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.

Age, not autism, influences multisensory integration of speech stimuli among adults in a McGurk/MacDonald paradigm.

Differences between autistic and non-autistic individuals in perception of the temporal relationships between sights and sounds are theorized to underlie difficulties in integrating relevant sensory information. These, in turn, are thought to contribute to problems with speech perception and higher level social behaviour. However, the literature establishing this connection often involves limited sample sizes and focuses almost entirely on children. To determine whether these differences persist into adulthood, we compared 496 autistic and 373 non-autistic adults (aged 17 to 75 years). Participants completed an online version of the McGurk/MacDonald paradigm, a multisensory illusion indicative of the ability to integrate audiovisual speech stimuli. Audiovisual asynchrony was manipulated, and participants responded both to the syllable they perceived (revealing their susceptibility to the illusion) and to whether or not the audio and video were synchronized (allowing insight into temporal processing). In contrast with prior research with smaller, younger samples, we detected no evidence of impaired temporal or multisensory processing in autistic adults. Instead, we found that in both groups, multisensory integration correlated strongly with age. This contradicts prior presumptions that differences in multisensory perception persist and even increase in magnitude over the lifespan of autistic individuals. It also suggests that the compensatory role multisensory integration may play as the individual senses decline with age is intact. These findings challenge existing theories and provide an optimistic perspective on autistic development. They also underline the importance of expanding autism research to better reflect the age range of the autistic population.

Predictive processing of music and language in autism: Evidence from Mandarin and English speakers.

Atypical predictive processing has been associated with autism across multiple domains, based mainly on artificial antecedents and consequents. As structured sequences where expectations derive from implicit learning of combinatorial principles, language and music provide naturalistic stimuli for investigating predictive processing. In this study, we matched melodic and sentence stimuli in cloze probabilities and examined musical and linguistic prediction in Mandarin- (Experiment 1) and English-speaking (Experiment 2) autistic and non-autistic individuals using both production and perception tasks. In the production tasks, participants listened to unfinished melodies/sentences and then produced the final notes/words to complete these items. In the perception tasks, participants provided expectedness ratings of the completed melodies/sentences based on the most frequent notes/words in the norms. While Experiment 1 showed intact musical prediction but atypical linguistic prediction in autism in the Mandarin sample that demonstrated imbalanced musical training experience and receptive vocabulary skills between groups, the group difference disappeared in a more closely matched sample of English speakers in Experiment 2. These findings suggest the importance of taking an individual differences approach when investigating predictive processing in music and language in autism, as the difficulty in prediction in autism may not be due to generalized problems with prediction in any type of complex sequence processing.

Perception of temporal synchrony not a prerequisite for multisensory integration.

Temporal alignment is often viewed as the most essential cue the brain can use to integrate information from across sensory modalities. However, the importance of conscious perception of synchrony to multisensory integration is a controversial topic. Conversely, the influence of cross-modal incongruence of higher level stimulus features such as phonetics on temporal processing is poorly understood. To explore the nuances of this relationship between temporal processing and multisensory integration, we presented 101 participants (ranging from 19 to 73 years of age) with stimuli designed to elicit the McGurk/MacDonald illusion (either matched or mismatched pairs of phonemes and visemes) with varying degrees of stimulus onset asynchrony between the visual and auditory streams. We asked them to indicate which syllable they perceived and whether the video and audio were synchronized on each trial. We found that participants often experienced the illusion despite not perceiving the stimuli as synchronous, and the same phonetic incongruence that produced the illusion also led to significant interference in simultaneity judgments. These findings challenge the longstanding assumption that perception of synchrony is a prerequisite to multisensory integration, support a more flexible view of multisensory integration, and suggest a complex, reciprocal relationship between temporal and multisensory processing.

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.

The integration of head and body cues during the perception of social interactions.

