ORCID Profile
0000-0002-7290-512X
Current Organisations
Institute of Chemistry Chinese Academy of Sciences
,
Texas A&M University
,
Murdoch Childrens Research Institute
,
Deakin University
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Publications
Lessons About Neurodevelopment From Anatomical Magnetic Resonance Imaging
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 02-2011
Characterizing neuroanatomic heterogeneity in people with and without ADHD based on subcortical brain volumes
Publisher: Wiley
Date: 30-03-2021
DOI: 10.1111/JCPP.13384
Abstract: Attention‐deficit/hyperactivity disorder (ADHD) is a prevalent neurodevelopmental disorder. Neuroanatomic heterogeneity limits our understanding of ADHD’s etiology. This study aimed to parse heterogeneity of ADHD and to determine whether patient subgroups could be discerned based on subcortical brain volumes. Using the large ENIGMA‐ADHD Working Group dataset, four subs les of 993 boys with and without ADHD and to subs les of 653 adult men, 400 girls, and 447 women were included in analyses. We applied exploratory factor analysis (EFA) to seven subcortical volumes in order to constrain the complexity of the input variables and ensure more stable clustering results. Factor scores derived from the EFA were used to build networks. A community detection (CD) algorithm clustered participants into subgroups based on the networks. Exploratory factor analysis revealed three factors (basal ganglia, limbic system, and thalamus) in boys and men with and without ADHD. Factor structures for girls and women differed from those in males. Given s le size considerations, we concentrated subsequent analyses on males. Male participants could be separated into four communities, of which one was absent in healthy men. Significant case–control differences of subcortical volumes were observed within communities in boys, often with stronger effect sizes compared to the entire s le. As in the entire s le, none were observed in men. Affected men in two of the communities presented comorbidities more frequently than those in other communities. There were no significant differences in ADHD symptom severity, IQ, and medication use between communities in either boys or men. Our results indicate that neuroanatomic heterogeneity in subcortical volumes exists, irrespective of ADHD diagnosis. Effect sizes of case–control differences appear more pronounced at least in some of the subgroups.
Neurite density index is sensitive to age related differences in the developing brain
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.NEUROIMAGE.2017.01.023
Abstract: White matter development during childhood and adolescence is characterised by increasing white matter coherence and organisation. Commonly used scalar metrics, such as fractional anisotropy (FA), are sensitive to multiple mechanisms of white matter change and therefore unable to distinguish between mechanisms that change during development. We investigate the relationship between age and neurite density index (NDI) from neurite orientation dispersion and density imaging (NODDI), and the age-classification accuracy of NDI compared with FA, in a developmental cohort. Diffusion-weighted imaging data from 72 children and adolescents between the ages of 4-19 was collected (M=10.42, SD=3.99, 36 male). We compared NODDI metrics against conventional DTI metrics (fractional anisotropy [FA], mean diffusivity [MD], axial diffusivity [AD] and radial diffusivity [RD]) in terms of their relationship to age. An ROC analysis was also performed to assess the ability of each metric to classify older and younger participants. NDI exhibited a stronger relationship with age (median R Our results demonstrate the sensitivity of NDI to age-related differences in white matter microstructural organisation over development. Importantly, NDI is more sensitive to such developmental changes compared to commonly used DTI metrics. This knowledge provides justification for implementing NODDI metrics in developmental studies.
White matter alterations at pubertal onset
Publisher: Cold Spring Harbor Laboratory
Date: 19-04-2017
DOI: 10.1101/128165
Abstract: Recent neurodevelopmental research supports the contribution of pubertal stage to local and global grey and white matter remodelling. Little is known, however, about white matter microstructural alterations at pubertal onset. This study investigated differences in white matter properties between pre-pubertal and pubertal children using whole brain fixel-based analysis (FBA) of the microscopic density and macroscopic cross-section of fibre bundles. Diffusion-weighted imaging data were acquired for 74 typically developing children (M=10.4, SD=0.43 years, 31 female) at 3.0T (60 diffusion gradient directions, b-value=2800 s/mm 2 ). Group comparisons of fibre density (FD) and fibre cross-section (FC) were made between age-matched pre-pubertal and pubertal groups, and post-hoc analyses were performed on regions of interest (ROIs) defined in the splenium, body and genu of the corpus callosum. Significant fixel-wise differences in FD were observed between the pubertal groups, where the pubertal group had significantly higher FD compared with age-matched pre-pubertal children, localised to the posterior corpus callosum. Post-hoc analyses on mean FD in the corpus callosum ROIs revealed group differences between the pubertal groups in the splenium, but not body or genu. The observed higher apparent fibre density in the splenium suggests that pubertal onset coincides with white matter differences explained by increasing axon diameter. This may be an important effect to account for over pubertal development, particularly for group studies where age-matched clinical and typical populations may be at various stages of puberty.
Human Medial Frontal Cortex Activity Predicts Learning from Errors
Publisher: Oxford University Press (OUP)
Date: 05-12-2007
Abstract: Learning from errors is a critical feature of human cognition. It underlies our ability to adapt to changing environmental demands and to tune behavior for optimal performance. The posterior medial frontal cortex (pMFC) has been implicated in the evaluation of errors to control behavior, although it has not previously been shown that activity in this region predicts learning from errors. Using functional magnetic resonance imaging, we examined activity in the pMFC during an associative learning task in which participants had to recall the spatial locations of 2-digit targets and were provided with immediate feedback regarding accuracy. Activity within the pMFC was significantly greater for errors that were subsequently corrected than for errors that were repeated. Moreover, pMFC activity during recall errors predicted future responses (correct vs. incorrect), despite a sizeable interval (on average 70 s) between an error and the next presentation of the same recall probe. Activity within the hippoc us also predicted future performance and correlated with error-feedback-related pMFC activity. A relationship between performance expectations and pMFC activity, in the absence of differing reinforcement value for errors, is consistent with the idea that error-related pMFC activity reflects the extent to which an outcome is "worse than expected."
Corticolimbic connectivity mediates the relationship between pubertal timing and mental health problems
Publisher: Cambridge University Press (CUP)
Date: 02-06-2023
DOI: 10.1017/S0033291723001472
Abstract: Undergoing puberty ahead of peers (‘earlier pubertal timing’) is an important risk factor for mental health problems during early adolescence. The current study examined pathways between pubertal timing and mental health via connectivity of neural systems implicated in emotional reactivity and regulation (specifically corticolimbic connections) in 9- to 14-year-olds. Research questions were examined in the Adolescent Brain Cognitive Development (ABCD) Study, a large population representative s le in the United States. Linear mixed models examined associations between pubertal timing and resting-state corticolimbic connectivity. Significant connections were examined as potential mediators of the relationship between pubertal timing and mental health (withdrawn depressed and rule-breaking) problems. Exploratory analyses interrogated whether the family environment moderated neural risk patterns in those undergoing puberty earlier than their peers. Earlier pubertal timing was related to decreased connectivity between limbic structures (bilateral amygdala and right hippoc us) and the cingulo-opercular network, left amygdala and somatomotor (mouth) network, as well as between the left hippoc us and ventral attention network and visual network. Corticolimbic connections also mediated the relationship between earlier pubertal timing and increased withdrawn depressed problems (but not rule-breaking problems). Finally, parental acceptance buffered against connectivity patterns that were implicated in withdrawn depressed problems in those undergoing puberty earlier than their peers. Findings highlight the role of decreased corticolimbic connectivity in mediating pathways between earlier pubertal timing and withdrawn depressed problems, and we present preliminary evidence that the family environment may buffer against these neural risk patterns during early adolescence.
Understanding motor difficulties in children with ADHD: A fixel-based analysis of the corticospinal tract
Publisher: Elsevier BV
Date: 03-2021
Phenanthriplatin(iv ) conjugated multifunctional up-converting nanoparticles for drug delivery and biomedical imaging
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8TB01034J
Abstract: Platinum-based drugs cisplatin, carboplatin, and oxaliplatin are widely used in the clinical treatment of cancer.
Cortical structural and functional coupling during development and implications for Attention Deficit Hyperactivity Disorder
Publisher: Research Square Platform LLC
Date: 10-01-2023
DOI: 10.21203/RS.3.RS-2331408/V1
Abstract: Objective: Functional connectivity is scaffolded by the structural connections of the brain. Disruptions of either structural or functional connectivity can lead to deficits in cognitive functions and increase risk for neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD). To date, very little research has examined the association between structural and functional connectivity in typical development, while no studies have attempted to understand the development of structure-function coupling in children with ADHD. Methods: 175 in iduals (84 typically developing children and 91 children with ADHD) participated in a longitudinal neuroimaging study with up to three waves. In total, we collected 278 observations between the ages 9 and 14 (139 each in typically developing controls and ADHD). Regional measures of structure-function coupling were calculated at each timepoint using Spearman’s rank correlation and mixed effect models were used to determine group differences and longitudinal changes in coupling over time. Results: In typically developing children, we observed increases in structure-function coupling strength across multiple higher-order cognitive and sensory regions. Overall, weaker coupling was observed in children with ADHD, mainly in prefrontal cortex, superior temporal gyrus and inferior parietal cortex. Further, children with ADHD showed an increased rate of coupling strength predominantly in the inferior frontal gyrus, superior parietal cortex, precuneus, mid cingulate, and visual cortex, compared to no corresponding change over time in typically developing controls. Conclusions: This study provides evidence of the joint maturation of structural and functional brain connections in typical development across late childhood to mid-adolescence, particularly in regions that support cognitive maturation. Findings also suggest that children with ADHD exhibit different patterns of structure-function coupling, suggesting atypical patterns of coordinated white matter and functional connectivity development predominantly in the regions overlapping with the default mode network, salience network and dorsal attention network during late childhood to mid-adolescence.
Uncovering the neuroanatomical correlates of cognitive, affective and conative theory of mind in paediatric traumatic brain injury: a neural systems perspective
Publisher: Oxford University Press (OUP)
Date: 15-05-2017
DOI: 10.1093/SCAN/NSX066
Visuospatial processing and the function of prefrontal-parietal networks in autism spectrum disorders: A functional MRI study
Publisher: American Psychiatric Association Publishing
Date: 08-2006
DOI: 10.1176/AJP.2006.163.8.1440
Abstract: In iduals with autism spectrum disorders typically have normal visuospatial abilities but impaired executive functioning, particularly in abilities related to working memory and attention. The aim of this study was to elucidate the functioning of frontoparietal networks underlying spatial working memory processes during mental rotation in persons with autism spectrum disorders. Seven adolescent males with normal IQ with an autism spectrum disorder and nine age- and IQ-matched male comparison subjects underwent functional magnetic resonance imaging scans while performing a mental rotation task. The autism spectrum disorders group showed less activation in lateral and medial premotor cortex, dorsolateral prefrontal cortex, anterior cingulate gyrus, and caudate nucleus. The finding of less activation in prefrontal regions but not in parietal regions supports a model of dysfunction of frontostriatal networks in autism spectrum disorders.
Consortium neuroscience of attention deficit/hyperactivity disorder and autism spectrum disorder: The ENIGMA adventure
Publisher: Wiley
Date: 18-05-2020
DOI: 10.1002/HBM.25029
Abstract: Neuroimaging has been extensively used to study brain structure and function in in iduals with attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) over the past decades. Two of the main shortcomings of the neuroimaging literature of these disorders are the small s le sizes employed and the heterogeneity of methods used. In 2013 and 2014, the ENIGMA‐ADHD and ENIGMA‐ASD working groups were respectively, founded with a common goal to address these limitations. Here, we provide a narrative review of the thus far completed and still ongoing projects of these working groups. Due to an implicitly hierarchical psychiatric diagnostic classification system, the fields of ADHD and ASD have developed largely in isolation, despite the considerable overlap in the occurrence of the disorders. The collaboration between the ENIGMA‐ADHD and ‐ASD working groups seeks to bring the neuroimaging efforts of the two disorders closer together. The outcomes of case–control studies of subcortical and cortical structures showed that subcortical volumes are similarly affected in ASD and ADHD, albeit with small effect sizes. Cortical analyses identified unique differences in each disorder, but also considerable overlap between the two, specifically in cortical thickness. Ongoing work is examining alternative research questions, such as brain laterality, prediction of case–control status, and anatomical heterogeneity. In brief, great strides have been made toward fulfilling the aims of the ENIGMA collaborations, while new ideas and follow‐up analyses continue that include more imaging modalities (diffusion MRI and resting‐state functional MRI), collaborations with other large databases, and s les with dual diagnoses.
Associations Between ADHD, Sleep Problems, and Mental Health Symptoms in Adolescents
Publisher: SAGE Publications
Date: 17-02-2023
DOI: 10.1177/10870547231155871
Abstract: This study examined associations between objective and subjective sleep parameters, and mental health symptoms (internalizing symptoms, externalizing symptoms, and irritability) and whether these relationships differed for adolescents with and without ADHD. Participants were 373 adolescents aged 10 to 19 years ( M = 13.21, SD = 2.37). Sleep was measured both via actigraphy and self- and parent-report scales. Mental health symptoms were measured via a range of validated measures. Few relationships were detected when examining actigraphy variables. Subjective sleep parameters were associated with almost all mental health variables. Some relationships were moderated by ADHD status, generally consistent with stronger relationships between subjective sleep quality and mental health in the non-ADHD group. Sleep problems, particularly subjective difficulties, are associated with a range of mental health outcomes, regardless of the presence of ADHD. Sleep problems may be a beneficial intervention target for adolescents experiencing mental health issues.
Structural development of the basal ganglia in attention deficit hyperactivity disorder: A diffusion tensor imaging study
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.PSCYCHRESNS.2008.07.003
Abstract: One of the most consistently reported brain regions of structural and functional difference in attention deficit hyperactivity disorder (ADHD) is the basal ganglia, particularly the caudate nucleus. Examining the structural organization of the basal ganglia in ADHD is important because it is the center of wider fronto-striatal networks, reported to be dysfunctional in ADHD. Fifteen right-handed 8- to 18-year-old males with ADHD-combined type and 15 right-handed, age- and performance IQ-matched healthy males underwent diffusion tensor imaging. Caudate, putamen and thalamus were manually identified as regions of interest (ROIs) and tested for differences in fractional anisotropy and mean diffusivity. Measures of fractional anisotropy (FA) showed the expected increase with age within the whole-brain volume and within putamen and thalamus ROIs for both ADHD and control groups. In the caudate nucleus, however, developmental changes in FA with age were significantly different between ADHD and control groups. This study shows that the developmental trajectory of micro-structural organization within the caudate nucleus is different in children with ADHD compared with controls over ages 8-18 years. We suggest that the difference in developmental trajectories arises predominantly during mid-late adolescence and may reflect a developmental delay that begins to normalise over this critical late adolescent age.
Categorical and dimensional approaches to the developmental relationship between ADHD and irritability
Publisher: Wiley
Date: 11-05-2023
DOI: 10.1111/JCPP.13818
Abstract: Attention deficit hyperactivity disorder (ADHD) and irritability commonly co‐occur, and follow similar developmental trajectories from childhood to adolescence. Understanding of the developmental relationship between these co‐occurrences is limited. This study provides a longitudinal assessment of how ADHD diagnostic status and symptom patterns predict change in irritability. A community s le of 337 participants (45.2% ADHD), recruited for the Childhood Attention Project, completed the Affective Reactivity Index (ARI) to measure irritability at baseline (mean age 10.5 years) and follow‐up after 18‐months. Latent change score models were used to assess how (a) baseline ADHD vs. control group status, (b) baseline symptom domain (inattention, hyperactivity–impulsivity) and (c) longitudinal change in ADHD symptom severity predicted change in irritability. Irritability was significantly higher among the ADHD group than controls however, change in irritability over time did not differ between groups. When assessed across the entire cohort, change in irritability was predicted by higher symptom count in the hyperactive–impulsive domain, but not the inattentive domain. Greater declines in ADHD symptoms over time significantly predicted greater declines in irritability. Baseline ADHD symptom severity was found to significantly predict change in irritability however, baseline irritability did not significantly predict change in ADHD symptoms. ADHD symptoms—particularly hyperactive–impulsive symptoms—predict the degree and trajectory of irritability during childhood and adolescence, even when symptoms are below diagnostic thresholds. The use of longitudinal, dimensional and symptom domain‐specific measures provides additional insight into this relationship.
