DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY
Free Papers (In Order of Presentation) The power of early intervention J OATES The Open University, Milton Keynes, UK
English policies and practices for the support of children and young people with special educational needs and disabilities are undergoing major changes, with statutory requirements for new ways of working coming into force in September this year. A number of Pathfinder sites have been trialling and developing innovative approaches, in which key-working and Early Support principles are embedded. This lecture will review the main features of the new policies, the role of these principles in guiding practice, and resources that are available. (This lecture will be on-line only.)
Plasticity in the developing brain B KOLB University of Lethbridge, Alberta, Canada
Neocortical development represents more than a simple unfolding of a genetic blueprint but rather represents a complex dance of genetic and environmental events that interact to adapt the brain to fit a particular environmental context. As the brain develops it progresses through a series of stages beginning with neurogenesis and progressing to neural migration, maturation, synaptogenesis, pruning, and myelin formation. The developing normal brain shows a remarkable capacity for plastic changes in response to a wide range of pre- and postnatal experiences. This review will examine the ways in which early experiences alter brain development, including environmental events such as sensory stimuli, early stress, psychoactive drugs, parent–child relationships, peer relationships, intestinal flora, diet, and radiation. This sensitivity of the brain to early experiences has important implications for understanding neurodevelopmental disorders as well as the effect of behavioural and medical interventions in children.
Early nutrition: its role in the development of brain and cognition
ABSTRACTS
been able to employ methods to demonstrate effects on neural substrates; until recently, such methods were not available for use with humans. With the advent of neuroimaging and, particularly, of techniques for post-acquisition processing of scans, has come the opportunity to study the human brain in vivo. In this talk, I will give a quick overview of early nutrition as a programming agent for subsequent brain/cognitive development and then concentrate on one particular cohort of preterm infants who took part in a post-natal randomised controlled trial of infant feeding and who have been followed up extensively since birth. I will describe studies investigating the effects of the different early feeding regimes on their subsequent cognitive development and also on underlying brain structure. Delineating the long-term effects of early infant feeding is particularly important as nutrition is probably the most easily manipulated of environmental variables.
What determines outcome in infants at-risk for common developmental disorders? M JOHNSON Centre for Brain and Cognitive Development, Birkbeck, University of London, London, UK
I will address the question in my title by focusing on the emergence of the ‘social brain’ network during human development. A brief overview of evidence from typical development highlights the importance of a sub-cortical brain route for orienting toward social stimuli over the first months of life. Following this, a prolonged process of increasing functional specialization of key cortical regions and their patterns of connectivity can be observed, consistent with activitydependent processes (and the ‘Interactive Specialisation’ framework). Turning to atypical development, a number of lines of evidence indicate that a key feature of autism is a lack of specialization (tuning) of cortical structures in the social brain. But how does this atypical phenotypic end-state of human development arise? I review three causal developmental hypotheses in relation to emerging evidence from longitudinal studies of infants at-risk for later autism, and speculate that the final common pathway for autism lies in a common adaptive response of the brain to a range of different molecular and genetic threats to optimal synaptic function. By this view autism is an alternative trajectory of human functional brain development, triggered by an early life period of poor fidelity neural processing.
E ISAACS University College London Institute of Child Health, London, UK
Observational studies in developing countries have reported that poor nutrition in humans is associated with non-optimal cognitive development, but confounding factors made this difficult to interpret. More recently, randomised controlled trials have provided more reliable evidence that early nutrition can influence or ‘programme’ both cognitive development and later behaviour. Animal studies concur with this but have also
2
Stress, relationships, and development: what we know and what we still need to learn M GUNNAR University of Minnesota, Minneapolis, MN, USA
Relationships play a critical role, for better or worse, in regulating stress biology during human development. In this talk I will review what we know about relationships as stress
© 2014 The Authors. Development Medicine & Child Neurology © 2014 Mac Keith Press, 56 (Suppl. S3), 2–6 DOI: 10.1111/dmcn.12459
regulators and how the absence of supportive relationship regulation impacts human development. As I overview the state of our knowledge, I will point out where the gaps are and what we need to know in order best to use research on stress and relationships to foster the healthy development of all children.
Impact of anti-epileptic drugs on the developing brain: an unfolding story G BAKER University Department of Neurosciences, Walton Centre for Neurology and Neurosurgery, Liverpool, UK
Similar to alcohol, some antiepileptic drugs (AEDs) can cause widespread neuronal apoptosis in the immature animal brain. This effect is dose-dependent, occurs at therapeutically relevant blood levels, and requires only brief exposure. The associated behavioral deficits in animals may be more due to dysfunction in the surviving neurons than the loss of neurons. Consistent with these findings in animals, some AEDs have been associated with reduced cognitive abilities in children exposed in utero. Six-year cognitive outcomes recently reported by the NEAD study group indicated that children with fetal valproate exposure continued to exhibit significantly lower IQ than children exposed to carbamazepine, lamotrigine, or phenytoin. In addition, valproate-exposed children performed more poorly than children exposed to the other three AEDs on measures of linguistic functioning and learning/memory. Only a higher valproate dose continued to be negatively associated with performance on measures of intelligence, linguistic functions, nonverbal abilities, learning/memory, and executive functions. The Liverpool and Manchester Neurodevelopment Group was established in 1999 as a collaboration to investigate our understanding of the potential risks associated with in utero exposure to antiepileptic drugs. To date the team in collaboration with colleagues in the US have published over 25 papers, contributed to medical guidelines in the Europe and the US and influenced prescribing practices internationally. This presentation will focus on the work of the Liverpool and Manchester Neurodevelopment Group and describe the history of our research from clinical observations to large multicenter International Observational studies. The presenter will outline both advances in scientific knowledge and the practical implications of our research findings with recommendations for current and future research.
