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Ziegler, G.

Publications and source records attributed to Ziegler, G..

28 records · Page 2Linked to original sources

Bayesian model selection favors parametric over categorical models of the fMRI subsequent memory effect in young and elderly adults

Subsequent memory paradigms allow to identify neural correlates of successful encoding by separating brain responses as a function of memory performance during later retrieval. In functional magnetic resonance imaging (fMRI), the paradigm typically elicits activations of medial temporal lobe, prefrontal and parietal cortical structures in young, healthy participants. This categorical approach is, however, limited by insufficient memory performance in older and particularly memory-impaired individuals. A parametric modulation of encoding-related activations with memory confidence could overcome this limitation. Here, we applied cross-validated Bayesian model selection (cvBMS) for first-level fMRI models to a visual subsequent memory paradigm in young (18-35 years) and older (51-80 years) adults. Nested cvBMS revealed that parametric models, especially with non-linear transformations of memory confidence ratings, outperformed categorical models in explaining the fMRI signal variance during encoding. We thereby provide a framework for improving the modeling of encoding-related activations and for applying subsequent memory paradigms to memory-impaired individuals.

neuroscience↗

Genomewide association study reveals transient loci underlying the genetic architecture of biomass accumulation under cold stress in Sorghum.

Sorghum bicolor is a promising cellulosic feedstock crop for bioenergy because of its potential for high biomass yields. However, in its early growth phases, sorghum is sensitive to cold stress, preventing early planting in temperate environments. Cold temperature adaptability is vital for the successful cultivation of both bioenergy and grain sorghum at higher latitudes and elevations, and for early season planting or to extend the growing season. Identification of genes and alleles that enhance biomass accumulation of sorghum grown under early cold stress would enable the development of improved bioenergy sorghum through breeding or genetic engineering. We conducted image-based phenotyping on 369 accessions from the sorghum Bioenergy Association Panel (BAP) in a controlled environment with early cold treatment. The BAP is a collection of densely genotyped and racially, geographically, and phenotypically diverse accessions. The plants were weighed, watered, and imaged daily to measure growth dynamics and water use efficiency (WUE). Daily, non-destructive imaging allowed for a temporal analysis of growth-related traits in response to cold stress. We performed a genome-wide association study (GWAS) to identify candidate genomic intervals and genes controlling response to early cold stress. GWAS identified transient quantitative trait loci (QTL) strongly associated with each growth-related trait, permitting an investigation into the genetic basis of cold stress response at different stages of development. The analysis identified a priori and novel candidate genes associated with growth-related traits and the temporal response to cold stress.\n\nSIGNIFICANCE STATEMENTGenome-wide association study of bioenergy sorghum accessions phenotyped under early season cold stress revealed transient QTLs for highly heritable biomass and growth-related traits that appeared as the temperature increased and plants developed. Sorghum accessions clustered into multiple groups for each heritable trait with distinct growth profiles. GWAS identified candidate genes associated with growth traits and cold stress responses. The top-performing accessions with the highest growth-related trait values over time and temperature shifts will be useful for further genetic analysis and breeding or engineering efforts directed at biomass yield enhancements.

plant biology↗

Childhood socio-economic disadvantage predicts reduced myelin growth across adolescence and young adulthood

Socio-economic disadvantage (SED) increases exposure to life stressors. Animal research suggests early life stressors affect later neurodevelopment, including myelin developmental growth. To determine whether human childhood SED affects myelination in adolescence and early adulthood we measured the developmental increase of a sensitive myelin marker, magnetization transfer (MT), in a longitudinal study. Childhood SED was associated with globally reduced MT, as well as slower intra-cortical MT increase in widespread sensory-motor, cingulate, insular and prefrontal areas and subcortical areas. Parental education partially accounted for the SED effects on MT increase, while positive parenting provided a partial protection against the impact of SED. Thus, early socio-economic disadvantage, a vulnerability factor for a range of ill-health outcomes, is a risk factor for aberrant myelin growth during a critical developmental period that is associated with a high risk of psychiatric disorder.

