Elizabeth Shephard.

O transtorno do espectro do autismo (TEA) e o transtorno do déficit de atenção/hiperatividade (TDAH) são condições comuns e prejudiciais ao neurodesenvolvimento. A identificação precoce de bebês em risco de desenvolver TEA e/ou TDAH e o uso de intervenções preventivas para limitar o surgimento e o impacto dos sintomas são estratégias preventivas importantes para reduzir o impacto desses transtornos. O principal objetivo deste projeto de Jovem Pesquisador é estabelecer o primeiro estudo longitudinal prospectivo de bebês em risco familiar para TEA e TDAH em um contexto de país de baixa e média renda (LMIC - Brasil). O estudo investigará como o risco familiar de TEA e TDAH afeta trajetórias precoces de neurodesenvolvimento em bebês que vivem em um LMIC, como as alterações nas trajetórias precoces de neurodesenvolvimento se relacionam com o surgimento de TEA e TDAH posteriormente no desenvolvimento, e se fatores de risco biológicos (inflamação, função do sistema de resposta ao estresse) e ambientais (pobreza, trauma na infância, estresse materno) mediam os efeitos negativos do risco familiar de TEA e TDAH nas vias neurodesenvolvimentais precoces. Os resultados deste projeto farão uma contribuição significativa para a literatura existente de países de alta renda (HICs) sobre como o risco familiar de TEA e TDAH afeta o desenvolvimento infantil e a generalização de descobertas anteriores para bebês que crescem em ambientes desfavorecidos. Os resultados também fornecerão novas evidências cruciais relação à eficácia da intervenção psicossocial preventiva para bebês vulneráveis em LMICs, que atualmente é uma prioridade global.

A regulação emocional corresponde à capacidade de o indivíduo, por uma série de mecanismos, modular as respostas emocionalmente evocadas pelos mais diversos estímulos de forma a controlar e eventualmente alterar seu estado emocional conforme a situação, oferecendo possibilidades adaptativas do comportamento bastante importantes na vida social dos indivíduos e na conquista de seus objetivos. Esses mecanismos, conforme sugerido por uma série de evidências, estão de alguma forma alterados em transtornos do neurodesenvolvimento, com destaque para o TDAH (Transtorno do Déficit de Atenção com Hiperatividade). O presente estudo visa a propor uma análise dos correlatos eletrofisiológicos, especificamente os ERPs (potenciais relacionados a eventos), do processamento emocional em crianças pré-escolares com TDAH. Esse projeto irá contribuir significativamente para o campo dos estudos em neurodesenvolvimento por fornecer novas informações sobre os mecanismos neurais subjacentes aos problemas de regulação emocional em jovens crianças diagnosticadas com TDAH.

The objective of this fellowship project is to design and implement longitudinal multimodal neuroimaging methods for investigating changes in neural circuitry in infants and young children that are associated with early interventions for neurodevelopmental disorders (NDs). Brain activity will be assessed using two neuroimaging techniques, electroencephalography (EEG) and functional near infra-red spectroscopy (fNIRS), to measure brain circuits on complementary spatiotemporal scales. Neuroimaging data will be collected in a prospective longitudinal design with assessments conducted pre- and post- early interventions. These methods will be employed across three randomised controlled trials (RCTs) of early interventions for different neurodevelopmental problems (autism spectrum disorder, attention-deficit/hyperactivity disorder, and infants of adolescent mothers living in poverty). Across all three interventions, graph-theoretical and longitudinal statistical analysis methods will be used to compute and analyse pre- vs. post-intervention changes in neural circuitry of the participating infants and young children and assess how those changes relate to improvements in children?s cognition, behaviour and symptoms of NDs. The results of this project will yield novel information about the neurobiological effects of currently available early interventions for a range of neurodevelopmental problems, which could be used to promote the use of specific interventions and in supporting public policies for early intervention use in vulnerable populations.

