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Post-traumatic stress disorder symptoms following exposure to acute psychological trauma in children aged 8-16 years in South Africa: protocol for the Sinethemba longitudinal study
Abstract Introduction Children exposed to trauma are vulnerable to developing posttraumatic stress disorder (PTSD) and other adverse mental health outcomes. In low-and-middle-income countries (LMICs), children are at increased risk of exposure to severe trauma and co-occurring adversities. However, relative to high income countries, there is limited evidence of the factors that predict good versus poor psychological recovery following trauma exposure in LMIC children, and the role of caregiver support in these high-adversity communities. Methods and analysis We will conduct a longitudinal, observational study of 250 children aged 8-16 years and their caregivers in South Africa, following child exposure to acute trauma. Dyads will be recruited from community hospitals following a potentially traumatic event, such as a motor vehicle accident or assault. Potential participants will be identified during their hospital visit, and if they agree, will subsequently be contacted by study researchers. Assessments will take place within 4 weeks of the traumatic event, with 3-month and 6-month follow-up assessments. Participants will provide a narrative description of the traumatic event and complete questionnaires designed to give information about social and psychological risk factors. Child PTSD symptoms will be the primary outcome, and wider trauma-related mental health (depression, anxiety, behavioral problems) will be secondary outcomes. Regression-based methods will be used to examine the association of psychosocial factors in the acute phase following trauma, including caregiver support and responding, with child PTSD and wider mental health outcomes. Ethics and dissemination Ethical approvals have been granted by Stellenbosch University and the University of Bath, with additional to recruit via hospitals and healthcare clinics being granted by the University of Cape Town, the Department of Health, and the City of Cape Town. Study findings will be disseminated via publication in journals, workshops for practitioners and policymakers, and public engagement events. Strengths and Limitations • Longitudinal methods were piloted in settlement communities of Cape Town, enabling strong links to be established with proposed recruitment sites. • Focus groups have been conducted with members of the community to ensure proposed study methods and materials are culturally sensitive. • Pilot work has demonstrated excellent retention rates, however some missing data will be expected due to study participant attrition. This will be managed using multiple imputation methods during analysis. • A limited set of biological samples will be collected, including heart rate data and dried blood spot samples. This will allow a robust examination of the biological predictors of childhood PTSD whilst maximizing study acceptability.
Multilevel sociality in the spotted hyaena: How to live in large groups without falling prey to the infertility trap
Spotted hyaenas live in unusually large social groups for a carnivore. Since, all else equal, the ‘infertility trap’ (a negative relationship between fertility and the number of females in a group) limits social group sizes to ~5 reproductive females in mammals, hyaena must, like other very social species, have found a way to mitigate the stresses involved in order to do so. From a comparative analysis of data from 19 well-studied Crocuta crocuta populations, I show (1) that the distribution of hyaena clan sizes is multimodal, with a fractal scaling ratio close to 3 and a base unit of 12–15 individuals (3–5 reproductive females), (2) that fertility is a negative function of number of females in the group and (3) that there is a trade-off between the benefits of having more males in the group and the costs incurred by having more females. Although females do buffer themselves against the infertility trap by forming matrilineal alliances (thereby creating a primate-like multilevel structure), males seem to play an important role, such that, in areas with a low density of males, clan sizes are much smaller.
Functional differences between the extraordinary eyes of deep-sea hyperiid amphipods.
The ocean's midwater is a uniquely challenging yet predictable and simple visual environment. The need to see without being seen in this dim, open habitat has led to extraordinary visual adaptations. To understand these adaptations, we compared the morphological and functional differences between the eyes of three hyperiid amphipods-Hyperia galba, Streetsia challengeri and Phronima sedentaria. Combining micro-CT data with computational modelling, we mapped visual field topography and predicted detection distances for visual targets viewed in different directions through mesopelagic depths. Hyperia's eyes provide a wide visual field optimized for spatial vision over short distances, while Phronima's and Streetsia's eyes have the potential to achieve greater sensitivity and longer detection distances using spatial summation. These improvements come at the cost of smaller visual fields, but this loss is compensated for by a second pair of eyes in Phronima and by behaviour in Streetsia. The need to improve sensitivity while minimizing visible eye size to maintain crypsis has likely driven the evolution of hyperiid eye diversity. Our results provide an integrative look at how these elusive animals have adapted to the unique visual challenges of the mesopelagic.
