We investigated infant’s manual motor behaviour; specifically behaviours crossing the body midline. Infants at elevated likelihood of Autism Spectrum Disorder (ASD) and/or Attention Deficit ...Hyperactivity Disorder (ADHD) produced fewer manual behaviours that cross the midline compared to infants with a typical likelihood of developing these disorders; however this effect was limited to 10-month-olds and not apparent at age 5 and 14 months. Although, midline crossing did not predict ASD traits, it was related to ADHD traits at 2 years of age. We rule out motor ability and hand dominance as possible explanations for this pattern of behaviour, positing that these results may be a consequence of multisensory integration abilities, and the neurobehavioural shift period, in the first year of life.
Background
Although autism spectrum disorder (ASD) is heritable, the mechanisms through which genes contribute to symptom emergence remain unclear. Investigating candidate intermediate phenotypes ...such as the pupillary light reflex (PLR) prospectively from early in development could bridge genotype and behavioural phenotype.
Methods
Using eye tracking, we longitudinally measured the PLR at 9, 14 and 24 months in a sample of infants (N = 264) enriched for a family history of ASD; 27 infants received an ASD diagnosis at 3 years. We examined the 9‐ to 24‐month developmental trajectories of PLR constriction latency (onset; ms) and amplitude (%) and explored their relation to categorical 3‐year ASD outcome, polygenic liability for ASD and dimensional 3‐year social affect (SA) and repetitive/restrictive behaviour (RRB) traits. Polygenic scores for ASD (PGSASD) were calculated for 190 infants.
Results
While infants showed a decrease in latency between 9 and 14 months, higher PGSASD was associated with a smaller decrease in latency in the first year (β = −.16, 95% CI = −0.31, −0.002); infants with later ASD showed a significantly steeper decrease in latency (a putative ‘catch‐up’) between 14 and 24 months relative to those with other outcomes (typical: β = .54, 95% CI = 0.08, 0.99; other: β = .53, 95% CI = 0.02, 1.04). Latency development did not associate with later dimensional variation in ASD‐related traits. In contrast, change in amplitude was not related to categorical ASD or genetics, but decreasing 9‐ to 14‐month amplitude was associated with higher SA (β = .08, 95% CI = 0.01, 0.14) and RRB (β = .05, 95% CI = 0.004, 0.11) traits.
Conclusions
These findings corroborate PLR development as possible intermediate phenotypes being linked to both genetic liability and phenotypic outcomes. Future work should incorporate alternative measures (e.g. functionally informed structural and genetic measures) to test whether distinct neural mechanisms underpin PLR alterations.
Background
Primary tauopathies are neurodegenerative disorders that result from the accumulation of aggregated tau in the brain. Frontotemporal lobar degeneration with tau (FTLD‐tau) is a tauopathy ...that underlies ∼50% of cases of frontotemporal dementia (FTD). The discovery of genetic risk variants related to innate/adaptive immunity have highlighted a potential role for neuroinflammation in FTLD. Furthermore, studies have shown microglial and astrocyte activation together with T cell infiltration in the brain of THY‐Tau22 tauopathy mice.
Methods
To study the relationship between tau and neuroinflammation we obtained FFPE brain tissue from 12 FTLD‐MAPT, 33 Pick’s Disease (PiD), 45 Progressive Supranuclear Palsy (PSP) patients and 55 controls, via Brain UK. Using immunohistochemistry, we assessed tau pathology using antibodies 8 epitopes of tau with phosphorylation are different site. The immunophenotype of microglia were assessed with phenotypic markers and their morphology (ramified, reactive, ameboid) was analysed using Iba1. Astrocytic phenotype and T cell infiltration exploration is currently ongoing.
