The roles of sensory hyperreactivity and hyporeactivity in understanding infant fearfulness and emerging autistic traits.

BACKGROUND: Existing evidence indicates that atypical sensory reactivity is a core characteristic of autism, and has been linked to both anxiety (and its putative infant precursor of fearfulness) and repetitive behaviours. However, most work has used cross-sectional designs and not considered the differential roles of hyperreactivity and hyporeactivity to sensory inputs, and is thus limited in specificity. METHODS: 161 infants with and without an elevated likelihood of developing autism and attention-deficit hyperactivity disorder (ADHD) were followed from 10 to 36 months of age. Parents rated an infant precursor of later anxiety (fearfulness) using the Infant Behaviour Questionnaire at 10 and 14 months, and the Early Childhood Behavioural Questionnaire at 24 months, and sensory hyperreactivity and hyporeactivity at 10, 14 and 24 months using the Infant Toddler Sensory Profile. Domains of autistic traits (restrictive and repetitive behaviours; RRB, and social communication interaction, SCI) were assessed using the parent-rated Social Responsiveness Scale at 36 months. Cross-lagged models tested (a) paths between fearfulness and hyperreactivity at 10-24 months, and from fearfulness and hyperreactivity to later autism traits, (b) the specificity of hyperreactivity effects by including hyporeactivity as a correlated predictor. RESULTS: Hyperreactivity at 14 months was positively associated with fearfulness at 24 months, and hyperreactivity at 24 months was positively associated with SCI and RRB at 36 months. When hyporeactivity was included in the model, paths between hyperreactivity and fearfulness remained, but paths between hyperreactivity and autistic traits became nonsignificant. CONCLUSIONS: Our findings indicate that alterations in early sensory reactivity may increase the likelihood of showing fearfulness in infancy, and relate to later social interactions and repetitive behaviours, particularly in individuals with a family history of autism or ADHD.

Phenotypic and Genetic Associations Between Preschool Fine Motor Skills and Later Neurodevelopment, Psychopathology, and Educational Achievement.

BACKGROUND: Fine motor skills are heritable and comprise important milestones in development, and some evidence suggests that impairments in fine motor skills are associated with neurodevelopmental conditions, psychiatric disorders, and poor educational outcomes. METHODS: In a preregistered study of 9625 preschool children from TEDS (Twins Early Development Study), fine motor assessments (drawing, block building, folding, and questionnaires) were conducted at 2, 3, and 4 years of age. A cross-age fine motor score was derived using principal component analysis. Multivariate regression analysis was used to examine the relationships between the fine motor score and neurodevelopmental traits, psychopathology, and educational outcomes at 3 later ages (7-8, 12, and 16 years) and cross-age psychopathology composite scores. Polygenic scores (PGSs) were created for attention-deficit/hyperactivity disorder (ADHD), autism, schizophrenia, anxiety, major depressive disorder, obsessive-compulsive disorder, and years of education. We ran single-PGS models and a multi-PGS model. RESULTS: Fine motor skills were negatively associated with neurodevelopmental traits and psychopathology across childhood and adolescence and positively associated with educational achievement in adolescence (ß = 0.25, p < .001). Superior fine motor skills were associated with a higher years-of-education PGS (ß = 0.07, p < .001), a lower ADHD PGS (ß = -0.04, p = .011), and a higher anxiety PGS (ß = 0.03, p = .040). Similarly, the multi-PGS model retained the PGSs for years of education (ß = 0.07), ADHD (ß = -0.03), and anxiety (ß = 0.01). A non-preregistered analysis in an independent preschool sample replicated the ADHD PGS association, but not the years of education or anxiety PGS associations. CONCLUSIONS: Fine motor skills are linked genetically and phenotypically to later neurodevelopment, psychopathology, and educational outcomes. Future work should investigate the mechanisms that underlie the role of fine motor development in later outcomes.

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.

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.

Infant excitation/inhibition balance interacts with executive attention to predict autistic traits in childhood.

