performance: An R package for assessment, comparison and testing of statistical models

A crucial part of statistical analysis is evaluating a model’s quality and fit, or performance. During analysis, especially with regression models, investigating the fit of models to data also often involves selecting the best fitting model amongst many competing models. Upon investigation, fit indices should also be reported both visually and numerically to bring readers in on the investigative effort. The performance R-package (R Core Team, 2021) provides utilities for computing measures to assess model quality, many of which are not directly provided by R’s base or stats packages. These include measures like R2, intraclass correlation coefficient (ICC), root mean squared error (RMSE), or functions to check for vexing issues like overdispersion, singularity, or zeroinflation. These functions support a large variety of regression models including generalized linear models, (generalized) mixed-effects models, their Bayesian cousins, and many others

Induced pluripotent stem cells from hair follicles as a cellular model for neurodevelopmental disorders

AbstractDisease-specific induced pluripotent stem cells (iPSC) allow unprecedented experimental platforms for basic research as well as high-throughput screening. This may be particularly relevant for neuropsychiatric disorders, in which the affected neuronal cells are not accessible. Keratinocytes isolated from hair follicles are an ideal source of patients' cells for reprogramming, due to their non-invasive accessibility and their common neuroectodermal origin with neurons, which can be important for potential epigenetic memory. From a small number of plucked human hair follicles obtained from two healthy donors we reprogrammed keratinocytes to pluripotent iPSC. We further differentiated these hair follicle-derived iPSC to neural progenitors, forebrain neurons and functional dopaminergic neurons.This study shows that human hair follicle-derived iPSC can be differentiated into various neural lineages, suggesting this experimental system as a promising in vitro model to study normal and pathological neural developments, avoiding the invasiveness of commonly used skin biopsies

Toddlers later diagnosed with autism exhibit multiple structural abnormalities in temporal corpus callosum fibers

Interhemispheric functional connectivity abnormalities are often reported in autism and it is thus not surprising that structural defects of the corpus callosum (CC) are consistently found using both traditional MRI and DTI techniques. Past DTI studies however, have subdivided the CC into 2 or 3 segments without regard for where fibers may project to within the cortex, thus placing limitations on our ability to understand the nature, timing and neurobehavioral impact of early CC abnormalities in autism. Leveraging a unique cohort of 97 toddlers (68 autism; 29 typical) we utilized a novel technique that identified seven CC tracts according to their cortical projections. Results revealed that younger (<2.5 years old), but not older toddlers with autism exhibited abnormally low mean, radial, and axial diffusivity values in the CC tracts connecting the occipital lobes and the temporal lobes. Fractional anisotropy and the cross sectional area of the temporal CC tract were significantly larger in young toddlers with autism. These findings indicate that water diffusion is more restricted and unidirectional in the temporal CC tract of young toddlers who develop autism. Such results may be explained by a potential overabundance of small caliber axons generated by excessive prenatal neural proliferation as proposed by previous genetic, animal model, and postmortem studies of autism. Furthermore, early diffusion measures in the temporal CC tract of the young toddlers were correlated with outcome measures of autism severity at later ages. These findings regarding the potential nature, timing, and location of early CC abnormalities in autism add to accumulating evidence, which suggests that altered inter-hemispheric connectivity, particularly across the temporal lobes, is a hallmark of the disorder

Rapid online assessment of reading ability

Published18 March 2021An accurate model of the factors that contribute to individual differences in reading ability depends on data collection in large, diverse and representative samples of research participants. However, that is rarely feasible due to the constraints imposed by standardized measures of reading ability which require test administration by trained clinicians or researchers. Here we explore whether a simple, two-alternative forced choice, time limited lexical decision task (LDT), self-delivered through the webbrowser, can serve as an accurate and reliable measure of reading ability. We found that performance on the LDT is highly correlated with scores on standardized measures of reading ability such as the Woodcock-Johnson Letter Word Identification test (r = 0.91, disattenuated r = 0.94). Importantly, the LDT reading ability measure is highly reliable (r = 0.97). After optimizing the list of words and pseudowords based on item response theory, we found that a short experiment with 76 trials (2–3 min) provides a reliable (r = 0.95) measure of reading ability. Thus, the self-administered, Rapid Online Assessment of Reading ability (ROAR) developed here overcomes the constraints of resourceintensive, in-person reading assessment, and provides an efficient and automated tool for effective online research into the mechanisms of reading (dis)ability.We would like to thank the Pavlovia and PsychoPy team for their support on the browser-based experiments. This work was funded by NIH NICHD R01HD09586101, research grants from Microsoft and Jacobs Foundation Research Fellowship to J.D.Y

Sp1 Expression Is Disrupted in Schizophrenia; A Possible Mechanism for the Abnormal Expression of Mitochondrial Complex I Genes, NDUFV1 and NDUFV2

The prevailing hypothesis regards schizophrenia as a polygenic disease, in which multiple genes combine with each other and with environmental stimuli to produce the variance of its clinical symptoms. We investigated whether the ubiquitous transcription factor Sp1 is abnormally expressed in schizophrenia, and consequently can affect the expression of genes implicated in this disorder. promoter by binding to its three GC-boxes. Both activation and binding were inhibited by mithramycin.These findings suggest that abnormality in Sp1, which can be the main activator/repressor or act in combination with additional transcription factors and is subjected to environmental stimuli, can contribute to the polygenic and clinically heterogeneous nature of schizophrenia

