Scalable Transdiagnostic Early Assessment of Mental Health (STREAM): a study protocol.

INTRODUCTION: Early childhood development forms the foundations for functioning later in life. Thus, accurate monitoring of developmental trajectories is critical. However, such monitoring often relies on time-intensive assessments which necessitate administration by skilled professionals. This difficulty is exacerbated in low-resource settings where such professionals are predominantly concentrated in urban and often private clinics, making them inaccessible to many. This geographic and economic inaccessibility contributes to a significant 'detection gap' where many children who might benefit from support remain undetected. The Scalable Transdiagnostic Early Assessment of Mental Health (STREAM) project aims to bridge this gap by developing an open-source, scalable, tablet-based platform administered by non-specialist workers to assess motor, social and cognitive developmental status. The goal is to deploy STREAM through public health initiatives, maximising opportunities for effective early interventions. METHODS AND ANALYSIS: The STREAM project will enrol and assess 4000 children aged 0-6 years from Malawi (n=2000) and India (n=2000). It integrates three established developmental assessment tools measuring motor, social and cognitive functioning using gamified tasks, observation checklists, parent-report and audio-video recordings. Domain scores for motor, social and cognitive functioning will be developed and assessed for their validity and reliability. These domain scores will then be used to construct age-adjusted developmental reference curves. ETHICS AND DISSEMINATION: Ethical approval has been obtained from local review boards at each site (India: Sangath Institutional Review Board; All India Institute of Medical Science (AIIMS) Ethics Committee; Indian Council of Medical Research-Health Ministry Screening Committee; Malawi: College of Medicine Research and Ethics Committee; Malawi Ministry of Health-Blantyre District Health Office). The study adheres to Good Clinical Practice standards and the ethical guidelines of the 6th (2008) Declaration of Helsinki. Findings from STREAM will be disseminated to participating families, healthcare professionals, policymakers, educators and researchers, at local, national and international levels through meetings, academic journals and conferences.

Using mobile health technology to assess childhood autism in low-resource community settings in India: An innovation to address the detection gap.

LAY ABSTRACT: Autism is diagnosed by highly trained professionals- but most autistic people live in parts of the world that harbour few or no such autism specialists and little autism awareness. So many autistic people go undiagnosed, misdiagnosed, and misunderstood. We designed an app (START) to identify autism and related conditions in such places, in an attempt to address this global gap in access to specialists. START uses computerised games and activities for children and a questionnaire for parents to measure social, sensory, and motor skills. To check whether START can flag undiagnosed children likely to have neurodevelopmental conditions, we tested START with children whose diagnoses already were known: Non-specialist health workers with just a high-school education took START to family homes in poor neighbourhoods of Delhi, India to work with 131 two-to-seven-year-olds. Differences between typically and atypically developing children were highlighted in all three types of skills that START assesses: children with neurodevelopmental conditions preferred looking at geometric patterns rather than social scenes, were fascinated by predictable, repetitive sensory stimuli, and had more trouble with precise hand movements. Parents' responses to surveys further distinguished autistic from non-autistic children. An artificial-intelligence technique combining all these measures demonstrated that START can fairly accurately flag atypically developing children. Health workers and families endorsed START as attractive to most children, understandable to health workers, and adaptable within sometimes chaotic home and family environments. This study provides a proof of principle for START in digital screening of autism and related conditions in community settings.

Digital tools for direct assessment of autism risk during early childhood: A systematic review.

