Melbourne School of Psychological Sciences - Research Publications
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ItemBrain volumetric correlates of inhibition and cognitive flexibility 16 years following childhood traumatic brain injury(WILEY, 2018-04)Executive functions (EFs), such as inhibition and cognitive flexibility, are essential for everyday functioning, including regulation of socially appropriate emotional responses. These skills develop during childhood and continue maturing into early adulthood. The current study aimed to investigate the very long-term impact of childhood traumatic brain injury (TBI) on inhibition and cognitive flexibility, and to examine whether global white matter is associated with these abilities. Twenty-eight young adult survivors of childhood TBI (mean age at 16-year follow-up = 21.67 years, SD = 2.70) and 16 typically developing controls (TDCs), group-matched for age, sex, and socioeconomic status, completed tests of inhibition and cognitive flexibility and underwent structural MRI. Survivors of childhood TBI did not significantly differ from TDCs on EF or white matter volume. However, the relationship between EF and white matter volume differed between survivors of TBI and TDCs. Survivors of TBI did not mimic the brain behavior relationship that characterized EF in TDCs. The inverse brain behavior relationship, exhibited by childhood TBI survivors, suggests disruptions in the whole brain underpinning EF following childhood TBI.
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ItemThe relationship between cognitive and neuroimaging outcomes in children treated for acute lymphoblastic leukemia with chemotherapy only: A systematic review(WILEY, 2017-02)Cognitive late-effects have been identified in patients treated with chemotherapy-only protocols for childhood acute lymphoblastic leukemia (ALL), yet the underlying neuropathology is not well understood. This review synthesized recent findings from eight articles investigating the relationship between neurocognitive and neuroimaging outcomes for patients treated for ALL with chemotherapy-only protocols. Reported cognitive domains, imaging methods, and neuroanatomy examined were variable. Despite this, 62.5% (n = 5) of the reviewed studies found a significant relationship between cognitive and imaging outcomes. Greater understanding of the effects of treatment on neuroanatomy and cognitive outcomes is critical for proactively managing ALL cognitive late-effects. Research directions are suggested.
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ItemProtocol for a prospective, longitudinal, cohort study of postconcussive symptoms in children: the Take CARe (Concussion Assessment and Recovery Research) study(BMJ PUBLISHING GROUP, 2016)INTRODUCTION: A substantial minority of children who sustain a concussion suffer prolonged postconcussive symptoms. These symptoms can persist for more than 1 month postinjury and include physical, cognitive, behavioural and emotional changes. Those affected can develop significant disability, diminishing their quality of life. The precise prevalence of postconcussive symptoms following child concussion is unclear, with heterogeneous and at times conflicting results published regarding factors that predict children at risk for developing long-lasting postconcussive symptoms. The aim of the Take C.A.Re (Concussion Assessment and Recovery Research) study is to provide an in-depth multidimensional description of the postconcussive recovery trajectories from a physical, neurocognitive and psychosocial perspective in the 3 months following concussion, with a focus on the early postconcussive period, and identification of factors associated with prolonged recovery. METHODS AND ANALYSIS: Take C.A.Re is a prospective, longitudinal study at a tertiary children's hospital, recruiting and assessing patients aged 5-<18 years who present to the emergency department with a concussion and following them at 1-4 days, 2 weeks, 1 month and 3 months postinjury. Multiple domains are assessed: postconcussive symptoms, balance and coordination, neurocognition, behaviour, quality of life, fatigue, post-traumatic stress symptoms, parental distress and family burden. 'Delayed recovery' is operationalised as the presence of ≥ 3 symptoms on the Post Concussive Symptoms Inventory rated as worse compared with baseline. Main analyses comprise analysis of variance (recovery trajectories, delayed vs normal recovery groups) and regression analyses of predictors of recovery (preinjury, acute and family factors). ETHICS AND DISSEMINATION: Ethical approval has been obtained through the Royal Children's Hospital Melbourne Human Research Ethics Committee (33122). We aim to disseminate the findings through international conferences, international peer-reviewed journals and social media. TRIAL REGISTRATION NUMBER: ACTRN12615000316505.
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ItemBrain extraction using the watershed transform from markers(FRONTIERS MEDIA SA, 2013)Isolation of the brain from other tissue types in magnetic resonance (MR) images is an important step in many types of neuro-imaging research using both humans and animal subjects. The importance of brain extraction is well appreciated-numerous approaches have been published and the benefits of good extraction methods to subsequent processing are well known. We describe a tool-the marker based watershed scalper (MBWSS)-for isolating the brain in T1-weighted MR images built using filtering and segmentation components from the Insight Toolkit (ITK) framework. The key elements of MBWSS-the watershed transform from markers and aggressive filtering with large kernels-are techniques that have rarely been used in neuroimaging segmentation applications. MBWSS is able to reliably isolate the brain without expensive preprocessing steps, such as registration to an atlas, and is therefore useful as the first stage of processing pipelines. It is an informative example of the level of accuracy achievable without using priors in the form of atlases, shape models or libraries of examples. We validate the MBWSS using a publicly available dataset, a paediatric cohort, an adolescent cohort, intra-surgical scans and demonstrate flexibility of the approach by modifying the method to extract macaque brains.