BACKGROUND: Autism is proposed to be characterised by an atypical balance of cortical excitation and inhibition (E/I). However, most studies have examined E/I alterations in older autistic individuals, meaning that findings could in part reflect homeostatic compensation. To assess the directionality of effects, it is necessary to examine alterations in E/I balance early in the lifespan before symptom emergence. Recent explanatory frameworks have argued that it is also necessary to consider how early risk features interact with later developing modifier factors to predict autism outcomes. METHOD: We indexed E/I balance in early infancy by extracting the aperiodic exponent of the slope of the electroencephalogram (EEG) power spectrum ('1/f'). To validate our index of E/I balance, we tested for differences in the aperiodic exponent in 10-month-old infants with (n = 22) and without (n = 27) neurofibromatosis type 1 (NF1), a condition thought to be characterised by alterations to cortical inhibition. We then tested for E/I alterations in a larger heterogeneous longitudinal cohort of infants with and without a family history of neurodevelopmental conditions (n = 150) who had been followed to early childhood. We tested the relevance of alterations in E/I balance and our proposed modifier, executive attention, by assessing whether associations between 10-month aperiodic slope and 36-month neurodevelopmental traits were moderated by 24-month executive attention. Analyses adjusted for age at EEG assessment, sex and number of EEG trials. RESULTS: Infants with NF1 were characterised by a higher aperiodic exponent, indicative of greater inhibition, supporting our infant measure of E/I. Longitudinal analyses showed a significant interaction between aperiodic slope and executive attention, such that higher aperiodic exponents predicted greater autistic traits in childhood, but only in infants who also had weaker executive functioning abilities. LIMITATIONS: The current study relied on parent report of infant executive functioning-type abilities; future work is required to replicate effects with objective measures of cognition. CONCLUSIONS: Results suggest alterations in E/I balance are on the developmental pathway to autism outcomes, and that higher executive functioning abilities may buffer the impact of early cortical atypicalities, consistent with proposals that stronger executive functioning abilities may modify the impact of a wide range of risk factors.

Early Developmental Trajectories in Infants With Neurofibromatosis 1.

Objective: To examine the trajectories of cognitive, motor and behavioural development in infants with NF1 compared to infants without a family history of neurodevelopmental difficulties. Study design: Infants with NF1 and low-risk controls were recruited from 5 months of age and followed longitudinally. Data from standardised tests was gathered at 5, 10 and 14 months and developmental trajectories of motor, language, behaviour, sleep, social development and parent-infant interaction were examined. Linear mixed modelling was used to estimate group differences in cognitive and behavioural measures over time. Results: No group differences were observed on Mullen Scale of Early Learning, overall adaptive functioning, temperament or behavioural measures. There were no group differences observed on measures of social communication or parent-infant interaction. Over the course of development, the NF1 group slept less and took more time to settle to sleep as compared to the control group. Maternal education was significantly associated with cognitive and behavioural developmental outcomes in both groups. Conclusion: Cognitive, social and behavioural impairments are a cause of significant functional morbidity in children with NF1. This report is the first study to investigate the trajectories of cognitive, motor and behavioural development in infancy in NF1. Our results demonstrate that overall cognitive and behavioural developmental trajectories of the NF1 group in the infancy period are similar to controls. Given previous reports of delayed development in the NF1 cohort by 40 months, early clinical interventions strategies to promote sleep hygiene may be beneficial to optimise developmental outcomes.

Neuronal gating of tactile input and sleep in 10-month-old infants at typical and elevated likelihood for autism spectrum disorder.

Sleep problems in Autism Spectrum Disorder (ASD) emerge early in development, yet the origin remains unclear. Here, we characterise developmental trajectories in sleep onset latency (SOL) and night awakenings in infants at elevated likelihood (EL) for ASD (who have an older sibling with ASD) and infants at typical likelihood (TL) for ASD. Further, we test whether the ability to gate tactile input, using an EEG tactile suppression index (TSI), associates with variation in SOL and night awakenings. Parent-reported night awakenings and SOL from 124 infants (97 at EL for ASD) at 5, 10 and 14 months were analyzed using generalized estimating equations. Compared to TL infants, infants at EL had significantly more awakenings and longer SOL at 10 and 14 months. The TSI predicted SOL concurrently at 10 months, independent of ASD likelihood status, but not longitudinally at 14 months. The TSI did not predict night awakenings concurrently or longitudinally. These results imply that infants at EL for ASD wake up more frequently during the night and take longer to fall asleep from 10 months of age. At 10 months, sensory gating predicts SOL, but not night awakenings, suggesting sensory gating differentially affects neural mechanisms of sleep initiation and maintenance.

