HIV-associated neurocognitive disorders (HAND) remain prevalent despite improved antiretroviral treatment (ART), and it is essential to have a sensitive and specific HAND screening tool.
Participants ...were 200 HIV-infected US military beneficiaries, managed early in the course of HIV infection, had few comorbidities, and had open access to ART. Participants completed a comprehensive, seven-domain (16-test), neuropsychological battery (∼120 min); neurocognitive impairment (NCI) was determined using a standardized score derived from demographically adjusted T-scores (global deficit score ≥0.5). Restricting the estimated administration time of the screening battery to < = 20 minutes, we examined the sensitivity and specificity of detecting NCI for all possible combinations of 2-, 3-, and 4- tests from the comprehensive battery.
Participants were relatively healthy (median CD4 count: 546 cells/mm(3)) with 64% receiving ART. Prevalence of NCI was low (19%). The best 2-test screener included the Stroop Color Test and the Hopkins Verbal Learning Test-Revised (11 min; sensitivity = 73%; specificity = 83%); the best 3-test screener included the above measures plus the Paced Auditory Serial Addition Test (PASAT; 16 min; sensitivity = 86%; specificity = 75%). The addition of Action Fluency to the above three tests improved specificity (18 min; sensitivity = 86%; specificity = 87%).
Combinations of widely accepted neuropsychological tests with brief implementation time demonstrated good sensitivity and specificity compared to a time intensive neuropsychological test battery. Tests of verbal learning, attention/working memory, and processing speed are particularly useful in detecting NCI. Utilizing validated, easy to administer, traditional neuropsychological tests with established normative data may represent an excellent approach to screening for NCI in HIV.
Background
Prenatal alcohol exposure (PAE) is associated with abnormalities in cortical structure and maturation, including cortical thickness (CT), cortical volume, and surface area. This study ...provides a longitudinal context for the developmental trajectory and timing of abnormal cortical maturation in PAE.
Methods
We studied 35 children with PAE and 30 nonexposed typically developing children (Comparisons), aged 8–17 at enrollment, who were recruited from the University of Minnesota FASD Program. Participants were matched on age and sex. They underwent a formal evaluation of growth and dysmorphic facial features associated with PAE and completed cognitive testing. MRI data were collected on a Siemens Prisma 3T scanner. Two sessions, each including MRI scans and cognitive testing, were spaced approximately 15 months apart on average. Change in CT and performance on tests of executive function (EF) were examined.
Results
Significant age‐by‐group (PAE vs. Comparison) linear interaction effects in CT were observed in the parietal, temporal, occipital, and insular cortices suggesting altered developmental trajectories in the PAE vs. Comparison groups. Results suggest a pattern of delayed cortical thinning in PAE, with the Comparison group showing more rapid thinning at younger ages and those with PAE showing accelerated thinning at older ages. Overall, children in the PAE group showed reduced cortical thinning across time relative to the Comparison participants. Symmetrized percent change (SPC) in CT in several regions was significantly correlated with EF performance at 15‐month follow‐up for the Comparison group but not the group with PAE.
Conclusions
Regional differences were seen longitudinally in the trajectory and timing of CT change in children with PAE, suggesting delayed cortical maturation and an atypical pattern of development compared with typically developing individuals. In addition, exploratory correlation analyses of SPC and EF performance suggest the presence of atypical brain–behavior relationships in PAE. The findings highlight the potential role of altered developmental timing of cortical maturation in contributing to long‐term functional impairment in PAE.
Prenatal alcohol exposure (PAE) is associated with cross‐sectional brain anomalies, and emerging data suggest atypical trajectories of cortical maturation. This longitudinal study adds to the existing literature by demonstrating that youth age 8‐17 with PAE have reduced age‐related cortical thickness change compared to non‐exposed Comparisons as well as a delayed trajectory of cortical maturation. Such anomalies may relate to neurodevelopmental challenges associated with PAE. Understanding brain maturation in PAE may inform and improve targeted, developmentally‐sensitive interventions.
