Development and validation of the Early Executive Functions Questionnaire: A carer‐administered measure of Executive Functions suitable for 9‐ to 30‐month‐olds

Executive functions (EFs) enable us to control our attention and behavior in order to set and work toward goals. Strong EF skills are linked to better academic performance, and greater health, wealth, and happiness in later life. Research into EF development has been hampered by a lack of scalable measures suitable for infancy through to toddlerhood. The 31-item Early Executive Functions Questionnaire (EEFQ) complements temperament measures by targeting cognitive and regulatory capabilities. Exploratory Factor Analysis (n = 486 8- to 30-month-olds) and Confirmatory Factor Analysis (n = 317 9- to 30-month-olds) indicate Inhibitory Control, Flexibility, and Working Memory items load onto a common “Cognitive Executive Function (CEF)” factor, while Regulation items do not. The CEF factor shows strong factorial measurement invariance for sex, and partial strong factorial measurement invariance for age. CEF and Regulation scores show limited floor and ceiling effects, good internal consistency, short-term stability, and convergent validity with carer-report measures of attentional control. The EEFQ is sensitive to developmental change. Results indicate that the widely overlooked period between late infancy and early toddlerhood may be a sensitive period for EF development. The low-resource demands of the EEFQ afford the possibility to study emergent EFs at scale; opening up new opportunities in basic developmental and intervention research

Studies on the Flagellar Attachment of African Trypanosomes

Attachment of trypanosomes by the flagellum to a host internal surface is believed to represent an important stage in the development of these parasites in their vectors. This thesis is concerned with an investigation into various aspects of the flagellar attachment of Trypanosoma congolense epimastigotes. The morphology of the attachment is described in both the tsetse fly labrum and in vitro where the epimastigotes attach to the plastic wall of the culture flask. Epimastigotes attach to the substratum at one or more sites along the length of the flagellum. At the attachment site the flagellar membrane is extended from the axis and an electron dense, hemidesmosome-like plaque (approx. 35nm wide) forms on the cytoplasmic face of the membrane. 5nm fiIaiments converge on the plaque and associate with similar filaments emanating from flagellum-cell body attachment plaques. Filaments form at the attachment site soon after contact with the substratum. Plaques form subsequently and become more compact with advancing epimastigote age. An extracellular gap (15nm) is present between flagellum and substratum. Ruthenium red binding in this gap indicates that glycoproteins are situated there. Differentiated attachment plaques appear to be specific to attached epimastigotes and are absent from detached epimastigotes. They are absent from the flagella of bloodstream trypomastigotes of T. congolense even though the flagellar tip of this stage in the tryp-anosome's life cycle attaches the parasite to the endothelium of bloodvessel walls. The necessity of attachment for epimastigote proliferation and for differentiation of the mammal-infecting metacyclic stage from the epimastigote has been examined. Prevention of epimastigote attachment by shaking cultures or growing trypanosomes on a polypropylene substratum does not affect the rate of epimastigote division. Metacyclogenesis does not occur in unattached trypanosomes, however, suggesting that, in this species, attachment is a necessary prerequisite for this developmental step. Interference reflection microscopy has been used to visualize the effect on extracellular gap width of agents added to the culture medium. An increase in gap width following trypsinization on addition of Concanavalin A, Lentil lectin and Wheatgerm Agglutinin indicate that protein, D-mannose and N-acetyl-D-glucosamine are present in this location. External serum concentration, monovalent ion concentrations and the presence of tunicamycin have little effect on the interfer-ometry pattern. Tunicamycin insensitivity reflects a lack of glycoprotein turnover at the site. Divalent cation removal decreases the gap width. The binding of epimastigotes to positively charged Sephadex beads indicates a net negative surface charge. This charge maybe less negative in the region of the attachment as binding to positively charged beads is reduced at the flagellar tip. Indirect immunofluorescence and indirect immunogold electron microscopical cytochemistry indicate that the proteins actin, vinculin, filamin, intermediate filament proteins and desmoplakins (found associated with morphologically similar metazoan cell attachment structures - hemidesmosomes and focal adhesions) are absent from the epimastigote attachment. Immunofluorescence reactions suggest that actin and intermediate filaments are present in these cells but not localized in their distribution. Confirmation of the presence of these proteins can be obtained with SDS-PAGE and associated Western blotting experiments of both whole cell and cytoskeleton preparations. Comparative 2D-gel electrophoresis of attached and unattached whole epimastigotes and cytoskeletons shows the presence of a novel group of proteins (approx. Mr=70kd) in attached preparations. It is suggested that these proteins maybe involved in the attachment complex