LAY ABSTRACT: The challenge of finding autistic children, and finding them early enough to make a difference for them and their families, becomes all the greater in parts of the world where human and material resources are in short supply. Poverty of resources delays interventions, translating into a poverty of outcomes. Digital tools carry potential to lessen this delay because they can be administered by non-specialists in children's homes, schools or other everyday environments, they can measure a wide range of autistic behaviours objectively and they can automate analysis without requiring an expert in computers or statistics. This literature review aimed to identify and describe digital tools for screening children who may be at risk for autism. These tools are predominantly at the 'proof-of-concept' stage. Both portable (laptops, mobile phones, smart toys) and fixed (desktop computers, virtual-reality platforms) technologies are used to present computerised games, or to record children's behaviours or speech. Computerised analysis of children's interactions with these technologies differentiates children with and without autism, with promising results. Tasks assessing social responses and hand and body movements are the most reliable in distinguishing autistic from typically developing children. Such digital tools hold immense potential for early identification of autism spectrum disorder risk at a large scale. Next steps should be to further validate these tools and to evaluate their applicability in a variety of settings. Crucially, stakeholders from underserved communities globally must be involved in this research, lest it fail to capture the issues that these stakeholders are facing.

Quantifying preference for social stimuli in young children using two tasks on a mobile platform.

Children typically prefer to attend to social stimuli (e.g. faces, smiles) over non-social stimuli (e.g. natural scene, household objects). This preference for social stimuli is believed to be an essential building block for later social skills and healthy social development. Preference for social stimuli are typically measured using either passive viewing or instrumental choice paradigms, but not both. Since these paradigms likely tap into different mechanisms, the current study addresses this gap by administering both of these paradigms on an overlapping sample. In this study, we use a preferential looking task and an instrumental choice task to measure preference for social stimuli in 3-9 year old typically developing children. Children spent longer looking at social stimuli in the preferential looking task but did not show a similar preference for social rewards on the instrumental choice task. Task performance in these two paradigms were not correlated. Social skills were found to be positively related to the preference for social rewards on the choice task. This study points to putatively different mechanisms underlying the preference for social stimuli, and highlights the importance of choice of paradigms in measuring this construct.

Validation of revised reading the mind in the eyes test in the Indian (Bengali) population: A preliminary study.

BACKGROUND: Social cognition deficits are common in clinical populations but there is a dearth of standardized social cognition assessment tools in India. Theory of mind (ToM) is an important aspect of social cognition which is often assessed with the revised reading the mind in eyes test (RMET-R). However, we do not have a statistically validated version of the test for the Indian population. AIM: This study aims to assess the acceptability, reliability, and validity of the Bengali version of the RMET-R. MATERIALS AND METHODS: We administered the RMET-R to 23 patients with chronic schizophrenia (SCZ), 22 patients with bipolar disorder, and 104 healthy controls (HCs) to evaluate the reliability and validity of the instrument in the Indian (Bengali) population. RESULTS: We obtained moderate internal consistency (Cronbach's alpha = 0.6) and test-retest reliability (intraclass correlation coefficient = 0.64, P < 0.001). Positive correlations were found between RMET-R and Wechsler picture arrangement (r = 0.60, P < 0.001), picture completion (r = 0.54, P < 0.001), and comprehension subtests (r = 0.48, P < 0.001). Patients with SCZ (M = 49.7, standard deviation [SD] = 16.5) scored significantly lower than HCs (M = 68.9, SD = 13.8) (P = 0.008; Cohen's d = 1.3) on the RMET-R. Thus this tool could discriminate patients who are reported to have Theory of Mind deficits from healthy controls. CONCLUSION: The Bengali version of the RMET-R is a reliable and valid tool for assessing first-order ToM insofar as the original RMET-R measures this construct.

Overcoming hurdles to intervention studies with autistic children with profound communication difficulties and their families.

LAY ABSTRACT: Autistic children who speak few or no words or who have an intellectual disability are the most in need of new understandings and treatments, but the most often left out of the research that can bring these benefits. Researchers perceive difficulties around compliance with instructions, testing, challenging behaviours and family stress. Although research with these children can indeed be difficult, their continuing exclusion is unethical and unacceptable. Drawing on our experiences testing a possible treatment for children with profound autism, we provide 10 practical guidelines related to (1) interacting physically, (2) combining play and testing, (3) responding to challenging behaviour, (4) finding suitable tests, (5) relationships with parents, (6) relationships with siblings, (7) involving stakeholders, (8) planning the testing times, (9) the role of the clinical supervisor and (10) recruiting and retaining participants. We hope that these guidelines will prepare and embolden other research teams to work with profoundly autistic children, ending their historical exclusion from research. These guidelines also could be useful for conducting research with children with intellectual disabilities.

