Software Development Standard Processes (SDSP)

A JPL-created set of standard processes is to be used throughout the lifecycle of software development. These SDSPs cover a range of activities, from management and engineering activities, to assurance and support activities. These processes must be applied to software tasks per a prescribed set of procedures. JPL s Software Quality Improvement Project is currently working at the behest of the JPL Software Process Owner to ensure that all applicable software tasks follow these procedures. The SDSPs are captured as a set of 22 standards in JPL s software process domain. They were developed in-house at JPL by a number of Subject Matter Experts (SMEs) residing primarily within the Engineering and Science Directorate, but also from the Business Operations Directorate and Safety and Mission Success Directorate. These practices include not only currently performed best practices, but also JPL-desired future practices in key thrust areas like software architecting and software reuse analysis. Additionally, these SDSPs conform to many standards and requirements to which JPL projects are beholden

Subcortical volumes across the lifespan: Data from 18,605 healthy individuals aged 3–90 years

Age has a major effect on brain volume. However, the normative studies available are constrained by small sample sizes, restricted age coverage and significant methodological variability. These limitations introduce inconsistencies and may obscure or distort the lifespan trajectories of brain morphometry. In response, we capitalized on the resources of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Consortium to examine age‐related trajectories inferred from cross‐sectional measures of the ventricles, the basal ganglia (caudate, putamen, pallidum, and nucleus accumbens), the thalamus, hippocampus and amygdala using magnetic resonance imaging data obtained from 18,605 individuals aged 3–90 years. All subcortical structure volumes were at their maximum value early in life. The volume of the basal ganglia showed a monotonic negative association with age thereafter; there was no significant association between age and the volumes of the thalamus, amygdala and the hippocampus (with some degree of decline in thalamus) until the sixth decade of life after which they also showed a steep negative association with age. The lateral ventricles showed continuous enlargement throughout the lifespan. Age was positively associated with inter‐individual variability in the hippocampus and amygdala and the lateral ventricles. These results were robust to potential confounders and could be used to examine the functional significance of deviations from typical age‐related morphometric patterns

Cortical thickness across the lifespan: Data from 17,075 healthy individuals aged 3-90 years

Delineating the association of age and cortical thickness in healthy individuals is critical given the association of cortical thickness with cognition and behavior. Previous research has shown that robust estimates of the association between age and brain morphometry require large‐scale studies. In response, we used cross‐sectional data from 17,075 individuals aged 3–90 years from the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Consortium to infer age‐related changes in cortical thickness. We used fractional polynomial (FP) regression to quantify the association between age and cortical thickness, and we computed normalized growth centiles using the parametric Lambda, Mu, and Sigma method. Interindividual variability was estimated using meta‐analysis and one‐way analysis of variance. For most regions, their highest cortical thickness value was observed in childhood. Age and cortical thickness showed a negative association; the slope was steeper up to the third decade of life and more gradual thereafter; notable exceptions to this general pattern were entorhinal, temporopolar, and anterior cingulate cortices. Interindividual variability was largest in temporal and frontal regions across the lifespan. Age and its FP combinations explained up to 59% variance in cortical thickness. These results may form the basis of further investigation on normative deviation in cortical thickness and its significance for behavioral and cognitive outcomes

Brain volume reductions in adolescent heavy drinkers

Background: Brain abnormalities in adolescent heavy drinkers may result from alcohol exposure, or stem from pre-existing neural features. Methods: This longitudinal morphometric study investigated 40 healthy adolescents, ages 12–17 at study entry, half of whom (n = 20) initiated heavy drinking over the 3-year follow-up. Both assessments included high-resolution magnetic resonance imaging. FreeSurfer was used to segment brain volumes, which were measured longitudinally using the newly developed quantitative anatomic regional change analysis (QUARC) tool. Results: At baseline, participants who later transitioned into heavy drinking showed smaller left cingulate, pars triangularis, and rostral anterior cingulate volume, and less right cerebellar white matter volumes (p < .05), compared to continuous non-using teens. Over time, participants who initiated heavy drinking showed significantly greater volume reduction in the left ventral diencephalon, left inferior and middle temporal gyrus, and left caudate and brain stem, compared to substance-naïve youth (p < .05). Conclusion: Findings suggest pre-existing volume differences in frontal brain regions in future drinkers and greater brain volume reduction in subcortical and temporal regions after alcohol use was initiated. This is consistent with literature showing pre-existing cognitive deficits on tasks recruited by frontal regions, as well as post-drinking consequences on brain regions involved in language and spatial tasks