Biophysical and cellular insights into the membrane insertion mechanism of CLIC1

Chloride intracellular channel 1 (CLIC1) is a human protein expressed in the cytosol that has a remarkable feature – it can transition into an active chloride channel in nuclear, endoplasmic reticulum or plasma membranes. This metamorphic nature makes CLIC1 a potential drug target as overexpression of the membrane channel form in cells is implicated in neurodegenerative disease progression and tumour proliferation especially in cancers with poor prognosis such as glioblastomas. The mechanism of CLIC1 activation and membrane insertion, as well as the oligomerisation state and structure of the channel, still remain elusive, therefore my PhD focuses on deciphering more information about how and why CLIC1 forms a chloride channel. Combining biophysical and microscopy techniques we have discovered that, upon binding to divalent cations Ca2+ and Zn2+, CLIC1 relocalises and inserts into the plasma membrane to form an active chloride channel in both in vitro and in vivo experiments. Previous literature heavily implicates the role of cysteine oxidation in CLIC1 channel formation but the use of solution NMR studies confirmed that both the soluble and membrane bound forms of CLIC1 are in the same oxidation state, further supporting the hypothesis divalent cations are the trigger for this translocation from a cytosolic globular protein to integral membrane chloride channel. The identification of the molecular switch that promotes CLIC1 membrane insertion is a significant discovery as it provides a model that can enable mechanistic studies of CLIC1 translocation and structural investigation of the channel form, known to have clinical relevance. Additional research focused on how CLIC1 interacts with divalent cations in a cellular environment aiming to elucidate information about the conformational changes the protein undergoes in vivo

Associations between touchscreen exposure and hot and cool inhibitory control in 10-month-old infants

Touchscreen use amongst young children has proliferated in recent years, yet little is known about the association between daily touchscreen exposure and inhibitory control in the first year of life. Previous research has found a negative association between the amount of television viewing and inhibitory control in early childhood, but it is unclear whether negative associations with screen use extend to touchscreens. The current study presents an exploratory analysis of the cross-sectional associations between inhibitory control and the amount of touchscreen use amongst 10-month-olds (n = 128–156). Touchscreen exposure was assessed via parent-report. In order to include a range of “hot” and “cool” aspects of inhibitory control, these skills were assessed using lab-based response inhibition and prohibition tasks as well as parent-reported observations of infants’ inhibitory control abilities and broader regulatory behaviors. A “Cognitive Executive Function (EEFQ-CEF)” score (encompassing Inhibitory Control, Flexibility, and Working Memory items) was included as a secondary broader executive function construct to examine whether effects showed specificity to inhibitory control rather than executive functions more generally. Correlation analyses indicated no association between touchscreen exposure and the four indices of IC. However, a positive association was found for the amount of touchscreen exposure and EEFQ-CEF once accounting for sociodemographic variables. The implications of these findings and future directions are discussed

Do pre-schoolers with high touchscreen use show executive function differences?