Humans spend a large proportion of time participating in social interactions. The ability to accurately detect and respond to human interactions is vital for social functioning, from early childhood through to older adulthood. This detection ability arguably relies on integrating sensory information from the interactants. Within the visual modality, directional information from a person's eyes, head, and body are integrated to inform where another person is looking and who they are interacting with. To date, social cue integration research has focused largely on the perception of isolated individuals. Across two experiments, we investigated whether observers integrate body information with head information when determining whether two people are interacting, and manipulated frame of reference (one of the interactants facing observer vs. facing away from observer) and the eye-region visibility of the interactant. Results demonstrate that individuals integrate information from the body with head information when perceiving dyadic interactions, and that integration is influenced by the frame of reference and visibility of the eye-region. Interestingly, self-reported autistics traits were associated with a stronger influence of body information on interaction perception, but only when the eye-region was visible. This study investigated the recognition of dyadic interactions using whole-body stimuli while manipulating eye visibility and frame of reference, and provides crucial insights into social cue integration, as well as how autistic traits affect cue integration, during perception of social interactions.

Emotion dysregulation modulates visual perspective taking and spontaneous facial mimicry.

Understanding and sharing others' emotions (i.e., empathy) requires the ability to manage one's own emotions (i.e., emotion regulation). Indeed, empirical evidence suggests that empathy and emotion regulation are related. This evidence is largely based on self-report measures of both constructs. The current study examined how task measures that assess processes related to empathy are associated with self-reported emotion dysregulation in a young adult sample. An eye-tracking-based perspective-taking task was used as a proxy measure of cognitive empathy. A spontaneous facial mimicry (SFM) task, wherein the activation of the Zygomaticus Major and the Corrugator Supercilii was measured during the passive viewing of happy and angry faces, was used as a proxy measure of affective empathy. The perspective-taking task metric showed a negative relationship with emotion dysregulation. The overall SFM metric was not significantly associated with emotion dysregulation. Follow-up analyses revealed that SFM for angry faces was inversely proportional to emotion dysregulation; no such relationship was observed for SFM for happy faces. These findings build upon prior work by demonstrating a positive relationship between adaptive emotion regulation and a behavioral measure of cognitive empathy. The findings for affective empathy are suggestive of a valence-specific relationship between SFM and emotion regulation. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Autism community priorities in diverse low-resource settings: A country-wide scoping exercise in India.

LAY ABSTRACT: It is vital to directly engage with the autism community in order to develop better services and drive the research agenda. While some studies in high-income countries have mapped the priorities of the autism community, there is a severe dearth of such efforts in the global south. Five million autistic individuals are estimated to live in India alone, and there has been little effort to map their priorities. Moreover, studies in high-income countries focused largely on research priorities, and not so much on skills training and interventions. Keeping these needs in mind, we conducted an online survey followed by an in-depth conversation with parents of autistic children and autistic adults drawn from across India. We found that the respondents reported self-help skills to be the most important for training, as they considered it fundamental for every other aspect of life. Speech and language therapy was considered to be the highest intervention priority for this group, highlighting the importance of social communication. Mental health counselling was also considered to be a high priority, but several parents identified it as being more relevant for themselves rather than for their children. Within research, the topmost priority was to understand ways in which the community can better support autistic people. We hope that these findings will help researchers, policymakers and service providers to be able to make well-informed decisions, develop relevant services and shape future research.

Brain-charting autism and attention deficit hyperactivity disorder reveals distinct and overlapping neurobiology.