Cognition in children with focal epilepsy and the impact of neurosurgery T BALDEWEG University College London Institute of Child Health, London, UK
Cognitive development can be compromised in children with focal epilepsy, with serious implications for educational achievements. Understanding the clinical factors and neurobiological mechanisms which impact on cognitive function are important for successful remediation. I will review evidence on the role of epilepsy-related factors as well as the impact on
structural and functional brain development. Children with medication-resistant epilepsy are often most severely affected and neurosurgical treatment can be an effective intervention. I will show recent developments in using non-invasive neuroimaging to help guide such interventions. Finally I will review the evidence on the impact of neurosurgical treatments on cognitive and educational outcomes in children with focal epilepsy.
Hypoxia-ischaemia and hippocampal damage: from memory impairment to developmental amnesia F VARGHA-KHADEM University College London Institute of Child Health, London, UK
In this lecture I will describe the spectrum of hippocampal abnormality and associated memory impairment that can result from hypoxic ischaemic episodes sustained early in life. Comparison of groups of patients with perinatal versus childhood exposure to hypoxia-ischaemia reveal that the pattern of selective hippocampal pathology and associated memory impairment is not dependent on the age at onset of injury. I will describe the features of developmental amnesia and explain how this selective form of memory impairment presents in the clinical setting. I will also highlight the three dissociations in cognitive memory that are characteristic of the syndrome of developmental amnesia. Neuropsychological and neuroimaging data from large cohorts of children, adolescents and adult patients will be presented to provide evidence of a causal sequence starting from neonatal exposure to hypoxia-ischaemia leading to bilateral hippocampal pathology, and, consequently, to selective deficits in episodic memory, recall, and recollection.
On the cognitive and neural bases of language impairments in SLI and ASD H TAGER-FLUSBERG Center for Autism Research Excellence, Boston University, MA, USA
Although according to the recently published DSM5 language impairments are no longer considered to be primary deficits in ASD, the majority of children later diagnosed with the disorder are significantly delayed in the early milestones of language development. While problems in using language effectively in social contexts (pragmatics) is impaired in all individuals with ASD, deficits in structural aspects of language are far more variable, with some people achieving age-appropriate skills in phonology, vocabulary and grammar, others remaining non-verbal, and the majority, acquiring spoken language but remaining behind their peers. A number of researchers have highlighted the parallels between language deficits in verbal children with ASD and in specific language impairment (SLI) arguing that SLI may represent a co-morbid neurodevelopmental disorder in ASD. Research addressing this claim will be presented beginning with behavioural studies on the two key clinical markers of
Free Papers 3
SLI (for English-speakers): nonsense word repetition and grammatical marking obligatory tense. Studies on the neural bases for language processing will be presented, including structural and functional neuroimaging studies, with a particular emphasis on functional magnetic resonance imaging studies of nonsense word repetition and grammatical tense. Discussion will focus on the current evidence that language deficits in ASD share some common features with SLI and the implications of this claim for clinical practice.
Stress and the developing brain B KOLB University of Lethbridge, Alberta, Canada
The developing brain is especially sensitive to stress, both prenatally, in infancy, and in adolescence. Such stress has been linked to abnormal cognitive, behavioural and psychosocial outcomes in both laboratory animals and humans. These behavioural changes are related to changes in neuronal organization of the cerebral cortex, and especially the prefrontal cortex, and hippocampus and amygdala, as well as changes in gene expression in cortex and hippocampus. One long-term effect of early stressors is a change in response to a wide variety of experiences later in life, including learning and response to psychoactive drugs as well aversive childhood experiences. This talk will review the stressors at different times in development (prenatal, infant, adolescent, adult) and consider the impact on brain development, behaviour, and later brain plasticity.
Early experiences, stress and neurobehavioural development M GUNNAR University of Minnesota, Minneapolis, MN, USA
The study of children adopted from institutional care provides a window on the impact of early experiences and the capacity for recovery. Post-institutionalized children show remarkable recovery in many functions, yet two areas continue to show the residue of early deprivation: attention and defensive systems. Both areas of altered functioning would be anticipated based on animal models of early deprivation. The findings of our group and of others studying these children point to the possibility of an early sensitive period for organizing attention and defensive systems; however, recent data raise the possibility that puberty may open another period for at least partial recalibration.