The Virgo Environmental Survey Tracing Ionised Gas Emission (VESTIGE) is a blind narrow-band Hα + NII imaging survey carried out with MegaCam at the Canada-France-Hawaii Telescope. During pilot ...observations taken in the spring of 2016 we observed NGC 4330, an intermediate mass (M* ≃ 109.8 M⊙) edge-on star forming spiral currently falling into the core of the Virgo cluster. While previous Hα observations showed a clumpy complex of ionised gas knots outside the galaxy disc, new deep observations revealed a low surface brightness ~10 kpc tail exhibiting a peculiar filamentary structure. The filaments are remarkably parallel to one another and clearly indicate the direction of motion of the galaxy in the Virgo potential. Motivated by the detection of these features which indicate ongoing gas stripping, we collected literature photometry in 15 bands from the far-UV to the far-IR and deep optical long-slit spectroscopy using the FORS2 instrument at the ESO Very Large Telescope. Using a newly developed Monte Carlo code that jointly fits spectroscopy and photometry, we reconstructed the star formation histories in apertures along the major axis of the galaxy. Our results have been validated against the output of CIGALE, a fitting code which has been previously used for similar studies. We found a clear outside-in gradient with radius of the time when the quenching event started: the outermost radii were stripped ~500 Myr ago, while the stripping reached the inner 5 kpc from the centre in the last 100 Myr. Regions at even smaller radii are currently still forming stars fueled by the presence of HI and H2 gas. When compared to statistical studies of the quenching timescales in the local Universe we find that ram pressure stripping of the cold gas is an effective mechanism to reduce the transformation times for galaxies falling into massive clusters. Future systematic studies of all the active galaxies observed by VESTIGE in the Virgo cluster will extend these results to a robust statistical framework.
Context. Low surface brightness galaxies (LSBGs) represent a significant percentage of local galaxies but their formation and evolution remain elusive. They may hold crucial information for our ...understanding of many key issues (i.e., census of baryonic and dark matter, star formation in the low density regime, mass function). The most massive examples - the so called giant LSBGs - can be as massive as the Milky Way, but with this mass being distributed in a much larger disk. Aims. Malin 1 is an iconic giant LSBG - perhaps the largest disk galaxy known. We attempt to bring new insights on its structure and evolution on the basis of new images covering a wide range in wavelength. Methods. We have computed surface brightness profiles (and average surface brightnesses in 16 regions of interest), in six photometric bands (FUV, NUV, u, g, i, z). We compared these data to various models, testing a variety of assumptions concerning the formation and evolution of Malin1. Results. We find that the surface brightness and color profiles can be reproduced by a long and quiet star-formation history due to the low surface density; no significant event, such as a collision, is necessary. Such quiet star formation across the giant disk is obtained in a disk model calibrated for the Milky Way, but with an angular momentum approximately 20 times larger. Signs of small variations of the star-formation history are indicated by the diversity of ages found when different regions within the galaxy are intercompared. Conclusions. For the first time, panchromatic images of Malin 1 are used to constrain the stellar populations and the history of this iconic example among giant LSBGs. Based on our model, the extreme disk of Malin 1 is found to have a long history of relatively low star formation (about 2 M sub(middot in circle)yr super(-1)). Our model allows us to make predictions on its stellar mass and metallicity.
The complexity of brain signals may hold clues to understand brain-based disorders. Sample entropy, an index that captures the predictability of a signal, is a promising tool to measure signal ...complexity. However, measurement of sample entropy from fMRI signals has its challenges, and numerous questions regarding preprocessing and parameter selection require research to advance the potential impact of this method. For one example, entropy may be highly sensitive to the effects of motion, yet standard approaches to addressing motion (e.g., scrubbing) may be unsuitable for entropy measurement. For another, the parameters used to calculate entropy need to be defined by the properties of data being analyzed, an issue that has frequently been ignored in fMRI research. The current work sought to rigorously address these issues and to create methods that could be used to advance this field.