Background: Autism and attention deficit hyperactivity disorder (ADHD) are heterogeneous neurodevelopmental conditions with complex underlying neurobiology. Despite overlapping presentation and sex-biased prevalence, autism and ADHD are rarely studied together, and sex differences are often overlooked. Normative modelling provides a unified framework for studying age-specific and sex-specific divergences in neurodivergent brain development. Methods: Here we use normative modelling and a large, multi-site neuroimaging dataset to characterise cortical anatomy associated with autism and ADHD, benchmarked against models of typical brain development based on a sample of over 75,000 individuals. We also examined sex and age differences, relationship with autistic traits, and explored the co-occurrence of autism and ADHD (autism+ADHD). Results: We observed robust neuroanatomical signatures of both autism and ADHD. Overall, autistic individuals showed greater cortical thickness and volume localised to the superior temporal cortex, whereas individuals with ADHD showed more global effects of cortical thickness increases but lower cortical volume and surface area across much of the cortex. The autism+ADHD group displayed a unique pattern of widespread increases in cortical thickness, and certain decreases in surface area. We also found evidence that sex modulates the neuroanatomy of autism but not ADHD, and an age-by-diagnosis interaction for ADHD only. Conclusions: These results indicate distinct cortical differences in autism and ADHD that are differentially impacted by age, sex, and potentially unique patterns related to their co-occurrence.

Greater interpersonal distance in adults with autism.

Social interactions are often shaped by the space we prefer to maintain between us and others, that is, interpersonal distance. Being too distant or too close to a stranger can often be perceived as odd, and lead to atypical social interactions. This calibration of appropriate interpersonal distance thus constitutes an important social skill. Individuals with autism spectrum disorder (ASD, hereafter autism) often experience difficulties with this skill, and anecdotal accounts suggest atypical interpersonal distances in their social interactions. In the current study, we systematically measured interpersonal distance in individuals with autism using immersive virtual reality (IVR) to recreate a naturalistic interaction with a full body avatar of a similar age. Participants observed their own virtual body in first-person perspective, and the other avatar in two tasks: in the first task, they approached the other avatar (active), in the second one they were approached by the other avatar (passive). Two groups of neurotypical and autistic adults, performed both tasks. Autistic adults showed greater interpersonal distance when compared to non-autistic adults. Additionally, the difference between the passive and active conditions was smaller for non-autistic compared to autistic adults. Across the full sample, greater interpersonal distance was associated with higher autism-related traits. This study provides systematic evidence for greater interpersonal distance in autistic adults using a paradigm with high ecological validity and can be useful in informing the design of appropriate environmental adjustments for shared spaces.

Autistic traits modulate the influence of face masks on gaze perception.

Detecting when others are looking at us is a crucial social skill. Accordingly, a range of gaze angles is perceived as self-directed; this is termed the "cone of direct gaze" (CoDG). Multiple cues, such as nose and head orientation, are integrated during gaze perception. Thus, occluding the lower portion of the face, such as with face masks during the COVID-19 pandemic, may influence how gaze is perceived. Individual differences in the prioritisation of eye-region and non-eye-region cues may modulate the influence of face masks on gaze perception. Autistic individuals, who may be more reliant on non-eye-region directional cues during gaze perception, might be differentially affected by face masks. In the present study, we compared the CoDG when viewing masked and unmasked faces (N = 157) and measured self-reported autistic traits. The CoDG was wider for masked compared to unmasked faces, suggesting that reduced reliability of lower face cues increases the range of gaze angles perceived as self-directed. Additionally, autistic traits positively predicted the magnitude of CoDG difference between masked and unmasked faces. This study provides crucial insights into the effect of face masks on gaze perception, and how they may affect autistic individuals to a greater extent.

Gamma aminobutyric acid production by commercially available probiotic strains.