ADHD: the final common pathway? V ANDERSON Murdoch Children’s Research Institute, Vic, Australia
ADHD is a common developmental disorder, characterised by inattention, hyperactivity and impulsivity, and causing significant functional difficulties, including behavioural and social problems, as well as poor educational achievement. While
4 UKPNS Abstracts
some children demonstrate ‘pure’ ADHD’ a large proportion exhibit a range of co-morbidities, including learning problems, speech and language difficulties, social communication problems and conduct disorder. ADHD symptoms are also common in children with a history of brain insult, highlighting the multiple potential pathways to the disorder. The majority of studies addressing ADHD have used clinic-derived samples, where it might be expected that symptoms are more severe and co-morbidities more likely. This presentation will describe preliminary findings from a recently-conducted large-scale, community based study of ADHD, the Children’s Attention Project (CAP). The study recruited 6 year-old children, with and without symptoms of ADHD, and followed them up over 18 months, and collected data on a range of outcomes including behaviour profiles, co-morbidities, neuropsychological function and educational achievement. This paper will discuss findings from the CAP study, and compare them to results from other conditions with high risk of ADHD symptoms (e.g., acquired brain injury), in order to better understand the psychological precursors to ADHD.
Early risk markers for autism spectrum disorder: evidence from studies of infant siblings H TAGER-FLUSBERG Center for Autism Research Excellence, Boston University, MA, USA
Autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder, with core impairments in social, communicative development that emerge over the second year of life expressed in reduced social engagement, vocalization, communication and often poor emotional regulation. Over the past decade a number of research groups have begun exploring the developmental origins and trajectories of ASD by studying infants who have an older sibling with ASD, who are at significantly increased risk for ASD, and comparing them to infants at low risk. One of the earliest concerns that parents express about their child with ASD is in the domain of language. In collaboration with Dr. Charles Nelson (Children’s Hospital Boston/ Harvard Medical School), we have been investigating the development of language and communication in infants at risk for ASD with a focus on behavioural development and brain functioning. At 12 months, infants who were later diagnosed with ASD vocalized significantly less than other high risk or low risk infants. They also gestured significantly less than other infants, though these behavioural differences were not related to the rate at which their mothers spoke or gestured to them. Using both functional near-infra red spectroscopy (fNIRS) and event-related EEG measures of coherence we found that at 12 months, infants at risk for ASD showed significantly reduced functional connectivity between frontal and posterior language regions, and event-related potentials to speech suggested that language was less lateralized in these infants compared to low risk infants. Importantly there was not a strong relationship between these neural markers of risk and later ASD or even language outcomes in these high-risk infants. Future directions for how we might interpret these
complex patterns of brain and behavioural development in this unique population will be discussed.
Thinking about the developmental consequences of ‘mindblindness’ in autism F HAPPE´ Institute of Psychiatry, King’s College London, UK
Many of the social and communication difficulties that define autism spectrum disorder (ASD) can be well understood as reflecting impairment in theory of mind or ‘mentalising’. For example, delays or deficits in attributing mental states would make it hard to comprehend deception, keep secrets, track others’ pretend play, and interpret irony. However, beyond these ‘on-line’ effects, deficits or delays in mentalising have significant developmental consequences. This talk presents on-going and past research on downstream effects of mindblindness in ASD, including impact on measured intelligence, language, and self-awareness. Mentalising can be seen as a gatekeeper, opening the way to skills and knowledge acquired through social osmosis. Gatekeepers also keep things out; I will suggest that mentalising is obligatory in neurotypical (non-autistic) people, and that mindblindness in ASD may also carry some benefits.
role of volumetric and perfusion imaging and diffusion tensor imaging alongside functional MRI may provide clinically relevant data for children presenting with hemiplegia. Obtaining a better understanding of patterns of neural connectivity in CH corresponding to bimanual skill acquisition will enable us to obtain critical information for predicting response to treatment to develop patient-focussed therapies and improve functional outcomes.
The DSM V: implications for UK practice G BAIRD King’s College London, UK
The classification systems of DSM5 and ICD11 will be discussed with particular reference to Neurodevelopmental disorders. The basis of the current thinking and proposals for both classification systems for individual disorders will be discussed. DSM5 is published (2013) but ICD11 is not. This talk is an opportunity for participants to critically appraise work so far and even influence the outcome!
