Experience-based specialisation: underpinnings of communication in typical and atypical development

Autism Spectrum Disorder (ASD) is an umbrella term encompassing several neurodevelopmental conditions with complex, heterogeneous symptomatology. One way in which I addressed this complexity is by looking at a specific aspect of the phenotype to understand the contributing mechanisms. Communication difficulties are prevalent in ASD, and it has been suggested that this is a downstream effect of atypical functional specialisation in processing of both social and non-social auditory input in the brain. This thesis aimed to identify robust markers of specialisation across several methodologies and assess the links with the behavioural phenotype. First, a series of eye tracking studies was carried out with typically developing infants to identify age and language experience effects on speech perception and whether these can be linked to brain-based markers of specialisation. Then, three auditory EEG paradigms were used to measure differences in auditory perception in infants with increased familial likelihood of ASD and/or ADHD, as well as in a unique population of infants with NF1, who experience elevated rates of ASD and other neurodevelopmental conditions as part of the clinical symptomology. Through inclusion of several different participant groups, it was possible to examine whether atypical auditory processing was a specific marker of familial and/or monogenic likelihood of ASD or a general predictor of atypical development. Chapter 2 outlined the main techniques used to measure experience-dependent specialisation, including eye tracking, EEG and behavioural assessments. Chapter 3 investigated specialisation towards native speech perception though several novel paradigms in a longitudinal sample of neurotypical infants at 5, 10 and 14 months of age, as well as associations with parent and observer-rated language abilities. Chapter 4 examined the relationship between eye tracking, neural indices of vowel perception and communication skills in neurotypical infants and how these EEG-based indices may differ in a group of infants with NF1 at 5 and 10 months. Chapter 5 investigated differences in neural habituation and change detection responses across time and time-frequency analyses in 8-month-old infants with low and high familial likelihood of ASD and how these relate to language and ASD symptomology at three years. Lastly, Chapter 6 examined steady-state responses in the gamma frequency range in 14-month-old infants and whether this auditory marker can be used to differentiate between neurotypical infants and those with familial likelihood of ASD or ADHD or an NF1 diagnosis and to predict individual differences in communication skills. Taken together, the present work explored early markers of functional specialisation of auditory processing in typical and atypical development in association with parent/observer ratings of early language ability. Additionally, findings are reported from the first study of early brain development in infants with NF1. This is integral to the current understanding of pathways to ASD, with a further aim of informing clinical and research practices in rare genetic disorders

Early development of infants with neurofibromatosis type 1: a case series

Background Prospective studies of infants at familial risk for autism spectrum disorder (ASD) have yielded insights into the earliest signs of the disorder but represent heterogeneous samples of unclear aetiology. Complementing this approach by studying cohorts of infants with monogenic syndromes associated with high rates of ASD offers the opportunity to elucidate the factors that lead to ASD. Methods We present the first report from a prospective study of ten 10-month-old infants with neurofibromatosis type 1 (NF1), a monogenic disorder with high prevalence of ASD or ASD symptomatology. We compared data from infants with NF1 to a large cohort of infants at familial risk for ASD, separated by outcome at age 3 of ASD (n = 34), atypical development (n = 44), or typical development (n = 89), and low-risk controls (n = 75). Domains assessed at 10 months by parent report and examiner observation include cognitive and adaptive function, sensory processing, social engagement, and temperament. Results Infants with NF1 showed striking impairments in motor functioning relative to low-risk infants; this pattern was seen in infants with later ASD from the familial cohort (HR-ASD). Both infants with NF1 and the HR-ASD group showed communication delays relative to low-risk infants. Conclusions Ten-month-old infants with NF1 show a range of developmental difficulties that were particularly striking in motor and communication domains. As with HR-ASD infants, social skills at this age were not notably impaired. This is some of the first information on early neurodevelopment in NF1. Strong inferences are limited by the sample size, but the findings suggest implications for early comparative developmental science and highlight motor functioning as an important domain to inform the development of relevant animal models. The findings have clinical implications in indicating an important focus for early surveillance and remediation in this early diagnosed genetic disorder

Early development of infants with neurofibromatosis type 1: a case series

Abstract Background Prospective studies of infants at familial risk for autism spectrum disorder (ASD) have yielded insights into the earliest signs of the disorder but represent heterogeneous samples of unclear aetiology. Complementing this approach by studying cohorts of infants with monogenic syndromes associated with high rates of ASD offers the opportunity to elucidate the factors that lead to ASD. Methods We present the first report from a prospective study of ten 10-month-old infants with neurofibromatosis type 1 (NF1), a monogenic disorder with high prevalence of ASD or ASD symptomatology. We compared data from infants with NF1 to a large cohort of infants at familial risk for ASD, separated by outcome at age 3 of ASD (n = 34), atypical development (n = 44), or typical development (n = 89), and low-risk controls (n = 75). Domains assessed at 10 months by parent report and examiner observation include cognitive and adaptive function, sensory processing, social engagement, and temperament. Results Infants with NF1 showed striking impairments in motor functioning relative to low-risk infants; this pattern was seen in infants with later ASD from the familial cohort (HR-ASD). Both infants with NF1 and the HR-ASD group showed communication delays relative to low-risk infants. Conclusions Ten-month-old infants with NF1 show a range of developmental difficulties that were particularly striking in motor and communication domains. As with HR-ASD infants, social skills at this age were not notably impaired. This is some of the first information on early neurodevelopment in NF1. Strong inferences are limited by the sample size, but the findings suggest implications for early comparative developmental science and highlight motor functioning as an important domain to inform the development of relevant animal models. The findings have clinical implications in indicating an important focus for early surveillance and remediation in this early diagnosed genetic disorder