Value of Self‐Disclosure to Parents and Peers During Adolescence
Publisher: Wiley
Date: 27-09-2023
DOI: 10.1111/JORA.12803
Abstract: Self‐disclosure is a crucial part of developing close interpersonal relationships during adolescence. In particular, sharing information with a greater depth of intimacy is thought to strengthen social bonds and thus support mental health. The current study investigated the value for different depths of self‐disclosures to close others (mothers and best friends) during adolescence and its association with mental health and well‐being. Fifty‐four girls (11.0–15.9 years) completed a forced‐choice monetary paradigm to assess value for self‐disclosures and questionnaires on mental health. Participants significantly valued (i.e., forfeited monetary reward) for disclosures to both mothers and best friends, although intimate disclosures were more “costly” than superficial disclosures. Greater value for intimate self‐disclosures to mothers was also associated with better mental health and well‐being.
Examination of Cerebellar Grey-Matter Volume in Children with Neurodevelopmental Disorders: a Coordinated Analysis Using the ACAPULCO Algorithm
Publisher: Springer Science and Business Media LLC
Date: 09-12-2022
Research Review: Language problems in children with Attention-Deficit Hyperactivity Disorder – a systematic meta-analytic review
Publisher: Wiley
Date: 10-02-2017
DOI: 10.1111/JCPP.12688
Abstract: Children with Attention-Deficit Hyperactivity Disorder (ADHD) appear to have a higher risk of language problems compared with typically developing children, although the types of language problems experienced are less clear. This review aims to establish the types of language problems experienced by children with ADHD according to systematically reviewed literature and determine the empirical evidence for language problems in children with ADHD compared with non-ADHD controls. A standardized search protocol was used on databases: CINAHL, Medline, and PsychINFO. We identified studies with the following inclusion criteria: (a) confirmed ADHD status at the time of the study, (b) inclusion of a non-ADHD control group, (c) use of a validated language measure, and (d) age ≤ 18. t-Tests, Pearson's r, and Hedges g effect sizes (ES) were calculated using summary statistics. Random effects meta-analyses were conducted for the language domain suitable for analysis. Publication bias was investigated using both the trim and fill and p-curve techniques. Twenty-one studies were included in the systematic review (ADHD = 1,209 Control = 1,101), within which 60 of 68 separate analyses found significant differences between the ADHD and control group on the language measures (p < .05). Follow-up meta-analyses found evidence for large deficits in the ADHD groups overall (10/11 studies met p < .05 weighted mean ES [WMES]: 1.04) expressive (10/10 met p < .05 WMES: 1.23) receptive (12/14 met p < .05 WMES: 0.97), and pragmatic language (4/4 studies met p < .05 WMES: 0.98) compared with controls. This study demonstrates that children with ADHD have poorer performance on measures of overall, expressive, receptive, and pragmatic language compared with controls. A screening of language functioning may be a valuable addition to the assessment of ADHD.
Does the Mind Wander When the Brain Takes a Break? Local Sleep in Wakefulness, Attentional Lapses and Mind-Wandering
Publisher: Frontiers Media SA
Date: 13-09-2019
Age, sex, and puberty related development of the corpus callosum: a multi-technique diffusion MRI study
Publisher: Springer Science and Business Media LLC
Date: 05-04-2017
Understanding autism spectrum disorder and social functioning in children with neurofibromatosis type 1: protocol for a cross-sectional multimodal study
Publisher: BMJ
Date: 09-2019
DOI: 10.1136/BMJOPEN-2019-030601
Abstract: 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. 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. This study has hospital ethics approval and the results will be disseminated through peer-reviewed publications and international conferences.
Examining the associations between attention‐deficit/hyperactivity disorder, sleep problems, and other mental health conditions in adolescents
Publisher: Wiley
Date: 12-03-2023
DOI: 10.1111/JSR.13830
Abstract: Adolescents with attention‐deficit/hyperactivity disorder (ADHD) often experience greater sleep difficulties compared to those without. However, findings are mixed, and other mental health conditions are often overlooked. This study aimed to examine the relationship between sleep problems, ADHD, and other mental health conditions in a s le of adolescents. Data from 373 adolescents aged 10–19 years was used as part of the wider ‘Healthy Brain Network’ study, which targets children and adolescents experiencing mental health and neurodevelopmental difficulties. Mental health conditions were assessed via a comprehensive assessment. Sleep was measured by self‐ and parent‐report, as well as via up to a month of actigraphy data. Actigraphy data were analysed using mixed‐methods modelling, while subjective sleep data were analysed using multiple regression. Subjectively‐reported sleep was generally worse in adolescents who had ADHD and other mental health conditions compared to those with ADHD but no other conditions. There were no associations between ADHD status and objective sleep measures or self‐reported measures, but a significant association was found between ADHD status and parent‐reported sleep difficulties, even when accounting for other conditions. Parent‐reported sleep problems were associated not only with ADHD, but also with anxiety, depression, and externalising disorders. The strength of association between ADHD and sleep problems is potentially not as strong as previously thought when considering the role of other mental health conditions. Clinicians should consider the role of other mental health conditions when sleep problems are present, and vice versa. The study also highlights the importance of comprehensive, multi‐informant assessment of mental health conditions, including sleep.
The effects of puberty and its hormones on subcortical brain development
Publisher: Elsevier BV
Date: 08-2021
Evidence accumulation during perceptual decisions in humans varies as a function of dorsal frontoparietal organization.
Publisher: Springer Science and Business Media LLC
Date: 20-04-2020
Cavum septum pellucidum in pediatric traumatic brain injury
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.PSCYCHRESNS.2013.03.001
Abstract: The cavum septum pellucidum (CSP) is a fluid-filled cavity in the thin midline structure of the septum pellucidum. The CSP has been linked to several neurodevelopmental disorders, but it also occurs as a result of head injury. The aims were to assess the presence and characterization of the CSP in youth with traumatic brain injury (TBI), to assess whether injury severity or IQ measures were related to CSP size, and to examine brain morphometry changes associated with the CSP size. Ninety-eight survivors of TBI and 34 control children underwent magnetic resonance imaging (MRI). Numerous methods were used to define the presence and characterization of the CSP including length, classification of abnormally large CSP, rating of the CSP, and volume. There was no difference in presence of CSP between TBI patients and controls however, there was larger and more severely graded CSP in the patient group. Size of the CSP correlated positively with injury severity, and regions that correlated most significantly with CSP size were the right entorhinal cortex and bilateral hippoc us. Characterizing the CSP and related brain changes may provide important information concerning disturbances seen after a TBI.
Altered structural connectivity in ADHD: a network based analysis
Publisher: Springer Science and Business Media LLC
Date: 11-06-2017
Associations between sleep, daytime sleepiness and functional outcomes in adolescents with ADHD
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.SLEEP.2021.08.021
Abstract: Adolescents with attention-deficit/hyperactivity disorder (ADHD) experience greater difficulties in the domains of sleep, daytime sleepiness, and functioning compared to their peers. However, the relationship between these domains has not been fully elucidated. This study aimed to examine the relationship between sleep problems (including daytime sleepiness), ADHD severity, and functional outcomes (irritability, sluggish cognitive tempo, homework difficulties, and substance use) in a s le of adolescents with ADHD. Eighty-two adolescents (13-17 years) and their families participated in the study. Sleep was measured by both adolescent and parent-report. Adolescent irritability and sluggish cognitive tempo were reported by both adolescents and parents, while other variables were reported by a single reporter (homework difficulties - parent ADHD severity - parent substance use - adolescent). Analyses controlled for demographic factors and internalising and externalising comorbidities. A weak relationship was found between adolescent-reported sleep problems and daytime sleepiness, which became non-significant in adjusted analyses (β = -0.19, p = 0.115). In adjusted analyses, there was an association between adolescent-reported sleep problems and adolescent-reported irritability (β = -0.27, p = 0.023) as well as between adolescent-reported daytime sleepiness and parent-reported sluggish cognitive tempo (β = 0.28, p = 0.033). In adjusted analyses, parent-reported adolescent sleep problems were associated with ADHD severity (β = 0.54, p = <0.001), parent-reported sluggish cognitive tempo (β = 0.64, p = <0.001), both reporters of irritability (parent-report: β = 0.32, p = 0.004 adolescent-report: β = 0.29, p = 0.022), and homework problems (β = 0.37, p = 0.003). Parent-reported daytime sleepiness was associated with parent-reported sluggish cognitive tempo (β = 0.34, p = 0.024). This study demonstrates the importance of a holistic assessment of adolescents with ADHD, not only focusing on symptomatology but also on sleep problems and functional outcomes. The importance of multi-informant assessment of sleep problems is also reinforced.
Fronto-parietal white matter microstructure associated with working memory performance in children with ADHD
Publisher: Elsevier BV
Date: 09-2023
Epigenetics and ADHD
Publisher: Springer International Publishing
Date: 2022
The Role of Sleep in the Relationship Between ADHD Symptoms and Stop Signal Task Performance.
Publisher: SAGE Publications
Date: 24-07-2020
Abstract: Background: ADHD commonly occurs with sleep problems and secondary cognitive impairments such as inhibitory control. Sleep problems may explain attentional lapses and inhibition performance variability in children with ADHD. This study applied Bayesian analyses to examine the relationship between ADHD symptoms, sleep problems, and inhibition. Methods: Participants included 73 children with ADHD and 73 non-ADHD controls, aged 10.5 to 13.5 years. The Stop Signal Task measured inhibition. Sleep problems were measured with the Adolescent Sleep Wake Scale and parent-report. Results: ADHD symptoms are associated with sleep problems and reaction time variability, however, sleep problems accounted for more variance in inhibition performance than both hyperactive and inattentive symptoms. Conclusion: Sleep problems account for inhibition performance over and above ADHD symptom severity in children with and without ADHD diagnoses. This suggests clinical utility in assessing sleep in children with manifestations of ADHD, and interventions targeting sleep problems concurrently with behavioral symptoms. This further adds to the discussion on overdiagnosis of ADHD due to behavioral presentations of underlying sleep disorders. Treatment for phenotypes of ADHD could be enhanced by targeting sleep problems, in addition to inhibition deficits and attentional lapses.
Meta-analysis of the neural correlates of vigilant attention in children and adolescents
Publisher: Elsevier BV
Date: 11-2020
“Puberty age gap”: New method of assessing pubertal timing and its association with mental health problems
Publisher: Cold Spring Harbor Laboratory
Date: 16-05-2022
DOI: 10.1101/2022.05.13.22275069
Abstract: Puberty is linked to mental health problems during adolescence, and in particular, the timing of puberty is thought to be an important risk factor. This study developed a new measure of pubertal timing using multiple pubertal features and nonlinear associations with age and investigated its association with mental health problems. Using the Adolescent Brain Cognitive Development (ABCD) cohort, we implemented three models of pubertal timing by predicting chronological age from i) observed physical development, ii) hormones (testosterone and dehydroepiandrosterone [DHEA]), and iii) a combination of the two, using a supervised machine learning method (n ∼9,900). Accuracy of the new models, and their associations with mental health problems were evaluated. The new pubertal timing measure performed better in capturing age variance compared to a commonly used method, and the physical measure accounted for more variance in mental health, such that earlier pubertal timing was associated with higher symptoms. This study demonstrates the utility for a new model of pubertal timing and suggests that physical maturation may play a predominant role in predicting mental health problems in early adolescence.
Adolescents with ADHD and co-occurring motor difficulties show a distinct pattern of maturation within the corticospinal tract from those without: A longitudinal fixel-based study
Publisher: Wiley
Date: 22-08-2023
DOI: 10.1002/HBM.26462
Abstract: It is well documented that attention‐deficit hyperactivity disorder (ADHD) often presents with co‐occurring motor difficulties. However, little is known about the biological mechanisms that explain compromised motor skills in approximately half of those with ADHD. To provide insight into the neurobiological basis of poor motor outcomes in ADHD, this study profiled the development of white matter organization within the cortico‐spinal tract (CST) in adolescents with ADHD with and without co‐occurring motor problems, as well as non‐ADHD control children with and without motor problems. Participants were 60 children aged 9–14 years, 27 with a history of ADHD and 33 controls. All underwent high‐angular resolution diffusion MRI data at up to three time points (115 in scans total). We screened for motor impairment in all participants at the third time point (≈14 years) using the Developmental Coordination Disorder Questionnaire (DCD‐Q). Following pre‐processing of diffusion MRI scans, fixel‐based analysis was performed, and the bilateral CST was delineated using TractSeg. Mean fiber density (FD) and fiber cross‐section (FC) were extracted for each tract at each time‐point. To investigate longitudinal trajectories of fiber development, linear mixed models were performed separately for the left and right CST, controlling for nuisance variables. To examine possible variations in fiber development between groups, we tested whether the inclusion of group and the interaction between age and group improved model fit. At ≈10 years, those with ADHD presented with lower FD within the bilateral CST relative to controls, irrespective of their prospective motor status. While these microstructural abnormalities persisted into adolescence for in iduals with ADHD and co‐occurring motor problems, they resolved for those with ADHD alone. Divergent maturational pathways of motor networks (i.e., the CST) may, at least partly, explain motor problems in iduals with ADHD.
Persistence of disruptive mood dysregulation disorder in children with attention-deficit/hyperactivity disorder.
Publisher: Elsevier BV
Date: 2020
Right parietal dysfunction in children with attention deficit hyperactivity disorder, combined type: a functional MRI study
Publisher: Springer Science and Business Media LLC
Date: 05-2007
Abstract: Attention deficit hyperactivity disorder, combined type (ADHD-CT) is associated with spatial working memory deficits. These deficits are known to be subserved by dysfunction of neural circuits involving right prefrontal, striatal and parietal brain regions. This study determines whether decreased right prefrontal, striatal and parietal activation with a mental rotation task shown in adolescents with ADHD-CT is also evident in children with ADHD-CT. A cross-sectional study of 12 pre-pubertal, right-handed, 8-12-year-old boys with ADHD-CT and 12 pre-pubertal, right-handed, performance IQ-matched, 8-12-year-old healthy boys, recruited from local primary schools, was completed. Participants underwent functional magnetic resonance imaging while performing a mental rotation task that requires spatial working memory. The two groups did not differ in their accuracy or response times for the mental rotation task. The ADHD-CT group showed significantly less activation in right parieto-occipital areas (cuneus and precuneus, BA 19), the right inferior parietal lobe (BA 40) and the right caudate nucleus. Our findings with a child cohort confirm previous reports of right striatal-parietal dysfunction in adolescents with ADHD-CT. This dysfunction suggests a widespread maturational deficit that may be developmental stage independent.
Reduced fine motor competence in children with ADHD is associated with atypical microstructural organization within the superior longitudinal fasciculus.
Publisher: Springer Science and Business Media LLC
Date: 24-04-2020
White-matter abnormalities in attention deficit hyperactivity disorder: A diffusion tensor imaging study
Publisher: Wiley
Date: 23-12-2009
DOI: 10.1002/HBM.20703
Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium
Publisher: Proceedings of the National Academy of Sciences
Date: 15-05-2018
Abstract: Left–right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population and how biological factors such as age, sex, and genetic variation affect these asymmetries. Here, we describe by far the largest-ever study of cerebral cortical asymmetry, based on data from 17,141 participants. We found a global anterior–posterior “torque” pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an online resource that will serve future studies of human brain anatomy in health and disease.