Dyslexia: how multiple deficit models explain individual variation V MUTER University College London Institute of Child Health, London, UK
The magic of movement: neural plasticity and influence on outcomes in childhood motor disorders D GREEN Oxford Brookes University, Oxford, UK
Childhood hemiplegia (CH), characterised by predominant unilateral motor impairment, is the most common type of cerebral palsy but may also be acquired later in childhood. Damage to the developing central nervous system is typically the result of brain malformation, unilateral bias of periventricular haemorrhage and or peri-ventricular leukomalacia, middle cerebral artery infarct or posthaemorrhagic porencphaly with consequent variability in impact on motor areas and corpus callosum and corticospinal tract (CST) integrity and severity of hand function impairment. Motor therapies have been shown to have a positive effect on hand function for many but not all children with hemiplegia. Neuroplastic changes prior to intervention may predict differential responses to unimanual or bimanual therapies. Our previous research suggests potential brain changes in CH that may affect temporal coupling of bimanual actions and critical periods of change in response to bimanual intervention. This lecture will present details across case series and intervention studies investigating relationships between hand function and lesion type/severity and white matter integrity in CH before and after a magic themed intensive bimanual intervention programme. Several imaging biomarkers have been detected correlating with clinical and behavioural assessments and clinical outcomes. The
Over the last 10 years, there has been a significant change in how we view developmental disorders, including dyslexia. This is due to the shift away from the single deficit model of learning disorders which is based on the theory that there are innate specific cognitive modules corresponding to identifiable brain regions that process certain kinds of information; in the case of reading, the module is a phonological processor located in the left temporal-parietal lobe which if damaged will result in a literacy disorder. However, recent neuroscience research has shown us that the human brain does not operate in this simple modular ‘cause and effect’ way. Single deficit models are inadequate in explaining individual variations in developmental disorders such as dyslexia and in accounting for the high incidence of co-morbidity with other disorders. Multiple deficit models far better explain how dyslexia can be expressed in any one child while at the same time providing a strong theoretical and empirical basis for understanding the nature of co-morbidity. This talk will look at first, how multiple deficit models have advanced our understanding of dyslexia and second, at why there is frequent co-occurrence with other learning problems (including language disorders, attention deficits and maths problems). The implications for assessment and ‘diagnosis’ for the individual child will be considered; in particular, the need for multiple measures of reading and for assessments of co-occurring difficulties. Formulating an individual child’s pattern of learning strengths and weaknesses is essential in planning an intervention and management package that addresses all their needs.
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Dyscalculia: from brain to education B BUTTERWORTH University College London, UK
Here I set out what is known about the mathematical brain, including the brain networks for arithmetic, its development and the role of learning in the changing brain. I will argue that the mathematical brain has inherited a special core capacity for processing numerosity of sets, and make references to human heritability studies but also studies of ancestral versions of our capacity. Dyscalculia, I claim, is a core deficit in this inherited numerosity processing, which is easy to identify with simple tests. Dyscalculic brains have abnormalities abnormal structure and functioning in the numerosity processing regions, and that remediating dyscalculia means strengthening numerosity processing. I will conclude by explaining why dyscalculia is important for all of us.
Traumatic brain injury and crime: causal links and emerging interventions H WILLIAMS Centre for Clinical Neuropsychology Research, University of Exeter, UK
Recent advances in developmental neuroscience show that disorders such as Traumatic Brain Injury (TBI) can be linked to longer term social violence. Injury may, of course, be a ‘marker’ for many factors that indicate risk of injury and crime, but may also be an additive, independent, risk factor. Injury to the developing brain may be associated with long term deficits in social reasoning and executive control linked to behavioural disturbance. Indeed, in our work with adolescent and adult offenders, we have shown a substantial degree of early TBI in such groups. And that many have ongoing symptoms of TBI that may be interfering with their forensic rehabilitation. There is a significant need, therefore, for better means to provide effective, targeted interventions to reduce lifetime risk of social violence in children and adolescents with TBI. This involves better links between health and education systems to ensure that those who are injured are supported to stay in society – particularly at school. Also, there is a need to
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develop neuro-rehabilitation approaches for offenders with TBI. From generic systems for ensuring that TBI is assessed for, and managed, through to direct rehabilitation of some of the key underlying deficits in processing that may be linked to such behaviours as social violence.
Neuropsychological rehabilitation in cerebral palsy: treating the child with an eye on the Future L BRAGA SARAH Network, Brazil
Cerebral palsy (CP) constitutes a range of conditions caused by non-progressive lesions to the brain early in a child’s development. The neuropsychological rehabilitation of the child with CP must be based on a thorough understanding not only of the natural history of the disease, but also on the potential, setting and needs of each individual. The impact of CP on a developing brain renders it a life-long challenge that pervades every aspect of the child’s (and later, the adult’s) life. Treatment focusing on the future of these children increases the effectiveness and sustainability of interventions geared towards improving motor, cognitive, neuropsychological and quality of life in the long-term. This presentation will address the wide gamut of issues pertaining to CP, e.g., how to best establish diagnosis and forge realistic prognoses based on each child’s environment and strengths; and how to incorporate our knowledge of neuroplasticity into planning the most appropriate programs for these children. Ecological rehabilitation, which centers on the needs of each individual, requires a shift in approach to treatment as the child grows. Initially, a family-based methodology has been shown to yield the most beneficial results in infancy, while during the preadolescent and adolescent stages, the increasing importance of peers and social settings renders a metacognitive-based approach more ecologically sound for the developing teenager. Both ecologically-based programs, will be discussed, within the scope of an overarching goal: treating not only the child, but the future adult, for a life of greater productivity, meaningfulness, and autonomy.