Neuroanatomical Pattern of Mitochondrial Complex I Pathology Varies between Schizophrenia, Bipolar Disorder and Major Depression

BACKGROUND:Mitochondrial dysfunction was reported in schizophrenia, bipolar disorderand major depression. The present study investigated whether mitochondrial complex I abnormalities show disease-specific characteristics. METHODOLOGY/PRINCIPAL FINDINGS:mRNA and protein levels of complex I subunits NDUFV1, NDUFV2 and NADUFS1, were assessed in striatal and lateral cerebellar hemisphere postmortem specimens and analyzed together with our previous data from prefrontal and parieto-occipital cortices specimens of patients with schizophrenia, bipolar disorder, major depression and healthy subjects. A disease-specific anatomical pattern in complex I subunits alterations was found. Schizophrenia-specific reductions were observed in the prefrontal cortex and in the striatum. The depressed group showed consistent reductions in all three subunits in the cerebellum. The bipolar group, however, showed increased expression in the parieto-occipital cortex, similar to those observed in schizophrenia, and reductions in the cerebellum, yet less consistent than the depressed group. CONCLUSIONS/SIGNIFICANCE:These results suggest that the neuroanatomical pattern of complex I pathology parallels the diversity and similarities in clinical symptoms of these mental disorders

Iron Storage within Dopamine Neurovesicles Revealed by Chemical Nano-Imaging

Altered homeostasis of metal ions is suspected to play a critical role in neurodegeneration. However, the lack of analytical technique with sufficient spatial resolution prevents the investigation of metals distribution in neurons. An original experimental setup was developed to perform chemical element imaging with a 90 nm spatial resolution using synchrotron-based X-ray fluorescence. This unique spatial resolution, combined to a high brightness, enables chemical element imaging in subcellular compartments. We investigated the distribution of iron in dopamine producing neurons because iron-dopamine compounds are suspected to be formed but have yet never been observed in cells. The study shows that iron accumulates into dopamine neurovesicles. In addition, the inhibition of dopamine synthesis results in a decreased vesicular storage of iron. These results indicate a new physiological role for dopamine in iron buffering within normal dopamine producing cells. This system could be at fault in Parkinson's disease which is characterized by an increased level of iron in the substancia nigra pars compacta and an impaired storage of dopamine due to the disruption of vesicular trafficking. The re-distribution of highly reactive dopamine-iron complexes outside neurovesicles would result in an enhanced death of dopaminergic neurons

Picturing words? Sensorimotor cortex activation for printed words in child and adult readers

Learning to read involves associating abstract visual shapes with familiar meanings. Embodiment theories suggest that word meaning is at least partially represented in distributed sensorimotor networks in the brain (Barsalou, 2008; Pulvermueller, 2013). We explored how reading comprehension develops by tracking when and how printed words start activating these “semantic” sensorimotor representations as children learn to read. Adults and children aged 7–10 years showed clear category-specific cortical specialization for tool versus animal pictures during a one-back categorisation task. Thus, sensorimotor representations for these categories were in place at all ages. However, co-activation of these same brain regions by the visual objects’ written names was only present in adults, even though all children could read and comprehend all presented words, showed adult-like task performance, and older children were proficient readers. It thus takes years of training and expert reading skill before spontaneous processing of printed words’ sensorimotor meanings develops in childhood

Pooled analysis of iron-related genes in Parkinson's disease: Association with transferrin

Pathologic features of Parkinson's disease (PD) include death of dopaminergic neurons in the substantia nigra, presence of α-synuclein containing Lewy bodies, and iron accumulation in PD-related brain regions. The observed iron accumulation may be contributing to PD etiology but it also may be a byproduct of cell death or cellular dysfunction. To elucidate the possible role of iron accumulation in PD, we investigated genetic variation in 16 genes related to iron homeostasis in three case-control studies from the United States, Australia, and France. After screening 90 haplotype tagging single nucleotide polymorphisms (SNPs) within the genes of interest in the US study population, we investigated the five most promising gene regions in two additional independent case-control studies. For the pooled data set (1289 cases, 1391 controls) we observed a protective association (OR. = 0.83, 95% CI: 0.71-0.96) between PD and a haplotype composed of the A allele at rs1880669 and the T allele at rs1049296 in transferrin (TF; GeneID: 7018). Additionally, we observed a suggestive protective association (OR. = 0.87, 95% CI: 0.74-1.02) between PD and a haplotype composed of the G allele at rs10247962 and the A allele at rs4434553 in transferrin receptor 2 (TFR2; GeneID: 7036). We observed no associations in our pooled sample for haplotypes in SLC40A1, CYB561, or HFE. Taken together with previous findings in model systems, our results suggest that TF or a TF- TFR2 complex may have a role in the etiology of PD, possibly through iron misregulation or mitochondrial dysfunction within dopaminergic neurons