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Maternal prenatal depression can affect child brain and behavioural development. Specifically, altered limbic network structure and function is a likely mechanism through which prenatal depression impacts the life-long mental health of exposed children. While developmental trajectories are influenced by many factors that exacerbate risk or promote resiliency, the role of child age and sex in the relationship between prenatal depression and the child brain remains unclear. Here, we review studies of associations between prenatal depression and brain structure and function, with a focus on the role of age and sex in these relationships. After exposure to prenatal depression, altered amygdala, hippocampal and frontal cortical structure, as well as changes in functional and structural connectivity within the limbic network are evident during the fetal, infant, preschool, childhood, and adolescent stages of development. Sex appears to play a key role in this relationship, with evidence of differential findings particularly in infants, with males showing smaller and females larger hippocampal and amygdala volumes following prenatal depression. Longitudinal studies in this area have only begun to emerge within the last five years and will be key to understanding critical windows of opportunity. Future research focused on the role of age and sex in this relationship is essential to further inform screening, policy, and interventions for children exposed to prenatal depression, interrupt the intergenerational transmission of depression, and ultimately support healthy brain development.
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Making causal inferences regarding human behaviour is difficult given the complex interplay between countless contributors to behaviour, including factors in the external world and our internal states. We provide a non-technical conceptual overview of challenges and opportunities for causal inference on human behaviour. The challenges include our ambiguous causal language and thinking, statistical under- or over-control, effect heterogeneity, interference, timescales of effects and complex treatments. We explain how methods optimized for addressing one of these challenges frequently exacerbate other problems. We thus argue that clearly specified research questions are key to improving causal inference from data. We suggest a triangulation approach that compares causal estimates from (quasi-)experimental research with causal estimates generated from observational data and theoretical assumptions. This approach allows a systematic investigation of theoretical and methodological factors that might lead estimates to converge or diverge across studies.
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Causalidade , Humanos , Comportamento , Projetos de PesquisaRESUMO
BACKGROUND: Adverse childhood experiences (ACEs) are often reported by youths with chronic pain, and both ACEs and chronic pain disrupt how information is processed. However, it is unknown whether changes to shared neural networks underlie the relationship between ACEs and the development of pain symptoms. This study explored the relationships between ACEs, brain efficiency, and pain symptomology in youth. METHODS: A community sample of youths aged 14-18 years underwent MRIs, answered trauma and pain questionnaires, and underwent pain sensory testing, twice, 3 months apart (Nbaseline = 44; Nfollow-up = 42). Sensory testing determined thresholds for mechanical and thermal stimuli. Global and local network efficiencies were evaluated using graph theory. Generalized estimating equations were applied to examine whether brain efficiency moderated the relationships between ACEs, pain intensity, and pain sensitivity (i.e., mechanical detection, heat pain, and temperature change thresholds). RESULTS: There was a significant interaction between ACEs and global brain efficiency in association with pain intensity (ß = -0.31, p = 0.02) and heat pain (ß = -0.29, p = 0.004). Lower global brain efficiency exacerbated the relationship between ACEs and pain intensity (θX â Y|W = -1.16 = 0.37, p = 0.05), and heat pain sensitivity (θX â Y|W = -1.30 = 0.44, p = 0.05). Higher global brain efficiency ameliorated the relationship between ACEs and pain intensity (θX â Y|W = 1.75 = -0.53, p = 0.05). CONCLUSIONS: The relationship between ACEs and pain symptomology was comparable to chronic pain phenotypes (i.e., higher pain intensity and pain thresholds) and may vary as a function of brain efficiency in youth. This stresses the importance of assessing for pain symptoms in trauma-exposed youth, as earlier identification and intervention are critical in preventing the chronification of pain. SIGNIFICANCE: This article explores the relationship between ACEs, pain symptomology, and brain efficiency in youth. ACEs may affect how the brain processes information, including pain. Youths with lower brain efficiencies that were exposed to more ACEs have pain symptomology comparable to youths with chronic pain. Understanding this relationship is important for the earlier identification of pain symptoms, particularly in vulnerable populations such as youths exposed to trauma, and is critical for preventing the chronification of pain.