Free Papers (In Order of Presentation) The power of early intervention J OATES The Open University, Milton Keynes, UK
English policies and practices for the support of children and young people with special educational needs and disabilities are undergoing major changes, with statutory requirements for new ways of working coming into force in September this year. A number of Pathfinder sites have been trialling and developing innovative approaches, in which key-working and Early Support principles are embedded. This lecture will review the main features of the new policies, the role of these principles in guiding practice, and resources that are available. (This lecture will be on-line only.)
Plasticity in the developing brain B KOLB University of Lethbridge, Alberta, Canada
Neocortical development represents more than a simple unfolding of a genetic blueprint but rather represents a complex dance of genetic and environmental events that interact to adapt the brain to fit a particular environmental context. As the brain develops it progresses through a series of stages beginning with neurogenesis and progressing to neural migration, maturation, synaptogenesis, pruning, and myelin formation. The developing normal brain shows a remarkable capacity for plastic changes in response to a wide range of pre- and postnatal experiences. This review will examine the ways in which early experiences alter brain development, including environmental events such as sensory stimuli, early stress, psychoactive drugs, parent–child relationships, peer relationships, intestinal flora, diet, and radiation. This sensitivity of the brain to early experiences has important implications for understanding neurodevelopmental disorders as well as the effect of behavioural and medical interventions in children.
Early nutrition: its role in the development of brain and cognition
ABSTRACTS
been able to employ methods to demonstrate effects on neural substrates; until recently, such methods were not available for use with humans. With the advent of neuroimaging and, particularly, of techniques for post-acquisition processing of scans, has come the opportunity to study the human brain in vivo. In this talk, I will give a quick overview of early nutrition as a programming agent for subsequent brain/cognitive development and then concentrate on one particular cohort of preterm infants who took part in a post-natal randomised controlled trial of infant feeding and who have been followed up extensively since birth. I will describe studies investigating the effects of the different early feeding regimes on their subsequent cognitive development and also on underlying brain structure. Delineating the long-term effects of early infant feeding is particularly important as nutrition is probably the most easily manipulated of environmental variables.
What determines outcome in infants at-risk for common developmental disorders? M JOHNSON Centre for Brain and Cognitive Development, Birkbeck, University of London, London, UK
I will address the question in my title by focusing on the emergence of the ‘social brain’ network during human development. A brief overview of evidence from typical development highlights the importance of a sub-cortical brain route for orienting toward social stimuli over the first months of life. Following this, a prolonged process of increasing functional specialization of key cortical regions and their patterns of connectivity can be observed, consistent with activitydependent processes (and the ‘Interactive Specialisation’ framework). Turning to atypical development, a number of lines of evidence indicate that a key feature of autism is a lack of specialization (tuning) of cortical structures in the social brain. But how does this atypical phenotypic end-state of human development arise? I review three causal developmental hypotheses in relation to emerging evidence from longitudinal studies of infants at-risk for later autism, and speculate that the final common pathway for autism lies in a common adaptive response of the brain to a range of different molecular and genetic threats to optimal synaptic function. By this view autism is an alternative trajectory of human functional brain development, triggered by an early life period of poor fidelity neural processing.
E ISAACS University College London Institute of Child Health, London, UK
Observational studies in developing countries have reported that poor nutrition in humans is associated with non-optimal cognitive development, but confounding factors made this difficult to interpret. More recently, randomised controlled trials have provided more reliable evidence that early nutrition can influence or ‘programme’ both cognitive development and later behaviour. Animal studies concur with this but have also
2
Stress, relationships, and development: what we know and what we still need to learn M GUNNAR University of Minnesota, Minneapolis, MN, USA
Relationships play a critical role, for better or worse, in regulating stress biology during human development. In this talk I will review what we know about relationships as stress
© 2014 The Authors. Development Medicine & Child Neurology © 2014 Mac Keith Press, 56 (Suppl. S3), 2–6 DOI: 10.1111/dmcn.12459
regulators and how the absence of supportive relationship regulation impacts human development. As I overview the state of our knowledge, I will point out where the gaps are and what we need to know in order best to use research on stress and relationships to foster the healthy development of all children.
Impact of anti-epileptic drugs on the developing brain: an unfolding story G BAKER University Department of Neurosciences, Walton Centre for Neurology and Neurosurgery, Liverpool, UK
Similar to alcohol, some antiepileptic drugs (AEDs) can cause widespread neuronal apoptosis in the immature animal brain. This effect is dose-dependent, occurs at therapeutically relevant blood levels, and requires only brief exposure. The associated behavioral deficits in animals may be more due to dysfunction in the surviving neurons than the loss of neurons. Consistent with these findings in animals, some AEDs have been associated with reduced cognitive abilities in children exposed in utero. Six-year cognitive outcomes recently reported by the NEAD study group indicated that children with fetal valproate exposure continued to exhibit significantly lower IQ than children exposed to carbamazepine, lamotrigine, or phenytoin. In addition, valproate-exposed children performed more poorly than children exposed to the other three AEDs on measures of linguistic functioning and learning/memory. Only a higher valproate dose continued to be negatively associated with performance on measures of intelligence, linguistic functions, nonverbal abilities, learning/memory, and executive functions. The Liverpool and Manchester Neurodevelopment Group was established in 1999 as a collaboration to investigate our understanding of the potential risks associated with in utero exposure to antiepileptic drugs. To date the team in collaboration with colleagues in the US have published over 25 papers, contributed to medical guidelines in the Europe and the US and influenced prescribing practices internationally. This presentation will focus on the work of the Liverpool and Manchester Neurodevelopment Group and describe the history of our research from clinical observations to large multicenter International Observational studies. The presenter will outline both advances in scientific knowledge and the practical implications of our research findings with recommendations for current and future research.