neuroscience↗

Dynamics of cortical degeneration over a decade in Huntington's Disease

The neurodegenerative process is typically slowly progressive and complex. While simple models of neurodegeneration suggest that brain changes progress at a near constant rate, previous research shows regional variation within the temporal progression of atrophy, indicating that over the course of neurodegeneration, different regions may undergo changing rates of atrophy. Characterization of long-term dynamic brain changes in neurodegeneration requires both extensive longitudinal MRI datasets and an advanced modeling framework. Until recently, both of these elements were not available. Here, we implement a novel dynamic systems approach to infer patterns of regional progression spatially and temporally in a unique longitudinal dataset with up to seven annual individual brain scans per participant from 49 Huntingtons Disease (HD) gene-carriers. We map participant-and group-level trajectories of cortical atrophy in HD using a decade of data that encompasses motor symptom onset and, for the first time, show that neurodegenerative brain changes exhibit complex temporal dynamics of atrophy with substantial regional variation in progressive cortical atrophy. Some fronto-occipital cortical areas show an almost constant rate of atrophy, while medial-inferior temporal areas undergo only minor change. Interestingly, cortical sensory-motor areas were found to show a noticeable acceleration of atrophy following HD diagnosis. Furthermore, we establish links between individual atrophy and genetic markers of HD (CAG repeat length), as well as showing that cortical motor network changes predict subsequent decline in task-based motor performance, demonstrating face-validity of the model. Our findings highlight the complex pattern of dynamic cortical change occurring in HD that can help to resolve the biological underpinnings of HD progression.

neuroscience↗

Brain-behaviour modes of covariation in healthy and clinically depressed young people

Understanding how variations in dimensions of psychometrics, IQ and demographics relate to changes in brain connectivity during the critical developmental period of adolescence and early adulthood is a major challenge. This has particular relevance for mental health disorders where a failure to understand these links might hinder the development of better diagnostic approaches and therapeutics. Here, we investigated this question in 306 adolescents and young adults (14-24y, 25 clinically depressed) using a multivariate statistical framework, based on canonical correlation analysis (CCA). By linking individual functional brain connectivity profiles to self-report questionnaires, IQ and demographic data we identified two distinct modes of covariation. The first mode mapped onto an externalization/internalization axis and showed a strong association with sex. The second mode mapped onto a well-being/distress axis independent of sex. Interestingly, both modes showed an association with age. Crucially, the changes in functional brain connectivity associated with changes in these phenotypes showed marked developmental effects. The findings point to a role for the default mode, frontoparietal and limbic networks in psychopathology and depression.

neuroscience↗

A curated list of genes that control elemental accumulation in plants.

Understanding the mechanisms underlying plants adaptation to their environment will require knowledge of the genes and alleles underlying elemental composition. Modern genetics is capable of quickly, and cheaply indicating which regions of DNA are associated with particular phenotypes in question, but most genes remain poorly annotated, hindering the identification of candidate genes. To help identify candidate genes underlying elemental accumulations, we have created the known ionome gene (KIG) list: a curated collection of genes experimentally shown to change uptake, accumulation, and distribution of elements. We have also created an automated computational pipeline to generate lists of KIG orthologs in other plant species using the PhytoMine database. The current version of KIG consists of 176 known genes covering 5 species, 23 elements and their 1588 orthologs in 10 species. Analysis of the known genes demonstrated that most were identified in the model plant Arabidopsis thaliana, and that transporter coding genes and genes altering the accumulation of iron and zinc are overrepresented in the current list.

plant biology↗

Compulsivity and impulsivity are linked to distinct aberrant developmental trajectories of fronto-striatal myelination

The transition from adolescence into adulthood is a period where rapid brain development coincides with an enhanced incidence of psychiatric disorder. The precise developmental brain changes that account for this emergent psychiatric symptomatology remain obscure. Capitalising on a unique longitudinal dataset, that includes in-vivo myelin-sensitive magnetization transfer (MT) MRI, we show this transition period is characterised by brain-wide growth in MT, within both gray matter and adjacent juxta-cortical white matter. We show that an expression of common developmental psychiatric risk symptomatology in this otherwise healthy population, specifically compulsivity and impulsivity, is tied to regionally specific aberrant unfolding of these MT trajectories. This is most marked in frontal midline structures for compulsivity, and in lateral frontal areas for impulsivity. The findings highlight a brain developmental linkage for emergent psychiatric risk features, evident in regionally specific perturbations in the expansion of MT-related myelination.

