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Epigenetic processes, such as DNA methylation, show potential as biological markers and mechanisms underlying gene-environment interplay in the prediction of mental health and other brain-based phenotypes. However, little is known about how peripheral epigenetic patterns relate to individual differences in the brain itself. An increasingly popular approach to address this is by combining epigenetic and neuroimaging data; yet, research in this area is almost entirely comprised of cross-sectional studies in adults. To bridge this gap, we established the Methylation, Imaging and NeuroDevelopment (MIND) Consortium, which aims to bring a developmental focus to the emerging field of Neuroimaging Epigenetics by (i) promoting collaborative, adequately powered developmental research via multi-cohort analyses; (ii) increasing scientific rigor through the establishment of shared pipelines and open science practices; and (iii) advancing our understanding of DNA methylation-brain dynamics at different developmental periods (from birth to emerging adulthood), by leveraging data from prospective, longitudinal pediatric studies. MIND currently integrates 15 cohorts worldwide, comprising (repeated) measures of DNA methylation in peripheral tissues (blood, buccal cells, and saliva) and neuroimaging by magnetic resonance imaging across up to five time points over a period of up to 21 years (Npooled DNAm = 11,299; Npooled neuroimaging = 10,133; Npooled combined = 4,914). By triangulating associations across multiple developmental time points and study types, we hope to generate new insights into the dynamic relationships between peripheral DNA methylation and the brain, and how these ultimately relate to neurodevelopmental and psychiatric phenotypes.
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BACKGROUND: Despite higher rates of irritability and socioemotional symptoms in ADHD, consensus is lacking regarding their developmental relationship and whether it differs by ADHD status. This longitudinal study sought to evaluate how peer and emotional difficulties relate to irritability in ADHD and control groups. METHODS: A community sample of 336 participants (45 % ADHD) were recruited for the Children's Attention Project. Participants completed the Affective Reactivity Index and the Strengths and Difficulties Questionnaire's emotional and peer difficulties scales at baseline (mean age 10.5 years) and 18-month follow-up. Latent Change Score models assessed how emotional and peer difficulties related to irritability at baseline and longitudinally. RESULTS: For both groups, more severe baseline difficulties were associated with higher concurrent irritability, and reductions in emotional and peer difficulties were associated with declining irritability. Baseline emotional difficulties predicted change in irritability for the ADHD group, while baseline peer difficulties predicted change in irritability for both groups. Baseline irritability did not predict change in emotional or peer difficulties for either. The ADHD group showed elevated irritability, emotional, and peer difficulties, and stronger baseline correlation between peer difficulties and irritability. LIMITATIONS: Only two timepoints were captured, and associations with ADHD symptom severity and presentation were not investigated. Doing so may facilitate additional insights. CONCLUSIONS: Change in irritability corresponded to change in socioemotional difficulties, and was driven by earlier levels of socioemotional difficulties. ADHD exacerbated aspects of the relationship between socioemotional difficulties and irritability. Socioemotional difficulties drive irritability, so may represent targets for clinical interventions.
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Trastorno por Déficit de Atención con Hiperactividad , Niño , Humanos , Trastorno por Déficit de Atención con Hiperactividad/psicología , Estudios Longitudinales , Genio IrritableRESUMEN
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 individuals 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 individuals with ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , Sustancia Blanca , Niño , Humanos , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Tractos Piramidales/diagnóstico por imagen , Estudios Prospectivos , Encéfalo , Sustancia Blanca/diagnóstico por imagenRESUMEN
BACKGROUND: 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. METHODS: A community sample 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. RESULTS: 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. CONCLUSIONS: 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.
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Trastorno por Déficit de Atención con Hiperactividad , Adolescente , Humanos , Niño , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Conducta Impulsiva , Genio Irritable , CogniciónRESUMEN
OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: The Strengths and Difficulties Questionnaire should not be used with Aboriginal and Torres Strait Islander children.
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Aborigenas Australianos e Isleños del Estrecho de Torres , Problema de Conducta , Niño , Femenino , Humanos , Masculino , Estudios Longitudinales , Padres , Encuestas y Cuestionarios , Preescolar , AdolescenteRESUMEN
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.
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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.