The emergence of age-dependent social cognitive deficits after generalized insult to the developing brain: A longitudinal prospective analysis using susceptibility-weighted imaging
Publisher: Wiley
Date: 23-12-2015
DOI: 10.1002/HBM.22729
Brain extraction using the watershed transform from markers
Publisher: Frontiers Media SA
Date: 2013
Dusty Starbursts Masquerading as Ultra-high Redshift Galaxies in JWST CEERS Observations
Publisher: American Astronomical Society
Date: 25-01-2023
Abstract: Lyman-break galaxy (LBG) candidates at z ≳ 10 are rapidly being identified in James Webb Space Telescope (JWST)/NIRCam observations. Due to the (redshifted) break produced by neutral hydrogen absorption of rest-frame UV photons, these sources are expected to drop out in the bluer filters while being well detected in redder filters. However, here we show that dust-enshrouded star-forming galaxies at lower redshifts ( z ≲ 7) may also mimic the near-infrared (near-IR) colors of z 10 LBGs, representing potential contaminants in LBG candidate s les. First, we analyze CEERS-DSFG-1, a NIRCam dropout undetected in the F115W and F150W filters but detected at longer wavelengths. Combining the JWST data with (sub)millimeter constraints, including deep NOEMA interferometric observations, we show that this source is a dusty star-forming galaxy (DSFG) at z ≈ 5.1. We also present a tentative 2.6 σ SCUBA-2 detection at 850 μ m around a recently identified z ≈ 16 LBG candidate in the same field and show that, if the emission is real and associated with this candidate, the available photometry is consistent with a z ∼ 5 dusty galaxy with strong nebular emission lines despite its blue near-IR colors. Further observations on this candidate are imperative to mitigate the low confidence of this tentative submillimeter emission and its positional uncertainty. Our analysis shows that robust (sub)millimeter detections of NIRCam dropout galaxies likely imply z ∼ 4–6 redshift solutions, where the observed near-IR break would be the result of a strong rest-frame optical Balmer break combined with high dust attenuation and strong nebular line emission, rather than the rest-frame UV Lyman break. This provides evidence that DSFGs may contaminate searches for ultra-high redshift LBG candidates from JWST observations.
Effects of dietary omega-3 intake on vigilant attention and resting-state functional connectivity in neurotypical children and adolescents
Publisher: Informa UK Limited
Date: 09-08-2022
A longitudinal analysis of puberty-related cortical development
Publisher: Cold Spring Harbor Laboratory
Date: 06-11-2020
DOI: 10.1101/2020.11.05.370460
Abstract: The brain undergoes extensive structural changes during adolescence, concurrent to puberty-related physical and hormonal changes. While animal research suggests these biological processes are related to one another, our knowledge of brain development in humans is largely based on age-related processes. Thus, the current study characterized puberty-related changes in human brain structure, by combining data from two longitudinal neuroimaging cohorts. Beyond normative changes in cortical thickness, we examined whether in idual differences in the rate of pubertal maturation (or “pubertal tempo”) was associated with variations in cortical trajectories. Participants (N = 192 scans = 366) completed up to three waves of MRI assessments between 8.5 and 14.5 years of age, as well as questionnaire assessments of pubertal stage at each wave. Generalized additive mixture models were used to characterize trajectories of cortical development. Results revealed widespread linear puberty-related changes across much of the cortex. Many of these changes, particularly within the frontal and parietal cortices, were independent of age-related development. Males exhibiting faster pubertal tempo demonstrated greater thinning in the precuneus and frontal cortices than same-aged and -sex peers. Findings suggest that the unique influence of puberty on cortical development may be more extensive than previously identified, and also emphasize important in idual differences in the coupling of these developmental processes.
Childhood conduct problems are associated with reduced white matter fibre density and morphology
Publisher: Cold Spring Harbor Laboratory
Date: 31-05-2020
DOI: 10.1101/2020.05.29.123364
Abstract: Childhood conduct problems are an important public health issue as these children are at-risk of adverse outcomes. Studies using diffusion Magnetic Resonance Imaging (dMRI) have found that conduct problems in adults are characterised by abnormal white-matter microstructure within a range of white matter pathways underpinning socio-emotional processing, while evidence within children and adolescents has been less conclusive based on non-specific diffusion tensor imaging metrics. Fixel-based analysis (FBA) provides measures of fibre density and morphology that are more sensitive to developmental changes in white matter microstructure. The current study used FBA to investigate whether childhood conduct problems were related both cross-sectionally and longitudinally to microstructural alterations within the fornix, inferior fronto-occipital fasciculus (IFOF), inferior longitudinal fasciculus (ILF), superior longitudinal fasciculus (SLF), and the uncinate fasciculus (UF). dMRI data was obtained for 130 children across two time-points in a community s le with high levels of externalising difficulties (age: time-point 1 = 9.47 – 11.86 years, time-point 2 = 10.67 −13.45 years). Conduct problems were indexed at each time-point using the Conduct Problems subscale of the parent-informant Strengths and Difficulties Questionnaire (SDQ). Conduct problems were related to lower fibre density in the fornix at both time-points, and in the ILF at time-point 2. We also observed lower fibre cross-section in the UF at time-point 1. The change in conduct problems did not predict longitudinal changes in white-matter microstructure across time-points. The current study suggests that childhood conduct problems are related to reduced fibre-specific microstructure within white matter fibre pathways implicated in socio-emotional functioning.
No Evidence of a Difference in Susceptibility-Weighted Imaging Lesion Burden or Functional Network Connectivity between Children with Typical and Delayed Recovery Two Weeks Post-Concussion
Publisher: Mary Ann Liebert Inc
Date: 15-09-2021
Abstract: Susceptibility weighted imaging (SWI) and resting state functional magnetic resonance imaging have been highlighted as two novel neuroimaging modalities that have been underutilized when attempting to predict whether a child with concussion will recover normally or have a delayed recovery course. This study aimed to investigate whether there was a difference between children who recover normally from a concussion and children with delayed recovery in terms of SWI lesion burden and resting state network makeup. Forty-one children who presented to the emergency department of a tertiary level pediatric hospital with concussion participated in this study as a part of a larger prospective, longitudinal observational cohort study into concussion assessment and recovery. Children underwent neuroimaging 2 weeks post-injury and were classified as either normally recovering (
Atypical neuronal activation during a spatial working memory task in 13-year-old very preterm children
Publisher: Wiley
Date: 20-09-2017
DOI: 10.1002/HBM.23820
Executive function and attention in children and adolescents with depressive disorders: a systematic review
Publisher: Springer Science and Business Media LLC
Date: 30-01-2015
DOI: 10.1007/S00787-015-0675-7
Abstract: Numerous studies have shown that Major Depressive Disorder (MDD) in adults is associated with deficits in cognitive control. Particularly, impairment on executive function (EF) tasks has been observed. Research into EF deficits in children and adolescents with MDD has reported mixed results and it is currently unclear whether paediatric MDD is characterised by impairments in EF and attention. PsycInfo, Scopus and Medline were systematically searched to identify all studies that have investigated EF and attention in paediatric depressive disorders between 1994 and 2014. 33 studies meeting inclusion/exclusion criteria were identified. While across different domains of EF some studies identified a deficit in the clinical group, the majority of studies failed to find deficits in response inhibition, attentional set shifting, selective attention, verbal working memory, and verbal fluency. More research is needed to clarify the relationship between depressive disorders in children and adolescents and spatial working memory processing, sustaining attention, planning, negative attentional bias and measures of 'hot' EF. There is little support for EF deficits in paediatric depression. However, there are numerous methodological problems that may account for null findings. Alternatively, chronicity and/or severity of symptoms may explain discrepancies between cognitive deficits in adult and paediatric MDD. Recommendations for future studies are discussed.
Longitudinal patterns of white matter fibre density and morphology in children are associated with age and pubertal stage.
Publisher: Elsevier BV
Date: 10-2020
Developmental brain changes during puberty and associations with mental health problems
Publisher: Elsevier BV
Date: 04-2023
White matter organization in developmental coordination disorder: A pilot study exploring the added value of constrained spherical deconvolution
Publisher: Elsevier BV
Date: 2019
Examining Microstructural White Matter Differences between Children with Typical and Those with Delayed Recovery Two Weeks Post-Concussion
Publisher: Mary Ann Liebert Inc
Date: 06-2020
Abstract: Delayed recovery from concussion can dramatically affect a child's social, emotional, and educational development, yet little is known about what causes some children to recover faster than others. The contribution of white matter disruption in children with delayed recovery has been hypothesized, but findings are limited by methodological issues such as: small heterogeneous s les, bias toward children with delayed recovery, and inconsistencies in timing of brain imaging, both within and between studies. The aim of the present study was to assess diffusion neuroimaging correlates of delayed recovery post-concussion in children. A prospective, longitudinal, observational cohort study was conducted at a statewide tertiary pediatric hospital. Forty-three children who presented to the emergency department (ED) with concussion (defined according to the Zurich/Berlin Consensus Statement on Concussion in Sport) underwent magnetic resonance imaging (MRI) at a 2 weeks post-injury and were classified as either normally recovering (
Longitudinal developmental trajectories of inhibition and white-matter maturation of the fronto-basal-ganglia circuits
Publisher: Elsevier BV
Date: 12-2022
OSARI, an Open-Source Anticipated Response Inhibition Task
Publisher: Springer Science and Business Media LLC
Date: 09-11-2021
DOI: 10.3758/S13428-021-01680-9
Abstract: The stop-signal paradigm has become ubiquitous in investigations of inhibitory control. Tasks inspired by the paradigm, referred to as stop-signal tasks, require participants to make responses on go trials and to inhibit those responses when presented with a stop-signal on stop trials. Currently, the most popular version of the stop-signal task is the ‘choice-reaction’ variant, where participants make choice responses, but must inhibit those responses when presented with a stop-signal. An alternative to the choice-reaction variant of the stop-signal task is the ‘anticipated response inhibition’ task. In anticipated response inhibition tasks, participants are required to make a planned response that coincides with a predictably timed event (such as lifting a finger from a computer key to stop a filling bar at a predefined target). Anticipated response inhibition tasks have some advantages over the more traditional choice-reaction stop-signal tasks and are becoming increasingly popular. However, currently, there are no openly available versions of the anticipated response inhibition task, limiting potential uptake. Here, we present an open-source, free, and ready-to-use version of the anticipated response inhibition task, which we refer to as the OSARI (the Open-Source Anticipated Response Inhibition) task.
Associations Between Limbic System White Matter Structure and Socio-Emotional Functioning in Children with ADHD + ASD
Publisher: Springer Science and Business Media LLC
Date: 11-10-2020
Recovery of White Matter following Pediatric Traumatic Brain Injury Depends on Injury Severity
Publisher: Mary Ann Liebert Inc
Date: 15-02-2017
Abstract: Previous studies in pediatric traumatic brain injury (TBI) have been variable in describing the effects of injury severity on white-matter development. The present study used diffusion tensor imaging to investigate prospective sub-acute and longitudinal relationships between early clinical indicators of injury severity, diffusion metrics, and neuropsychological outcomes. Pediatric patients with TBI underwent magnetic resonance imaging (MRI) (n = 78, mean [M] = 10.56, standard deviation [SD] = 2.21 years) at the sub-acute stage after injury (M = 5.55, SD = 3.05 weeks), and typically developing children were also included and imaged (n = 30, M = 10.60, SD = 2.88 years). A sub-set of the patients with TBI (n = 15) was followed up with MRI 2 years post-injury. Diffusion MRI images were acquired at sub-acute and 2-year follow-up time points and analyzed using Tract-Based Spatial Statistics. At the sub-acute stage, mean diffusivity and axial diffusivity were significantly higher in the TBI group compared with matched controls (p < 0.05). TBI severity significantly predicted diffusion profiles at the sub-acute and 2-year post-injury MRI. Patients with more severe TBI also exhibited poorer information processing speed at 6-months post-injury, which in turn correlated with their diffusion metrics. These findings highlight that the severity of the injury not only has an impact on white-matter microstructure, it also impacts its recovery over time. Moreover, findings suggest that sub-acute microstructural changes may represent a useful prognostic marker to identify children at elevated risk for longer term deficits.
A Neuroethics Framework for the Australian Brain Initiative
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.NEURON.2019.01.004
Abstract: Neuroethics is central to the Australian Brain Initiative's aim to sustain a thriving and responsible neurotechnology industry. Diverse and inclusive community and stakeholder engagement and a trans-disciplinary approach to neuroethics will be key to the success of the Australian Brain Initiative.
Analysis of structural brain asymmetries in attention‐deficit/hyperactivity disorder in 39 datasets
Publisher: Wiley
Date: 22-03-2021
DOI: 10.1111/JCPP.13396
Abstract: Some studies have suggested alterations of structural brain asymmetry in attention‐deficit/hyperactivity disorder (ADHD), but findings have been contradictory and based on small s les. Here, we performed the largest ever analysis of brain left‐right asymmetry in ADHD, using 39 datasets of the ENIGMA consortium. We analyzed asymmetry of subcortical and cerebral cortical structures in up to 1,933 people with ADHD and 1,829 unaffected controls. Asymmetry Indexes (AIs) were calculated per participant for each bilaterally paired measure, and linear mixed effects modeling was applied separately in children, adolescents, adults, and the total s le, to test exhaustively for potential associations of ADHD with structural brain asymmetries. There was no evidence for altered caudate nucleus asymmetry in ADHD, in contrast to prior literature. In children, there was less rightward asymmetry of the total hemispheric surface area compared to controls ( t = 2.1, p = .04). Lower rightward asymmetry of medial orbitofrontal cortex surface area in ADHD ( t = 2.7, p = .01) was similar to a recent finding for autism spectrum disorder. There were also some differences in cortical thickness asymmetry across age groups. In adults with ADHD, globus pallidus asymmetry was altered compared to those without ADHD. However, all effects were small (Cohen’s d from −0.18 to 0.18) and would not survive study‐wide correction for multiple testing. Prior studies of altered structural brain asymmetry in ADHD were likely underpowered to detect the small effects reported here. Altered structural asymmetry is unlikely to provide a useful biomarker for ADHD, but may provide neurobiological insights into the trait.
Longitudinal maturation of resting state networks: Relevance to sustained attention and attention deficit/hyperactivity disorder
Publisher: Springer Science and Business Media LLC
Date: 08-06-2022
DOI: 10.3758/S13415-022-01017-9
Abstract: The transition from childhood to adolescence involves important neural function, cognition, and behavior changes. However, the links between maturing brain function and sustained attention over this period could be better understood. This study examined typical changes in network functional connectivity over childhood to adolescence, developmental differences in attention deficit/hyperactivity disorder (ADHD), and how functional connectivity might underpin variability in sustained attention development in a longitudinal s le. A total of 398 resting state scans were collected from 173 children and adolescents (88 ADHD, 85 control) at up to three timepoints across ages 9-14 years. The effects of age, sex, and diagnostic group on changes in network functional connectivity were assessed, followed by relationships between functional connectivity and sustained attention development using linear mixed effects modelling. The ADHD group displayed greater decreases in functional connectivity between salience and visual networks compared with controls. Lower childhood functional connectivity between the frontoparietal and several brain networks was associated with more rapid sustained attention development, whereas frontoparietal to dorsal attention network connectivity related to attention trajectories in children with ADHD alone. Brain network segregation may increase into adolescence as predicted by key developmental theories however, participants with ADHD demonstrated altered developmental trajectories between salience and visual networks. The segregation of the frontoparietal network from other brain networks may be a mechanism supporting sustained attention development. Frontoparietal to dorsal attention connectivity can be a focus for further work in ADHD.
Epigenetic Influences on Neurodevelopment at 11 Years of Age: Protocol for the Longitudinal Peri/Postnatal Epigenetic Twins Study at 11 Years of Age (PETS@11)
Publisher: Cambridge University Press (CUP)
Date: 12-2019
DOI: 10.1017/THG.2019.120
Abstract: Neurodevelopment is sensitive to genetic and pre ostnatal environmental influences. These effects are likely mediated by epigenetic factors, yet current knowledge is limited. Longitudinal twin studies can delineate the link between genetic and environmental factors, epigenetic state at birth and neurodevelopment later in childhood. Building upon our study of the Peri ostnatal Epigenetic Twin Study (PETS) from gestation to 6 years of age, here we describe the PETS 11-year follow-up in which we will use neuroimaging and cognitive testing to examine the relationship between early-life environment, epigenetics and neurocognitive outcomes in mid-childhood. Using a within-pair twin model, the primary aims are to (1) identify early-life epigenetic correlates of neurocognitive outcomes (2) determine the developmental stability of epigenetic effects and (3) identify modifiable environmental risk factors. Secondary aims are to identify factors influencing gut microbiota between 6 and 11 years of age to investigate links between gut microbiota and neurodevelopmental outcomes in mid-childhood. Approximately 210 twin pairs will undergo an assessment at 11 years of age. This includes a direct child cognitive assessment, multimodal magnetic resonance imaging, biological s ling, anthropometric measurements and a range of questionnaires on health and development, behavior, dietary habits and sleeping patterns. Data from complementary data sources, including the National Assessment Program — Literacy and Numeracy and the Australian Early Development Census, will also be sought. Following on from our previous focus on relationships between growth, cardiovascular health and oral health, this next phase of PETS will significantly advance our understanding of the environmental interactions that shape the developing brain.