neuroscience↗

Multivariate analysis of the cotton seed ionome reveals integrated genetic signatures of abiotic stress response

To mitigate the effects of heat and drought stress, a better understanding of the genetic control of physiological responses to these environmental conditions is needed. To this end, we evaluated an upland cotton (Gossypium hirsutum L.) mapping population under water-limited and well-watered conditions in a hot, arid environment. The elemental concentrations (ionome) of seed samples from the population were profiled in addition to those of soil samples taken from throughout the field site to better model environmental variation. The elements profiled in seeds exhibited moderate to high heritabilities, as well as strong phenotypic and genotypic correlations between elements that were not altered by the imposed irrigation regimes. Quantitative trait loci (QTL) mapping results from a Bayesian classification method identified multiple genomic regions where QTL for individual elements colocalized, suggesting that genetic control of the ionome is highly interrelated. To more fully explore this genetic architecture, multivariate QTL mapping was implemented among groups of biochemically related elements. This analysis revealed both additional and pleiotropic QTL responsible for coordinated control of phenotypic variation for elemental accumulation. Machine learning algorithms that utilized only ionomic data predicted the irrigation regime under which genotypes were evaluated with very high accuracy. Taken together, these results demonstrate the extent to which the seed ionome is genetically interrelated and predictive of plant physiological responses to adverse environmental conditions.\n\nOne sentence summaryThe cotton seed ionome has a shared genetic basis that provides insight into the physiological status of the plant.

genetics↗

Elemental Accumulation in Kernels of the Maize Nested Association Mapping Panel Reveals Signals of Gene by Environment Interactions

Elemental accumulation in seeds is the product of a combination of environment and a wide variety of genetically controlled physiological processes. We measured the kernel elemental composition of the Nested Association Mapping (NAM) of maize (Zea mays L.) grown in 4 different environments. Analysis of variance revealed strong effects of genotype, environment and genotype by environment interactions. Using Joint-linkage mapping on a set of 7000 markers we identified 354 quantitative trait loci (QTL) across 20 elements, four environments and a combination of the environments. Leveraging 20 M SNPs derived from genome resequencing on the parents of the population, genome-wide association mapping studies (GWAS) detected 8573 loci. While most of the GWAS SNPs were located near genes not previously implicated in elemental regulation, several SNPs were located next to orthologs of well-characterized elemental regulation genes.

plant biology↗

Developmental cognitive neuroscience using Latent Change Score models: A tutorial and applications

Assessing and analysing individual differences in change over time is of central scientific importance to developmental neuroscience. However, the literature is based largely on cross-sectional comparisons, which reflect a variety of influences and cannot directly represent change. We advocate using latent change score (LCS) models in longitudinal samples as a statistical framework to tease apart the complex processes underlying lifespan development in brain and behaviour using longitudinal data. LCS models provide a flexible framework that naturally accommodates key developmental questions as model parameters and can even be used, with some limitations, in cases with only two measurement occasions. We illustrate the use of LCS models with two empirical examples. In a lifespan cognitive training study (COGITO, N=204 (N=32 imaging) on two waves) we observe correlated change in brain and behaviour in the context of a high-intensity training intervention. In an adolescent development cohort (NSPN, N=176, two waves) we find greater variability in cortical thinning in males than in females. To facilitate the adoption of LCS by the developmental community, we provide analysis code that can be adapted by other researchers and basic primers in two freely available SEM software packages (lavaan and {Omega}nyx).\n\nHighlightsO_LIWe describe Latent change score modelling as a flexible statistical tool\nC_LIO_LIKey developmental questions can be readily formalized using LCS models\nC_LIO_LIWe provide accessible open source code and software examples to fit LCS models\nC_LIO_LIWhite matter structural change is negatively correlated with processing speed gains\nC_LIO_LIFrontal lobe thinning in adolescence is more variable in males than females\nC_LI

neuroscience↗