Autistic traits and individual brain differences: functional network efficiency reflects attentional and social impairments, structural nodal efficiencies index systemising and theory-of-mind skills.

BACKGROUND: Autism is characterised not only by impaired social cognitive 'empathising' but also by superior rule-based 'systemising'. These cognitive domains intertwine within the categorical diagnosis of autism, yet behavioural genetics suggest largely independent heritability, and separable brain mechanisms. We sought to determine whether quantitative behavioural measures of autistic traits are dimensionally associated with structural and functional brain network integrity, and whether brain bases of autistic traits vary independently across individuals. METHODS: Thirty right-handed neurotypical adults (12 females) were administered psychometric (Social Responsiveness Scale, Autism Spectrum Quotient and Systemising Quotient) and behavioural (Attention Network Test and theory-of-mind reaction time) measures of autistic traits, and structurally (diffusion tensor imaging) and functionally (500 s of 2 Hz eyes-closed resting fMRI) derived graph-theoretic measures of efficiency of information integration were computed throughout the brain and within subregions. RESULTS: Social impairment was positively associated with functional efficiency (r = .47, p = .006), globally and within temporo-parietal and prefrontal cortices. Delayed orienting of attention likewise was associated with greater functional efficiency (r = - .46, p = .0133). Systemising was positively associated with global structural efficiency (r = .38, p = 0.018), driven specifically by temporal pole; theory-of-mind reaction time was related to structural efficiency (r = - .40, p = 0.0153) within right supramarginal gyrus. LIMITATIONS: Interpretation of these relationships is complicated by the many senses of the term 'connectivity', including functional, structural and computational; by the approximation inherent in group functional anatomical parcellations when confronted with individual variation in functional anatomy; and by the validity, sensitivity and specificity of the several survey and experimental behavioural measures applied as correlates of brain structure and function. CONCLUSIONS: Functional connectivities highlight distributed networks associated with domain-general properties such as attentional orienting and social cognition broadly, associating more impaired behaviour with more efficient brain networks that may reflect heightened feedforward information flow subserving autistic strengths and deficits alike. Structural connectivity results highlight specific anatomical nodes of convergence, reflecting cognitive and neuroanatomical independence of systemising and theory-of-mind. In addition, this work shows that individual differences in theory-of-mind related to brain structure can be measured behaviourally, and offers neuroanatomical evidence to pin down the slippery construct of 'systemising' as the capacity to construct invariant contextual associations.

Other and other waters in the river: Autism and the futility of prediction.

Autism has been described as a neural deficit in prediction, people with autism manifest low perceptual construal and are impaired at traversing psychological distances, and Gilead et al.'s hierarchy from iconic to multimodal to fully abstract, socially communicated representations is exactly the hierarchy of representational impairment in autism, making autism a natural behavioural and neurophysiological test case for the prediction-abstraction relationship.

Point OutWords: protocol for a feasibility randomised controlled trial of a motor skills intervention to promote communicative development in non-verbal children with autism.