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Arginine vasopressin (AVP) neurons of the hypothalamic paraventricular region (AVPPVN) mediate sex-biased social behaviors across most species, including mammals. In mice, neural sex differences are thought to be established during a critical window around birth ( embryonic (E) day 18 to postnatal (P) day 2) whereby circulating testosterone from the fetal testis is converted to estrogen in sex-dimorphic brain regions. Here, we found that AVPPVN neurons are sexually dimorphic by E15.5, prior to this critical window, and that gestational bisphenol A (BPA) exposure permanently masculinized female AVPPVN neuronal numbers, projections, and electrophysiological properties, causing them to display male-like phenotypes into adulthood. Moreover, we showed that nearly twice as many neurons that became AVP+ by P0 were born at E11 in males and BPA-exposed females compared to control females, suggesting that AVPPVN neuronal masculinization occurs between E11 and P0. We further narrowed this sensitive period to around the timing of neurogenesis by demonstrating that exogenous estrogen exposure from E14.5 to E15.5 masculinized female AVPPVN neuronal numbers, whereas a pan-estrogen receptor antagonist exposed from E13.5 to E15.5 blocked masculinization of males. Finally, we showed that restricting BPA exposure to E7.5-E15.5 caused adult females to display increased social dominance over control females, consistent with an acquisition of male-like behaviors. Our study reveals an E11.5 to E15.5 window of estrogen sensitivity impacting AVPPVN sex differentiation, which is impacted by prenatal BPA exposure.
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Compostos Benzidrílicos , Neurônios , Fenóis , Diferenciação Sexual , Animais , Compostos Benzidrílicos/toxicidade , Fenóis/toxicidade , Feminino , Masculino , Camundongos , Diferenciação Sexual/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Gravidez , Hipotálamo/metabolismo , Hipotálamo/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Arginina Vasopressina/metabolismo , Vasopressinas/metabolismo , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Núcleo Hipotalâmico Paraventricular/efeitos dos fármacos , Núcleo Hipotalâmico Paraventricular/metabolismo , Camundongos Endogâmicos C57BL , Estrogênios/metabolismo , Estrogênios/farmacologiaRESUMO
Chronic headache (persistent or recurrent headache for 3-months or longer) is highly prevalent among youth. While sleep disturbances have been associated with headache, their inter-relationship with brain connectivity remains unknown. This observational study examined whether self-report and actigraphy measures of sleep were associated with alterations to white matter tracts (i.e., uncinate fasciculus and cingulum) in youth with chronic headache versus healthy controls. Thirty youth aged 10-18 years with chronic headache and thirty controls underwent an MRI. Diffusion tensor images were obtained and mean fractional anisotropy values of the cingulum and uncinate were extracted. One-week prior to their MRI, youth wore an actigraph to obtain sleep duration, wake after sleep onset and sleep efficiency measures. Moreover, they completed questionnaires regarding their sleep quality and pain symptomatology. Linear regression was applied to examine the relationships between sleep (self-report and actigraphy), fractional anisotropy, and number of headache days per month. Self-report and actigraphy measures of sleep did not differ between patients and controls. However, poorer self-reported sleep quality was associated with lower fractional anisotropy values in the left uncinate (P = 0.05). Lower left uncinate fractional anisotropy was related to increased headache frequency (P = 0.002) in youth with chronic headache. Therefore, alterations to connectivity may be associated with the relationship between altered perceptions of sleep and headache chronicity.
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Prenatal alcohol exposure (PAE) occurs in ~11% of North American pregnancies and is the most common known cause of neurodevelopmental disabilities such as fetal alcohol spectrum disorder (FASD; ~2-5% prevalence). PAE has been consistently associated with smaller gray matter volumes in children, adolescents, and adults. A small number of longitudinal studies show altered gray matter development trajectories in late childhood/early adolescence, but patterns in early childhood and potential sex differences have not been characterized in young children. Using longitudinal T1-weighted MRI, the present study characterized gray matter volume development in young children with PAE (N = 42, 84 scans, ages 3-8 years) compared to unexposed children (N = 127, 450 scans, ages 2-8.5 years). Overall, we observed altered global and regional gray matter development trajectories in the PAE group, wherein they had attenuated age-related increases and more volume decreases relative to unexposed children. Moreover, we found more pronounced sex differences in children with PAE; females with PAE having the smallest gray matter volumes and the least age-related changes of all groups. This pattern of altered development may indicate reduced brain plasticity and/or accelerated maturation and may underlie the cognitive/behavioral difficulties often experienced by children with PAE. In conjunction with previous research on older children, adolescents, and adults with PAE, our results suggest that gray matter volume differences associated with PAE vary by age and may become more apparent in older children.