Cognition in children with focal epilepsy and the impact of neurosurgery T BALDEWEG University College London Institute of Child Health, London, UK
Cognitive development can be compromised in children with focal epilepsy, with serious implications for educational achievements. Understanding the clinical factors and neurobiological mechanisms which impact on cognitive function are important for successful remediation. I will review evidence on the role of epilepsy-related factors as well as the impact on
structural and functional brain development. Children with medication-resistant epilepsy are often most severely affected and neurosurgical treatment can be an effective intervention. I will show recent developments in using non-invasive neuroimaging to help guide such interventions. Finally I will review the evidence on the impact of neurosurgical treatments on cognitive and educational outcomes in children with focal epilepsy.
Hypoxia-ischaemia and hippocampal damage: from memory impairment to developmental amnesia F VARGHA-KHADEM University College London Institute of Child Health, London, UK
In this lecture I will describe the spectrum of hippocampal abnormality and associated memory impairment that can result from hypoxic ischaemic episodes sustained early in life. Comparison of groups of patients with perinatal versus childhood exposure to hypoxia-ischaemia reveal that the pattern of selective hippocampal pathology and associated memory impairment is not dependent on the age at onset of injury. I will describe the features of developmental amnesia and explain how this selective form of memory impairment presents in the clinical setting. I will also highlight the three dissociations in cognitive memory that are characteristic of the syndrome of developmental amnesia. Neuropsychological and neuroimaging data from large cohorts of children, adolescents and adult patients will be presented to provide evidence of a causal sequence starting from neonatal exposure to hypoxia-ischaemia leading to bilateral hippocampal pathology, and, consequently, to selective deficits in episodic memory, recall, and recollection.
On the cognitive and neural bases of language impairments in SLI and ASD H TAGER-FLUSBERG Center for Autism Research Excellence, Boston University, MA, USA
Although according to the recently published DSM5 language impairments are no longer considered to be primary deficits in ASD, the majority of children later diagnosed with the disorder are significantly delayed in the early milestones of language development. While problems in using language effectively in social contexts (pragmatics) is impaired in all individuals with ASD, deficits in structural aspects of language are far more variable, with some people achieving age-appropriate skills in phonology, vocabulary and grammar, others remaining non-verbal, and the majority, acquiring spoken language but remaining behind their peers. A number of researchers have highlighted the parallels between language deficits in verbal children with ASD and in specific language impairment (SLI) arguing that SLI may represent a co-morbid neurodevelopmental disorder in ASD. Research addressing this claim will be presented beginning with behavioural studies on the two key clinical markers of
Free Papers 3
SLI (for English-speakers): nonsense word repetition and grammatical marking obligatory tense. Studies on the neural bases for language processing will be presented, including structural and functional neuroimaging studies, with a particular emphasis on functional magnetic resonance imaging studies of nonsense word repetition and grammatical tense. Discussion will focus on the current evidence that language deficits in ASD share some common features with SLI and the implications of this claim for clinical practice.
Stress and the developing brain B KOLB University of Lethbridge, Alberta, Canada
The developing brain is especially sensitive to stress, both prenatally, in infancy, and in adolescence. Such stress has been linked to abnormal cognitive, behavioural and psychosocial outcomes in both laboratory animals and humans. These behavioural changes are related to changes in neuronal organization of the cerebral cortex, and especially the prefrontal cortex, and hippocampus and amygdala, as well as changes in gene expression in cortex and hippocampus. One long-term effect of early stressors is a change in response to a wide variety of experiences later in life, including learning and response to psychoactive drugs as well aversive childhood experiences. This talk will review the stressors at different times in development (prenatal, infant, adolescent, adult) and consider the impact on brain development, behaviour, and later brain plasticity.
Early experiences, stress and neurobehavioural development M GUNNAR University of Minnesota, Minneapolis, MN, USA
The study of children adopted from institutional care provides a window on the impact of early experiences and the capacity for recovery. Post-institutionalized children show remarkable recovery in many functions, yet two areas continue to show the residue of early deprivation: attention and defensive systems. Both areas of altered functioning would be anticipated based on animal models of early deprivation. The findings of our group and of others studying these children point to the possibility of an early sensitive period for organizing attention and defensive systems; however, recent data raise the possibility that puberty may open another period for at least partial recalibration.