BACKGROUND: Point OutWords is a caregiver-delivered, iPad-assisted intervention for non-verbal or minimally verbal children with autism. It aims to develop prerequisite skills for communication such as manual and oral motor skills, sequencing, and symbolic representation. This feasibility trial aims to determine the viability of evaluating the clinical efficacy of Point OutWords. METHODOLOGY: We aim to recruit 46 non-verbal or minimally verbal children with autism and their families, approximately 23 per arm. Children in the intervention group will use Point OutWords for half an hour, five times a week, for 8 weeks. Children in the control group will have equal caregiver-led contact time with the iPad using a selection of control apps (e.g. sensory apps, drawing apps). Communication, motor, and daily living skills are assessed at baseline and post-intervention. Parents will keep diaries during the intervention period and will take part in focus groups when the intervention is completed. DISCUSSION: Point OutWords was developed in collaboration with children with autism and their caregivers, to provide an intervention for a subgroup of autism that has been historically underserved. As autism is a heterogeneous condition, it is unlikely that one style of intervention will address all aspects of its symptomatology; the motor skills approach of Point OutWords can complement other therapies that address core autistic symptoms of social cognition and communication more directly. The current feasibility trial can inform the selection of outcome measures and design for future full-scale randomised controlled trials of Point OutWords and of other early interventions in autism. TRIAL REGISTRATION: ISRCTN, ISRCTN12808402. Prospectively registered on 12 March 2019.

Reduction in lower-alpha power during Ganzfeld flicker stimulation is associated with the production of imagery and trait positive schizotypy.

Light-flicker Ganzfeld (LFG) induces a lower to upper-alpha frequency shift. However, it is unclear how this neurophysiological response might relate to LFG-induced pseudo-hallucinatory phenomena. It is also unknown whether emotional states (e.g., fear) or traits associated with risk for psychosis (e.g., proneness to perceptual anomalies, ability to produce vivid mental imagery) affect such neurophysiological and/or perceptual responses to LFG. The present study investigated alpha sub-bands during LFG across several flicker frequencies, in relation to individual differences in propensity for Ganzfeld-induced imagery (GI), positive schizotypy and trait mental imagery, and in relation to manipulations of affective state. Given previously reported sex differences in risk for psychosis and response to Ganzfeld, the effect of sex on GI was also studied. Forty-six healthy adults (16 men) completed psychometric measures of trait mental imagery and positive schizotypy before undergoing three LFG (20 min each) conditions. In each condition, participants wore white-out goggles and listened to either mood-inducing soundscapes (fear, serenity) or pink noise (control) through headphones. Greatest propensity for GI arose between 13.1 and 16.0 Hz flicker, with a peak at 16.0 Hz flicker. Occipital lower-alpha was reduced for lower flicker frequencies (13.1-16.0 Hz) and was inversely associated with GI. Upper-alpha power was not significantly related to GI or to other measures. Fear-induction was associated with reduction in alpha power, but did not significantly affect GI. Men reported more GI than women. Findings support a role for cortical destabilisation, as reflected in reduced lower-alpha, in perceptual anomalies; and, by extension, LFG as an experimental model of liability for psychosis.

Engagement of the motor system in position monitoring: reduced distractor suppression and effects of internal representation quality on motor kinematics.

The position monitoring task is a measure of divided spatial attention in which participants track the changing positions of one or more objects, attempting to represent positions with as much precision as possible. Typically precision of representations declines with each target object added to participants' attention load. Since the motor system requires precise representations of changing target positions, we investigated whether position monitoring would be facilitated by increasing engagement of the motor system. Using motion capture, we recorded the positions of participants' index finger during pointing responses. Participants attempted to monitor the changing positions of between one and four target discs as they moved randomly around a large projected display. After a period of disc motion, all discs disappeared and participants were prompted to report the final position of one of the targets, either by mouse click or by pointing to the final perceived position on the screen. For mouse click responses, precision declined with attentional load. For pointing responses, precision declined only up to three targets and remained at the same level for four targets, suggesting obligatory attention to all four objects for loads above two targets. Kinematic profiles for pointing responses for highest and lowest loads showed greater motor adjustments during the point, demonstrating that, like external environmental task demands, the quality of internal representations affects motor kinematics. Specifically, these adjustments reflect the difficulty of both pointing to very precisely represented locations as well as keeping representations distinct from one another.

Slower resting alpha frequency is associated with superior localisation of moving targets.