The recent increase in children's use of digital media, both TV and touchscreen devices (e.g., tablets and smartphones), has been associated with developmental differences in Executive Functions (EF). It has been hypothesised that early exposure to attention-commanding and contingent stimulation provided by touchscreens may increase reliance on bottom-up perceptual processes and limit the opportunity for practice of voluntary (i.e., top-down) attention leading to differences in EF. This study tests the concurrent and longitudinal associations between touchscreen use (high use, HU ≥ 15 min/day; low use, LU < 15 min/day), and two components of EF (working-memory/cognitive-flexibility, and impulse/self-control), building explicitly on recent developmental models that point to a bidimensional structure of EF during toddlerhood and pre-school years. A longitudinal sample of 46 3.5-year-olds (23 girls) was tested on a battery of lab-based measures and matched at 12 months on a range of background variables including temperament. Touchscreen HU showed significantly reduced performance in lab-based Working Memory/Cognitive Flexibility, although this became non-significant when controlling for background TV. Impulse/Self-control was not significantly associated with touchscreen use but was negatively associated with non-child-directed television. Our results provide partial support for the hypothesis that using touchscreen devices might reduce capacity for top-down behaviour control, and indicate that broader media environment may be implicated in early executive function development. However, it may also be the case that individuals who are predisposed towards exogenous stimulation are more drawn to screen use. Future studies are needed to replicate findings, demonstrate causality, and investigate bidirectionality

Intimate partner violence identified through routine antenatal screening and maternal and perinatal health outcomes

Background: This study investigated the association between intimate partner violence (IPV) identified on routine prenatal screening and perinatal outcomes for mother and infant. Methods: Routinely collected perinatal data for a cohort of all women and their infants born in public health facilities in Sydney (Australia) over the period 2014-2016 (N = 52,509) were analysed to investigate the risk of adverse maternal and perinatal outcomes associated with a history of IPV. The association between an affirmative response on prenatal IPV screening and low birth weight (LBW) < 2.5 kg, preterm birth < 37 weeks, breastfeeding indicators and postnatal depressive symptoms (PND) was investigated in a series of logistic regression models. Results: IPV was associated with an increased risk of PND (OR = 2.53, 95% CI 1.76-3.63), not breastfeeding at birth (OR = 1.65, 95% CI 1.30-2.09), non-exclusive breastfeeding at discharge (OR = 1.66, 95% CI 1.33-2.07) and first post-natal visit (OR = 1.54, 95% CI 1.24-1.91). Self-reported fear of a partner was strongly associated with an increased risk of PND (OR = 3.53, 95% CI 2.50-5.00), and also LBW (OR = 1.58, 95% CI 1.12-2.22), preterm birth (OR = 1.38, 95% CI 1.08-1.76), lack of early initiation of breastfeeding (OR = 1.67, 95% CI 1.28-2.17), non-exclusive breastfeeding at discharge from hospital (OR = 1.60, 95% CI 1.24-2.06) and at the first post-natal visit (OR = 1.27, 95% CI 0.99-3.04). Conclusions: IPV reported at the time of pregnancy was associated with adverse infant and maternal health outcomes. Although women may be disinclined to report IPV during pregnancy, universal, routine antenatal assessment for IPV is essential for early identification and appropriate management to improve maternal and newborn health

Infant regulatory function acts as a protective factor for later traits of autism spectrum disorder and attention deficit/hyperactivity disorder but not callous unemotional traits.