Altered theta-beta ratio in infancy associates with family history of ADHD and later ADHD-relevant temperamental traits.

BACKGROUND: Uncovering the neural mechanisms that underlie symptoms of attention deficit hyperactivity disorder (ADHD) requires studying brain development prior to the emergence of behavioural difficulties. One new approach to this is prospective studies of infants with an elevated likelihood of developing ADHD. METHODS: We used a prospective design to examine an oscillatory electroencephalography profile that has been widely studied in both children and adults with ADHD - the balance between lower and higher frequencies operationalised as the theta-beta ratio (TBR). In the present study, we examined TBR in 136 10-month-old infants (72 male and 64 female) with/without an elevated likelihood of developing ADHD and/or a comparison disorder (Autism Spectrum Disorder; ASD). RESULTS: Infants with a first-degree relative with ADHD demonstrated lower TBR than infants without a first-degree relative with ADHD. Further, lower TBR at 10 months was positively associated with temperament dimensions conceptually related to ADHD at 2 years. TBR was not altered in infants with a family history of ASD. CONCLUSIONS: This is the first demonstration that alterations in TBR are present prior to behavioural symptoms of ADHD. However, these alterations manifest differently than those sometimes observed in older children with an ADHD diagnosis. Importantly, altered TBR was not seen in infants at elevated likelihood of developing ASD, suggesting a degree of specificity to ADHD. Taken together, these findings demonstrate that there are brain changes associated with a family history of ADHD observable in the first year of life.

INTERSTAARS: Attention training for infants with elevated likelihood of developing ADHD: A proof-of-concept randomised controlled trial.

Attention-deficit/hyperactivity disorder (ADHD) is first diagnosed during middle childhood, when patterns of difficulty are often established. Pre-emptive approaches that strengthen developing cognitive systems could offer an alternative to post-diagnostic interventions. This proof-of-concept randomised controlled trial (RCT) tested whether computerised gaze-based attention training is feasible and improves attention in infants liable to develop ADHD. Forty-three 9- to 16-month-old infants with a first-degree relative with ADHD were recruited (11/2015-11/2018) at two UK sites and randomised with minimisation by site and sex to receive 9 weekly sessions of either (a) gaze-contingent attention training (intervention; n = 20); or (b) infant-friendly passive viewing of videos (control, n = 23). Sessions were delivered at home with blinded outcome assessments. The primary outcome was a composite of attention measures jointly analysed via a multivariate ANCOVA with a combined effect size (ES) from coefficients at baseline, midpoint and endpoint (Registration: ISRCTN37683928 ). Uptake and compliance was good but intention-to-treat analysis showed no significant differences between 20 intervention and 23 control infants on primary (ES -0.4, 95% CI -0.9 to 0.2; Complier-Average-Causal Effect ES -0.6, 95% CI -1.6 to 0.5) or secondary outcomes (behavioural attention). There were no adverse effects on sleep but a small increase in post-intervention session fussiness. Although feasible, there was no support for short-term effects of gaze-based attention training on attention skills in early ADHD. Longer-term outcomes remain to be assessed. The study highlights challenges and opportunities for pre-emptive intervention approaches to the management of ADHD.

Development of the pupillary light reflex from 9 to 24 months: association with common autism spectrum disorder (ASD) genetic liability and 3-year ASD diagnosis.