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OBJECTIVES: This study aimed to explore how the unprecedented stressors associated with the COVID-19 pandemic may have contributed to heightened levels of depression and anxiety among pregnant Indigenous persons, and identify protective individual-level factors. DESIGN: The current study used a mixed-methods design including standardised questionnaires and open-ended response questions. Using hierarchical regression models, we examined the extent to which COVID-19-related factors of service disruption (ie, changes to prenatal care, changes to birth plans and social support) were associated with mental well-being. Further, through qualitative analyses of open-ended questions, we examined the coping strategies used by pregnant Indigenous persons in response to the pandemic. SETTING: Participants responded to an online questionnaire consisting of standardised measures from 2020 to 2021. PARTICIPANTS: The study included 336 self-identifying Indigenous pregnant persons in Canada. RESULTS: Descriptive results revealed elevated rates of clinically relevant depression (52.7%) and anxiety (62.5%) symptoms among this population. 76.8% of participants reported prenatal care service disruptions, including appointment cancellations. Thematic analyses identified coping themes of staying informed, social and/or cultural connections and activities, and internal mental well-being strategies. Disruptions to services and decreased quality of prenatal care negatively impacted mental well-being of Indigenous pregnant persons during the COVID-19 pandemic. CONCLUSIONS: Given the potential for mental well-being challenges to persist and long-term effects of perinatal distress, it is important to examine the quality of care that pregnant individuals receive. Service providers should advance policies and practices that promote relationship quality and health system engagement as key factors linked to well-being during the perinatal period for Indigenous persons.
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COVID-19 , Pandemias , Feminino , Gravidez , Humanos , COVID-19/epidemiologia , Canadá/epidemiologia , Apoio Social , Cuidado Pré-NatalRESUMO
Pre-reading abilities are predictive of later reading ability and can be assessed before reading begins. However, the neural correlates of pre-reading abilities in young children are not fully understood. To address this, we examined 246 datasets collected in an accelerated longitudinal design from 81 children aged 2-6 years (age = 4.6 ± 0.98 years, 47 males). Children completed pre-reading assessments (NEPSY-II Phonological Processing and Speeded Naming) and underwent a diffusion magnetic resonance imaging (MRI) scan to assess white matter connectivity. We defined a core neural network of reading and language regions based on prior literature, and structural connections within this network were assessed using graph theory analysis. Linear mixed models accounting for repeated measures were used to test associations between children's pre-reading performance and graph theory measures for the whole bilateral reading network and each hemisphere separately. Phonological Processing scores were positively associated with global efficiency, local efficiency, and clustering coefficient in the bilateral and right hemisphere networks, as well as local efficiency and clustering coefficient in the left hemisphere network. Our findings provide further evidence that structural neural correlates of Phonological Processing emerge in early childhood, before and during early reading instruction.
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Substância Branca , Masculino , Humanos , Pré-Escolar , Imagem de Difusão por Ressonância Magnética , Imageamento por Ressonância Magnética , Cognição , Idioma , EncéfaloRESUMO
We examine structural brain characteristics across three diagnostic categories: at risk for serious mental illness; first-presenting episode and recurrent major depressive disorder (MDD). We investigate whether the three diagnostic groups display a stepwise pattern of brain changes in the cortico-limbic regions. Integrated clinical and neuroimaging data from three large Canadian studies were pooled (total n = 622 participants, aged 12-66 years). Four clinical profiles were used in the classification of a clinical staging model: healthy comparison individuals with no history of depression (HC, n = 240), individuals at high risk for serious mental illness due to the presence of subclinical symptoms (SC, n = 80), first-episode depression (FD, n = 82), and participants with recurrent MDD in a current major depressive episode (RD, n = 220). Whole-brain volumetric measurements were extracted with FreeSurfer 7.1 and examined using three different types of analyses. Hippocampal volume decrease and cortico-limbic thinning were the most informative features for the RD vs HC comparisons. FD vs HC revealed that FD participants were characterized by a focal decrease in cortical thickness and global enlargement in amygdala volumes. Greater total amygdala volumes were significantly associated with earlier onset of illness in the FD but not the RD group. We did not confirm the construct validity of a tested clinical staging model, as a differential pattern of brain alterations was identified across the three diagnostic groups that did not parallel a stepwise clinical staging approach. The pathological processes during early stages of the illness may fundamentally differ from those that occur at later stages with clinical progression.