ADHD: the final common pathway? V ANDERSON Murdoch Children’s Research Institute, Vic, Australia
ADHD is a common developmental disorder, characterised by inattention, hyperactivity and impulsivity, and causing significant functional difficulties, including behavioural and social problems, as well as poor educational achievement. While
4 UKPNS Abstracts
some children demonstrate ‘pure’ ADHD’ a large proportion exhibit a range of co-morbidities, including learning problems, speech and language difficulties, social communication problems and conduct disorder. ADHD symptoms are also common in children with a history of brain insult, highlighting the multiple potential pathways to the disorder. The majority of studies addressing ADHD have used clinic-derived samples, where it might be expected that symptoms are more severe and co-morbidities more likely. This presentation will describe preliminary findings from a recently-conducted large-scale, community based study of ADHD, the Children’s Attention Project (CAP). The study recruited 6 year-old children, with and without symptoms of ADHD, and followed them up over 18 months, and collected data on a range of outcomes including behaviour profiles, co-morbidities, neuropsychological function and educational achievement. This paper will discuss findings from the CAP study, and compare them to results from other conditions with high risk of ADHD symptoms (e.g., acquired brain injury), in order to better understand the psychological precursors to ADHD.
Early risk markers for autism spectrum disorder: evidence from studies of infant siblings H TAGER-FLUSBERG Center for Autism Research Excellence, Boston University, MA, USA
Autism spectrum disorder (ASD) is the fastest growing neurodevelopmental disorder, with core impairments in social, communicative development that emerge over the second year of life expressed in reduced social engagement, vocalization, communication and often poor emotional regulation. Over the past decade a number of research groups have begun exploring the developmental origins and trajectories of ASD by studying infants who have an older sibling with ASD, who are at significantly increased risk for ASD, and comparing them to infants at low risk. One of the earliest concerns that parents express about their child with ASD is in the domain of language. In collaboration with Dr. Charles Nelson (Children’s Hospital Boston/ Harvard Medical School), we have been investigating the development of language and communication in infants at risk for ASD with a focus on behavioural development and brain functioning. At 12 months, infants who were later diagnosed with ASD vocalized significantly less than other high risk or low risk infants. They also gestured significantly less than other infants, though these behavioural differences were not related to the rate at which their mothers spoke or gestured to them. Using both functional near-infra red spectroscopy (fNIRS) and event-related EEG measures of coherence we found that at 12 months, infants at risk for ASD showed significantly reduced functional connectivity between frontal and posterior language regions, and event-related potentials to speech suggested that language was less lateralized in these infants compared to low risk infants. Importantly there was not a strong relationship between these neural markers of risk and later ASD or even language outcomes in these high-risk infants. Future directions for how we might interpret these
complex patterns of brain and behavioural development in this unique population will be discussed.
Thinking about the developmental consequences of ‘mindblindness’ in autism F HAPPE´ Institute of Psychiatry, King’s College London, UK
Many of the social and communication difficulties that define autism spectrum disorder (ASD) can be well understood as reflecting impairment in theory of mind or ‘mentalising’. For example, delays or deficits in attributing mental states would make it hard to comprehend deception, keep secrets, track others’ pretend play, and interpret irony. However, beyond these ‘on-line’ effects, deficits or delays in mentalising have significant developmental consequences. This talk presents on-going and past research on downstream effects of mindblindness in ASD, including impact on measured intelligence, language, and self-awareness. Mentalising can be seen as a gatekeeper, opening the way to skills and knowledge acquired through social osmosis. Gatekeepers also keep things out; I will suggest that mentalising is obligatory in neurotypical (non-autistic) people, and that mindblindness in ASD may also carry some benefits.
role of volumetric and perfusion imaging and diffusion tensor imaging alongside functional MRI may provide clinically relevant data for children presenting with hemiplegia. Obtaining a better understanding of patterns of neural connectivity in CH corresponding to bimanual skill acquisition will enable us to obtain critical information for predicting response to treatment to develop patient-focussed therapies and improve functional outcomes.
The DSM V: implications for UK practice G BAIRD King’s College London, UK
The classification systems of DSM5 and ICD11 will be discussed with particular reference to Neurodevelopmental disorders. The basis of the current thinking and proposals for both classification systems for individual disorders will be discussed. DSM5 is published (2013) but ICD11 is not. This talk is an opportunity for participants to critically appraise work so far and even influence the outcome!