Results
Tau epitopes AT8, AT100, PHF1, CP13 and Tau‐2 were increased in PiD, PSP and FTLD‐MAPT compared to controls, with expression levels significantly correlated between tau epitopes. Others are currently under analysis. Microglial markers Iba1, CD68, HLA‐DR and CD64 showed no difference between groups. However, CD16 was significantly increased in FTLD‐MAPT vs. control (p = 0.03) and correlations between tau and microglial markers (except with Iba1) were detected between disease groups. Morphological assessment revealed that ameboid microglia were the highest represented population in PiD and FTLD‐MAPT (p<0.0001 and p<0.0001, respectively); while reactive microglia were the most abundant population in PSP (p<0.0001). Preliminary observation of T cell staining confirms their recruitment in FTLD‐tau.
Conclusion
These findings support the involvement of microglia in FTLD‐tau. Additional immuno‐phenotyping is necessary for further defining their role as well as T cell involvement in the disease pathogenesis.
•Visuospatial orienting efficiency increases with symptom severity in idiopathic ASD.•Children with Down syndrome and comorbid ASD display superior search performance.•Visuo-spatial orienting ability ...and visual search performance appears unrelated.
Children with Down syndrome (DS) are at increased likelihood of Autism Spectrum Disorder (ASD) relative to the general population. To better understand the nature of this comorbidity, we examined the visuo-attentional processes associated with autistic trait expression in children with DS, focusing specifically on attentional disengagement and visual search performance.
We collected eye-tracking data from children with DS (n = 15) and children with idiopathic ASD (iASD, n = 16) matched according to chronological age. Seven children with DS had a formal clinical diagnosis of ASD (DS+ASD).
In children with iASD, but not DS, higher autistic trait levels were associated with decreased temporal facilitation on a gap-overlap task, implying increased visuospatial orienting efficiency. In all cases, higher autistic trait levels were associated with improved visual search performance according to decreased target detection latency. On a visual search task, children with DS+ASD outperformed their peers with DS-ASD, mirroring the phenotypic advantage associated with iASD. We found no evidence of a relationship between attentional disengagement and visual search performance, providing preliminary evidence of a differentiation in terms of underlying visuo-attentional mechanism.
We illustrate the value of progressing beyond insensitive behavioural measures of phenotypic description to examine, in a more fine-grained way, the attentional features associated with ASD comorbidity in children with DS.
Measures of early neuro‐cognitive development that are suitable for use in low‐resource settings are needed to enable studies of the effects of early adversity on the developing brain in a global ...context. These measures should have high acquisition rates and good face and construct validity. Here, we investigated the feasibility of a naturalistic electroencephalography (EEG) paradigm in a low‐resource context during childhood. Additionally, we examined the sensitivity of periodic and aperiodic EEG metrics to social and non‐social stimuli. We recorded simultaneous 20‐channel EEG and eye‐tracking in 72 children aged 4–12 years (45 females) while they watched videos of women singing nursery rhymes and moving toys, selected to represent familiar childhood experiences. These measures were part of a feasibility study that assessed the feasibility and acceptability of a follow‐up data collection of the South African Safe Passage Study, which tracks environmental adversity and brain and cognitive development from before birth up until childhood. We examined whether data quantity and quality varied with child characteristics and the sensitivity of varying EEG metrics (canonical band power in the theta and alpha band and periodic and aperiodic features of the power spectra). We found that children who completed the EEG and eye‐tracking assessment were, in general, representative of the full cohort. Data quantity was higher in children with greater visual attention to the stimuli. Out of the tested EEG metrics, periodic measures in the theta frequency range were most sensitive to condition differences, compared to alpha range measures and canonical and aperiodic EEG measures. Our results show that measuring EEG during ecologically valid social and non‐social stimuli is feasible in low‐resource settings, is feasible for most children, and produces robust indices of social brain function. This work provides preliminary support for testing longitudinal links between social brain function, environmental factors, and emerging behaviors.