We examined the neurophysiological underpinnings of individual differences in the ability to maintain up-to-date representations of the positions of moving objects. In two experiments similar to the multiple object tracking (MOT) task, we asked observers to monitor continuously one or several targets as they moved unpredictably for a semi-random period. After all objects disappeared, observers were immediately prompted to report the perceived final position of one queried target. Precision of these position reports declined with attentional load, and reports tended to best resemble positions occupied by the queried target between 0 and 30ms in the past. Measurement of event-related potentials showed a contralateral delay activity over occipital scalp, maximal in the right hemisphere. The peak power-spectral frequency of observers' eyes-closed resting occipital alpha oscillations reliably predicted performance, such that lower-frequency alpha was associated with superior spatial localisation. Slower resting alpha might be associated with a cognitive style that depends less on memory-related processing and instead emphasises attention to changing stimuli.

Prevalence of autism spectrum disorder and autistic symptoms in a school-based cohort of children in Kolkata, India.

Despite housing ∼18% of the world's population, India does not yet have an estimate of prevalence of autism. This study was carried out to estimate the prevalence of autism in a selected population of school-children in India. N = 11,849 children (mean age = 5.9 [SD = 1.3], 39.5% females) were selected from various school types from three boroughs in Kolkata, India. Parents/caregivers and teachers filled in the social and communication disorders checklist (SCDC). Children meeting cutoff on parent-reported SCDC were followed up with the social communication questionnaire (SCQ). SCQ-positive children were administered the autism diagnostic observation schedule (ADOS). Teacher report on SCDC was available on all 11,849 children. Parent-report SCDC scores were obtained for 5,947 children. Mean scores on teacher SCDC were significantly lower than parent SCDC. Out of 1,247 SCDC-positive children, 882 answered the SCQ, of whom 124 met the cutoff score of 15. Six of these children met criteria for autism, autism spectrum disorder (ASD), or broader autism spectrum on the ADOS. The weighted estimate of supra-threshold SCQ scores was 3.54% (CI: 2.88-4.3%). The weighted prevalence estimate of positive scores (for broader autism spectrum + ASD + autism) was 0.23% (0.07-0.46%). As ∼20% children in this state are known to be out of the school system, and ASD prevalence is likely to be higher in this group, this estimate is likely to represent the lower-bound of the true prevalence. This study provides preliminary data on the prevalence of broader-spectrum autism and supra-threshold autistic traits in a population sample of school children in Eastern India. Autism Res 2017, 10: 1597-1605. ©2017 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.

Bengali translation and characterisation of four cognitive and trait measures for autism spectrum conditions in India.

BACKGROUND: Autism is characterised by atypical social-communicative behaviour and restricted range of interests and repetitive behaviours. These features exist in a continuum in the general population. Behavioural measures validated across cultures and languages are required to quantify the dimensional traits of autism in these social and non-social domains. Bengali is the seventh most spoken language in the world. However, there is a serious dearth of data on standard measures of autism-related social and visual cognition in Bengali. METHODS: Bengali translations of two measures related to social-communicative functioning (the Children's Reading the Mind in the Eyes Test (RMET) and a facial emotion recognition test with stimuli taken from the Karolinska Directed Emotional Faces database), one measure of visual perceptual disembedding (the Embedded Figures Test), and a questionnaire measure (the Children's Empathy Quotient) were tested in 25 children with autism spectrum conditions (ASC) and 26 control children (mean age = 10.7 years) in Kolkata, India. Group differences were analysed by t test and multiple regression (after accounting for potential effects of gender, IQ, and age). RESULTS: Behavioural and trait measures were associated with group differences in the expected directions: ASC children scored lower on the Children's Empathy Quotient and the RMET, as well as on facial emotion recognition, but were faster and more accurate on the Embedded Figures Test. Distributional properties of these measures within groups are similar to those reported in Western countries. CONCLUSIONS: These results provide an empirical demonstration of cross-cultural generalisability and applicability of these standard behavioural and trait measures related to autism, in a major world language.