General mechanisms of task engagement in the primate frontal cortex.
Staying engaged is necessary to maintain goal-directed behaviors. Despite this, engagement exhibits continuous, intrinsic fluctuations. Even in experimental settings, animals, unlike most humans, repeatedly and spontaneously move between periods of complete task engagement and disengagement. We, therefore, looked at behavior in male macaques (macaca mulatta) in four tasks while recording fMRI signals. We identified consistent autocorrelation in task disengagement. This made it possible to build models capturing task-independent engagement. We identified task general patterns of neural activity linked to impending sudden task disengagement in mid-cingulate gyrus. By contrast, activity centered in perigenual anterior cingulate cortex (pgACC) was associated with maintenance of performance across tasks. Importantly, we carefully controlled for task-specific factors such as the reward history and other motivational effects, such as response vigor, in our analyses. Moreover, we showed pgACC activity had a causal link to task engagement: transcranial ultrasound stimulation of pgACC changed task engagement patterns.
Machine learning approach for ambient-light-corrected parameters and the Pupil Reactivity (PuRe) score in smartphone-based pupillometry.
INTRODUCTION: The pupillary light reflex (PLR) is the constriction of the pupil in response to light. The PLR in response to a pulse of light follows a complex waveform that can be characterized by several parameters. It is a sensitive marker of acute neurological deterioration, but is also sensitive to the background illumination in the environment in which it is measured. To detect a pathological change in the PLR, it is therefore necessary to separate the contributions of neuro-ophthalmic factors from ambient illumination. Illumination varies over several orders of magnitude and is difficult to control due to diurnal, seasonal, and location variations. METHODS AND RESULTS: We assessed the sensitivity of seven PLR parameters to differences in ambient light, using a smartphone-based pupillometer (AI Pupillometer, Solvemed Inc.). Nine subjects underwent 345 measurements in ambient conditions ranging from complete darkness (<5 lx) to bright lighting (≲10,000 lx). Lighting most strongly affected the initial pupil size, constriction amplitude, and velocity. Nonlinear models were fitted to find the correction function that maximally stabilized PLR parameters across different ambient light levels. Next, we demonstrated that the lighting-corrected parameters still discriminated reactive from unreactive pupils. Ten patients underwent PLR testing in an ophthalmology outpatient clinic setting following the administration of tropicamide eye drops, which rendered the pupils unreactive. The parameters corrected for lighting were combined as predictors in a machine learning model to produce a scalar value, the Pupil Reactivity (PuRe) score, which quantifies Pupil Reactivity on a scale 0-5 (0, non-reactive pupil; 0-3, abnormal/"sluggish" response; 3-5, normal/brisk response). The score discriminated unreactive pupils with 100% accuracy and was stable under changes in ambient illumination across four orders of magnitude. DISCUSSION: This is the first time that a correction method has been proposed to effectively mitigate the confounding influence of ambient light on PLR measurements, which could improve the reliability of pupillometric parameters both in pre-hospital and inpatient care settings. In particular, the PuRe score offers a robust measure of Pupil Reactivity directly applicable to clinical practice. Importantly, the formulae behind the score are openly available for the benefit of the clinical research community.
Dopamine encoding of novelty facilitates efficient uncertainty-driven exploration.
When facing an unfamiliar environment, animals need to explore to gain new knowledge about which actions provide reward, but also put the newly acquired knowledge to use as quickly as possible. Optimal reinforcement learning strategies should therefore assess the uncertainties of these action-reward associations and utilise them to inform decision making. We propose a novel model whereby direct and indirect striatal pathways act together to estimate both the mean and variance of reward distributions, and mesolimbic dopaminergic neurons provide transient novelty signals, facilitating effective uncertainty-driven exploration. We utilised electrophysiological recording data to verify our model of the basal ganglia, and we fitted exploration strategies derived from the neural model to data from behavioural experiments. We also compared the performance of directed exploration strategies inspired by our basal ganglia model with other exploration algorithms including classic variants of upper confidence bound (UCB) strategy in simulation. The exploration strategies inspired by the basal ganglia model can achieve overall superior performance in simulation, and we found qualitatively similar results in fitting model to behavioural data compared with the fitting of more idealised normative models with less implementation level detail. Overall, our results suggest that transient dopamine levels in the basal ganglia that encode novelty could contribute to an uncertainty representation which efficiently drives exploration in reinforcement learning.