BACKGROUND: Reduced executive functions (EF) are commonly associated with developmental conditions (e.g., autism spectrum disorder, ASD; attention deficit/hyperactivity disorder, ADHD), although EF seems to be typical in children with callous unemotional (CU) traits. Regulatory function (RF) is a proposed infant precursor that maps on onto factors driving later EF. Here, we first test whether RF is specifically and negatively associated with ASD and ADHD traits, but not CU traits. Second, we test whether RF can act as a protective factor, by moderating the association between infant markers and subsequent ASD and ADHD traits. METHODS: Participants were 79 infants at high (N = 42) and low (N = 37) familial risk for ASD. Data come from the 14-month infant visit (Autism Observational Scale for Infants; AOSI; activity level and RF from the Infant Behavior Questionnaire; IBQ) and the 7-year visit (ASD traits: Social Responsiveness Scale, SRS; ADHD traits: Conners 3, CU traits: Inventory of Callous Unemotional Traits). RESULTS: Infant RF was negatively associated with later traits of ASD (B = - 0.5, p = 0.01) and ADHD inattention (B = - 0.24, p = 0.02) but not hyperactivity (B = - 0.25, p = 0.10) or CU traits (B = 0.02, p = 0.86). RF moderated the association between infant AOSI score and ASD traits, with a significant effect in those with low RF (B = 0.10, p = 0.006), not high RF (B = 0.01, p = 0.78). Similarly, for ADHD, infant activity level was associated with later ADHD inattention in those with low (B = 0.17, p = 0.04) but not high RF (B = 0.07, p = 0.48). For ADHD hyperactivity symptoms, activity level was predictive at both high and low levels of RF. CONCLUSIONS: Strong RF may allow children to compensate for other atypicalities, thus attenuating the association between infant markers and later disorder traits. Whilst infant RF was associated with both ASD and ADHD inattention traits, there was no association with ADHD hyperactivity or CU traits. This suggests that any protective effect may not be universal and emphasises the need for a better understanding of the underlying moderating mechanisms

Development of directed global inhibition, competitive inhibition and behavioural inhibition during the transition between infancy and toddlerhood.

Inhibitory control (IC) is a core executive function integral to self-regulation and cognitive control, yet is itself multi-componential. Directed global inhibition entails stopping an action on demand. Competitive inhibition is engaged when an alternative response must also be produced. Related, but not an executive function, is temperamentally-driven wariness of novelty, known as behavioural inhibition. Understanding early development of these components has been hampered by a shortage of suitable measures. We combine established and novel measures to capture directed global inhibition (Toy Prohibition, Touchscreen Prohibition), competitive inhibition (A-not-B, Early Childhood Inhibitory Touchscreen Task; ECITT) and behavioural inhibition (Touchscreen Approach) in 113 10- and 16-month-olds (73 seen longitudinally). ECITT performance shows good 1-week test-retest reliability at 10-months (r = 0.30-0.60) but little stability to 16-months. Directed global inhibition performance shows developmental progression but little stability of individual differences from 10 to 16 months. Performance on measures targeting similar IC components shows greater coherence at 16-months (r = 0.23-0.59) compared with 10-months (r = 0.09-0.35). Probing of ECITT condition effects indicates toddlers are more able, compared with infants, to override immediate prepotencies; indicative of increasingly flexible control over behaviour. However, exerting IC over cumulative prepotencies appears just as challenging for toddlers as infants. Exploratory analyses show little evidence for cross-sectional or longitudinal associations between behavioural, directed global and competitive inhibition. In combination, these findings indicate that IC is not yet a stable, unidimensional construct during the transition between infancy and toddlerhood, and highlight the need for careful selection of multiple measures for those interested in capturing early variation in IC

Toward a dimensional model of risk and protective factors influencing children's early cognitive, social, and emotional development during the COVID-19 pandemic

Variation in infants’ home environment is implicated in their cognitive and psycho-social development. The pandemic has intensified variations in home environments through exacerbating socioeconomic inequalities, and increasing psychological stressors for some families. This study investigates the effects of parental (predominantly maternal) mental health, enriching activities and screen use on 280 24- to 52-month-olds’ executive functions, internalising and externalising problems, and pro-social behaviour; with socioeconomic status and social support as contextual factors. Our results indicate that aspects of the home environment are differentially associated with children’s cognitive and psycho-social development. Parents who experienced sustained mental distress during the pandemic tended to report higher child externalising and internalising problems, and executive function difficulties at follow-up. Children who spent more time engaged in enriching activities with their parents showed stronger executive functions and social competence six months later. Screen use levels during the first year of the pandemic were not associated with outcomes. To mitigate the risk of persistent negative effects for this ‘pandemic generation’ of infants, our study highlights the importance of supporting parents’ mental health. As our results demonstrate the impact of social support on mental health, investing in support services and interventions promoting building support networks are likely to be beneficial