Human neurocognitive development: Early-stage processing, modifiers, and outcomes

Developmental disorders such as Autism Spectrum Disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) are rarely diagnosed before age 3. Understanding the emergence of these disorders during the first years is critical to improving early identification and treatment options. We aim to understand how brain development over the first years of life relates to both typical and atypical developmental outcomes. To do this, we will conduct two large projects. First, we will follow infants who are more likely to develop common conditions like autism and ADHD from five months to toddlerhood (Part A). Second, we will study typically developing babies from pregnancy to early infancy (Part B). Both parts of our programme aim to: (1) find markers of how babies process sounds, sights and touch (sensory processing); (2) understand later-emerging skills like social motivation or self-regulation that can help babies compensate for any early difficulties in sensory processing; (3) understand how these factors might shape and predict later behavioural difficulties, like problems with social communication or attention and activity level.

In Part A we build on our long experience in working with infants with a family member with ASD, who have a 1/5 chance of going on to a diagnosis themselves. We will further expand our work to infants with a family member with ADHD, who have a similarly heightened likelihood of receiving an ADHD diagnosis. We will also work with a new group of infants diagnosed with Neurofibromatosis 1, a genetic condition that frequently leads to a later ASD or ADHD diagnosis. We will compare the development of brain and cognitive functions in these groups to other babies who do not have a family history of a developmental disorder. All these groups of babies will take part in our study where we follow babies over five visits to our laboratory over the first three years of life. We study brain development using a variety of baby-friendly methods such as Near InfraRed Spectroscopy (NIRS - a type of light imaging), electroencephalography (EEG), eye-tracking, and parent-infant interaction. We have chosen to compare infant routes to autism and ADHD risk for several reasons. One of these is to determine how specific the early warning signs are for particular later outcomes. Another reason is that we know that these conditions quite commonly co-occur in the same children. We also work with international partners to join together to ask important questions about early signs and interventions for autism and ADHD.

Birth is the single most dramatic change in environment that a brain experiences in its lifetime, yet its consequences for emerging functions remain surprisingly unknown. In Part B we will conduct a basic science study of typical development from pregnancy to age 5 months. We will look at whether individual differences in how foetuses respond to lights and sounds measured with ultrasound are maintained after birth. Further, we will ask whether or not there are dramatic changes in brain function that happen over the first weeks post-birth. Finally, we will study how infant's experiences interacting with other people in early infancy influences their brain development. Taken together, this project will provide deep insights into a vital period of human development.

Little is currently known about the emergence of ASD and ADHD during infancy, and the modifying factors that may compound or alleviate initial risk. In Part A we will advance our current studies of infants at-risk for a later diagnosis of autism or ADHD by virtue of being young siblings of a diagnosed child, to also include infants diagnosed with Neurofibromatosis 1, a genetic condition that frequently leads to a later ASD or ADHD diagnosis. We will compare the development of brain and cognitive functions in these groups alongside typical (low-risk) infants using a variety of methods such as Near InfraRed Spectroscopy, EEG, eye-tracking, standardised assessments, and parent-infant interaction. This work will allow us to dissociate early stage markers associated with poor synaptic efficiency in posterior sensory and motor cortices, from later developing neurocognitive factors associated with anterior (frontal) systems that can compound or alleviate symptoms in the course of subsequent development. Part A is embedded within national and international collaborative networks in order to increase the number of babies studied on some key measures, and correspondingly increase our ability to detect effects. Birth is the single most dramatic change in environment that a brain experiences in its lifetime, yet its consequences for emerging brain functions remain surprisingly unknown. In Part B we will conduct a basic science study of typical development over this period to ask fundamental questions such as whether individual differences in foetal behaviour are maintained after birth, whether or not there are dramatic changes in brain function triggered by birth, and what is the role of social interaction with other humans during the first weeks of life on infant brain development.

We envisage several groups of non-academic beneficiaries for our research; (i) the families of children at risk for developmental disorders, (ii) individuals with a general interest in child development, and those about to transition into parenthood, (iii) policy-makers within government interested in investment in early child development (e.g. "The 1001 critical days" Cross-party manifesto, 2014), (iv) professionals, managers and commissioners responsible for the care of individuals with autism/ADHD and their families, (v) commercial enterprises interested in new software and hardware development to aid attention and learning early in life, and in the development of treatments for autism and ADHD, and (vi) charities both in the UK (The Neuro Foundation, Autistica, CHADD) and at an international level (Children's Tumor Foundation, Autism Speaks), which provide educational resources, support and networking opportunities for schools and families. We will continue to monitor and review our impact during the project lifecycle.

Autism and ADHD are lifelong neurodevelopmental disorders that in many cases bring considerable burden and cost to the individual, their family and society. About 1% of children are on the autism spectrum and the prevalence for ADHD is estimated at 5%. Recent estimates of the UK annual societal cost of ASD exceed £32 billion (nationalautismproject.org.uk/the-report). Total ADHD annual cost in the US has been put at between $143 and $266 billion (www.ncbi.nlm.nih.gov/pubmed/24911948). Recent financial analyses show that even high cost early intervention has the potential for large lifetime cost savings (www.ncbi.nlm.nih.gov/pubmed/28838582). The study of infant siblings is vital for early detection, improving diagnostic strategies, and providing the basis for early interventions aimed at improving the independence and quality of life of those who are affected. For example, our current PG has allowed us to prove the efficacy of a parent-mediated intervention for individuals with high likelihood for ASD (Green et al., 2017). Such interventions have the potential to capitalise on maximal neural plasticity and may have a cascading impact on later cognitive function.

In Part B of the grant we trace neurocognitive development in the understudied but critical pre and early post-natal period. The first year of life is a time of rapid neural development that lays the foundation for later cognitive abilities and educational performance. This basic research will underpin future translational studies in infants with early developmental risk factors such as premature birth, or global health risks such as under-nutrition. In addition, sharing information about early development with parents of low risk infants also promotes infant and family wellbeing.

Our PG will also provide a fertile training environment for young scientists. PI Johnson has supervised over 60 students and postdocs, who have gone on to a variety of academic and research appointments, and is to receive the 2019 APS mentorship award. He is also co-author of a leading textbook. Indeed, BBK site lead Jones was mentored as a postdoctoral fellow by Johnson and now holds a permanent Lectureship. Further, we regularly host volunteers and placement students from a range of backgrounds (circa 10 per year). Our training environment focuses on both scientific excellence, but also a broad range of generalisable skills to prepare students for careers beyond academia. These include working with families, complex data management, presentation and communication skills, clinical experience, independence and time management, and working in industry. Further, through data sharing we have provided critical scientific resources to a range of PhD students from other groups, spreading expertise from our network.