The effects of pramipexole on motivational vigour during a saccade task: a placebo-controlled study in healthy adults.
Motivation allows us to energise actions when we expect reward and is reduced in depression. This effect, termed motivational vigour, has been proposed to rely on central dopamine, with dopaminergic agents showing promise in the treatment of depression. This suggests that dopaminergic agents might act to reduce depression by increasing the effects of reward or by helping energise actions. The aim of the current study was to investigate whether the dopamine agonist pramipexole enhanced motivational vigour during a rewarded saccade task. In addition, we asked whether the effects of pramipexole on vigour differ between reward contingent on performance and guaranteed reward. Healthy adult participants were randomised to receive either pramipexole (n = 19) or placebo (controls n = 18) for 18 days. The vigour of saccades was measured twice, once before the administration of study medication (Time 1) and after taking it for 12-15 days (Time 2). To separate motivation by contingency vs. reward, saccadic vigour was separately measured when (1) rewards were contingent on performance (2) delivered randomly with matched frequency, (3) when reward was guaranteed, (4) when reward was not present at all. Motivation increased response vigour, as expected. Relative to placebo, pramipexole also increased response vigour. However, there was no interaction, meaning that the effects of reward were not modulated by drug, and there was no differential drug effect on contingent vs. guaranteed rewards. The effect of pramipexole on vigour could not be explained by a speed/accuracy trade-off, nor by autonomic arousal as indexed by pupillary dilation. Chronic D2 stimulation increases general vigour, energising movements in healthy adults irrespective of extrinsic reward.
Relationship of plasma biomarkers to digital cognitive tests in Alzheimer's disease.
INTRODUCTION: A major limitation in Alzheimer's disease (AD) research is the lack of the ability to measure cognitive performance at scale-robustly, remotely, and frequently. Currently, there are no established online digital platforms validated against plasma biomarkers of AD. METHODS: We used a novel web-based platform that assessed different cognitive functions in AD patients (N = 46) and elderly controls (N = 53) who were also evaluated for plasma biomarkers (amyloid beta 42/40 ratio, phosphorylated tau ([p-tau]181, glial fibrillary acidic protein, neurofilament light chain). Their cognitive performance was compared to a second, larger group of elderly controls (N = 352). RESULTS: Patients with AD were significantly impaired across all digital cognitive tests, with performance correlating with plasma biomarker levels, particularly p-tau181. The combination of p-tau181 and the single best-performing digital test achieved high accuracy in group classification. DISCUSSION: These findings show how online testing can now be deployed in patients with AD to measure cognitive function effectively and related to blood biomarkers of the disease. HIGHLIGHTS: This is the first study comparing online digital testing to plasma biomarkers.Alzheimer's disease patients and two independent cohorts of elderly controls were assessed.Cognitive performance correlated with plasma biomarkers, particularly phosphorylated tau (p-tau)181.Glial fibrillary acidic protein and neurofilament light chain, and less so the amyloid beta 42/40 ratio, were also associated with performance.The best cognitive metric performed at par to p-tau181 in group classification.
Bridging the gap from medical to psychological safety assessment: consensus study in a digital mental health context
Background Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence. Aims The aim of this study was to generate an experts’ consensus on how the medical regulatory method used for assessing safety could best be adapted for DMHIs. Method An online Delphi study containing three rounds was conducted with an international panel of 20 experts with experience/knowledge in the field of UK digital mental health. Results Sixty-four items were generated, of which 41 achieved consensus (64%). Consensus emerged around ten recommendations, falling into five main themes: Enhancing the quality of adverse events data in DMHIs; Re-defining serious adverse events for DMHIs; Reassessing short-term symptom deterioration in psychological interventions as a therapeutic risk; Maximising the benefit of the Yellow Card Scheme; and Developing a harmonised approach for assessing the safety of psychological interventions in general. Conclusion The implementation of the recommendations provided by this consensus could improve the assessment of safety of DMHIs, making them more effective in detecting and mitigating risk.