We developed and tested a novel windowing approach to select and concatenate (ignoring connecting volumes) low-motion windows in fMRI data to reduce the impact of motion on sample entropy estimates. We created utilities (implementing autoregressive models and a grid search function) to facilitate selection of the matching length
parameter and the error tolerance
parameter. We developed an approach to apply these methods at every grayordinate of the brain, creating a whole-brain dense entropy map. These methods and tools have been integrated into a publicly available R package ("powseR"). We demonstrate these methods using data from the ABCD study. After applying the windowing procedure to allow sample entropy calculation on the lowest-motion windows from runs 1 and 2 (combined) and those from runs 3 and 4 (combined), we identified the optimal
and
parameters for these data. To confirm the impact of the windowing procedure, we compared entropy values and their relationship with motion when entropy was calculated using the full set of data vs. those calculated using the windowing procedure. We then assessed reproducibility of sample entropy calculations using the windowed procedure by calculating the intraclass correlation between the earlier and later entropy measurements at every grayordinate.
When applying these optimized methods to the ABCD data (from the subset of individuals who had enough windows of continuous "usable" volumes), we found that the novel windowing procedure successfully mitigated the large inverse correlation between entropy values and head motion seen when using a standard approach. Furthermore, using the windowed approach, entropy values calculated early in the scan (runs 1 and 2) are largely reproducible when measured later in the scan (runs 3 and 4), although there is some regional variability in reproducibility.
We developed an optimized approach to measuring sample entropy that addresses concerns about motion and that can be applied across datasets through user-identified adaptations that allow the method to be tailored to the dataset at hand. We offer preliminary results regarding reproducibility. We also include recommendations for fMRI data acquisition to optimize sample entropy measurement and considerations for the field.
Fetal alcohol spectrum disorder (FASD), a life-long condition resulting from prenatal alcohol exposure (PAE), is associated with structural brain anomalies and neurobehavioral differences. Evidence ...from longitudinal neuroimaging suggest trajectories of white matter microstructure maturation are atypical in PAE. We aimed to further characterize longitudinal trajectories of developmental white matter microstructure change in children and adolescents with PAE compared to typically-developing Controls using diffusion-weighted Neurite Orientation Dispersion and Density Imaging (NODDI).
Participants: Youth with PAE (
= 34) and typically-developing Controls (
= 31) ages 8-17 years at enrollment. Participants underwent formal evaluation of growth and facial dysmorphology. Participants also completed two study visits (17 months apart on average), both of which involved cognitive testing and an MRI scan (data collected on a Siemens Prisma 3 T scanner). Age-related changes in the orientation dispersion index (ODI) and the neurite density index (NDI) were examined across five corpus callosum (CC) regions defined by tractography.
While linear trajectories suggested similar overall microstructural integrity in PAE and Controls, analyses of symmetrized percent change (SPC) indicated group differences in the timing and magnitude of age-related increases in ODI (indexing the bending and fanning of axons) in the central region of the CC, with PAE participants demonstrating atypically steep increases in dispersion with age compared to Controls. Participants with PAE also demonstrated greater increases in ODI in the mid posterior CC (trend-level group difference). In addition, SPC in ODI and NDI was differentially correlated with executive function performance for PAE participants and Controls, suggesting an atypical relationship between white matter microstructure maturation and cognitive function in PAE.
Preliminary findings suggest subtle atypicality in the timing and magnitude of age-related white matter microstructure maturation in PAE compared to typically-developing Controls. These findings add to the existing literature on neurodevelopmental trajectories in PAE and suggest that advanced biophysical diffusion modeling (NODDI) may be sensitive to biologically-meaningful microstructural changes in the CC that are disrupted by PAE. Findings of atypical brain maturation-behavior relationships in PAE highlight the need for further study. Further longitudinal research aimed at characterizing white matter neurodevelopmental trajectories in PAE will be important.
Fetal alcohol spectrum disorder (FASD) is a lifelong condition. Early interventions targeting core neurocognitive deficits have the potential to confer long-term neurodevelopmental benefits. ...Time-targeted choline supplementation is one such intervention that has been shown to provide neurodevelopmental benefits that emerge with age during childhood. We present a long-term follow-up study evaluating the neurodevelopmental effects of early choline supplementation in children with FASD approximately 7 years on average after an initial efficacy trial.