AIMS: Certain bacteria can produce gamma aminobutyric acid (GABA) from glutamate in the human intestinal tract, leading to the possibility of altering GABA levels through diet. To this end, we assessed the ability of seven commercially available probiotic supplements to produce GABA. METHOD AND RESULTS: Probiotic strains were compared for GABA production in pure culture. The bacteria were inoculated at a concentration of 107 CFU ml-1 in 10 ml MRS supplemented with monosodium glutamate (1% w/v), both with and without oligofructose-enriched inulin (OFI) (1% w/v). Two strains with the highest production of GABA were further assessed for 48 h in pH-controlled anaerobic batch cultures inoculated with faecal bacteria. Liquid chromatography-mass spectrometry (LC-MS) was used for quantification of GABA and microbiota composition was determined through 16S rRNA gene sequencing. Levilactobacillus brevis LB01 (CGMCC 16921) and Lactiplantibacillus plantarum 299v (DSM 9843) were the most efficient producers of GABA. High GABA levels (28.32 mmol l-1 ± 0.29) were produced by the probiotic strain L. brevis LB01 at pH 5.4-5.6. This was significantly higher than the levels of GABA produced by L. plantarum (4.8 mmol l-1 ± 6.8) and a negative control (2.9 mM ± 3.1). The addition of OFI did not further stimulate GABA production under the conditions tested. The ability of these strains to produce GABA in-vitro was further evaluated in a faecal microbiota environment. Once again, L.brevis LB01 produced the highest levels of GABA (40.24 mmol l-1 ± 20.98). CONCLUSIONS: L. brevis LB01 was found to be the most efficient probiotic strain, of those tested, for GABA production.

Investigating the relationship between pain indicators and observers' judgements of pain.

BACKGROUND: Due to the inherent subjectivity of pain, it is difficult to make accurate judgements of pain in others. Research has found discrepancies between the ways in which perceived "objective" (e.g., medical evidence of injury) and "subjective" information (e.g., self-report) influence judgements of pain. This study aims to explore which potential cues (depictions of sensory input, brain activation, self-reported pain and facial expressions) participants are most influenced by when evaluating pain in others. METHODS: First, 60 participants (23 women, 36 ± 10 years old) judged who was in more pain between two different pain indicators representing two different patients. These trials revealed which congruent indicator (i.e., two high pain indicators) would most influence participant decisions. Second, participants prescribed quantities of analgesia for one patient's pain based on two different pain indicators. These trials revealed which incongruent indicators (i.e., one high and one low indicator) would most influence participant decisions. RESULTS: As predicted, facial expressions were perceived as subjective and were the least likely, among all pain indicators, to influence observer's judgements of pain. Participants relied upon indicators they perceived as objective. Self-report pain ratings had the greatest influence on participants judgements about how much analgesic cream to prescribe and was perceived as objective by half of the participants. CONCLUSIONS: We found that in situations where incongruent information was presented about an individual's pain, participants relied on pain indicators that they perceived to be objective. The current study provides important insights about biases that people hold when making judgements of pain in others. SIGNIFICANCE: Interpretation and assessment of pain remains one of the largest barriers to pain management and involves complex, idiosyncratic processing. This study provides insights into what information participants view as critical in making attributions of pain when presented with multiple, seemingly incongruent sources of information.

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.

Cognitive and Affective Empathy Relate Differentially to Emotion Regulation.

The constructs of empathy (i.e., understanding and/or sharing another's emotion) and emotion regulation (i.e., the processes by which one manages emotions) have largely been studied in relative isolation of one another. To better understand the interrelationships between their various component processes, this manuscript reports two studies that examined the relationship between empathy and emotion regulation using a combination of self-report and task measures. In study 1 (N = 137), trait cognitive empathy and affective empathy were found to share divergent relationships with self-reported emotion dysregulation. Trait emotion dysregulation was negatively related to cognitive empathy but did not show a significant relationship with affective empathy. In the second study (N = 92), the magnitude of emotion interference effects (i.e., the extent to which inhibitory control was impacted by emotional relative to neutral stimuli) in variants of a Go/NoGo and Stroop task were used as proxy measures of implicit emotion regulation abilities. Trait cognitive and affective empathy were differentially related to both task metrics. Higher affective empathy was associated with increased emotional interference in the Emotional Go/NoGo task; no such relationship was observed for trait cognitive empathy. In the Emotional Stroop task, higher cognitive empathy was associated with reduced emotional interference; no such relationship was observed for affective empathy. Together, these studies demonstrate that greater cognitive empathy was broadly associated with improved emotion regulation abilities, while greater affective empathy was typically associated with increased difficulties with emotion regulation. These findings point to the need for assessing the different components of empathy in psychopathological conditions marked by difficulties in emotion regulation. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-021-00062-w.