Prevalence and Predictors of Medication Use in Children with Attention-Deficit/Hyperactivity Disorder: Evidence from a Community-Based Longitudinal Study
Publisher: Mary Ann Liebert Inc
Date: 02-2019
Abstract: To determine, in a community-based s le of primary school-aged children meeting diagnostic criteria for attention-deficit/hyperactivity disorder (ADHD), (1) the proportion of children with ADHD treated with medication (2) predictors of medication use and (3) the association between medication use and psychological service utilization. Grade 1 children with ADHD were recruited through 43 schools in Melbourne, Australia, using a two-stage screening and case confirmation procedure. Parent report of medication treatment, clinician diagnosis, and psychological service use were collected at ages 7 and 10 years. Medication use was analyzed by ADHD subtype. Predictors of medication treatment examined included ADHD symptom severity and persistence, externalizing comorbidities, poor academic performance, and social disadvantage. Unadjusted and adjusted logistic regression were used to identify the predictors of medication status. One hundred seventy-nine children with ADHD were recruited. At baseline, 17.3% had been clinically diagnosed with ADHD, increasing to 37.7% at age 10 years. At baseline, 13.6% were taking ADHD medications, increasing to 25.6% at age 10. Children with the combined and hyperactive-impulsive subtypes were more likely to be taking medication than those with inattentive subtype (age 7: p = 0.002 age 10: p = 0.03). ADHD symptom severity (Conners 3 ADHD Index) at baseline was concurrently and prospectively associated with medication use at both ages (both p = 0.01), and ADHD symptom severity at age 10 was also associated with medication use at age 10 (p = 0.01). Baseline area-level disadvantage was associated with medication use at age 7 (p = 0.04). At 10 years, children receiving medication were more likely, compared with those who were not, to be receiving psychological services (p = 0.001). In this study, only a minority of children meeting diagnostic criteria for ADHD were diagnosed clinically or treated with ADHD medication by age 10. The strongest predictors of medication treatment were ADHD symptom severity and area disadvantage.
Erratum: A Neuroethics Framework for the Australian Brain Initiative (Neuron (2019) 101(3) (365–369), (S0896627319300054), (10.1016/j.neuron.2019.01.004))
Publisher: Elsevier BV
Date: 2020
Methylphenidate Enhances Spontaneous Fluctuations in Reward and Cognitive Control Networks in Children With Attention-Deficit/Hyperactivity Disorder
Publisher: Elsevier BV
Date: 03-2023
Corticolimbic connectivity mediates the relationship between pubertal timing and mental health problems
Publisher: Cold Spring Harbor Laboratory
Date: 14-02-2023
DOI: 10.1101/2023.02.13.528385
Abstract: Undergoing puberty ahead of peers (“earlier pubertal timing”) is an important risk factor for mental health problems during early adolescence. The current study examined pathways between pubertal timing and mental health via connectivity of neural systems implicated in emotional reactivity and regulation (specifically corticolimbic connections) in 9- to 14-year-olds. Research questions were examined in the Adolescent Brain Cognitive Development (ABCD) Study, a large population representative s le in the United States. Linear mixed models examined associations between pubertal timing and resting-state corticolimbic connectivity. Significant connections were examined as potential mediators of the relationship between pubertal timing and mental health (withdrawn depressed and rule-breaking delinquency) problems. Exploratory analyses interrogated whether the family environment moderated neural risk patterns in those undergoing puberty earlier than their peers. Earlier pubertal timing was related to decreased connectivity between limbic structures (bilateral amygdala and right hippoc us) and the cingulo-opercular network (CON), as well as between the left hippoc us and ventral attention network (VAN). Corticolimbic connections also mediated the relationship between earlier pubertal timing and increased withdrawn depressed problems (but not rule-breaking delinquency). Finally, parental acceptance buffered against limbic-CON connectivity patterns that were implicated in withdrawn depressed problems in those undergoing puberty earlier than their peers. Findings highlight the role of decreased corticolimbic connectivity in mediating pathways between earlier pubertal timing and withdrawn depressed problems, and we present preliminary evidence that the family environment may buffer against these neural risk patterns during early adolescence.
Reproducibility in the absence of selective reporting: An illustration from large‐scale brain asymmetry research
Publisher: Wiley
Date: 25-08-2020
DOI: 10.1002/HBM.25154
Abstract: The problem of poor reproducibility of scientific findings has received much attention over recent years, in a variety of fields including psychology and neuroscience. The problem has been partly attributed to publication bias and unwanted practices such as p ‐hacking. Low statistical power in in idual studies is also understood to be an important factor. In a recent multisite collaborative study, we mapped brain anatomical left–right asymmetries for regional measures of surface area and cortical thickness, in 99 MRI datasets from around the world, for a total of over 17,000 participants. In the present study, we revisited these hemispheric effects from the perspective of reproducibility. Within each dataset, we considered that an effect had been reproduced when it matched the meta‐analytic effect from the 98 other datasets, in terms of effect direction and significance threshold. In this sense, the results within each dataset were viewed as coming from separate studies in an “ideal publishing environment,” that is, free from selective reporting and p hacking. We found an average reproducibility rate of 63.2% ( SD = 22.9%, min = 22.2%, max = 97.0%). As expected, reproducibility was higher for larger effects and in larger datasets. Reproducibility was not obviously related to the age of participants, scanner field strength, FreeSurfer software version, cortical regional measurement reliability, or regional size. These findings constitute an empirical illustration of reproducibility in the absence of publication bias or p hacking, when assessing realistic biological effects in heterogeneous neuroscience data, and given typically‐used s le sizes.
Subcortical Brain Volume, Regional Cortical Thickness, and Cortical Surface Area Across Disorders: Findings From the ENIGMA ADHD, ASD, and OCD Working Groups
Publisher: American Psychiatric Association Publishing
Date: 09-2020
Mapping Cortical Brain Asymmetry in 17,141 Healthy Individuals Worldwide via the ENIGMA Consortium
Publisher: Cold Spring Harbor Laboratory
Date: 10-2017
DOI: 10.1101/196634
Abstract: Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here the ENIGMA consortium presents the largest ever analysis of cerebral cortical asymmetry and its variability across in iduals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy in iduals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippoc al gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and brain size (indexed by intracranial volume). Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets ( N = 1,443 and 1,113, respectively), we found several asymmetries showing modest but highly reliable heritability. The structural asymmetries identified, and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders. Left-right asymmetry is a key feature of the human brain's structure and function. It remains unclear which cortical regions are asymmetrical on average in the population, and how biological factors such as age, sex and genetic variation affect these asymmetries. Here we describe by far the largest ever study of cerebral cortical brain asymmetry, based on data from 17,141 participants. We found a global anterior-posterior 'torque' pattern in cortical thickness, together with various regional asymmetries at the population level, which have not been previously described, as well as effects of age, sex, and heritability estimates. From these data, we have created an on-line resource that will serve future studies of human brain anatomy in health and disease.
Head Motion During MRI Predicted by out-of-Scanner Sustained Attention Performance in Attention-Deficit/Hyperactivity Disorder
Publisher: SAGE Publications
Date: 19-03-2020
Abstract: Objective: To characterize head movements in children with ADHD using an ex-Gaussian distribution and examine associations with out-of-scanner sustained attention. Method: Fifty-six children with ADHD and 61 controls aged 9 to 11 years completed the Sustained Attention to Response Task (SART) and resting-state functional magnetic resonance imaging (fMRI). In-scanner head motion was calculated using ex-Gaussian estimates for mu, sigma, and tau in delta variation signal and framewise displacement. Sustained attention was evaluated through omission errors and tau in response time on the SART. Results: Mediation analysis revealed that out-of-scanner attention lapses (omissions during the SART) mediated the relationship between ADHD diagnosis and in-scanner head motion (tau in delta variation signal), indirect effect: B = 1.29, 95% confidence interval (CI) = [0.07, 3.15], accounting for 29% of the association. Conclusion: Findings suggest a critical link between trait-level sustained attention and infrequent large head movements during scanning (tau in head motion) and highlight fundamental challenges in measuring the neural basis of sustained attention.
ADHD at Age 7 and Functional Impairments at Age 10
Publisher: American Academy of Pediatrics (AAP)
Date: 11-2020
Abstract: Attention-deficit/hyperactivity disorder (ADHD) cohort studies have typically involved clinical s les and have usually recruited children across wide age ranges, limiting generalizability across complexity and developmental stage. We compared academic, emotional-behavioral and social functioning at age 10, and predictors of outcomes, in a nonreferred cohort of children recruited at age 7, between those with full-syndrome (FS) ADHD and controls with no ADHD. This was a prospective cohort study with a 3-year follow-up period. Children were recruited from 43 socioeconomically erse schools in Melbourne, Australia. Multi-informant outcomes at age 10 were academic functioning (Wide Range Achievement Test 4 Social Skills Improvement System), emotional-behavioral functioning (Strengths and Difficulties Questionnaire total), and social functioning (Strengths and Difficulties Questionnaire peer problems). Outcomes were compared across the groups by using adjusted random-effects linear regression analyses. In total, 477 children (62% male) were recruited at a mean (SD) age of 7.3 years (0.4). There were 179 participants with FS ADHD, 86 with ST ADHD, and 212 controls. S le retention was 78.2% at 3-year follow-up. Both the FS and ST groups were functioning worse than controls on almost all outcome measures. The best predictors of outcome for children with ADHD were working memory (academic outcome, P & .001), ADHD symptom severity (emotional-behavioral outcome, parent: P & .001 teacher: P & .01), and autism spectrum disorder symptoms (emotional-behavioral outcome, parent P = .003 social outcome, parent P = .001). Children with FS and ST ADHD at age 7 experience persisting functional impairments across domains at age 10. The predictors identified at age 7 present potential targets for intervention to ameliorate impairments.
Manual dexterity in late childhood is associated with maturation of the corticospinal tract
Publisher: Elsevier BV
Date: 02-2021
The effect of single-dose methylphenidate on resting-state network functional connectivity in ADHD
Publisher: Springer Science and Business Media LLC
Date: 12-10-2017
DOI: 10.1007/S11682-016-9620-8
Abstract: We examined the effect of a single dose of methylphenidate (MPH) on whole brain functional connectivity, assessed using resting state functional MRI (rsfMRI), in young people with ADHD. 16 young people with ADHD participated in two rsfMRI scans in a randomized, placebo-controlled study with an acute dose of MPH (20 mg). 15 typically developing controls also performed the task under placebo conditions. The network-based statistic (NBS) was used to identify differential connectivity patterns between the MPH and placebo conditions in the ADHD group. Mean connectivity of the resulting sub-network was examined in the ADHD and control groups. Resting state functional connectivity (RSFC) analysis revealed significantly reduced connectivity under MPH compared to placebo in young people with ADHD. Findings were robust across a range of thresholds. No sub-networks of increased connectivity were found at any threshold. Mean connectivity of the identified sub-network was significantly higher in ADHD in iduals in the placebo condition compared to controls, however there was no difference between MPH condition and controls. We demonstrated a significant MPH-related reduction in RSFC in a large, robust network primarily involving occipital, temporal and cerebellar regions, and visual, executive and default mode networks. These findings suggest that MPH is 'normalising' a higher RSFC in young people with ADHD. This study is a novel addition to the understanding of treatment effects on the brain in ADHD.
Editorial: Understanding the Link Between the Developing Brain and Behavior in Adolescents
Publisher: Frontiers Media SA
Date: 07-05-2021
A network analysis approach to ADHD symptoms: More than the sum of its parts
Publisher: Public Library of Science (PLoS)
Date: 18-01-2019
Virtual Histology of Cortical Thickness and Shared Neurobiology in 6 Psychiatric Disorders
Publisher: American Medical Association (AMA)
Date: 2021
Longitudinal Trajectories of White Matter Development in Attention-Deficit/Hyperactivity Disorder
Publisher: Elsevier BV
Date: 03-2023
Multimodal Structural Neuroimaging Markers of Brain Development and ADHD Symptoms
Publisher: American Psychiatric Association Publishing
Date: 2019
DOI: 10.1176/APPI.AJP.2018.18010034
Abstract: Attention deficit hyperactivity disorder (ADHD) is a multifactorial disorder with erse associated risk factors and comorbidities. In this study, the authors sought to understand ADHD from a dimensional perspective and to identify neuroanatomical correlates of traits and behaviors that span diagnostic criteria. Multimodal neuroimaging data and multi-informant cognitive and clinical data were collected in a densely phenotyped pediatric cohort (N=160 70 with ADHD age range, 9-12 years). Multivariate analysis identified associations between clinical and cognitive factors and multimodal neuroimaging markers (across tissue volume, cortical thickness, cortical area, and white matter microstructure). The resulting imaging markers were validated in an independent cohort (N=231 132 with ADHD age range, 7-18 years). Four novel patterns of neuroanatomical variation that related to phenotypic variation were identified. The first imaging pattern captured association of head size with sex, socioeconomic status, and mathematics and reading performance. The second pattern captured variation associated with development and showed that in iduals with delayed development were more likely to be receiving ADHD medication. The third pattern was associated with hyperactivity, greater comorbidities, poorer cognition, lower parental education, and lower quality of life. The fourth pattern was associated with a particular profile of poorer cognition and irritability independent of ADHD. The authors further demonstrated that these imaging patterns could predict variation in age and ADHD symptoms in an independent cohort. The findings suggest that ADHD presentation may arise from a summation of several clinical, developmental, or cognitive factors, each with a distinct neuroanatomical foundation. This informs the neurobiological foundations of ADHD and highlights the value of detailed phenotypic data in understanding the neurobiology underlying neurodevelopmental disorders.
White matter microstructure predicts longitudinal social cognitive outcomes after paediatric traumatic brain injury: a diffusion tensor imaging study
Publisher: Cambridge University Press (CUP)
Date: 07-08-2017
DOI: 10.1017/S0033291717002057
Abstract: Deficits in social cognition may be among the most profound and disabling sequelae of paediatric traumatic brain injury (TBI) however, the neuroanatomical correlates of longitudinal outcomes in this domain remain unexplored. This study aimed to characterize social cognitive outcomes longitudinally after paediatric TBI, and to evaluate the use of sub-acute diffusion tensor imaging (DTI) to predict these outcomes. The s le included 52 children with mild complex-severe TBI who were assessed on cognitive theory of mind (ToM), pragmatic language and affective ToM at 6- and 24-months post-injury. For comparison, 43 typically developing controls (TDCs) of similar age and sex were recruited. DTI data were acquired sub-acutely (mean = 5.5 weeks post-injury) in a subset of 65 children (TBI = 35 TDC = 30) to evaluate longitudinal prospective relationships between white matter microstructure assessed using Tract-Based Spatial Statistics and social cognitive outcomes. Whole brain voxel-wise analysis revealed significantly higher mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) in the sub-acute TBI group compared with TDC, with differences observed predominantly in the splenium of the corpus callosum (sCC), sagittal stratum (SS), dorsal cingulum (DC), uncinate fasciculus (UF) and middle and superior cerebellar peduncles (MCP & SCP, respectively). Relative to TDCs, children with TBI showed poorer cognitive ToM, affective ToM and pragmatic language at 6-months post-insult, and those deficits were related to abnormal diffusivity of the sCC, SS, DC, UF, MCP and SCP. Moreover, children with TBI showed poorer affective ToM and pragmatic language at 24-months post-injury, and those outcomes were predicted by sub-acute alterations in diffusivity of the DC and MCP. Abnormal microstructure within frontal-temporal, limbic and cerebro-cerebellar white matter may be a risk factor for long-term social difficulties observed in children with TBI. DTI may have potential to unlock early prognostic markers of long-term social outcomes.