The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2.5 to 5 year olds with FASD. Participants in this long-term follow-up study include 18 children (9 placebo; 9 choline) seen 7 years on average following initial trial completion. The mean age at follow-up was 11.0 years old. Diagnoses were 28% fetal alcohol syndrome (FAS), 28% partial FAS, and 44% alcohol-related neurodevelopmental disorder. The follow-up included measures of executive functioning and an MRI scan.
Children who received choline had better performance on several tasks of lower-order executive function (e.g., processing speed) and showed higher white matter microstructure organization (i.e., greater axon coherence) in the splenium of the corpus callosum compared to the placebo group.
These preliminary findings, although exploratory at this stage, highlight potential long-term benefits of choline as a neurodevelopmental intervention for FASD and suggest that choline may affect white matter development, representing a potential target of choline in this population.
Prior to enrollment, this trial was registered with clinicaltrials.gov ( NCT01149538 ) on June 23, 2010.
The childhood-to-adolescence transition is a notable period of change including pubertal development, neurodevelopment, and psychopathology onset, that occurs in divergent patterns between sexes. ...This study examined the effects of sex and puberty on cortical thickness (CT) in children and explored whether CT changes over time related to emergence of psychopathology in early adolescence.
We used longitudinal data (baseline ages 9–10 and Year 2 Y2 ages 11–12) from the ABCD Study (n = 9985). Linear and penalized function-on-function regressions modeled the impact of puberty, as it interacts with sex, on CT. Focusing on regions that showed sex differences, linear and logistic regressions modeled associations between change in CT and internalizing problems and suicide ideation.
We identified significant sex differences in the inverse relation between puberty and CT in fifteen primarily posterior brain regions. Nonlinear pubertal effects across age were identified in the fusiform, isthmus cingulate, paracentral, and precuneus. All effects were stronger for females relative to males during this developmental window. We did not identify associations between CT change and early adolescent clinical outcomes.
During this age range, puberty is most strongly associated with regional changes in CT in females, which may have implications for the later emergence of psychopathology.
During pilot observations of the Virgo Environmental Survey Tracing Galaxy Evolution (VESTIGE), a blind narrow-band Hα + NII imaging survey of the Virgo cluster carried out with MegaCam at the CFHT, ...we have observed the spiral galaxy NGC 4254 (M99). Deep Hα + NII narrow-band and GALEX UV images reveal the presence of 60 compact (70–500 pc radius) star-forming regions up to ≃20 kpc outside the optical disc of the galaxy. These regions are located along a tail of HI gas stripped from the disc of the galaxy after a rapid gravitational encounter with another Virgo cluster member that simulations indicate occurred 280–750 Myr ago. We have combined the VESTIGE data with multifrequency data from the UV to the far-infrared to characterise the stellar populations of these regions and study the star formation process in an extreme environment such as the tails of stripped gas embedded in the hot intracluster medium. The colour, spectral energy distribution (SED), and linear size consistently indicate that these regions are coeval and have been formed after a single burst of star formation that occurred ≲100 Myr ago. These regions might become free floating objects within the cluster potential well, and be the local analogues of compact sources produced after the interaction of gas-rich systems that occurred during the early formation of clusters.
Abstract
Theoretical models group maladaptive behaviors in addiction into neurocognitive domains such as incentive salience (IS), negative emotionality (NE), and executive functioning (EF). ...Alterations in these domains lead to relapse in alcohol use disorder (AUD). We examine whether microstructural measures in the white matter pathways supporting these domains are associated with relapse in AUD. Diffusion kurtosis imaging data were collected from 53 individuals with AUD during early abstinence. We used probabilistic tractography to delineate the fornix (IS), uncinate fasciculus (NE), and anterior thalamic radiation (EF) in each participant and extracted mean fractional anisotropy (FA) and kurtosis fractional anisotropy (KFA) within each tract. Binary (abstained vs. relapsed) and continuous (number of days abstinent) relapse measures were collected over a 4-month period. Across tracts, anisotropy measures were typically (i) lower in those that relapsed during the follow-up period and (ii) positively associated with the duration of sustained abstinence during the follow-up period. However, only KFA in the right fornix reached significance in our sample. The association between microstructural measures in these fiber tracts and treatment outcome in a small sample highlights the potential utility of the three-factor model of addiction and the role of white matter alterations in AUD.
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