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ItemOptic Radiation Tractography in Pediatric Brain Surgery Applications: A Reliability and Agreement Assessment of the Tractography Method(FRONTIERS MEDIA SA, 2019-11-20)BACKGROUND: Optic radiation (OR) tractography may help predict and reduce post-neurosurgical visual field deficits. OR tractography methods currently lack pediatric and surgical focus. PURPOSE: We propose a clinically feasible OR tractography strategy in a pediatric neurosurgery setting and examine its intra-rater and inter-rater reliability/agreements. METHODS: Preoperative and intraoperative MRI data were obtained from six epilepsy and two brain tumor patients on 3 Tesla MRI scanners. Four raters with different clinical experience followed the proposed strategy to perform probabilistic OR tractography with manually drawing anatomical landmarks to reconstruct the OR pathway, based on fiber orientation distributions estimated from high angular resolution diffusion imaging data. Intra- and inter-rater reliabilities/agreements of tractography results were assessed using intraclass correlation coefficient (ICC) and dice similarity coefficient (DSC) across various tractography and OR morphological metrics, including the lateral geniculate body positions, tract volumes, and Meyer's loop position from temporal anatomical landmarks. RESULTS: Good to excellent intra- and inter-rater reproducibility was demonstrated for the majority of OR reconstructions (ICC = 0.70-0.99; DSC = 0.84-0.89). ICC was higher for non-lesional (0.82-0.99) than lesional OR (0.70-0.99). The non-lesional OR's mean volume was 22.66 cm3; the mean Meyer's loop position was 29.4 mm from the temporal pole, 5.89 mm behind of and 10.26 mm in front of the temporal ventricular horn. The greatest variations (± 1.00-3.00 mm) were observed near pathology, at the tract edges or at cortical endpoints. The OR tractography were used to assist surgical planning and guide lesion resection in all cases, no patient had new visual field deficits postoperatively. CONCLUSION: The proposed tractography strategy generates reliable and reproducible OR tractography images that can be reliably implemented in the routine, non-emergency pediatric neurosurgical setting.
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ItemUnderstanding autism spectrum disorder and social functioning in children with neurofibromatosis type 1: protocol for a cross-sectional multimodal study(BMJ PUBLISHING GROUP, 2019-09)INTRODUCTION: Children with the single-gene disorder neurofibromatosis type 1 (NF1) appear to be at an increased risk for autism spectrum disorder (ASD) and exhibit a unique social-cognitive phenotype compared with children with idiopathic ASD. A complete framework is required to better understand autism in NF1, from neurobiological levels through to behavioural and functional outcomes. The primary aims of this study are to establish the frequency of ASD in children with NF1, examine the social cognitive phenotype, investigate the neuropsychological processes contributing to ASD symptoms and poor social functioning in children with NF1, and to investigate novel structural and functional neurobiological markers of ASD and social dysfunction in NF1. The secondary aim of this study is to compare the neuropsychological and neurobiological features of ASD in children with NF1 to a matched group of patients with idiopathic ASD. METHODS AND ANALYSIS: This is an international, multisite, prospective, cross-sectional cohort study of children with NF1, idiopathic ASD and typically developing (TD) controls. Participants will be 200 children with NF1 (3-15 years of age), 70 TD participants (3-15 years) and 35 children with idiopathic ASD (7-15 years). Idiopathic ASD and NF1 cases will be matched on age, sex and intelligence. All participants will complete cognitive testing and parents will rate their child's behaviour on standardised questionnaires. Neuroimaging will be completed by a subset of participants aged 7 years and older. Children with NF1 that screen at risk for ASD on the parent-rated Social Responsiveness Scale 2nd Edition will be invited back to complete the Autism Diagnostic Observation Scale 2nd Edition and Autism Diagnostic Interview-Revised to determine whether they fulfil ASD diagnostic criteria. ETHICS AND DISSEMINATION: This study has hospital ethics approval and the results will be disseminated through peer-reviewed publications and international conferences.
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ItemProtocol for a prospective, longitudinal, cohort study of recovery pathways, acute biomarkers and cost for children with persistent postconcussion symptoms: the Take CARe Biomarkers study(BMJ PUBLISHING GROUP, 2019-06)INTRODUCTION: The majority of children who sustain a concussion will recover quickly, but a significant minority will experience ongoing postconcussive symptoms, known as postconcussion syndrome (PCS). These symptoms include emotional, behavioural, cognitive and physical symptoms and can lead to considerable disability. The neurobiological underpinnings of PCS are poorly understood, limiting potential clinical interventions. As such, patients and families frequently re-present to clinical services, who are often ill equipped to address the multifactorial nature of PCS. This contributes to the high cost of concussion management and the disability of children experiencing PCS. The aims of the present study are: (1) to plot and contrast recovery pathways for children with concussion from time of injury to 3 months postinjury, (ii) evaluate the contribution of acute biomarkers (ie, blood, MRI) to delayed recovery postconcussion and (3) estimate financial costs of child concussion to patients attending the emergency department (ED) of a tertiary children's hospital and factors predicting high cost. METHODS AND ANALYSIS: Take C.A.Re is a prospective, longitudinal study at a tertiary children's hospital, recruiting and assessing 525 patients aged 5-<18 years (400 concussion, 125 orthopaedic injury) who present to the ED with a concussion and following them at 1-4 days, 2 weeks, 1 month and 3 months postinjury. Multiple domains are assessed: preinjury and postinjury, clinical, MRI, blood samples, neuropsychological, psychological and economic. PCS is defined as the presence of ≥2 symptoms on the Post Concussive Symptoms Inventory rated as worse compared with baseline 1 month postinjury. Main analyses comprise longitudinal Generalised Estimating Equation models and regression analyses of predictors of recovery and factors predicting high economic costs. ETHICS AND DISSEMINATION: Ethical approval has been obtained through the Royal Children's Hospital Melbourne Human Research Ethics Committee (33122). We aim to disseminate the findings through international conferences, international peer-reviewed journals and social media. TRIAL REGISTRATION NUMBER: ACTRN12615000316505; Results.