BACKGROUND: Although autism spectrum disorder (ASD) is heritable, the mechanisms through which genes contribute to symptom emergence remain unclear. Investigating candidate intermediate phenotypes such as the pupillary light reflex (PLR) prospectively from early in development could bridge genotype and behavioural phenotype. METHODS: Using eye tracking, we longitudinally measured the PLR at 9, 14 and 24 months in a sample of infants (N = 264) enriched for a family history of ASD; 27 infants received an ASD diagnosis at 3 years. We examined the 9- to 24-month developmental trajectories of PLR constriction latency (onset; ms) and amplitude (%) and explored their relation to categorical 3-year ASD outcome, polygenic liability for ASD and dimensional 3-year social affect (SA) and repetitive/restrictive behaviour (RRB) traits. Polygenic scores for ASD (PGSASD ) were calculated for 190 infants. RESULTS: While infants showed a decrease in latency between 9 and 14 months, higher PGSASD was associated with a smaller decrease in latency in the first year (ß = -.16, 95% CI = -0.31, -0.002); infants with later ASD showed a significantly steeper decrease in latency (a putative 'catch-up') between 14 and 24 months relative to those with other outcomes (typical: ß = .54, 95% CI = 0.08, 0.99; other: ß = .53, 95% CI = 0.02, 1.04). Latency development did not associate with later dimensional variation in ASD-related traits. In contrast, change in amplitude was not related to categorical ASD or genetics, but decreasing 9- to 14-month amplitude was associated with higher SA (ß = .08, 95% CI = 0.01, 0.14) and RRB (ß = .05, 95% CI = 0.004, 0.11) traits. CONCLUSIONS: These findings corroborate PLR development as possible intermediate phenotypes being linked to both genetic liability and phenotypic outcomes. Future work should incorporate alternative measures (e.g. functionally informed structural and genetic measures) to test whether distinct neural mechanisms underpin PLR alterations.

Early differences in auditory processing relate to Autism Spectrum Disorder traits in infants with Neurofibromatosis Type I.

BACKGROUND: Sensory modulation difficulties are common in children with conditions such as Autism Spectrum Disorder (ASD) and could contribute to other social and non-social symptoms. Positing a causal role for sensory processing differences requires observing atypical sensory reactivity prior to the emergence of other symptoms, which can be achieved through prospective studies. METHODS: In this longitudinal study, we examined auditory repetition suppression and change detection at 5 and 10 months in infants with and without Neurofibromatosis Type 1 (NF1), a condition associated with higher likelihood of developing ASD. RESULTS: In typically developing infants, suppression to vowel repetition and enhanced responses to vowel/pitch change decreased with age over posterior regions, becoming more frontally specific; age-related change was diminished in the NF1 group. Whilst both groups detected changes in vowel and pitch, the NF1 group were largely slower to show a differentiated neural response. Auditory responses did not relate to later language, but were related to later ASD traits. CONCLUSIONS: These findings represent the first demonstration of atypical brain responses to sounds in infants with NF1 and suggest they may relate to the likelihood of later ASD.

Behavioural Measures of Infant Activity but Not Attention Associate with Later Preschool ADHD Traits.

Mapping infant neurocognitive differences that precede later ADHD-related behaviours is critical for designing early interventions. In this study, we investigated (1) group differences in a battery of measures assessing aspects of attention and activity level in infants with and without a family history of ADHD or related conditions (ASD), and (2) longitudinal associations between the infant measures and preschool ADHD traits at 3 years. Participants (N = 151) were infants with or without an elevated likelihood for ADHD (due to a family history of ADHD and/or ASD). A multi-method assessment protocol was used to assess infant attention and activity level at 10 months of age that included behavioural, cognitive, physiological and neural measures. Preschool ADHD traits were measured at 3 years of age using the Child Behaviour Checklist (CBCL) and the Child Behaviour Questionnaire (CBQ). Across a broad range of measures, we found no significant group differences in attention or activity level at 10 months between infants with and without a family history of ADHD or ASD. However, parent and observer ratings of infant activity level at 10 months were positively associated with later preschool ADHD traits at 3 years. Observable behavioural differences in activity level (but not attention) may be apparent from infancy in children who later develop elevated preschool ADHD traits.

Behavioural and neural markers of tactile sensory processing in infants at elevated likelihood of autism spectrum disorder and/or attention deficit hyperactivity disorder.