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Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/patologia , Depressão , Imageamento por Ressonância Magnética/métodos , Canadá , NeuroimagemAssuntos
Identidade de Gênero , Minorias Sexuais e de Gênero , Feminino , Humanos , Masculino , Comportamento SexualRESUMO
OBJECTIVE: There is increasing interest in early intervention and detection strategies for youth at-risk of developing a serious mental illness (SMI). Little is known about early factors that may be related to the later development of a SMI; thus, the aim of this study was to determine what clinical factors might relate to the development of in this study psychosis, bipolar disorder and severe or recurrent major depression in at-risk youth. METHOD: The sample consisted of 162 youth aged 12-26 years at different stages of risk. Thirty-one participants developed a SMI during the study. Those who made a transition were compared on a range of baseline clinical and functional measures with those who did not make the transition. A Cox regression model was used to assess the association between measures and later development of a SMI. RESULTS: Female sex, attenuated psychotic symptoms as assessed with the Scale of Psychosis-Risk Symptoms (SOPS) and ratings on the K-10 Distress Scale, were found to be significantly associated with the later transition to mental illness. Females were 2.77 times more likely to transition compared to males. For the SOPS and K-10 scales, there is a 14% increase in the transition rate relative to a one-scale increase in SOPS and a 7% increase in the transition rate relative to a one-point increase in the K-10. CONCLUSIONS: Results from these longitudinal data provide further insight into the specific clinical measures that may be pertinent in early detection of mental illnesses.
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Transtorno Bipolar , Transtorno Depressivo , Transtornos Mentais , Transtornos Psicóticos , Masculino , Adolescente , Humanos , Feminino , Transtornos Mentais/diagnóstico , Transtornos Mentais/epidemiologia , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologia , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/epidemiologiaRESUMO
Advanced magnetic resonance imaging (MRI) techniques indicate that concussion (i.e., mild traumatic brain injury) disrupts brain structure and function in children. However, the functional connectivity of brain regions within global and local networks (i.e., functional connectome) is poorly understood in pediatric concussion. This prospective, longitudinal study addressed this gap using data from the largest neuroimaging study of pediatric concussion to date to study the functional connectome longitudinally after concussion as compared with mild orthopedic injury (OI). Children and adolescents (n = 967) 8-16.99 years with concussion or mild OI were recruited from pediatric emergency departments within 48 h post-injury. Pre-injury and 1-month post-injury symptom ratings were used to classify concussion with or without persistent symptoms based on reliable change. Subjects completed a post-acute (2-33 days) and chronic (3 or 6 months via random assignment) MRI scan. Graph theory metrics were derived from 918 resting-state functional MRI scans in 585 children (386 concussion/199 OI). Linear mixed-effects modeling was performed to assess group differences over time, correcting for multiple comparisons. Relative to OI, the global clustering coefficient was reduced at 3 months post-injury in older children with concussion and in females with concussion and persistent symptoms. Time post-injury and sex moderated group differences in local (regional) network metrics of several brain regions, including degree centrality, efficiency, and clustering coefficient of the angular gyrus, calcarine fissure, cuneus, and inferior occipital, lingual, middle occipital, post-central, and superior occipital gyrus. Relative to OI, degree centrality and nodal efficiency were reduced post-acutely, and nodal efficiency and clustering coefficient were reduced chronically after concussion (i.e., at 3 and 6 months post-injury in females; at 6 months post-injury in males). Functional network alterations were more robust and widespread chronically as opposed to post-acutely after concussion, and varied by sex, age, and symptom recovery at 1-month post-injury. Local network segregation reductions emerged globally (across the whole brain network) in older children and in females with poor recovery chronically after concussion. Reduced functioning between neighboring regions could negatively disrupt specialized information processing. Local network metric alterations were demonstrated in several posterior regions that are involved in vision and attention after concussion relative to OI. This indicates that functioning of superior parietal and occipital regions could be particularly susceptibile to the effects of concussion. Moreover, those regional alterations were especially apparent at later time periods post-injury, emerging after post-concussive symptoms resolved in most and persisted up to 6 months post-injury, and differed by biological sex. This indicates that neurobiological changes continue to occur up to 6 months after pediatric concussion, although changes emerge earlier in females than in males. Changes could reflect neural compensation mechanisms.