Genetic connectivity-correlated genetic control of cortical thickness, brain volume, and white matter

Magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) measures of brain volume, cortical thickness, and white matter (WM) integrity are commonly used in imaging genetics studies, but the genetic relationship between these measures is not well understood. Here we use structural equation models in a twin design to test the genetic correlation between these common imaging measures. MRI and DTI data from 442 participants (mean age: 23.5 years +/-2.1 SD; 151 women; 98 monozygotic pairs, 123 dizygotic pairs) were analyzed using standardized Enhancing Neuroimaging Genetics through Meta-Analysis protocols. We found significant genetic associations between measure of the integrity (fractional anisotropy, or FA) of several WM tracts and subcortical volume regions of interest, notably the thalamus and pallidum. Correlation was low between cortical thickness or volume and DTI measures from the WM. Total cortical surface area was, however, highly correlated with FA in several WM regions and all of the subcortical volume regions. These results may be useful for future studies assessing specific genetic associations and offer insight into the genetics underlying common imaging measures

A novel, likely pathogenic variant in UBTF‐related neurodegeneration with brain atrophy is associated with a severe divergent neurodevelopmental phenotype

Abstract Background A de novo, pathogenic, missense variant in UBTF, c.628G>A p.Glu210Lys, has been described as the cause of an emerging neurodegenerative disorder, Childhood‐Onset Neurodegeneration with Brain Atrophy (CONDBA). The p.Glu210Lys alteration yields a positively charged stretch of three lysine residues. Functional studies confirmed this change results in a stronger interaction with negatively charged DNA and gain‐of‐function activity when compared to the wild‐type sequence. The CONDBA phenotype reported in association with p.Glu210Lys consists of normal early‐neurodevelopment followed by progressive motor, cognitive, and behavioral regression in early‐to‐middle childhood. Methods and Results The current proband presented at 9 months of age with baseline developmental delay and more extensive neuroradiological findings, including pontine hypoplasia, thalamic volume loss and signal abnormality, and hypomyelination. Like the recurrent CONDBA p.Glu210Lys variant, this novel variant, c.608A>G p.(Gln203Arg) lies within the highly conserved second HMG‐box homology domain and involves the replacement of the wild‐type residue with a positively charged residue, arginine. Computational structural modeling demonstrates that this amino acid substitution potentiates the interaction between UBTF and DNA, likely resulting in a gain‐of‐function effect for the UBTF protein, UBF. Conclusion Here we present a new divergent phenotype associated with a novel, likely pathogenic, missense variant at a different position in the UBTF gene, c.608A>G p.(Gln203Arg)

Does degree of gyrification underlie the phenotypic and genetic associations between cortical surface area and cognitive ability?

The phenotypic and genetic relationship between global cortical size and general cognitive ability (GCA) appears to be driven by surface area (SA) and not cortical thickness (CT). Gyrification (cortical folding) is an important property of the cortex that helps to increase SA within a finite space, and may also improve connectivity by reducing distance between regions. Hence, gyrification may be what underlies the SA-GCA relationship. In previous phenotypic studies, a 3-dimensional gyrification index (3DGI) has been positively associated with cognitive ability and negatively associated with mild cognitive impairment, Alzheimer's disease, and psychiatric disorders affecting cognition. However, the differential genetic associations of 3DGI and SA with GCA are still unclear. We examined the heritability of 3DGI, and the phenotypic, genetic, and environmental associations of 3DGI with SA and GCA in a large sample of adult male twins (N = 512). Nearly 85% of the variance in 3DGI was due to genes, and 3DGI had a strong phenotypic and genetic association with SA. Both 3DGI and total SA had positive phenotypic correlations with GCA. However, the SA-GCA correlation remained significant after controlling for 3DGI, but not the other way around. There was also significant genetic covariance between SA and GCA, but not between 3DGI and GCA. Thus, despite the phenotypic and genetic associations between 3DGI and SA, our results do not support the hypothesis that gyrification underlies the association between SA and GCA