Intellectual functioning is a critical determinant of economic and personal productivity. Identifying early neural predictors of cognitive function in infancy will allow us to map the neurodevelopmental pathways that underpin individual differences in intellect. Here, in three different cohorts we investigate the association between a putative neurophysiological indicator of information encoding (change in frontal theta during a novel video) in infancy and later general cognitive outcome. In a discovery cohort of 12-month-old typically developing infants, we recorded EEG during presentation of dynamic movies of people and objects. Frontal theta power (3–6 Hz) significantly increased during the course of viewing each video. Critically, increase in frontal theta during viewing of a video was associated with a differential response to repetition of that specific video, confirming relation to learning. Further, individual differences in the magnitude of change in frontal theta power were related to concurrent nonverbal cognitive level. We then sought to extend this association in two independent samples enriched for variation in cognitive outcome due to the inclusion of infants at familial risk for autism. We observed similar patterns of theta EEG change at 12 months, and found a predictive relation to verbal and nonverbal cognitive skills measured at 2, 3 and 7 years of age. For the subset of high-risk infants later diagnosed with autism, infant theta EEG explained over 80% of the variance in nonverbal skills at age 3 years. We suggest that EEG theta change in infancy is an excellent candidate predictive biomarker that could yield substantial insight into the mechanisms that underlie individual differences in childhood intelligence, particularly in high risk populations.

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BackgroundAttention deficit hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder that can negatively impact on an individual’s quality of life. It is pathophysiologically complex and heterogeneous with different neuropsychological processes being impaired in different individuals. Executive function deficits, including those affecting attention, working memory and inhibitory control, are common. Cognitive training has been promoted as a treatment option, based on the notion that by strengthening the neurocognitive networks underlying these executive processes, ADHD symptoms will also be reduced. However, if implemented in childhood or later, when the full disorder has become well-established, cognitive training has only limited value. INTERSTAARS is a trial designed to test a novel approach to intervention, in which cognitive training is implemented early in development, before the emergence of the disorder. The aim of INTERSTAARS is to train early executive skills, thereby increasing resilience and reducing later ADHD symptoms and associated impairment.Methods/designFifty 10–14-month-old infants at familial risk of ADHD will participate in INTERSTAARS. Infants will be randomised to an intervention or a control group. The intervention aims to train early attention skills by using novel eye-tracking technology and gaze-contingent training paradigms. Infants view animated games on a screen and different events take place contingent on where on the screen the infant is looking. Infants allocated to the intervention will receive nine weekly home-based attention training sessions. Control group infants will also receive nine weekly home visits, but instead of viewing the training games during these visits they will view non-gaze-contingent age-appropriate videos. At baseline and post treatment, infant attention control will be assessed using a range of eye-tracking, observational, parent-report and neurophysiological measures. The primary outcome will be a composite of eye-tracking tasks used to assess infant attention skills. Follow-up data will be collected on emerging ADHD symptoms when the infants are 2 and 3 years old.DiscussionThis is the first randomised controlled trial to assess the potential efficacy of cognitive training as a prevention measure for infants at familial risk of ADHD. If successful, INTERSTAARS could offer a promising new approach for developing early interventions for ADHD.Trial registrationInternational Standard Randomised Controlled Trial registry: ISRCTN37683928. Registered on 22 June 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1727-0) contains supplementary material, which is available to authorized users.

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.

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.