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Concussão Encefálica , Conectoma , Adolescente , Criança , Feminino , Humanos , Masculino , Encéfalo/diagnóstico por imagem , Concussão Encefálica/diagnóstico por imagem , Estudos Longitudinais , Estudos ProspectivosRESUMO
Characterizing how, when and where the human brain changes across the lifespan is fundamental to our understanding of developmental processes of childhood and adolescence, degenerative processes of aging, and divergence from normal patterns in disease and disorders. We aimed to provide detailed descriptions of white matter pathways across the lifespan by thoroughly characterizing white matter microstructure, white matter macrostructure, and morphology of the cortex associated with white matter pathways. We analyzed 4 large, high-quality, publicly-available datasets comprising 2789 total imaging sessions, and participants ranging from 0 to 100 years old, using advanced tractography and diffusion modeling. We first find that all microstructural, macrostructural, and cortical features of white matter bundles show unique lifespan trajectories, with rates and timing of development and degradation that vary across pathways - describing differences between types of pathways and locations in the brain, and developmental milestones of maturation of each feature. Second, we show cross-sectional relationships between different features that may help elucidate biological changes occurring during different stages of the lifespan. Third, we show unique trajectories of age-associations across features. Finally, we find that age associations during development are strongly related to those during aging. Overall, this study reports normative data for several features of white matter pathways of the human brain that will be useful for studying normal and abnormal white matter development and degeneration.
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Adults with chronic headache have altered brain hippocampal efficiency networks. Less is known about the mechanisms underlying chronic headache in youth. In total, 29 youth with chronic headache (10-18 years), and 29 healthy, age- and sex-matched controls tracked their headache attacks daily for 1-month period. Following this, they underwent a resting state functional magnetic resonance imaging scan and self-reported on their pubertal status, post-traumatic stress, anxiety, and depression symptoms. Graph-based topological analyses of brain networks, rendering hippocampal efficiency values were performed. T-tests were used to compare hippocampal efficiency metrics between patients and controls. Linear regression was used to examine significant hippocampal efficiency metrics in relation to headache frequency in patients, controlling for age, sex, pubertal status, post-traumatic stress, anxiety, and depression symptoms. Patients had higher right hippocampal global efficiency, shorter right hippocampal path length, and higher right hippocampal clustering coefficient compared to controls (P < 0.05). Higher right hippocampal global efficiency, shorter right hippocampal path length, and higher right hippocampal clustering coefficients were positively associated with greater headache frequency (P < 0.05). The hippocampus is largely involved in memory formation and retrieval, and this data provides additional support for previous findings demonstrating the importance of the hippocampus and pain memories for the chronification of pain.