Dyslexia: how multiple deficit models explain individual variation V MUTER University College London Institute of Child Health, London, UK
The magic of movement: neural plasticity and influence on outcomes in childhood motor disorders D GREEN Oxford Brookes University, Oxford, UK
Childhood hemiplegia (CH), characterised by predominant unilateral motor impairment, is the most common type of cerebral palsy but may also be acquired later in childhood. Damage to the developing central nervous system is typically the result of brain malformation, unilateral bias of periventricular haemorrhage and or peri-ventricular leukomalacia, middle cerebral artery infarct or posthaemorrhagic porencphaly with consequent variability in impact on motor areas and corpus callosum and corticospinal tract (CST) integrity and severity of hand function impairment. Motor therapies have been shown to have a positive effect on hand function for many but not all children with hemiplegia. Neuroplastic changes prior to intervention may predict differential responses to unimanual or bimanual therapies. Our previous research suggests potential brain changes in CH that may affect temporal coupling of bimanual actions and critical periods of change in response to bimanual intervention. This lecture will present details across case series and intervention studies investigating relationships between hand function and lesion type/severity and white matter integrity in CH before and after a magic themed intensive bimanual intervention programme. Several imaging biomarkers have been detected correlating with clinical and behavioural assessments and clinical outcomes. The
Over the last 10 years, there has been a significant change in how we view developmental disorders, including dyslexia. This is due to the shift away from the single deficit model of learning disorders which is based on the theory that there are innate specific cognitive modules corresponding to identifiable brain regions that process certain kinds of information; in the case of reading, the module is a phonological processor located in the left temporal-parietal lobe which if damaged will result in a literacy disorder. However, recent neuroscience research has shown us that the human brain does not operate in this simple modular ‘cause and effect’ way. Single deficit models are inadequate in explaining individual variations in developmental disorders such as dyslexia and in accounting for the high incidence of co-morbidity with other disorders. Multiple deficit models far better explain how dyslexia can be expressed in any one child while at the same time providing a strong theoretical and empirical basis for understanding the nature of co-morbidity. This talk will look at first, how multiple deficit models have advanced our understanding of dyslexia and second, at why there is frequent co-occurrence with other learning problems (including language disorders, attention deficits and maths problems). The implications for assessment and ‘diagnosis’ for the individual child will be considered; in particular, the need for multiple measures of reading and for assessments of co-occurring difficulties. Formulating an individual child’s pattern of learning strengths and weaknesses is essential in planning an intervention and management package that addresses all their needs.
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Dyscalculia: from brain to education B BUTTERWORTH University College London, UK
Here I set out what is known about the mathematical brain, including the brain networks for arithmetic, its development and the role of learning in the changing brain. I will argue that the mathematical brain has inherited a special core capacity for processing numerosity of sets, and make references to human heritability studies but also studies of ancestral versions of our capacity. Dyscalculia, I claim, is a core deficit in this inherited numerosity processing, which is easy to identify with simple tests. Dyscalculic brains have abnormalities abnormal structure and functioning in the numerosity processing regions, and that remediating dyscalculia means strengthening numerosity processing. I will conclude by explaining why dyscalculia is important for all of us.
Traumatic brain injury and crime: causal links and emerging interventions H WILLIAMS Centre for Clinical Neuropsychology Research, University of Exeter, UK
Recent advances in developmental neuroscience show that disorders such as Traumatic Brain Injury (TBI) can be linked to longer term social violence. Injury may, of course, be a ‘marker’ for many factors that indicate risk of injury and crime, but may also be an additive, independent, risk factor. Injury to the developing brain may be associated with long term deficits in social reasoning and executive control linked to behavioural disturbance. Indeed, in our work with adolescent and adult offenders, we have shown a substantial degree of early TBI in such groups. And that many have ongoing symptoms of TBI that may be interfering with their forensic rehabilitation. There is a significant need, therefore, for better means to provide effective, targeted interventions to reduce lifetime risk of social violence in children and adolescents with TBI. This involves better links between health and education systems to ensure that those who are injured are supported to stay in society – particularly at school. Also, there is a need to
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develop neuro-rehabilitation approaches for offenders with TBI. From generic systems for ensuring that TBI is assessed for, and managed, through to direct rehabilitation of some of the key underlying deficits in processing that may be linked to such behaviours as social violence.
Neuropsychological rehabilitation in cerebral palsy: treating the child with an eye on the Future L BRAGA SARAH Network, Brazil
Cerebral palsy (CP) constitutes a range of conditions caused by non-progressive lesions to the brain early in a child’s development. The neuropsychological rehabilitation of the child with CP must be based on a thorough understanding not only of the natural history of the disease, but also on the potential, setting and needs of each individual. The impact of CP on a developing brain renders it a life-long challenge that pervades every aspect of the child’s (and later, the adult’s) life. Treatment focusing on the future of these children increases the effectiveness and sustainability of interventions geared towards improving motor, cognitive, neuropsychological and quality of life in the long-term. This presentation will address the wide gamut of issues pertaining to CP, e.g., how to best establish diagnosis and forge realistic prognoses based on each child’s environment and strengths; and how to incorporate our knowledge of neuroplasticity into planning the most appropriate programs for these children. Ecological rehabilitation, which centers on the needs of each individual, requires a shift in approach to treatment as the child grows. Initially, a family-based methodology has been shown to yield the most beneficial results in infancy, while during the preadolescent and adolescent stages, the increasing importance of peers and social settings renders a metacognitive-based approach more ecologically sound for the developing teenager. Both ecologically-based programs, will be discussed, within the scope of an overarching goal: treating not only the child, but the future adult, for a life of greater productivity, meaningfulness, and autonomy.