Brain structural correlates of autistic traits across the diagnostic divide: A grey matter and white matter microstructure study.

Autism Spectrum Disorders (ASD) are a set of neurodevelopmental conditions characterised by difficulties in social interaction and communication as well as stereotyped and restricted patterns of interest. Autistic traits exist in a continuum across the general population, whilst the extreme end of this distribution is diagnosed as clinical ASD. While many studies have investigated brain structure in autism using a case-control design, few have used a dimensional approach. To add to this growing body of literature, we investigated the structural brain correlates of autistic traits in a mixed sample of adult participants (25 ASD and 66 neurotypicals; age: 18-60 years). We examined the relationship between regional brain volumes (using voxel-based morphometry and surface-based morphometry) and white matter microstructure properties (using Diffusion Tensor Imaging) and autistic traits (using Autism Spectrum Quotient). Our findings show grey matter differences in regions including the orbitofrontal cortex and lingual gyrus, and suggestive evidence for white matter microstructure differences in tracts including the superior longitudinal fasciculus being related to higher autistic traits. These grey matter and white matter microstructure findings from our study are consistent with previous reports and support the brain structural differences in ASD. These findings provide further support for shared aetiology for autistic traits across the diagnostic divide.

Keeping in time with social and non-social stimuli: Synchronisation with auditory, visual, and audio-visual cues.

Everyday social interactions require us to closely monitor, predict, and synchronise our movements with those of an interacting partner. Experimental studies of social synchrony typically examine the social-cognitive outcomes associated with synchrony, such as affiliation. On the other hand, research on the sensorimotor aspects of synchronisation generally uses non-social stimuli (e.g. a moving dot). To date, the differences in sensorimotor aspects of synchronisation to social compared to non-social stimuli remain largely unknown. The present study aims to address this gap using a verbal response paradigm where participants were asked to synchronise a 'ba' response in time with social and non-social stimuli, which were presented auditorily, visually, or audio-visually combined. For social stimuli a video/audio recording of an actor performing the same verbal 'ba' response was presented, whereas for non-social stimuli a moving dot, an auditory metronome or both combined were presented. The impact of autistic traits on participants' synchronisation performance was examined using the Autism Spectrum Quotient (AQ). Our results revealed more accurate synchronisation for social compared to non-social stimuli, suggesting that greater familiarity with and motivation in attending to social stimuli may enhance our ability to better predict and synchronise with them. Individuals with fewer autistic traits demonstrated greater social learning, as indexed through an improvement in synchronisation performance to social vs non-social stimuli across the experiment.

Autistic differences in the temporal dynamics of social attention.

LAY ABSTRACT: One behaviour often observed in individuals with autism is that they tend to look less towards social stimuli relative to neurotypical individuals. For instance, many eye-tracking studies have shown that individuals with autism will look less towards people and more towards objects in scenes. However, we currently know very little about how these behaviours change over time. Tracking these moment-to-moment changes in looking behaviour in individuals with autism can more clearly illustrate how they respond to social stimuli. In this study, adults with and without autism were presented with displays of social and non-social stimuli, while looking behaviours were measured by eye-tracking. We found large differences in how the two groups looked towards social stimuli over time. Neurotypical individuals initially showed a high probability of looking towards social stimuli, then a decline in probability, and a subsequent increase in probability after prolonged viewing. By contrast, individuals with autism showed an initial increase in probability, followed by a continuous decline in probability that did not recover. This pattern of results may indicate that individuals with autism exhibit reduced responsivity to the reward value of social stimuli. Moreover, our data suggest that exploring the temporal nature of gaze behaviours can lead to more precise explanatory theories of attention in autism.