Childhood conduct problems are associated with reduced white matter fibre density and morphology
Publisher: Elsevier BV
Date: 02-2021
Evidence for similar structural brain anomalies in youth and adult attention-deficit/hyperactivity disorder: a machine learning analysis
Publisher: Springer Science and Business Media LLC
Date: 02-2021
DOI: 10.1038/S41398-021-01201-4
Abstract: Attention-deficit/hyperactivity disorder (ADHD) affects 5% of children world-wide. Of these, two-thirds continue to have impairing symptoms of ADHD into adulthood. Although a large literature implicates structural brain differences of the disorder, it is not clear if adults with ADHD have similar neuroanatomical differences as those seen in children with recent reports from the large ENIGMA-ADHD consortium finding structural differences for children but not for adults. This paper uses deep learning neural network classification models to determine if there are neuroanatomical changes in the brains of children with ADHD that are also observed for adult ADHD, and vice versa. We found that structural MRI data can significantly separate ADHD from control participants for both children and adults. Consistent with the prior reports from ENIGMA-ADHD, prediction performance and effect sizes were better for the child than the adult s les. The model trained on adult s les significantly predicted ADHD in the child s le, suggesting that our model learned anatomical features that are common to ADHD in childhood and adulthood. These results support the continuity of ADHD’s brain differences from childhood to adulthood. In addition, our work demonstrates a novel use of neural network classification models to test hypotheses about developmental continuity.
Enhancing neuroimaging genetics through meta-analysis for Tourette syndrome (ENIGMA-TS): A worldwide platform for collaboration
Publisher: Frontiers Media SA
Date: 18-08-2022
DOI: 10.3389/FPSYT.2022.958688
Abstract: Tourette syndrome (TS) is characterized by multiple motor and vocal tics, and high-comorbidity rates with other neuropsychiatric disorders. Obsessive compulsive disorder (OCD), attention deficit hyperactivity disorder (ADHD), autism spectrum disorders (ASDs), major depressive disorder (MDD), and anxiety disorders (AXDs) are among the most prevalent TS comorbidities. To date, studies on TS brain structure and function have been limited in size with efforts mostly fragmented. This leads to low-statistical power, discordant results due to differences in approaches, and hinders the ability to stratify patients according to clinical parameters and investigate comorbidity patterns. Here, we present the scientific premise, perspectives, and key goals that have motivated the establishment of the Enhancing Neuroimaging Genetics through Meta-Analysis for TS (ENIGMA-TS) working group. The ENIGMA-TS working group is an international collaborative effort bringing together a large network of investigators who aim to understand brain structure and function in TS and dissect the underlying neurobiology that leads to observed comorbidity patterns and clinical heterogeneity. Previously collected TS neuroimaging data will be analyzed jointly and integrated with TS genomic data, as well as equivalently large and already existing studies of highly comorbid OCD, ADHD, ASD, MDD, and AXD. Our work highlights the power of collaborative efforts and transdiagnostic approaches, and points to the existence of different TS subtypes. ENIGMA-TS will offer large-scale, high-powered studies that will lead to important insights toward understanding brain structure and function and genetic effects in TS and related disorders, and the identification of biomarkers that could help inform improved clinical practice.
Distinct Neural Profiles of Frontoparietal Networks in Boys with ADHD and Boys with Persistent Depressive Disorder
Publisher: Springer Science and Business Media LLC
Date: 29-03-2022
DOI: 10.3758/S13415-022-00999-W
Abstract: Working memory deficits are common in attention-deficit/hyperactivity disorder (ADHD) and depression-two common neurodevelopmental disorders with overlapping cognitive profiles but distinct clinical presentation. Multivariate techniques have previously been utilized to understand working memory processes in functional brain networks in healthy adults but have not yet been applied to investigate how working memory processes within the same networks differ within typical and atypical developing populations. We used multivariate pattern analysis (MVPA) to identify whether brain networks discriminated between spatial versus verbal working memory processes in ADHD and Persistent Depressive Disorder (PDD). Thirty-six male clinical participants and 19 typically developing (TD) boys participated in a fMRI scan while completing a verbal and a spatial working memory task. Within a priori functional brain networks (frontoparietal, default mode, salience), the TD group demonstrated differential response patterns to verbal and spatial working memory. The PDD group showed weaker differentiation than TD, with lower classification accuracies observed in primarily the left frontoparietal network. The neural profiles of the ADHD and PDD differed specifically in the SN where the ADHD group's neural profile suggests significantly less specificity in neural representations of spatial and verbal working memory. We highlight within-group classification as an innovative tool for understanding the neural mechanisms of how cognitive processes may deviate in clinical disorders, an important intermediary step towards improving translational psychiatry.
Abnormal asymmetry in frontostriatal white matter in children with attention deficit hyperactivity disorder
Publisher: Springer Science and Business Media LLC
Date: 02-11-2016
DOI: 10.1007/S11682-015-9470-9
Abstract: A growing body of work utilizing structural and functional brain imaging and neurocognitive measures of executive and attentional function indicates anomalous asymmetry in ADHD. This study examined the white-matter volume and diffusion properties of frontostriatal tracts, as a function of hemisphere, in ADHD and healthy controls. Forty-three young males (21 ADHD-Combined Type and 22 controls) aged 10-18 years underwent structural and diffusion weighted MRI. Tractography applying constrained spherical deconvolution (CSD) was used to construct frontostriatal tracts between each of caudate and putamen and each of dorsolateral prefrontal, ventrolateral prefrontal and orbitofrontal cortices (DLPFC, VLPFC and OFC) in each hemisphere, to examine both volumetric and diffusion microstructure properties. Young people with ADHD did not show the right hemisphere lateralization of volume in the Caudate-VLPFC and Caudate-DLPFC tracts that was evident in controls, however the ADHD group displayed a pronounced lateralization to the left for fractional anisotropy in the Putamen-VLPFC tracts. The degree of volume asymmetry did not correlate with symptom severity however fractional anisotropy (FA) values that were more strongly lateralized to the left in the Putamen-VLPFC white matter were associated with greater symptom severity. ADHD was associated with anomalous hemispheric asymmetries in both tract volume and underlying white-matter microstructure in major fibre tracts of the frontostriatal system. Our observations of both weaker lateralization to the right in terms of tract volume and stronger lateralization to the left in terms of FA values for the ADHD group, suggests that previous inconsistencies in the literature may reflect the influence of such asymmetries.
An fMRI investigation of right parietal function using a mental rotation task in pre-pubertal boys with ADHD, combined type
Publisher: Springer Science and Business Media LLC
Date: 27-08-2007
The Association Between Autism Symptoms and Child Functioning in a Sample With ADHD Recruited From the Community
Publisher: SAGE Publications
Date: 11-11-2021
Abstract: Objective: Although autism spectrum disorder (ASD) symptoms are associated with poorer functioning in children with attention-deficit/hyperactivity disorder (ADHD), it is unclear which ASD symptom domains are most impairing. This study investigated whether specific ASD symptom domains were associated with child functioning in children with ADHD. Method: Parents of 164 children with ADHD completed a diagnostic interview to assess ADHD and comorbidities. Parents reported on ASD symptoms (Social Communication Questionnaire) and child quality of life (Pediatric Quality of Life Inventory 4.0). Parents and teachers completed the Strengths and Difficulties Questionnaire (emotional, conduct, and peer problems). Results: Repetitive and stereotyped behaviors were independently associated with emotional ( p = .02) and conduct ( p = .03) problems, and poorer quality of life ( p = .004). Reciprocal social interaction deficits were independently associated with peer problems ( p = .03). Conclusion: Reciprocal social interaction deficits and repetitive and stereotyped behaviors are important areas that should be focused on in ADHD assessment and treatment.
Cortical structural and functional coupling during development and implications for attention deficit hyperactivity disorder
Publisher: Springer Science and Business Media LLC
Date: 11-07-2023
DOI: 10.1038/S41398-023-02546-8
Abstract: Functional connectivity is scaffolded by the structural connections of the brain. Disruptions of either structural or functional connectivity can lead to deficits in cognitive functions and increase the risk for neurodevelopmental disorders such as attention deficit hyperactivity disorder (ADHD). To date, very little research has examined the association between structural and functional connectivity in typical development, while no studies have attempted to understand the development of structure-function coupling in children with ADHD. 175 in iduals (84 typically developing children and 91 children with ADHD) participated in a longitudinal neuroimaging study with up to three waves. In total, we collected 278 observations between the ages 9 and 14 (139 each in typically developing controls and ADHD). Regional measures of structure-function coupling were calculated at each timepoint using Spearman’s rank correlation and mixed effect models were used to determine group differences and longitudinal changes in coupling over time. In typically developing children, we observed increases in structure-function coupling strength across multiple higher-order cognitive and sensory regions. Overall, weaker coupling was observed in children with ADHD, mainly in the prefrontal cortex, superior temporal gyrus, and inferior parietal cortex. Further, children with ADHD showed an increased rate of coupling strength predominantly in the inferior frontal gyrus, superior parietal cortex, precuneus, mid-cingulate, and visual cortex, compared to no corresponding change over time in typically developing controls. This study provides evidence of the joint maturation of structural and functional brain connections in typical development across late childhood to mid-adolescence, particularly in regions that support cognitive maturation. Findings also suggest that children with ADHD exhibit different patterns of structure-function coupling, suggesting atypical patterns of coordinated white matter and functional connectivity development predominantly in the regions overlapping with the default mode network, salience network, and dorsal attention network during late childhood to mid-adolescence.
The Social Determinants of Emotional and Behavioral Problems in Adolescents Experiencing Early Puberty
Publisher: Elsevier BV
Date: 09-2023
Widespread decreased grey and white matter in paediatric obsessive-compulsive disorder (OCD): A voxel-based morphometric MRI study
Publisher: Elsevier BV
Date: 07-2013
DOI: 10.1016/J.PSCYCHRESNS.2013.02.003
Abstract: Obsessive-compulsive disorder (OCD) is a chronic, relapsing anxiety disorder. To date, neuroimaging investigations of OCD have been variable and few studies have examined paediatric populations. Eight children with OCD and 12 typically developing children matched for age, gender, handedness and performance IQ underwent a high resolution T1-weighted structural magnetic resonance imaging (MRI) scan. A voxel-based morphometry (VBM) protocol (using DARTEL) compared the brains of the paediatric OCD children with those of typically developing children. Overall, children with OCD demonstrated significantly lower intra-cranial volume (ICV) and grey- and white-matter volumes. ICV was significantly reduced (∼9%) in the OCD group compared with the typically developing group. The VBM analysis demonstrated lower volumes in widespread grey matter in bilateral frontal, cingulate, temporal-parietal, occipital-frontal and right precuneus regions for OCD. Lower white matter volume was found bilaterally in the cingulate and occipital cortex, right frontal and parietal and left temporal regions, and the corpus callosum. In summary, this study provides further evidence of brain dysmorphology in paediatric OCD patients. In addition to fronto-striatal-thalamic neural networks, abnormalities in other brain regions, such as the parietal lobe and corpus callosum, were demonstrated. These brain regions may play an additional role in the pathophysiology of OCD.
White matter tract signatures of fiber density and morphology in ADHD
Publisher: Elsevier BV
Date: 05-2021
Longitudinal Changes of Resting-State Networks in Children With Attention-Deficit/Hyperactivity Disorder and Typically Developing Children
Publisher: Elsevier BV
Date: 05-2022
DOI: 10.1016/J.BPSC.2022.01.001
Abstract: Attention deficit hyperactivity disorder (ADHD) is a prevalent childhood neurodevelopmental disorder. Given the profound brain changes that occur across childhood and adolescence, it is important to identify functional networks that exhibit differential developmental patterns in children with ADHD. This study sought to examine whether children with ADHD exhibit differential developmental trajectories in functional connectivity, compared to typically developing controls using a network-based approach. 175 in iduals (91 children with ADHD and 84 non-ADHD controls) participated in a longitudinal neuroimaging study with up to three waves (173 total resting state scans children with ADHD and 197 in controls) between the ages 9 and 14. We adopted Network-Based Statistics to identify connected components with trajectories of development that differed between groups. In iduals with ADHD exhibited differential developmental trajectories compared to typically developing controls in cortico-limbic and visual-higher order cognitive networks. A pattern of reduction in functional connectivity between cortico-limbic networks was seen across development in controls that was not present in the ADHD group. Conversely, the ADHD group showed a significant decrease in connectivity between predominantly visual and higher order cognitive networks, that were not displayed in the control group. Our findings show that the developmental trajectories in ADHD children are characterized by a subnetwork involving different trajectories predominantly between cortico-limbic and visual-higher order cognitive network connections. These findings highlight the importance of examining the longitudinal maturational course to understand the development of functional connectivity networks in children with ADHD.
Assessing inhibitory control deficits in adult ADHD: A systematic review and meta-analysis of the stop-signal task
Publisher: Cold Spring Harbor Laboratory
Date: 10-07-2022
DOI: 10.1101/2022.07.09.22277429
Abstract: In recent years, there has been an increasing quest in improving our understanding of neurocognitive deficits underlying adult attention-deficit/hyperactivity disorder (ADHD). Current statistical manuals of psychiatric disorders emphasize inattention and hyperactivity-impulsivity symptoms, but empirical studies have also shown consistent alterations in inhibitory control. Thus far, there is no established neuropsychological test to assess inhibitory control deficits in adult ADHD. A common paradigm for assessing response inhibition is the stop-signal task (SST). Following PRISMA-selection criteria, our systematic review and meta-analysis integrated the findings of 26 publications with 27 studies examining the SST in adult ADHD. The meta-analysis, which included 883 patients with adult ADHD and 916 control participants, revealed reliable inhibitory control deficits, as expressed in prolonged SST response times, with a moderate effect size g = 0.51. The deficits were not moderated by study quality, s le characteristics or clinical parameters, suggesting that they may be a phenotype in this disorder. The analyses of secondary outcome measures revealed greater SST omission errors and reduced go accuracy in patients, indicative of altered sustained attention. However, only few (N ) studies were available for these measures. Our meta-analysis suggests that the SST could, in conjunction with other tests and questionnaires, become a valuable tool for the assessment of inhibitory control deficits in adult ADHD.
White matter and sustained attention in children with attention/deficit-hyperactivity disorder: A longitudinal fixel-based analysis
Publisher: Elsevier BV
Date: 12-2022
DOI: 10.1016/J.CORTEX.2022.09.006
Abstract: Sustained attention is a cognitive function with known links to academic success and mental health disorders such as attention/deficit-hyperactivity disorder (ADHD). Several functional networks are critical to sustained attention, however the association between white matter maturation in tracts linking functional nodes and sustained attention in typical and atypical development is unknown. 309 diffusion-weighted imaging scans were acquired from 161 children and adolescents (80 ADHD, 81 control) at up to three timepoints over ages 9-14. A fixel-based analysis approach was used to calculate mean fiber density and fiber-bundle cross section in tracts of interest. Sustained attention was measured using omission errors and response time variability on the out-of-scanner sustained attention to response task. Linear mixed effects models examined associations of age, group and white matter metrics with sustained attention. Greater fiber density in the bilateral superior longitudinal fasciculus (SLF) I and right SLF II was associated with fewer attention errors in the control group only. In ADHD and control groups, greater fiber density in the left ILF and right thalamo-premotor pathway, as well as greater fiber cross-section in the left SLF I and II and right SLF III, was associated with better sustained attention. Relationships were consistent across the age span. Results suggest that greater axon diameter or number in the dorsal and middle SLF may facilitate sustained attention in neurotypical children but does not assist those with ADHD potentially due to disorder-related alterations in this region. Greater capacity for information transfer across the SLF was associated with attention maintenance in 9-14-year-olds regardless of diagnostic status, suggesting white matter macrostructure may also be important for attention maintenance. White matter and sustained attention associations were consistent across the longitudinal study, according with the stability of structural organization over this time. Future studies can investigate modifiability of white matter properties through ADHD medications.
Relationships between acute imaging biomarkers and theory of mind impairment in post-acute pediatric traumatic brain injury: A prospective analysis using susceptibility weighted imaging (SWI)
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2014.10.040
Abstract: Theory of Mind (ToM) forms an integral component of socially skilled behavior, and is critical for attaining developmentally appropriate goals. The protracted development of ToM is mediated by increasing connectivity between regions of the anatomically distributed 'mentalizing network', and may be vulnerable to disruption from pediatric traumatic brain injury (TBI). The present study aimed to evaluate the post-acute effects of TBI on first-order ToM, and examine relations between ToM and both local and global indices of macrostructural damage detected using susceptibility-weighted imaging (SWI). 104 children and adolescents with TBI and 43 age-matched typically developing (TD) controls underwent magnetic resonance imaging including a susceptibility-weighted imaging (SWI) sequence 2-8 weeks post-injury and were assessed on cognitive ToM tasks at 6-months after injury. Compared to TD controls and children with mild-moderate injuries, children with severe TBI showed significantly poorer ToM. Moreover, impairments in ToM were related to diffuse neuropathology, and parietal lobe lesions. Our findings support the vulnerability of the immature social brain network to disruption from TBI, and suggest that global macrostructural damage commonly associated with traumatic axonal injury (TAI) may contribute to structural disconnection of anatomically distributed regions that underlie ToM. This study suggests that SWI may be a valuable imaging biomarker to predict outcome and recovery of social cognition after pediatric TBI.
