, mean-field treatment tends to overestimate the bistable effect.Comment: Published in JPSJ; minor typos correcte

The breakdown of the Nagaoka phase in the 2D t-J model

In the limit of weak exchange, J, at low hole concentration, the ground state of the 2D t-J model is believed to be ferromagnetic. We study the leading instability of this Nagaoka state, which emerges with increasing J. Both exact diagonalization of small clusters, and a semiclassical analytical calculation of larger systems show that above a certain critical value of the exchange, Nagaoka's state is unstable to phase separation. In a finite-size system a bubble of antiferromagnetic Mott insulator appears in the ground state above this threshold. The size of this bubble depends on the hole concentration and scales as a power of the system size, N

Common Variants in 40 Genes Assessed for Diabetes Incidence and Response to Metformin and Lifestyle Intervention in the Diabetes Prevention Program

OBJECTIVE: Genome-wide association studies have begun to elucidate the genetic architecture of type 2 diabetes. We examined whether single nucleotide polymorphisms (SNPs) identified through targeted complementary approaches affect diabetes incidence in the at-risk population of the Diabetes Prevention Program (DPP) and whether they influence a response to preventive interventions. RESEARCH DESIGN AND METHODS: We selected SNPs identified by prior genome-wide association studies for type 2 diabetes and related traits, or capturing common variation in 40 candidate genes previously associated with type 2 diabetes, implicated in monogenic diabetes, encoding type 2 diabetes drug targets or drug-metabolizing/transporting enzymes, or involved in relevant physiological processes. We analyzed 1,590 SNPs for association with incident diabetes and their interaction with response to metformin or lifestyle interventions in 2,994 DPP participants. We controlled for multiple hypothesis testing by assessing false discovery rates. RESULTS: We replicated the association of variants in the metformin transporter gene $SLC47A1$ with metformin response and detected nominal interactions in the AMP kinase (AMPK) gene $STK11$, the AMPK subunit genes $PRKAA1$ and $PRKAA2$, and a missense SNP in $SLC22A1$, which encodes another metformin transporter. The most significant association with diabetes incidence occurred in the AMPK subunit gene $PRKAG2$ (hazard ratio 1.24, 95% CI 1.09–1.40, P = 7 × 10$^{−4}$). Overall, there were nominal associations with diabetes incidence at 85 SNPs and nominal interactions with the metformin and lifestyle interventions at 91 and 69 mostly nonoverlapping SNPs, respectively. The lowest $P$ values were consistent with experiment-wide 33% false discovery rates. CONCLUSIONS: We have identified potential genetic determinants of metformin response. These results merit confirmation in independent samples

Common Variants in 40 Genes Assessed for Diabetes Incidence and Response to Metformin and Lifestyle Intervention in the Diabetes Prevention Program

OBJECTIVE: Genome-wide association studies have begun to elucidate the genetic architecture of type 2 diabetes. We examined whether single nucleotide polymorphisms (SNPs) identified through targeted complementary approaches affect diabetes incidence in the at-risk population of the Diabetes Prevention Program (DPP) and whether they influence a response to preventive interventions. RESEARCH DESIGN AND METHODS: We selected SNPs identified by prior genome-wide association studies for type 2 diabetes and related traits, or capturing common variation in 40 candidate genes previously associated with type 2 diabetes, implicated in monogenic diabetes, encoding type 2 diabetes drug targets or drug-metabolizing/transporting enzymes, or involved in relevant physiological processes. We analyzed 1,590 SNPs for association with incident diabetes and their interaction with response to metformin or lifestyle interventions in 2,994 DPP participants. We controlled for multiple hypothesis testing by assessing false discovery rates. RESULTS: We replicated the association of variants in the metformin transporter gene SLC47A1 with metformin response and detected nominal interactions in the AMP kinase (AMPK) gene STK11, the AMPK subunit genes PRKAA1 and PRKAA2, and a missense SNP in SLC22A1, which encodes another metformin transporter. The most significant association with diabetes incidence occurred in the AMPK subunit gene PRKAG2 (hazard ratio 1.24, 95% CI 1.09-1.40, P = 7 × 10(-4)). Overall, there were nominal associations with diabetes incidence at 85 SNPs and nominal interactions with the metformin and lifestyle interventions at 91 and 69 mostly nonoverlapping SNPs, respectively. The lowest P values were consistent with experiment-wide 33% false discovery rates. CONCLUSIONS: We have identified potential genetic determinants of metformin response. These results merit confirmation in independent samples

Increased power of mixed models facilitates association mapping of 10 loci for metabolic traits in an isolated population

The potential benefits of using population isolates in genetic mapping, such as reduced genetic, phenotypic and environmental heterogeneity, are offset by the challenges posed by the large amounts of direct and cryptic relatedness in these populations confounding basic assumptions of independence. We have evaluated four representative specialized methods for association testing in the presence of relatedness; (i) within-family (ii) within- and between-family and (iii) mixed-models methods, using simulated traits for 2906 subjects with known genome-wide genotype data from an extremely isolated population, the Island of Kosrae, Federated States of Micronesia. We report that mixed models optimally extract association information from such samples, demonstrating 88% power to rank the true variant as among the top 10 genome-wide with 56% achieving genome-wide significance, a >80% improvement over the other methods, and demonstrate that population isolates have similar power to non-isolate populations for observing variants of known effects. We then used the mixed-model method to reanalyze data for 17 published phenotypes relating to metabolic traits and electrocardiographic measures, along with another 8 previously unreported. We replicate nine genome-wide significant associations with known loci of plasma cholesterol, high-density lipoprotein, low-density lipoprotein, triglycerides, thyroid stimulating hormone, homocysteine, C-reactive protein and uric acid, with only one detected in the previous analysis of the same traits. Further, we leveraged shared identity-by-descent genetic segments in the region of the uric acid locus to fine-map the signal, refining the known locus by a factor of 4. Finally, we report a novel associations for height (rs17629022, P< 2.1 × 10−8