BACKGROUNDS: Atypicalities in tactile processing are reported in autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) but it remains unknown if they precede and associate with the traits of these disorders emerging in childhood. We investigated behavioural and neural markers of tactile sensory processing in infants at elevated likelihood of ASD and/or ADHD compared to infants at typical likelihood of the disorders. Further, we assessed the specificity of associations between infant markers and later ASD or ADHD traits. METHODS: Ninety-one 10-month-old infants participated in the study (n = 44 infants at elevated likelihood of ASD; n = 20 infants at elevated likelihood of ADHD; n = 9 infants at elevated likelihood of ASD and ADHD; n = 18 infants at typical likelihood of the disorders). Behavioural and EEG responses to pairs of tactile stimuli were experimentally recorded and concurrent parental reports of tactile responsiveness were collected. ASD and ADHD traits were measured at 24 months through standardized assessment (ADOS-2) and parental report (ECBQ), respectively. RESULTS: There was no effect of infants' likelihood status on behavioural markers of tactile sensory processing. Conversely, increased ASD likelihood associated with reduced neural repetition suppression to tactile input. Reduced neural repetition suppression at 10 months significantly predicted ASD (but not ADHD) traits at 24 months across the entire sample. Elevated tactile sensory seeking at 10 months moderated the relationship between early reduced neural repetition suppression and later ASD traits. CONCLUSIONS: Reduced tactile neural repetition suppression is an early marker of later ASD traits in infants at elevated likelihood of ASD or ADHD, suggesting that a common pathway to later ASD traits exists despite different familial backgrounds. Elevated tactile sensory seeking may act as a protective factor, mitigating the relationship between early tactile neural repetition suppression and later ASD traits.

Sensitivity to Visual-Tactile Colocation on the Body Prior to Skilled Reaching in Early Infancy.

Two experiments examined perceptual colocation of visual and tactile stimuli in young infants. Experiment 1 compared 4- (n = 15) and 6-month-old (n = 12) infants' visual preferences for visual-tactile stimulus pairs presented across the same or different feet. The 4- and 6-month-olds showed, respectively, preferences for colocated and noncolocated conditions, demonstrating sensitivity to visual-tactile colocation on their feet. This extends previous findings of visual-tactile perceptual colocation on the hands in older infants. Control conditions excluded the possibility that both 6- (Experiment 1), and 4-month-olds (Experiment 2, n = 12) perceived colocation on the basis of an undifferentiated supramodal coding of spatial distance between stimuli. Bimodal perception of visual-tactile colocation is available by 4 months of age, that is, prior to the development of skilled reaching.

Look duration at the face as a developmental endophenotype: elucidating pathways to autism and ADHD.

Identifying developmental endophenotypes on the pathway between genetics and behavior is critical to uncovering the mechanisms underlying neurodevelopmental conditions. In this proof-of-principle study, we explored whether early disruptions in visual attention are a unique or shared candidate endophenotype of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD). We calculated the duration of the longest look (i.e., peak look) to faces in an array-based eye-tracking task for 335 14-month-old infants with and without first-degree relatives with ASD and/or ADHD. We leveraged parent-report and genotype data available for a proportion of these infants to evaluate the relation of looking behavior to familial (n = 285) and genetic liability (using polygenic scores, n = 185) as well as ASD and ADHD-relevant temperament traits at 2 years of age (shyness and inhibitory control, respectively, n = 272) and ASD and ADHD clinical traits at 6 years of age (n = 94).Results showed that longer peak looks at the face were associated with elevated polygenic scores for ADHD (ß = 0.078, p = .023), but not ASD (ß = 0.002, p = .944), and with elevated ADHD traits in mid-childhood (F(1,88) = 6.401, p = .013, $\eta _p^2$=0.068; ASD: F (1,88) = 3.218, p = .076), but not in toddlerhood (ps > 0.2). This pattern of results did not emerge when considering mean peak look duration across face and nonface stimuli. Thus, alterations in attention to faces during spontaneous visual exploration may be more consistent with a developmental endophenotype of ADHD than ASD. Our work shows that dissecting paths to neurodevelopmental conditions requires longitudinal data incorporating polygenic contribution, early neurocognitive function, and clinical phenotypic variation.

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.

Atypical Development of Attentional Control Associates with Later Adaptive Functioning, Autism and ADHD Traits.