Oral motor deficits in speech-impaired children with autism.

Absence of communicative speech in autism has been presumed to reflect a fundamental deficit in the use of language, but at least in a subpopulation may instead stem from motor and oral motor issues. Clinical reports of disparity between receptive vs. expressive speech/language abilities reinforce this hypothesis. Our early-intervention clinic develops skills prerequisite to learning and communication, including sitting, attending, and pointing or reference, in children below 6 years of age. In a cohort of 31 children, gross and fine motor skills and activities of daily living as well as receptive and expressive speech were assessed at intake and after 6 and 10 months of intervention. Oral motor skills were evaluated separately within the first 5 months of the child's enrolment in the intervention programme and again at 10 months of intervention. Assessment used a clinician-rated structured report, normed against samples of 360 (for motor and speech skills) and 90 (for oral motor skills) typically developing children matched for age, cultural environment and socio-economic status. In the full sample, oral and other motor skills correlated with receptive and expressive language both in terms of pre-intervention measures and in terms of learning rates during the intervention. A motor-impaired group comprising a third of the sample was discriminated by an uneven profile of skills with oral motor and expressive language deficits out of proportion to the receptive language deficit. This group learnt language more slowly, and ended intervention lagging in oral motor skills. In individuals incapable of the degree of motor sequencing and timing necessary for speech movements, receptive language may outstrip expressive speech. Our data suggest that autistic motor difficulties could range from more basic skills such as pointing to more refined skills such as articulation, and need to be assessed and addressed across this entire range in each individual.

Autistic trait interactions underlie sex-dependent facial recognition abilities in the normal population.

Autistic face processing difficulties are either uniquely social or due to a piecemeal cognitive "style." Co-morbidity of social deficits and piecemeal cognition in autism makes teasing apart these accounts difficult. These traits vary normally, and are more separable in the general population, suggesting another way to compare accounts. Participants completed the Autism Quotient survey of autistic traits, and one of three face recognition tests: full-face, eyes-only, or mouth-only. Social traits predicted performance in the full-face condition in both sexes. Eyes-only males' performance was predicted by a social × cognitive trait interaction: attention to detail boosted face recognition in males with few social traits, but hindered performance in those reporting many social traits. This suggests social/non-social Autism Spectrum Conditions (ASC) trait interactions at the behavioral level. In the presence of few ASC-like difficulties in social reciprocity, an ASC-like attention to detail may confer advantages on typical males' face recognition skills. On the other hand, when attention to detail co-occurs with difficulties in social reciprocity, a detailed focus may exacerbate such already present social difficulties, as is thought to occur in autism.

More than maths and mindreading: sex differences in empathizing/systemizing covariance.

Empathizing-Systemizing theory posits a continuum of cognitive traits extending from autism into normal cognitive variation. Covariance data on empathizing and systemizing traits have alternately suggested inversely dependent, independent, and sex-dependent (one sex dependent, the other independent) structures. A total of 144 normal undergraduates (65 men, 79 women) completed the Reading the Mind in the Eyes, Embedded Figures, and Benton face recognition tests, the Autism Spectrum Quotient, and measures of digit length ratio and field of study; some also completed tests of motion coherence threshold (64) and go/no-go motor inhibition (128). Empathizing and systemizing traits were independent in women, but largely dependent in men. In men, level of systemizing skill required by field of study was directly related to social interactive and mindreading deficits; men's social impairments correlated with prolonged go/no-go response times, and men tended to apply systemizing strategies to solve problems of empathizing or global processing: rapid perceptual disembedding predicted heightened sensitivity to facial emotion. In women, level of systemizing in field was related to male-typical digit ratios and autistic superiorities in detail orientation, but not to autistic social and communicative impairments; and perceptual disembedding was related to social interactive skills but independent of facial emotion and visual motion perception.