Adolescent motherhood remains common in developing countries and is associated with a range of risk factors that adversely impact infant neurocognitive development, including socio-economic depravation, low maternal education, and increased maternal psychiatric problems. Yet, few empirical studies have examined neurocognitive functioning in infants born to adolescent mothers, and no published work has used neuroimaging or neurophysiology to directly assess how risk factors associated with adolescent motherhood in developing countries affect early-life brain development. Understanding precisely how brain development is affected in infants of adolescent mothers and which specific maternal risk-factors brain alterations relate to will be crucial in designing targeted and effective interventions to prevent impaired neurocognitive development in these infants. In this study, we are examining associations between maternal risk-factors (education level and symptoms of anxiety, depression and ADHD) and indices of infant
neurocognitive development (oscillatory power and functional connectivity obtained from resting-state EEG, cognitive and language ability, temperament) in a sample (n = 50) of adolescent mothers and their infants living in an impoverished area of São Paulo, Brazil.

Deep brain stimulation (DBS) is an effective treatment option for ~60% of individuals with refractory obsessive-compulsive disorder (OCD). Still, precisely how DBS changes brain function and how those changes lead to improvements (or non-improvements) in symptoms are not fully understood. In this project, we aim to address this issue by longitudinally examining gradual changes in both neural activity and OCD symptoms over a 1-year pre-to-post-surgery period in patients with refractory OCD undergoing DBS treatment. We aim to identify 1) electrophysiological correlates of symptom improvement that could be investigated in future as targets for non-invasive (TMS/tDCS) brain stimulation treatments, and 2) pre-surgery neural characteristics that differentiate DBS responders from non-responders.

The proposed visiting researcher grant will support research activities of Dr Elizabeth Shephard from the Institute of Psychiatry, Psychology, & Neuroscience, King?s College London, to be conducted at the Department of Psychiatry, University of São Paulo with the host Professor Euripedes Constantino Miguel. Dr Shephard has expertise in using cognitive neuroscience techniques to study neural and cognitive mechanisms involved in neurodevelopmental disorders, and in mapping risk pathways to neurodevelopmental disorders via longitudinal studies of children with familial or genetic risk. During the 12 months (26/02/2018 ? 25/02/2019) of the grant, Dr Shephard will analyse data from FAPESP-funded projects, including the National Institute for Developmental Psychiatry (INDP-II), applying her techniques to address three related questions about neurodevelopment in Brazilian infants, children, and young people: 1) Which cognitive factors mediate the relationship between exposure to family violence and conflict and the development of children?s social functioning? 2) How is the developmental trajectory of infant neurocognitive risk-markers for attention-deficit/hyperactivity disorder influenced by socioeconomic depravation and parenting intervention? 3) Can abnormalities in neural habituation and hyperconnectivity explain some of the symptoms of obsessive-compulsive disorder? Dr Shephard?s visit is in line with one of the key goals of the USP Department of Psychiatry and the INDP-II ? to increase internationalisation of developmental psychiatry research in São Paulo by exchange of researchers with other leading institutions around the world. In addition to providing analytical support to the research projects, she will give lectures and workshops in using neurophysiology to understand neuropsychiatric disorders, and participate in the Obsessive-Compulsive Disorders Program (PROTOC) at USP, assisting with the development of new research proposals.

This project seeks to characterise the nature of aberrant brain connectivity in ASD, ADHD and ASD+ADHD using methodologically rigorous state-of-the-art approaches and a novel research design that compares findings from cases of ASD, ADHD and ASD+ADHD with and without a specific genetic disorder (Tuberous Sclerosis) in two existing, well-characterised samples. We will examine the relationship between connectivity measures and other well-established neurophysiological and cognitive markers of ASD, ADHD and ASD+ADHD compared to controls. Together, the findings will elucidate the nature and specificity of abnormalities in brain circuitry in ASD, ADHD and ASD+ADHD.

In this project, we conducted a 7-year longitudinal follow-up of a cohort of infants at high familial risk for ASD seen previously by our group at ages 6 months to 3 years. At age 7 years, we re-examined symptoms of ASD and aspects of brain and behavioural functioning that were associated with high-risk status and ASD/atypical developmental outcome at 3 years. The aims were to investigate a) the stability of symptoms (and diagnoses) of ASD across childhood, and b) the longer-term developmental trajectory of neurocognitive characteristics associated with ASD or high-risk status and how these relate to mid-childhood developmental outcome. Furthermore, we examined whether the clinical and neurocognitive measures obtained in infancy and toddlerhood could predict developmental outcome (e.g. diagnosis of ASD) and neurocognitive functioning in mid-childhood. http://www.basisnetwork.org/