Autism is frequently associated with difficulties with top-down attentional control, which impact on individuals' mental health and quality of life. The developmental processes involved in these attentional difficulties are not well understood. Using a data-driven approach, 2 samples (N = 294 and 412) of infants at elevated and typical likelihood of autism were grouped according to profiles of parent report of attention at 10, 15 and 25 months. In contrast to the normative profile of increases in attentional control scores between infancy and toddlerhood, a minority (7-9%) showed plateauing attentional control scores between 10 and 25 months. Consistent with pre-registered hypotheses, plateaued growth of attentional control was associated with elevated autism and ADHD traits, and lower adaptive functioning at age 3 years.

Increased cortical reactivity to repeated tones at 8 months in infants with later ASD.

Dysregulation of cortical excitation/inhibition (E/I) has been proposed as a neuropathological mechanism underlying core symptoms of autism spectrum disorder (ASD). Determining whether dysregulated E/I could contribute to the emergence of behavioural symptoms of ASD requires evidence from human infants prior to diagnosis. In this prospective longitudinal study, we examine differences in neural responses to auditory repetition in infants later diagnosed with ASD. Eight-month-old infants with (high-risk: n = 116) and without (low-risk: n = 27) an older sibling with ASD were tested in a non-linguistic auditory oddball paradigm. Relative to high-risk infants with typical development (n = 44), infants with later ASD (n = 14) showed reduced repetition suppression of 40-60 Hz evoked gamma and significantly greater 10-20 Hz inter-trial coherence (ITC) for repeated tones. Reduced repetition suppression of cortical gamma and increased phase-locking to repeated tones are consistent with cortical hyper-reactivity, which could in turn reflect disturbed E/I balance. Across the whole high-risk sample, a combined index of cortical reactivity (cortical gamma amplitude and ITC) was dimensionally associated with reduced growth in language skills between 8 months and 3 years, as well as elevated levels of parent-rated social communication symptoms at 3 years. Our data show that cortical 'hyper-reactivity' may precede the onset of behavioural traits of ASD in development, potentially affecting experience-dependent specialisation of the developing brain.

Tactile localization performance in children with developmental coordination disorder (DCD) corresponds to their motor skill and not their cognitive ability.

When localizing touches to the hands, typically developing children and adults show a "crossed hands effect" whereby identifying which hand received a tactile stimulus is less accurate when the hands are crossed than uncrossed. This demonstrates the use of an external frame of reference for locating touches to one's own body. Given that studies indicate that developmental vision plays a role in the emergence of external representations of touch, and reliance on vision for representing the body during action is atypical in developmental coordination disorder (DCD), we investigated external spatial representations of touch in children with DCD using the "crossed hands effect". Nineteen children with DCD aged 7-11years completed a tactile localization task in which posture (uncrossed, crossed) and view (hands seen, unseen) were varied systematically. Their performance was compared to that of 35 typically developing controls (19 of a similar age and cognitive ability, and 16 of a younger age but similar fine motor ability). Like controls, the DCD group exhibited a crossed hands effect, whilst their overall tactile localization performance was weaker than their peers of similar age and cognitive ability, but in line with younger controls of similar motor ability. For children with movement difficulties, these findings indicate tactile localization impairments in relation to age expectations, but apparently typical use of an external reference frame for localizing touch.

Human infants' ability to perceive touch in external space develops postnatally.

Arriving in the outside world, the newborn infant has to determine how the tactile stimulation experienced in utero relates to the spatial environment newly offered up by vision, hearing and olfaction. We investigated this developmental process by tracing the origins of the influence of external spatial representation on young infants' orienting responses to tactile stimuli. When adults cross their hands or feet they typically make more tactile localization errors than otherwise, and this has been attributed to the conflicts between skin-based and external frames of reference and/or the usual and current locations of touches in external space [1,2]. Here, we report that a group of six-month-olds, like adults, showed a tactile localisation deficit with their feet crossed, indicating external spatial coding of touch; in striking contrast, four-month-olds outperformed the older infants showing no crossed-feet deficit. Thus, in the first months of life, infants perceive touches solipsistically, and only come to locate them in the external world after significant postnatal experience.