Frequency-specific abnormalities in regional homogeneity among children with attention deficit hyperactivity disorder: a resting-state fMRI study
Publisher: Elsevier BV
Date: 05-2016
Characterisation of depressive symptoms in young children with and without attention deficit hyperactivity disorder
Publisher: Springer Science and Business Media LLC
Date: 29-01-2019
DOI: 10.1007/S00787-018-01274-5
Abstract: Depressive symptoms and attention deficit hyperactivity disorder (ADHD) are prevalent and commonly co-occur in childhood. To assist with early identification of depression in children with ADHD, we aimed to: (1) use factor analysis to determine whether the construct of depression is measured consistently in those with and without ADHD and (2) determine whether overall depressive symptoms and specific depressive symptoms were elevated in children with ADHD relative to controls. Participants comprised a community-based s le of 179 children with ADHD (51% Combined presentation, 35% Inattentive presentation) and 212 non-ADHD controls aged 6-8 years. Participants were screened for ADHD and underwent a structured diagnostic interview which confirmed ADHD status and assessed depressive symptoms. The factor structure of depressive symptoms was similar, enabling comparisons between the two groups to be made. Eighteen children with ADHD (10%) and three control participants (1%) experienced either MDD or subthreshold MDD. Children with ADHD experienced more depressive symptoms than controls (Cohen's d =1.19, p < 0.001), with the following symptoms elevated in children with ADHD relative to controls: sadness (32% vs. 14%, p < 0.001), irritability (52% vs. 19%, p < 0.001), insomnia (56% vs. 22%, p < 0.001), psychomotor agitation (53% vs. 9%, p < 0.001), feeling bad about oneself (50% vs. 24%, p < 0.001), difficulty concentrating (75% vs. 14%, p < 0.001) and making decisions (56% vs. 17%, p < 0.001). This study provides support for the occurrence of depressive symptoms in children with ADHD as young as six and highlights the importance of early assessment for depressive symptoms in children with ADHD.
Mapping a network for tics in Tourette syndrome using causal lesions and structural alterations
Publisher: Oxford University Press (OUP)
Date: 2023
DOI: 10.1093/BRAINCOMMS/FCAD105
Abstract: Tics are sudden stereotyped movements or vocalizations. Cases of lesion-induced tics are invaluable, allowing for causal links between symptoms and brain structures. While a lesion network for tics has recently been identified, the degree to which this network translates to Tourette syndrome has not been fully elucidated. This is important given that patients with Tourette syndrome make up a large portion of tic cases therefore, existing and future treatments should apply to these patients. The aim of this study was to first localize a causal network for tics from lesion-induced cases and then refine and validate this network in patients with Tourette syndrome. We independently performed ‘lesion network mapping’ using a large normative functional connectome (n = 1000) to isolate a brain network commonly connected to lesions causing tics (n = 19) identified through a systematic search. The specificity of this network to tics was assessed through comparison to lesions causing other movement disorders. Using structural brain coordinates from prior neuroimaging studies (n = 7), we then derived a neural network for Tourette syndrome. This was done using standard anatomical likelihood estimation meta-analysis and a novel method termed ‘coordinate network mapping’, which uses the same coordinates, yet maps their connectivity using the aforementioned functional connectome. Conjunction analysis was used to refine the network for lesion-induced tics to Tourette syndrome by identifying regions common to both lesion and structural networks. We then tested whether connectivity from this common network is abnormal in a separate resting-state functional connectivity MRI data set from idiopathic Tourette syndrome patients (n = 21) and healthy controls (n = 25). Results showed that lesions causing tics were distributed throughout the brain however, consistent with a recent study, these were part of a common network with predominant basal ganglia connectivity. Using conjunction analysis, coordinate network mapping findings refined the lesion network to the posterior putamen, caudate nucleus, globus pallidus externus (positive connectivity) and precuneus (negative connectivity). Functional connectivity from this positive network to frontal and cingulate regions was abnormal in patients with idiopathic Tourette syndrome. These findings identify a network derived from lesion-induced and idiopathic data, providing insight into the pathophysiology of tics in Tourette syndrome. Connectivity to our cortical cluster in the precuneus offers an exciting opportunity for non-invasive brain stimulation protocols.
Against the use of the Strengths and Difficulties Questionnaire for Aboriginal and Torres Strait Islander children aged 2–15 years
Publisher: SAGE Publications
Date: 28-03-2023
DOI: 10.1177/00048674231161504
Abstract: The Strengths and Difficulties Questionnaire is a widely used screening tool for emotional and behavioural problems in children. Recent quantitative analyses have raised concerns regarding its structural validity in Aboriginal and Torres Strait Islander communities. This paper aims to extend upon existing findings by analysing the factor structure of both the parent- and teacher-reported Strengths and Difficulties Questionnaire in this population across a broader age range than in previous studies. Participants were the caregivers and teachers of 1624 Aboriginal and Torres Strait Islander children (820 male, 804 female) aged 2–15 years from Waves 2–11 of the Longitudinal Study of Indigenous Children. The majority of children were Aboriginal living in major cities and inner regional areas. Internal consistency was estimated with McDonald’s Omega. Exploratory structural equation modelling was conducted to investigate the factor structure of the parent-reported and teacher-reported versions of the Strengths and Difficulties Questionnaire. Responses from teachers demonstrated higher internal consistency than responses from parents, which was unacceptably low across most age groups. The purported five-factor structure of the Strengths and Difficulties Questionnaire failed to be replicated across both parent- and teacher-reported questionnaires. The results of bifactor and hierarchical exploratory structural equation models also failed to approximate the higher-order summary scales. These results indicate that the Strengths and Difficulties Questionnaire subscales and summary scores do not provide a valid index of emotional and behavioural problems in Aboriginal and Torres Strait Islander children. The Strengths and Difficulties Questionnaire should not be used with Aboriginal and Torres Strait Islander children.
Fixel-based Analysis of Diffusion MRI: Methods, Applications, Challenges and Opportunities
Publisher: Elsevier BV
Date: 11-2021
Sex differences in anxiety and depression in children with attention deficit hyperactivity disorder: Investigating genetic liability and comorbidity
Publisher: Wiley
Date: 03-05-2021
DOI: 10.1002/AJMG.B.32842
Abstract: It is unknown why attention deficit hyperactivity disorder (ADHD) is more common in males, whereas anxiety and depression show a female population excess. We tested the hypothesis that anxiety and depression risk alleles manifest as ADHD in males. We also tested whether anxiety and depression in children with ADHD show a different etiology to typical anxiety and depression and whether this differs by sex. The primary clinical ADHD s le consisted of 885 (14% female) children. Psychiatric symptoms were assessed using standardized interviews. Polygenic risk scores (PRS) were derived using large genetic studies. Replication s les included independent clinical ADHD s les ( N = 3,794 25.7% female) and broadly defined population ADHD s les ( N = 995 33.4% female). We did not identify sex differences in anxiety or depression PRS in children with ADHD. In the primary s le, anxiety PRS were associated with social and generalized anxiety in males, with evidence of a sex‐by‐PRS interaction for social anxiety. These results did not replicate in the broadly defined ADHD s le. Depression PRS were not associated with comorbid depression symptoms. The results suggest that anxiety and depression genetic risks are not more likely to lead to ADHD in males. Also, the evidence for shared etiology between anxiety symptoms in those with ADHD and typical anxiety was weak and needs replication.
The development of structural covariance networks during the transition from childhood to adolescence
Publisher: Springer Science and Business Media LLC
Date: 04-05-2021
DOI: 10.1038/S41598-021-88918-W
Abstract: Structural covariance conceptualizes how morphologic properties of brain regions are related to one another (across in iduals). It can provide unique information to cortical structure (e.g., thickness) about the development of functionally meaningful networks. The current study investigated how structural covariance networks develop during the transition from childhood to adolescence, a period characterized by marked structural re-organization. Participants (N = 192 scans = 366) completed MRI assessments between 8.5 and 14.5 years of age. A sliding window approach was used to create “age-bins”, and structural covariance networks (based on cortical thickness) were created for each bin. Next, generalized additive models were used to characterize trajectories of age-related changes in network properties. Results revealed nonlinear trajectories with “peaks” in mean correlation and global density that are suggestive of a period of convergence in anatomical properties across the cortex during early adolescence, prior to regional specialization. “Hub” regions in sensorimotor cortices were present by late childhood, but the extent and strength of association cortices as “hubs” increased into mid-adolescence. Moreover, these regional changes were found to be related to rates of thinning across the cortex. In the context of neurocognitive networks, the frontoparietal, default mode, and attention systems exhibited age-related increases in within-network and between-network covariance. These regional and modular developmental patterns are consistent with continued refinement of socioemotional and other complex executive functions that are supported by higher-order cognitive networks during early adolescence.
White matter abnormalities in pediatric obsessive-compulsive disorder
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.PSCYCHRESNS.2013.04.003
Abstract: Diffusion tensor imaging (DTI) has been useful in allowing us to examine the nature and extent of neuronal disruption associated with obsessive-compulsive disorder (OCD). However, little is known about the underlying brain structure in OCD. Diffusion-weighted magnetic resonance imaging was performed in 16 children with OCD and 22 typically developing children. Tract-based spatial statistics (TBSS) was used to compare the microstructure of white-matter tracts of OCD children with those of typically developing children. Correlation/regression analyses were also performed on each diffusion measure in order to detect any correlation of white-matter microstructure with scales of symptom severity. Analysis revealed significantly greater axial diffusivity in both the genu and the splenium of the corpus callosum in the control compared to the OCD group these regions consecutively connect bilateral medial frontal regions and bilateral parietal regions. Secondly, correlation and voxel-based regression analysis revealed that lower axial diffusion correlated with greater severity of symptoms within the OCD group, as measured by the Child Behaviour Checklist-Obsessive Compulsive Scale (CBCL-OCS). The findings demonstrated a correlation of axial diffusivity with severity of symptoms in children with OCD. DTI may provide novel ways to help reveal the relationships between clinical symptoms and altered brain regions.
A longitudinal analysis of puberty‐related cortical development
Publisher: Elsevier BV
Date: 03-2021
Virtual Ontogeny of Cortical Growth Preceding Mental Illness
Publisher: Elsevier BV
Date: 08-2022
DOI: 10.1016/J.BIOPSYCH.2022.02.959
Abstract: Morphology of the human cerebral cortex differs across psychiatric disorders, with neurobiology and developmental origins mostly undetermined. Deviations in the tangential growth of the cerebral cortex during pre erinatal periods may be reflected in in idual variations in cortical surface area later in life. Interregional profiles of group differences in surface area between cases and controls were generated using T1-weighted magnetic resonance imaging from 27,359 in iduals including those with attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depressive disorder, schizophrenia, and high general psychopathology (through the Child Behavior Checklist). Similarity of interregional profiles of group differences in surface area and prenatal cell-specific gene expression was assessed. Across the 11 cortical regions, group differences in cortical area for attention-deficit/hyperactivity disorder, schizophrenia, and Child Behavior Checklist were dominant in multimodal association cortices. The same interregional profiles were also associated with interregional profiles of (prenatal) gene expression specific to proliferative cells, namely radial glia and intermediate progenitor cells (greater expression, larger difference), as well as differentiated cells, namely excitatory neurons and endothelial and mural cells (greater expression, smaller difference). Finally, these cell types were implicated in known pre erinatal risk factors for psychosis. Genes coexpressed with radial glia were enriched with genes implicated in congenital abnormalities, birth weight, hypoxia, and starvation. Genes coexpressed with endothelial and mural genes were enriched with genes associated with maternal hypertension and preterm birth. Our findings support a neurodevelopmental model of vulnerability to mental illness whereby prenatal risk factors acting through cell-specific processes lead to deviations from typical brain development during pregnancy.
Longitudinal Trajectories of Sustained Attention Development in Children and Adolescents with ADHD
Publisher: Springer Science and Business Media LLC
Date: 05-09-2020
Spatial working memory and spatial attention rely on common neural processes in the intraparietal sulcus
Publisher: Elsevier BV
Date: 11-2010
DOI: 10.1016/J.NEUROIMAGE.2010.06.068
Abstract: Our ability to remember locations in space (spatial working memory) and our ability to direct attention to those locations (spatial attention) are two fundamental and closely related cognitive processes. A growing body of behavioural evidence suggests that spatial working memory and spatial attention share common resources, while neuroimaging studies show some overlap in the neural regions that mediate these two cognitive functions. The current study used fMRI to directly examine the extent to which spatial working memory and spatial attention rely on common underlying neural mechanisms. Twenty healthy participants underwent functional MRI while performing a dual task of spatial working memory incorporating a visual search task during the working memory retention interval. Working memory and visual search task loads were parametrically modulated. A wide network of prefrontal, premotor, and parietal regions showed increasing activity with increased spatial working memory load. Of these areas, part of the right supramarginal gyrus, lying along the intraparietal sulcus, showed a significant interaction such that the neural activity associated with spatial working memory load was significantly attenuated as visual search load in the dual task was increased. This interaction suggests that this part of the supramarginal gyrus, along the intraparietal sulcus, is critical for mediating both spatial working memory and shifts in spatial attention.
ENIGMA‐Sleep: Challenges, opportunities, and the road map
Publisher: Wiley
Date: 28-04-2021
DOI: 10.1111/JSR.13347
Abstract: Neuroimaging and genetics studies have advanced our understanding of the neurobiology of sleep and its disorders. However, in idual studies usually have limitations to identifying consistent and reproducible effects, including modest s le sizes, heterogeneous clinical characteristics and varied methodologies. These issues call for a large‐scale multi‐centre effort in sleep research, in order to increase the number of s les, and harmonize the methods of data collection, preprocessing and analysis using pre‐registered well‐established protocols. The Enhancing NeuroImaging Genetics through Meta‐Analysis (ENIGMA) consortium provides a powerful collaborative framework for combining datasets across in idual sites. Recently, we have launched the ENIGMA‐Sleep working group with the collaboration of several institutes from 15 countries to perform large‐scale worldwide neuroimaging and genetics studies for better understanding the neurobiology of impaired sleep quality in population‐based healthy in iduals, the neural consequences of sleep deprivation, pathophysiology of sleep disorders, as well as neural correlates of sleep disturbances across various neuropsychiatric disorders. In this introductory review, we describe the details of our currently available datasets and our ongoing projects in the ENIGMA‐Sleep group, and discuss both the potential challenges and opportunities of a collaborative initiative in sleep medicine.
Network Modeling of microRNA–mRNA Interactions in Neuroblastoma Tumorigenesis Identifies miR-204 as a Direct Inhibitor of MYCN
Publisher: American Association for Cancer Research (AACR)
Date: 14-06-2018
DOI: 10.1158/0008-5472.CAN-17-3034
Abstract: Neuroblastoma is a pediatric cancer of the sympathetic nervous system where MYCN lification is a key indicator of poor prognosis. However, mechanisms by which MYCN promotes neuroblastoma tumorigenesis are not fully understood. In this study, we analyzed global miRNA and mRNA expression profiles of tissues at different stages of tumorigenesis from TH-MYCN transgenic mice, a model of MYCN-driven neuroblastoma. On the basis of a Bayesian learning network model in which we compared pretumor ganglia from TH-MYCN+/+ mice to age-matched wild-type controls, we devised a predicted miRNA–mRNA interaction network. Among the miRNA–mRNA interactions operating during human neuroblastoma tumorigenesis, we identified miR-204 as a tumor suppressor miRNA that inhibited a subnetwork of oncogenes strongly associated with MYCN- lified neuroblastoma and poor patient outcome. MYCN bound to the miR-204 promoter and repressed miR-204 transcription. Conversely, miR-204 directly bound MYCN mRNA and repressed MYCN expression. miR-204 overexpression significantly inhibited neuroblastoma cell proliferation in vitro and tumorigenesis in vivo. Together, these findings identify novel tumorigenic miRNA gene networks and miR-204 as a tumor suppressor that regulates MYCN expression in neuroblastoma tumorigenesis. Significance: Network modeling of miRNA–mRNA regulatory interactions in a mouse model of neuroblastoma identifies miR-204 as a tumor suppressor and negative regulator of MYCN. Cancer Res 78(12) 3122–34. ©2018 AACR.