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Trastorno por Déficit de Atención con Hiperactividad , Trastorno Depresivo , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico por imagen , Encéfalo , Humanos , Imagen por Resonancia Magnética , Masculino , Memoria a Corto Plazo/fisiologíaRESUMEN
OBJECTIVE: To examine the impact of COVID-19 restrictions among children with attention-deficit/hyperactivity disorder (ADHD). METHODS: 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). RESULTS: 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. CONCLUSIONS: COVID-19 restrictions were associated with both negative and positive impacts among children with ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , COVID-19 , Adolescente , Trastorno por Déficit de Atención con Hiperactividad/epidemiología , Australia/epidemiología , Niño , Humanos , Salud Mental , Pandemias , SARS-CoV-2RESUMEN
Diffusion MRI has provided the neuroimaging community with a powerful tool to acquire in-vivo data sensitive to microstructural features of white matter, up to 3 orders of magnitude smaller than typical voxel sizes. The key to extracting such valuable information lies in complex modelling techniques, which form the link between the rich diffusion MRI data and various metrics related to the microstructural organization. Over time, increasingly advanced techniques have been developed, up to the point where some diffusion MRI models can now provide access to properties specific to individual fibre populations in each voxel in the presence of multiple "crossing" fibre pathways. While highly valuable, such fibre-specific information poses unique challenges for typical image processing pipelines and statistical analysis. In this work, we review the "Fixel-Based Analysis" (FBA) framework, which implements bespoke solutions to this end. It has recently seen a stark increase in adoption for studies of both typical (healthy) populations as well as a wide range of clinical populations. We describe the main concepts related to Fixel-Based Analyses, as well as the methods and specific steps involved in a state-of-the-art FBA pipeline, with a focus on providing researchers with practical advice on how to interpret results. We also include an overview of the scope of all current FBA studies, categorized across a broad range of neuro-scientific domains, listing key design choices and summarizing their main results and conclusions. Finally, we critically discuss several aspects and challenges involved with the FBA framework, and outline some directions and future opportunities.
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Encéfalo/citología , Encéfalo/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Procesamiento de Imagen Asistido por Computador/métodos , Sustancia Blanca/diagnóstico por imagen , Encéfalo/fisiología , Imagen de Difusión por Resonancia Magnética/tendencias , Humanos , Procesamiento de Imagen Asistido por Computador/tendencias , Fibras Nerviosas/fisiología , Sustancia Blanca/fisiologíaRESUMEN
Previous studies of white matter organization in sensorimotor tracts in developmental coordination disorder (DCD) have adopted diffusion tensor imaging (DTI), a method unable to reconcile pathways with 'crossing fibres'. In response to limitations of the commonly adopted DTI approach, the present study employed a framework that can reconcile the 'crossing fibre' problem (i.e., constrained spherical deconvolution- CSD) to characterize white matter tissue organization of sensorimotor tracts in young adults with DCD. Participants were 19 healthy adults aged 18-46: 7 met diagnostic criteria for DCD (4 females) and 12 were controls (3 females). All underwent high angular diffusion MRI. After preprocessing, the left and right corticospinal tracts (CST) and superior longitudinal fasciculi (SLF) were delineated and all tracts were then generated using both CSD and DTI tractography respectively. Based on the CSD model, individuals with DCD demonstrated significantly decreased mean apparent fibre density (AFD) in the left SLF relative to controls (with large effect size, Cohen's dâ¯=â¯1.32) and a trend for decreased tract volume of the right SLF (with medium-large effect size, Cohen's dâ¯=â¯0.73). No differences in SLF microstructure were found between groups using DTI, nor were differences in CST microstructure observed across groups regardless of hemisphere or diffusion model. Our data are consistent with the view that motor impairment characteristic of DCD may be subserved by white matter abnormalities in sensorimotor tracts, specifically the left and right SLF. Our data further highlight the benefits of higher order diffusion MRI (e.g. CSD) relative to DTI for clarifying earlier inconsistencies in reports speaking to white matter organization in DCD, and its contribution to poor motor skill in DCD.
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Encéfalo/diagnóstico por imagen , Encéfalo/patología , Procesamiento de Imagen Asistido por Computador/métodos , Trastornos de la Destreza Motora/diagnóstico por imagen , Trastornos de la Destreza Motora/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Adolescente , Adulto , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Tractos Piramidales/diagnóstico por imagen , Tractos Piramidales/patología , Adulto JovenRESUMEN
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 hippocampus 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."