More frequent naps are associated with lower cognitive development in a cohort of 8-38-month-old children, during the Covid-19 pandemic.
BACKGROUND: How often a child naps, during infancy, is believed to reflect both intrinsic factors, that is, the need of an immature brain to consolidate information soon after it is acquired, and environmental factors. Difficulty accounting for important environmental factors that interfere with a child's sleep needs (e.g., attending daycare) has clouded our ability to understand the role of intrinsic drivers of napping frequency. METHODS: Here we investigate sleep patterns in association with two measures of cognitive ability, vocabulary size, measured with the Oxford-Communicative Development Inventory (N = 298) and cognitive executive functions (EF), measured with the Early EF Questionnaire (N = 463), in a cohort of 8-38-month-olds. Importantly, because of the social distancing measures imposed during the Covid-19 Spring 2020 lockdown, in the UK, measures of sleep were taken when children did not access daycare settings. RESULTS: We find that children with more frequent but shorter naps than expected for their age had lower concurrent receptive vocabularies, lower cognitive EF and a slower increase in expressive vocabulary from spring to winter 2020, when age, sex, and SES were accounted for. The negative association between vocabulary and frequency of naps became stronger with age. CONCLUSIONS: These findings suggest that the structure of daytime sleep is an indicator of cognitive development and highlight the importance of considering environmental perturbations and age when investigating developmental correlates of sleep.
Cortical responses to social stimuli in infants at elevated likelihood of ASD and/or ADHD: A prospective cross-condition fNIRS study.
Autism spectrum disorders (ASD) and attention-deficit hyperactivity disorder (ADHD) are highly prevalent neurodevelopmental conditions that often co-occur and present both common and distinct neurodevelopmental profiles. Studying the developmental pathways leading to the emergence of ASD and/or ADHD symptomatology is crucial in understanding neurodiversity and discovering the mechanisms that underpin it. This study used functional near-infrared spectroscopy (fNIRS) to investigate differences in cortical specialization to social stimuli between 4- to 6-month-old infants at typical and elevated likelihood of ASD and/or ADHD. Results showed that infants at both elevated likelihood of ASD and ADHD had reduced selectivity to vocal sounds in left middle and superior temporal gyrus. Furthermore, infants at elevated likelihood of ASD showed attenuated responses to visual social stimuli in several cortical regions compared to infants at typical likelihood. Individual brain responses to visual social stimuli were associated with later autism traits, but not ADHD traits. These outcomes support our previous observations showing atypical social brain responses in infants at elevated likelihood of ASD and align with later atypical brain responses to social stimuli observed in children and adults with ASD. These findings highlight the importance of characterizing antecedent biomarkers of atypicalities in processing socially relevant information that might contribute to both phenotypic overlap and divergence across ASD and ADHD conditions and their association with the later emergence of behavioural symptoms.
Early Motor Differences in Infants at Elevated Likelihood of Autism Spectrum Disorder and/or Attention Deficit Hyperactivity Disorder.
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.
Investigating the Mechanisms Driving Referent Selection and Retention in Toddlers at Typical and Elevated Likelihood for Autism Spectrum Disorder.
It was suggested that children's referent selection may not lay memory traces sufficiently strong to lead to retention of new word-object mappings. If this was the case we expect incorrect selections to be easily rectified through feedback. Previous work suggested this to be the case in toddlers at typical likelihood (TL) but not in those at elevated likelihood (EL) for autism spectrum disorder (ASD) (Bedford et al., ). Yet group differences in lexical knowledge may have confounded these findings. Here, TL (N = 29) and EL toddlers (N = 75) chose one of two unfamiliar objects as a referent for a new word. Both groups retained the word-referent mapping above chance when their choices were immediately reinforced but were at chance after corrective feedback. The same pattern of results was obtained when children observed another experimenter make the initial referent choice. Thus, children's referent choices lay memory traces that compete with subsequent correction; these strong word-object associations are not a result of children actively choosing potential referents for new words.