Brain Imaging of the Cortex in ADHD: A Coordinated Analysis of Large-Scale Clinical and Population-Based Samples
Publisher: American Psychiatric Association Publishing
Date: 07-2019
Longitudinal white matter development in children is associated with puberty, attentional difficulties, and mental health
Publisher: Cold Spring Harbor Laboratory
Date: 12-04-2019
DOI: 10.1101/607671
Abstract: The pubertal period involves dynamic white matter development. This period also corresponds with rapid gains in higher cognitive functions including attention, as well as increased risk of developing mental health difficulties. This longitudinal study comprised children aged 9-13 years (n=130). Diffusion magnetic resonance imaging (dMRI) data were acquired (b=2800 s/mm 2 , 60 directions) at two time-points. We derived measures of fibre density and morphology using the fixel-based analysis framework and performed a tract-based mixed-effects modelling analysis to understand patterns of white matter development with respect to age, pubertal stage, attentional difficulties, and internalising and externalising problems. We observed significant increases in apparent fibre density across a large number of white matter pathways, including major association and commissural pathways. We observed a linear relationship between fibre density and morphology with pubertal stage, in the right superior longitudinal fasciculus and in the right inferior longitudinal fasciculus. In terms of symptom severity, fibre density was positively associated with attentional dysfunction in the right uncinate fasciculus. Overall, white matter development across ages 9-13 years involved the expansion of major white matter fibre pathways, with key right-lateralised association pathways linked with pubertal development and attentional difficulties.
Developmental brain trajectories in children with ADHD and controls: A longitudinal neuroimaging study
Publisher: Springer Science and Business Media LLC
Date: 11-03-2016
Distinct Neural Profiles of Frontoparietal Networks in Boys with ADHD and Boys with Persistent Depressive Disorder
Publisher: Cold Spring Harbor Laboratory
Date: 10-03-2021
DOI: 10.1101/2021.03.09.434662
Abstract: Working memory deficits are common in attention-deficit/hyperactivity disorder (ADHD) and depression, two common neurodevelopmental disorders with overlapping cognitive profiles but distinct clinical presentation. Multivariate techniques have previously been utilized to understand working memory processes in functional brain networks in healthy adults, but have not yet been applied to investigate how working memory processes within the same networks differ within typical and atypical developing populations. We used multivariate pattern analysis (MVPA) to identify whether brain networks discriminated between spatial vs. verbal working memory processes in ADHD and Persistent Depressive Disorder (PDD). 36 male clinical participants and 19 typically developing (TD) boys participated in a fMRI scan while completing a verbal and a spatial working memory task. Within a priori functional brain networks (frontoparietal, default mode, salience) the TD group demonstrated differential response patterns to verbal and spatial working memory. The PDD group showed weaker differentiation than TD, with lower classification accuracies observed in primarily the left frontoparietal network. The neural profiles of the ADHD and PDD differed specifically in the SN where the ADHD group’s neural profile suggests significantly less specificity in neural representations of spatial and verbal working memory. We highlight within-group classification as an innovative tool for understanding the neural mechanisms of how cognitive processes may deviate in clinical disorders, an important intermediary step towards improving translational psychiatry.
Mathematically gifted male adolescents activate a unique brain network during mental rotation
Publisher: Elsevier BV
Date: 10-2005
DOI: 10.1016/J.COGBRAINRES.2005.08.004
Abstract: Mental rotation involves the creation and manipulation of internal images, with the later being particularly useful cognitive capacities when applied to high-level mathematical thinking and reasoning. Many neuroimaging studies have demonstrated mental rotation to be mediated primarily by the parietal lobes, particularly on the right side. Here, we use fMRI to show for the first time that when performing 3-dimensional mental rotations, mathematically gifted male adolescents engage a qualitatively different brain network than those of average math ability, one that involves bilateral activation of the parietal lobes and frontal cortex, along with heightened activation of the anterior cingulate. Reliance on the processing characteristics of this uniquely bilateral system and the interplay of these anterior osterior regions may be contributors to their mathematical precocity.
Neural correlates of irritability in a community sample of children
Publisher: Elsevier BV
Date: 09-2021
Uncovering cortico-striatal correlates of cognitive fatigue in pediatric acquired brain disorder: Evidence from traumatic brain injury
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.CORTEX.2016.07.020
Abstract: Cognitive fatigue is among the most profound and disabling sequelae of pediatric acquired brain disorders, however the neural correlates of these symptoms in children remains unexplored. One hypothesis suggests that cognitive fatigue may arise from dysfunction of cortico-striatal networks (CSNs) implicated in effort output and outcome valuation. Using pediatric traumatic brain injury (TBI) as a model, this study investigated (i) the sub-acute effect of brain injury on CSN volume and (ii) potential relationships between cognitive fatigue and sub-acute volumetric abnormalities of the CSN. 3D T1 weighted magnetic resonance imaging sequences were acquired sub-acutely in 137 children (TBI: n = 103 typically developing - TD children: n = 34). 67 of the original 137 participants (49%) completed measures of cognitive fatigue and psychological functioning at 24-months post-injury. Results showed that compared to TD controls and children with milder injuries, children with severe TBI showed volumetric reductions in the overall CSN package, as well as regional gray matter volumetric change in cortical and subcortical regions of the CSN. Significantly greater cognitive fatigue in the TBI patients was associated with volumetric reductions in the CSN and its putative hub regions, even after adjusting for injury severity, socioeconomic status (SES) and depression. In the first study to evaluate prospective neuroanatomical correlates of cognitive fatigue in pediatric acquired brain disorder, these findings suggest that post-injury cognitive fatigue is related to structural abnormalities of cortico-striatal brain networks implicated in effort output and outcome valuation. Morphometric magnetic resonance imaging (MRI) may have potential to unlock early prognostic markers that may assist to identify children at elevated risk for cognitive fatigue post-TBI.
White matter alterations at pubertal onset
Publisher: Elsevier BV
Date: 08-2017
Assessing Inhibitory Control Deficits in Adult ADHD: A Systematic Review and Meta-analysis of the Stop-signal Task
Publisher: Springer Science and Business Media LLC
Date: 10-06-2023
DOI: 10.1007/S11065-023-09592-5
Abstract: In recent years, there has been an increasing quest in improving our understanding of the neurocognitive deficits underlying adult attention-deficit/hyperactivity disorder (ADHD). Current statistical manuals of psychiatric disorders emphasize inattention and hyperactivity-impulsivity symptoms, but empirical studies have also shown consistent alterations in inhibitory control. To date, there is no established neuropsychological test to assess inhibitory control deficits in adult ADHD. A common paradigm for assessing response inhibition is the stop-signal task (SST). Following PRISMA-selection criteria, our systematic review and meta-analysis integrated the findings of 26 publications with 27 studies examining the SST in adult ADHD. The meta-analysis, which included 883 patients with adult ADHD and 916 control participants, revealed reliable inhibitory control deficits, as expressed in prolonged SST response times, with a moderate effect size $$g$$ g = 0.51 (95% CI: 0.376–0.644, $$p$$ p 0.0001). The deficits were not moderated by study quality, s le characteristics or clinical parameters, suggesting that they may be a phenotype in this disorder. The analyses of secondary outcome measures revealed greater SST omission errors and reduced go accuracy in patients, indicative of altered sustained attention. However, only few ( N 10) studies were available for these measures. Our meta-analysis suggests that the SST, in conjunction with other tests and questionnaires, could become a valuable tool for assessing inhibitory control deficits in adult ADHD.
Global and local grey matter reductions in boys with ADHD combined type and ADHD inattentive type
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.PSCYCHRESNS.2016.06.008
Abstract: Attention-deficit/hyperactivity disorder (ADHD) has reliably been associated with global grey matter reductions but local alterations are largely inconsistent with perhaps the exception of the caudate nucleus. The aim of this study was to examine local and global brain volume differences between typically developing children (TD) and children with a diagnosis of ADHD. We also addressed whether these parameters would differ between children with the ADHD-combined type (ADHD-C) and those with the ADHD-inattentive type (ADHD-I). Using an ROI approach caudate volume differences were also examined. 79 boys between the ages of 8 and 17 participated in the study. Of those 33 met diagnostic criteria for the ADHD-C and 15 for the ADHD-I subtype. 31 boys were included in the TD group. Structural magnetic resonance imaging data were analysed using voxel-based morphometry. The ADHD group had significantly lower global and local grey matter volumes within clusters in the bilateral frontal, right parietal and right temporal regions compared to TD. A significant group by age interaction was found for right caudate nucleus volume. No differences between the ADHD-C and ADHD-I groups were found. Right caudate nucleus volume and age are more strongly related in ADHD than in TD consistent with previous research.
Fronto-parietal activation in attention-deficit hyperactivity disorder, combined type: Functional magnetic resonance imaging study
Publisher: Royal College of Psychiatrists
Date: 09-2005
Abstract: Afunctional magnetic resonance imaging mental rotation paradigm was used to investigate the patterns of activation of fronto-parietal brain areas in male adolescents with attention-deficit hyperactivity disorder, combined type (ADHD–CT) compared with age-, gender-, handedness- and performance IQ-matched healthy controls. The ADHD-CT group had (a) decreased activation of the ‘action-atttentional’ system (including Brodmann's areas (BA) 46, 39, 40) and the superior parietal (BA7) and middle frontal (BA10) areas and (b) increased activation of the posterior midline attentional system. These different neuroactivation patterns indicate widespread frontal, striatal and parietal dysfunction in adolescents with ADHD-CT.
Cortical morphometry in attention deficit/hyperactivity disorder: Contribution of thickness and surface area to volume
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.CORTEX.2016.05.012
Abstract: Although lower brain volume is a consistent neuroimaging finding in attention deficit hyperactivity disorder (ADHD), we lack an understanding of whether this effect is driven by changes in cortical thickness or surface area, which are governed by distinct neurodevelopmental processes. This study examined ADHD-control differences in cortical thickness, surface area and volume, and tests whether thickness and surface area mediates any observed volume differences. Magnetic resonance imaging (MRI) data was collected from 35 males with ADHD-combined type and 35 typically developing control participants aged 9-17 years. Morphometric measures were examined for between group differences and the specific contribution of surface area and thickness to group differences in volume tested using mediation analysis. In iduals with ADHD had smaller total cortical volume (7.3%), surface area (4.3%), and mean cortical thickness (2.8%) compared to controls. Differences were pronounced in frontal and parietal lobes. Variance in volume as a function of ADHD diagnosis was accounted for at least in part by the relationship between diagnosis and each of cortical thickness and surface area, with regional variation in the relative contributions of these measures. The surface area of the precuneus was a major driver of volume differences, attesting to the potential relevance of this region for neurodevelopment in ADHD. Both surface area and cortical thickness play a significant mediating role in determining diagnostic differences in volume, with regional variation in the contribution of thickness and surface area to those volume differences, highlighting the importance of examining both cortical thickness and surface area in examining ADHD.
Subcortical brain volume, regional cortical thickness and cortical surface area across attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorde
Publisher: Cold Spring Harbor Laboratory
Date: 18-06-2019
DOI: 10.1101/673012
Abstract: Attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder (ASD), and obsessive-compulsive disorder (OCD) are common neurodevelopmental disorders that frequently co-occur. We aimed to directly compare all three disorders. The ENIGMA consortium is ideally positioned to investigate structural brain alterations across these disorders. Structural T1-weighted whole-brain MRI of controls ( n =5,827) and patients with ADHD (n=2,271), ASD (n=1,777), and OCD (n=2,323) from 151 cohorts worldwide were analyzed using standardized processing protocols. We examined subcortical volume, cortical thickness and surface area differences within a mega-analytical framework, pooling measures extracted from each cohort. Analyses were performed separately for children, adolescents, and adults using linear mixed-effects models adjusting for age, sex and site (and ICV for subcortical and surface area measures). We found no shared alterations among all three disorders, while shared alterations between any two disorders did not survive multiple comparisons correction. Children with ADHD compared to those with OCD had smaller hippoc al volumes, possibly influenced by IQ. Children and adolescents with ADHD also had smaller ICV than controls and those with OCD or ASD. Adults with ASD showed thicker frontal cortices compared to adult controls and other clinical groups. No OCD-specific alterations across different age-groups and surface area alterations among all disorders in childhood and adulthood were observed. Our findings suggest robust but subtle alterations across different age-groups among ADHD, ASD, and OCD. ADHD-specific ICV and hippoc al alterations in children and adolescents, and ASD-specific cortical thickness alterations in the frontal cortex in adults support previous work emphasizing neurodevelopmental alterations in these disorders.
A Long Time Ago in a Galaxy Far, Far Away: A Candidate z ∼ 12 Galaxy in Early JWST CEERS Imaging
Publisher: American Astronomical Society
Date: 12-2022
Abstract: We report the discovery of a candidate galaxy with a photo- z of z ∼ 12 in the first epoch of the James Webb Space Telescope (JWST) Cosmic Evolution Early Release Science Survey. Following conservative selection criteria, we identify a source with a robust z phot = 11.8 − 0.2 + 0.3 (1 σ uncertainty) with m F200W = 27.3 and ≳7 σ detections in five filters. The source is not detected at λ 1.4 μ m in deep imaging from both Hubble Space Telescope (HST) and JWST and has faint ∼3 σ detections in JWST F150W and HST F160W, which signal a Ly α break near the red edge of both filters, implying z ∼ 12. This object (Maisie’s Galaxy) exhibits F115W − F200W 1.9 mag (2 σ lower limit) with a blue continuum slope, resulting in 99.6% of the photo- z probability distribution function favoring z 11. All data-quality images show no artifacts at the candidate’s position, and independent analyses consistently find a strong preference for z 11. Its colors are inconsistent with Galactic stars, and it is resolved ( r h = 340 ± 14 pc). Maisie’s Galaxy has log M * / M ⊙ ∼ 8.5 and is highly star-forming (log sSFR ∼ −8.2 yr −1 ), with a blue rest-UV color ( β ∼ −2.5) indicating little dust, though not extremely low metallicity. While the presence of this source is in tension with most predictions, it agrees with empirical extrapolations assuming UV luminosity functions that smoothly decline with increasing redshift. Should follow-up spectroscopy validate this redshift, our universe was already aglow with galaxies less than 400 Myr after the Big Bang.
Development of white matter fibre density and morphology over childhood: a longitudinal fixel-based analysis
Publisher: Cold Spring Harbor Laboratory
Date: 19-06-2018
DOI: 10.1101/342097
Abstract: White matter fibre development in childhood involves dynamic changes to microstructural organisation driven by increasing axon diameter, density, and myelination. However, there is a lack of longitudinal studies that have quantified advanced diffusion metrics to identify regions of accelerated fibre maturation, particularly across the early pubertal period. We applied a novel longitudinal fixel-based analysis (FBA) framework, in order to estimate microscopic and macroscopic white matter changes over time. Diffusion-weighted imaging (DWI) data were acquired for 59 typically developing children (27 female) aged 9 – 13 years at two time-points approximately 16 months apart (time-point 1: 10.4 ± 0.4 years, time-point 2: 11.7 ± 0.5 years). Whole brain FBA was performed using the connectivity-based fixel enhancement method, to assess longitudinal changes in fibre microscopic density and macroscopic morphological measures, and how these changes are affected by sex, pubertal stage, and pubertal progression. Follow-up analyses were performed in sub-regions of the corpus callosum to confirm the main findings using a Bayesian repeated measures approach. There was a statistically significant increase in fibre density over time localised to medial and posterior commissural and association fibres, including the forceps major and bilateral superior longitudinal fasciculus. Increases in fibre cross-section were substantially more widespread. The rate of fibre development was not associated with age or sex. In addition, there was no significant relationship between pubertal stage or progression and longitudinal fibre development over time. Follow-up Bayesian analyses were performed to confirm the findings, which supported the null effect of the longitudinal pubertal comparison. Using a novel longitudinal fixel-based analysis framework, we demonstrate that white matter fibre density and fibre cross-section increased within a 16-month scan rescan period in specific regions. The observed increases might reflect increasing axonal diameter or axon count. Pubertal stage or progression did not influence the rate of fibre development in the early stages of puberty. Future work should focus on quantifying these measures across a wider age range to capture the full spectrum of fibre development across the pubertal period.