Electroencephalography (EEG) has substantial potential value for examining individual differences during early development. Current challenges in developmental EEG research include high dropout rates ...and low trial numbers, which may in part be due to passive stimulus presentation. Comparability is challenged by idiosyncratic processing pipelines. We present a novel toolbox (“Braintools”) that uses gaze‐contingent stimulus presentation and an automated processing pipeline suitable for measuring visual processing through low‐density EEG recordings in the field. We tested the feasibility of this toolbox in 61 2.5‐ to 4‐year olds, and computed test–retest reliability (1‐ to 2‐week interval) of event‐related potentials (ERP) associated with visual (P1) and face processing (N290, P400). Feasibility was good, with 52 toddlers providing some EEG data at the first session. Reliability values for ERP features were moderate when derived from 20 trials; this would allow inclusion of 79% of the 61 toddlers for the P1 and 82% for the N290 and P400. P1 amplitude/latency were more reliable across sessions than for the N290 and P400. Amplitudes were generally more reliable than latencies. Automated and standardized solutions to collection and analysis of event‐related EEG data would allow efficient application in large‐scale global health studies, opening significant potential for examining individual differences in development.
Background
Children with neurodevelopmental disorders including autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) often experience sleep disturbances, but little is ...known about when these sleep differences emerge and how they relate to later development.
Methods
We used a prospective longitudinal design in infants with a family history of ASD and/or ADHD to examine infant sleep and its relation to trajectories of attention and later neurodevelopmental disorders. We formed factors of Day and Night Sleep from parent‐reported measures (including day/night sleep duration, number of naps in the day, frequency of night awakenings and sleep onset problems). We examined sleep in 164 infants at 5‐, 10‐ and 14‐months with/without a first‐degree relative with ASD and/or ADHD who underwent a consensus clinical assessment for ASD at age 3.
Results
By 14‐months, infants with a first‐degree relative with ASD (but not ADHD) showed lower Night Sleep scores than infants with no family history of ASD; lower Night Sleep scores in infancy were also associated with a later ASD diagnosis, decreased cognitive ability, increased ASD symptomatology at 3‐years, and developing social attention (e.g., looking to faces). We found no such effects with Day Sleep.
Conclusions
Sleep disturbances may be apparent at night from 14‐months in infants with a family history of ASD and also those with later ASD, but were not associated with a family history of ADHD. Infant sleep disturbances were also linked to later dimensional variation in cognitive and social skills across the cohort. Night Sleep and Social Attention were interrelated over the first 2 years of life, suggesting that this may be one mechanism through which sleep quality influences neurodevelopment. Interventions targeted towards supporting families with their infant's sleep problems may be useful in this population.
Impaired face processing is proposed to play a key role in the early development of autism spectrum disorder (ASD) and to be an endophenotypic trait which indexes genetic risk for the disorder. ...However, no published work has examined the development of face processing abilities from infancy into the school-age years and how they relate to ASD symptoms in individuals with or at high-risk for ASD. In this novel study we investigated neural and behavioural measures of face processing at age 7 months and again in mid-childhood (age 7 years) as well as social-communication and sensory symptoms in siblings at high (n = 42) and low (n = 35) familial risk for ASD. In mid-childhood, high-risk siblings showed atypical P1 and N170 event-related potential correlates of face processing and, for high-risk boys only, poorer face and object recognition ability compared to low-risk siblings. These neural and behavioural atypicalities were associated with each other and with higher social-communication and sensory symptoms in mid-childhood. Additionally, more atypical neural correlates of object (but not face) processing in infancy were associated with less right-lateralised (more atypical) N170 amplitudes and greater social-communication problems in mid-childhood. The implications for models of face processing in ASD are discussed.
Setting up a virtual machine (VM) in the cloud is a time-consuming task. Typically, VMs are created from so called VM images, a kind of blueprints used to configure and create a VM. However, to ...create a VM image manually might be very time-consuming, especially if the VM has to meet certain security benchmarks. In this paper, we present VM2 (Virtual Machine Vending Machine), a tool for creation of VM images and testing them wrt. security benchmarks as well as easy sharing the secure images. Our analysis demonstrated a significant reduction in security issues in hardened images created by VM2 in comparison with corresponding publicly available images. Moreover, our tool provided better results wrt. CIS benchmarks in comparison with the corresponding images commercially offered by CIS.
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