Infant sleep predicts trajectories of social attention and later autism traits.
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.
Leveraging epigenetics to examine differences in developmental trajectories of social attention: A proof-of-principle study of DNA methylation in infants with older siblings with autism.
Preliminary evidence suggests that changes in DNA methylation, a widely studied epigenetic mechanism, contribute to the etiology of Autism Spectrum Disorder (ASD). However, data is primarily derived from post-mortem brain samples or peripheral tissue from adults. Deep-phenotyped longitudinal infant cohorts are essential to understand how epigenetic modifications relate to early developmental trajectories and emergence of ASD symptoms. We present a proof-of-principle study designed to evaluate the potential of prospective epigenetic studies of infant siblings of children with ASD. Illumina genome-wide 450 K DNA methylation data from buccal swabs was generated for 63 male infants at multiple time-points from 8 months to 2 years of age (total N = 107 samples). 11 of those infants received a diagnosis of ASD at 3 years. We conducted a series of analyses to characterize DNA methylation signatures associated with categorical outcome and neurocognitive measures from parent-report questionnaire, eye-tracking and electro-encephalography. Effects observed across the entire genome (epigenome-wide association analyses) suggest that collecting DNA methylation samples within infant-sibling designs allows for the detection of meaningful signals with smaller sample sizes than previously estimated. Mapping networks of co-methylated probes associated with neural correlates of social attention implicated enrichment of pathways involved in brain development. Longitudinal modelling found covariation between phenotypic traits and DNA methylation levels in the proximity of genes previously associated with cognitive development, although larger samples and more complete datasets are needed to obtain generalizable results. In conclusion, assessment of DNA methylation profiles at multiple time-points in infant-sibling designs is a promising avenue to comprehend developmental origins and mechanisms of ASD.
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
Feasibility and acceptability of a parent‐toddler programme to support the development of executive functions in children at elevated likelihood of autism or ADHD: Pilot findings
AbstractThis study reports feasibility, fidelity and acceptability of a pilot of START; a 12‐week parent‐toddler, group‐based, neurodiversity‐affirming programme aiming to support executive function development in toddlers at elevated likelihood of autism or ADHD. After 4 days' training, community early years practitioner pairs delivered START to 13 UK families with a toddler showing elevated autistic traits, or with a parent or sibling with autism or ADHD, in groups of 6 and 7. Sessions were audio‐recorded and rated by practitioners and researchers regarding the extent to which programme and session aims were met. Practitioners' reflections on strengths and challenges in session delivery, adaptations to the session plan and researchers' observations from the audio recordings were probed in weekly debrief calls, and one‐to‐one interviews at programme end‐point. Recruitment and retention were monitored. Parent participants were asked to complete a feedback questionnaire after each session. Results show recruitment to the programme is feasible, but a large minority of parents experience barriers to regular attendance, which is a challenge for achieving exposure targets. Practitioners delivered the programme to a high quality and at least partially met programme and session‐specific aims in every session. The most significant barrier to fully meeting session aims was families' late arrival. Parents reported regularly engaging with the suggested activities at home and found the sessions useful, although not all parents responded each week. Overall, the results of this small‐scale pilot indicate START is feasible and acceptable as a parent‐mediated programme to support toddlers at elevated likelihood of autism or ADHD to thrive.
Caregiver sensitivity supported young children's vocabulary development during the Covid-19 UK lockdowns.
Previous studies have shown that caregivers' sensitive, responsive interactions with young children can boost language development. We explored the association between caregivers' sensitivity and the vocabulary development of their 8-to-36-month-olds during COVID-19 when family routines were unexpectedly disrupted. Measuring caregivers' sensitivity from home interaction videos at three timepoints, we found that children who experienced more-sensitive concurrent interactions had higher receptive and expressive vocabularies (N=100). Children whose caregivers showed more-sensitive interactions at the beginning of the pandemic showed greater expressive vocabulary growth six (but not 12) months later (n=58). Significant associations with receptive vocabulary growth were not observed. Our findings highlight the importance of sensitivity at a time when other positive influences on language development were compromised.