Theory of mind mediates the prospective relationship between abnormal social brain network morphology and chronic behavior problems after pediatric traumatic brain injury
Publisher: Oxford University Press (OUP)
Date: 21-01-2016
DOI: 10.1093/SCAN/NSW007
Influence of methylphenidate on spatial attention asymmetry in adolescents with attention deficit hyperactivity disorder (ADHD): Preliminary findings
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.NEUROPSYCHOLOGIA.2014.01.015
Abstract: Atypical asymmetries of spatial attention have been reported in children with attention deficit hyperactivity disorder (ADHD) and may be exacerbated by non-spatial factors such as attentional capacity. Although preliminary evidence suggests that asymmetries of attention in ADHD may be modifiable by the psychostimulant, methylphenidate, further placebo-controlled studies are required. This study first aimed to confirm recent evidence that increasing non-spatial processing load at fixation can unmask a spatial gradient of target detection in children with ADHD but not Controls. Second, we used placebo-controlled randomised trial methodology to ask whether 20mg of methylphenidate (MPH) could remediate any load-dependent asymmetry of spatial attention in adolescents with ADHD. Twelve male adolescents with ADHD were assessed twice in a double-blind, randomized design, under either placebo or an acute dose of methylphenidate. Thirteen typically developing adolescent Controls completed a single session under placebo. Participants completed a computer-based task in which they monitored a centrally presented rapid serial visual presentation stream for a probe stimulus, while also responding to brief peripheral events. The attentional load of the central task was manipulated by varying the target instructions but not the physical stimuli or the frequency of targets. Between-group analyses under placebo conditions indicated that increased attentional load induced a spatial gradient for target detection in the ADHD but not Controls, such that load slowed response times for left, but not, right hemi-field targets. This load-dependent spatial asymmetry in the adolescents with ADHD was abolished by administration of methylphenidate. Methylphenidate may "normalise" target detection between the hemi-fields in ADHD via enhancement of the right-lateralised ventral attention networks that support non-spatial attention.
Age, sex, and puberty related development of the corpus callosum: a multi-technique diffusion MRI study
Publisher: Cold Spring Harbor Laboratory
Date: 12-09-2017
DOI: 10.1101/187724
Abstract: The corpus callosum is integral to the central nervous system, and continually develops with age by virtue of increasing axon diameter and ongoing myelination. Magnetic resonance imaging (MRI) techniques offer a means to disentangle these two aspects of white matter development. We investigate the profile of microstructural metrics across the corpus callosum, and assess the impact of age, sex and pubertal development on these processes. This study made use of two independent paediatric populations. Multi-shell diffusion MRI data were analysed to produce a suite of diffusion tensor imaging (DTI), neurite orientation density and dispersion imaging (NODDI), and apparent fibre density (AFD) metrics. A multivariate profile analysis was performed for each diffusion metric across 10 sub isions of the corpus callosum. All diffusion metrics significantly varied across the length of the corpus callosum. AFD exhibited a strong relationship with age across the corpus callosum (partial η 2 = .65), particularly in the posterior body of the corpus callosum (partial η 2 = .72). In addition, females had significantly higher AFD compared with males, most markedly in the anterior splenium (partial η 2 = .14) and posterior genu (partial η 2 = .13). Age-matched pubertal group differences were localised to the splenium. We present evidence of a strong relationship between apparent fibre density and age, sex, and puberty during development. These results are consistent with ex vivo studies of fibre morphology, providing insights into the dynamics of axonal development in childhood and adolescence using diffusion MRI. Brain Structure & Function HBM NeuroImage Developmental Cognitive Neuroscience
Modeling the development of cognitive reserve in children: A residual index approach
Publisher: Cambridge University Press (CUP)
Date: 05-09-2023
Age-related resting-state functional connectivity of the Vigilant Attention network in children and adolescents
Publisher: Elsevier BV
Date: 11-2021
DOI: 10.1016/J.BANDC.2021.105791
Abstract: The development of Vigilant Attention (VA), the ability to focus and maintain our attention to repetitive and cognitively unchallenging tasks over time, has been investigated for more than a decade. The development of this critical executive function across the lifespan has been characterised by a rapid improvement in VA performance throughout childhood and adolescence, a steady improvement in adulthood and a slow decline in older adulthood. However, the development of the neural correlates of VA in children and adolescents remains poorly understood. Using a cross-sectional design, the present study used a meta-analytically defined VA network in children and adolescents to explore the developmental trend of the resting-state functional connectivity (rsFC) within the VA network across two independent cohorts. The results showed a linear and non-linear decrease of rsFC between the left and right VA brain regions across age. However, the results could not be reproduced in the replication cohort, potentially due to a smaller s le size. Based on previous findings from behavioural studies, the present findings suggest that changes in rsFC may underlie a developmental shift in cognitive strategies in neurotypical children and adolescents.
Development of white matter fibre density and morphology over childhood: A longitudinal fixel-based analysis
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.NEUROIMAGE.2018.08.043
Abstract: White matter fibre development in childhood involves dynamic changes to microstructural organisation driven by increasing axon diameter, density, and myelination. However, there is a lack of longitudinal studies that have quantified advanced diffusion metrics to identify regions of accelerated fibre maturation, particularly across the early pubertal period. We applied a novel longitudinal fixel-based analysis (FBA) framework, in order to estimate microscopic and macroscopic white matter changes over time. Diffusion-weighted imaging (DWI) data were acquired for 59 typically developing children (27 female) aged 9-13 years at two time-points approximately 16 months apart (time-point 1: 10.4 ± 0.4 years, time-point 2: 11.7 ± 0.5 years). Whole brain FBA was performed using the connectivity-based fixel enhancement method, to assess longitudinal changes in fibre microscopic density and macroscopic morphological measures, and how these changes are related to sex, pubertal stage, and pubertal progression. Follow-up analyses were performed in sub-regions of the corpus callosum to confirm the main findings using a Bayesian repeated measures approach. There was a statistically significant increase in fibre density over time localised to medial and posterior commissural and association fibres, including the forceps major and bilateral superior longitudinal fasciculus. Increases in fibre cross-section were substantially more widespread. The rate of fibre development was not associated with age or sex. In addition, there was no significant relationship between pubertal stage or progression and longitudinal fibre development over time. Follow-up Bayesian analyses were performed to confirm the findings, which supported the null effect of the longitudinal pubertal comparison. Using a novel longitudinal fixel-based analysis framework, we demonstrate that white matter fibre density and fibre cross-section increased within a 16-month scan rescan period in specific regions. The observed increases might reflect increasing axonal diameter or axon count. Pubertal stage or progression did not influence the rate of fibre development in the early stages of puberty. Future work should focus on quantifying these measures across a wider age range to capture the full spectrum of fibre development across the pubertal period.
Comorbidity and correlates of disruptive mood dysregulation disorder in 6–8-year-old children with ADHD
Publisher: Springer Science and Business Media LLC
Date: 30-06-2016
Dysfunction in the fronto-parietal network in attention deficit hyperactivity disorder (ADHD): An fMRI study
Publisher: Springer Science and Business Media LLC
Date: 18-01-2008
Physical Health, Media Use, and Mental Health in Children and Adolescents With ADHD During the COVID-19 Pandemic in Australia
Publisher: SAGE Publications
Date: 17-12-2020
Abstract: To examine the impact of COVID-19 restrictions among children with attention-deficit/hyperactivity disorder (ADHD). Parents of 213 Australian children (5–17 years) with ADHD completed a survey in May 2020 when COVID-19 restrictions were in place (i.e., requiring citizens to stay at home except for essential reasons). Compared to pre-pandemic, children had less exercise (Odds Ratio (OR) = 0.4 95% CI 0.3–0.6), less outdoor time (OR = 0.4 95% 0.3–0.6), and less enjoyment in activities (OR = 6.5 95% CI 4.0–10.4), while television (OR = 4.0 95% CI 2.5–6.5), social media (OR = 2.4 95% CI 1.3–4.5), gaming (OR = 2.0 95% CI 1.3–3.0), sad/depressed mood (OR = 1.8 95% CI 1.2–2.8), and loneliness (OR = 3.6 95% CI 2.3–5.5) were increased. Child stress about COVID-19 restrictions was associated with poorer functioning across most domains. Most parents (64%) reported positive changes for their child including more family time. COVID-19 restrictions were associated with both negative and positive impacts among children with ADHD.
Neural correlates of the emergence of consciousness of thirst
Publisher: Proceedings of the National Academy of Sciences
Date: 12-2012
Abstract: Thirst was induced by rapid i.v. infusion of hypertonic saline (0.51 M at 13.4 ml/min). Ten humans were neuroimaged by positron-emission tomography (PET) and four by functional MRI (fMRI). PET images were made 25 min after beginning infusion, when the sensation of thirst began to enter the stream of consciousness. The fMRI images were made when the maximum rate of increase of thirst occurred. The PET results showed regional cerebral blood flow changes similar to those delineated when thirst was maximal. These loci involved the phylogenetically ancient areas of the brain. fMRI showed activation in the anterior wall of the third ventricle, an area that is key in the genesis of thirst but is not an area revealed by PET imaging. Thus, this region plays as major a role in thirst for humans as for animals. Strong activations in the brain with fMRI included the anterior cingulate, parahippoc al gyrus, inferior and middle frontal gyri, insula, and cerebellum. When the subjects drank water to satiation, thirst declined immediately to baseline. A precipitate decline in intensity of activation signal occurred in the anterior cingulate area (Brodmann area 32) putatively related to consciousness of thirst. The intensity of activation in the anterior wall of the third ventricle was essentially unchanged, which is consistent with the fact that a significant time (15–20 min) would be needed before plasma Na concentration changed as a result of water absorption from the gut.
Examining the Prospective Relationship between Family Affective Responsiveness and Theory of Mind in Chronic Paediatric Traumatic Brain Injury
Publisher: Cambridge University Press (CUP)
Date: 11-10-2016
Abstract: Childhood and adolescence coincide with rapid structural and functional maturation of brain networks implicated in Theory of Mind (ToM) however, the impact of paediatric traumatic brain injury (TBI) on the development of these higher order skills is not well understood. ToM can be partitioned into conative ToM , defined as the ability to understand how indirect speech acts involving irony and empathy are used to influence the mental or affective state of the listener and affective ToM , concerned with understanding that facial expressions are often used for social purposes to convey emotions that we want people to think we feel. In a s le of 84 children with mild-severe TBI and 40 typically developing controls, this study examined the effect of paediatric TBI on affective and conative ToM and evaluated the respective contributions of injury-related factors (injury severity/lesion location) and non-injury-related environmental variables (socio-economic status (SES)/family functioning) to long-term ToM outcomes. Results showed that the poorest ToM outcomes were documented in association with mild-complicated and moderate TBI, rather than severe TBI. Lesion location and SES did not significantly contribute to conative or affective ToM. Post-injury family affective responsiveness was the strongest and most significant predictor of conative ToM. Results suggest that clinicians should exercise caution when prognosticating based on early clinical indicators, and that group and in idual-level outcome prediction should incorporate assessment of a range of injury- and non-injury-related factors. Moreover, the affective quality of post-injury family interactions represents a potentially modifiable risk factor, and might be a useful target for family-centred interventions designed to optimise social cognitive outcomes after paediatric TBI.
Frontoparietal function in young people with dysthymic disorder (DSM-5: Persistent depressive disorder) during spatial working memory
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.JAD.2014.01.024
Abstract: Dysthymic disorder (DD) is a depressive disorder characterised by persistent low and/or irritable mood and has been identified as a major risk factor for developing major depressive disorder (MDD). MDD and DD have been associated with executive function difficulties of working memory and attention. Little is known about how executive function networks in the brain are affected in children and adolescents with MDD and even less in DD. This study used fMRI and two spatial working memory paradigms to investigate associated brain function in young people with DD and an age-, gender- and IQ- matched typically developing group. Nineteen male patients with DD (mean age 11.2±1.5 years) diagnosed according to DSM-IV criteria and 16 typically developing boys (mean age 10.5±1.1 years) performed a mental rotation and a delay-match to s le (DMTS) task while undergoing fMRI. All participants were medication-naïve at the time of testing. Compared to typically developing young people, the DD group showed less activation in left frontal regions including left ventro- and dorsolateral prefrontal cortices (PFC) during mental rotation. Medial frontal regions including dorsomedial PFC, anterior cingulate cortex and frontal pole also showed relatively reduced activation. During the DMTS task patients showed significantly more activation in the right precuneus and posterior cingulate cortex. This was a cross-sectional study with a small s le limiting the generalizability of the results. The results complement previous findings in adults with MDD that have shown differential activation of left PFC regions during working memory tasks. Additionally, altered function of cortical midline structures in young patients with DD was identified. This supports findings in children, adolescents and adults with MDD suggesting that the pathophysiology of depressive disorders extends to DD as a risk factor for MDD and exhibits continuity over the lifespan.
White matter microstructure in boys with persistent depressive disorder
Publisher: Elsevier BV
Date: 10-2017
DOI: 10.1016/J.JAD.2017.06.020
Abstract: Persistent depressive symptoms in children and adolescents are considered a risk factor for the development of major depressive disorder (MDD) later in life. Previous research has shown alterations in white matter microstructure in pediatric MDD but discrepancies exist as to the specific tracts affected. The current study aimed to improve upon previous methodology and address the question whether previous findings of lower fractional anisotropy (FA) replicate in a s le of children with persistent depressive disorder characterized by mild but more chronic symptoms of depression. White matter microstructure was examined in 25 boys with persistent depressive disorder and 25 typically developing children. Tract specific analysis implemented with the Diffusion Tensor Imaging - ToolKit (DTI-TK) was used to probe fractional anisotropy (FA) in eleven major white matter tracts. Clusters within the left uncinate, inferior fronto-occipital and cerebrospinal tracts showed lower FA in the clinical group. FA in the left uncinate showed a negative association with self-reported symptoms of depression. The results demonstrate lower FA in several white matter tracts in children with persistent depressive disorder. These findings support the contention that early onset depression is associated with altered white matter microstructure, which may contribute to the maintenance and recurrence of symptoms.
Functional and structural brain network development in children with attention deficit hyperactivity disorder
Publisher: Wiley
Date: 29-03-2023
DOI: 10.1002/HBM.26288
Abstract: Attention deficit hyperactivity disorder (ADHD) is a prevalent childhood neurodevelopmental disorder. Given the profound brain changes that occur during childhood and adolescence, it is important to examine longitudinal changes of both functional and structural brain connectivity across development in ADHD. This study aimed to examine the development of functional and structural connectivity in children with ADHD compared to controls using graph metrics. One hundred and seventy five in iduals (91 children with ADHD and 84 non‐ADHD controls) participated in a longitudinal neuroimaging study with up to three waves. Graph metrics were derived from 370 resting state fMRI (197 Control, 173 ADHD) and 297 diffusion weighted imaging data (152 Control, 145 ADHD) acquired between the ages of 9 and 14. For functional connectivity, children with ADHD (compared to typically developing children) showed lower degree, local efficiency and betweenness centrality predominantly in parietal, temporal and visual cortices and higher degree, local efficiency and betweenness centrality in frontal, parietal, and temporal cortices. For structural connectivity, children with ADHD had lower local efficiency in parietal and temporal cortices and, higher degree and betweenness centrality in frontal, parietal and temporal cortices. Further, differential developmental trajectories of functional and structural connectivity for graph measures were observed in higher‐order cognitive and sensory regions. Our findings show that topology of functional and structural connectomes matures differently between typically developing controls and children with ADHD during childhood and adolescence. Specifically, functional and structural neural circuits associated with sensory and various higher order cognitive functions are altered in children with ADHD.
Related Organisations
Massachusetts Institute Of Technology
Location: United States of America
Chang Chun Institute Of Applied Chemistry Chinese Academy Of Sciences
Location: China
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Quantifying The Role Of Epigenetic Factors In Neurocognitive Outcomes: A Twin Study
Start Date: 2018
End Date: 2021
Funder: National Health and Medical Research Council
View Funded ActivityTrajectories In Brain Structure And Function For Children With And Without ADHD: Associations With Academic, Cognitive, Social, And Mental Health Outcomes
Start Date: 2014
End Date: 2018
Funder: National Health and Medical Research Council
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