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The COVID-19 pandemic was a substantial stressor, especially for pregnant individuals. We aimed to understand the impact of COVID-19-related stresses on pregnant individuals and their infants and collected survey-based data across Canada as part of the Pregnancy during the COVID-19 Pandemic (PdP) project. The dataset described here provides baseline prenatal data and basic birth outcomes from PdP participants. This data includes information from pregnant individuals as well as their infants. At enrolment and time of completion of the baseline survey, participants were pregnant, ≥17 years of age, ≤35 weeks of gestation, living in Canada, and able to read and write in English or French. Baseline data were collected between April 2020-April 2021. Infant data were collected between May 2020-December 2021. All data were collected via self-report using online questionnaires in REDCAP. Questionnaires were available in both English and French. Data were checked for completeness and plausibility, and duplicates were removed. The dataset described here includes age, education, and household income of the pregnant individuals reported at the baseline/enrollment survey. Raw scores are provided for the Edinburgh Postnatal Depression Scale (EPDS) and the PROMIS Anxiety scale. Ratings are also given for three variables describing fear of the COVID-19 virus. Birth outcomes are provided for infants, including gestational age at birth, birthweight, length, mode of delivery, and whether the infant spent time in the neonatal intensive care unit (NICU). Delivery date is reported as month and year. These data will be beneficial for anyone interested in researching stress during pregnancy or birth outcomes in the context of the COVID-19 pandemic. They will also be useful to researchers interested in examining more general effects of prenatal distress on birth outcomes in children. Data could also be compared to other datasets from the COVID-19 pandemic to establish generalizability, or to pre-pandemic datasets to determine the extent of changes during the COVID-19 pandemic.
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OBJECTIVE: Attempts by governments around the world to mitigate the spread of COVID-19 have substantially altered the early rearing environment, raising concerns about potential negative consequences for babies born during this time. The objective of this study was to determine whether infants born during the COVID-19 pandemic were at greater risk of screening positive for developmental delay compared with infants born before the pandemic. METHODS: Participants were from 2 longitudinal cohorts. The prepandemic cohort, Impact of Maternal and Paternal Postpartum Depression, recruited postpartum individuals in the period between 2015 and 2018. Infant development milestone data (Ages and Stages Questionnaire [ASQ-3]) were collected at 1-year postpartum (n = 2903), between 2016 and 2019. The pandemic cohort, Pregnancy during the Pandemic, recruited pregnant individuals between April 2020 and April 2021. Infant development milestone data (ASQ-3) were collected at 1-year postpartum (n = 3742), between May 2021 and December 2022. Sociodemographic information, pregnancy outcomes, and depression symptom data were also collected. RESULTS: In covariate-adjusted analyses, pandemic-born infants had lower mean scores and higher odds of screening positive for delay on the Communication, Gross Motor, and Personal-Social domains of the ASQ-3 compared with prepandemic infants. Sex differences showed that males and females screened "at risk" in different domains. CONCLUSION: Most pandemic-born infants display typical development, and differences between prepandemic and pandemic-born infants were small. Nevertheless, an increased risk for delayed development among pandemic-born infants suggests the need for ongoing monitoring to determine what, if any, resources and interventions are needed to support healthy child development.
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COVID-19 , Deficiências do Desenvolvimento , Criança , Gravidez , Humanos , Lactente , Masculino , Feminino , Deficiências do Desenvolvimento/epidemiologia , Deficiências do Desenvolvimento/etiologia , Pandemias , COVID-19/epidemiologia , Desenvolvimento Infantil , PaiRESUMO
BACKGROUND AND OBJECTIVES: This prospective, longitudinal cohort study examined trajectories of brain gray matter macrostructure after pediatric mild traumatic brain injury (mTBI). METHODS: Children aged 8-16.99 years with mTBI or mild orthopedic injury (OI) were recruited from 5 pediatric emergency departments. Reliable change between preinjury and 1 month postinjury symptom ratings was used to classify mTBI with or without persistent symptoms. Children completed postacute (2-33 days) and/or chronic (3 or 6 months) postinjury T1-weighted MRI, from which macrostructural metrics were derived using automated segmentation. Linear mixed-effects models were used, with multiple comparisons correction. RESULTS: Groups (N = 623; 407 mTBI/216 OI; 59% male; age mean = 12.03, SD = 2.38 years) did not differ in total brain, white, or gray matter volumes or regional subcortical gray matter volumes. However, time postinjury, age at injury, and biological sex-moderated differences among symptom groups in cortical thickness of the angular gyrus, basal forebrain, calcarine cortex, gyrus rectus, medial and posterior orbital gyrus, and the subcallosal area all corrected p < 0.05. Gray matter macrostructural metrics did not differ between groups postacutely. However, cortical thinning emerged chronically after mTBI relative to OI in the angular gyrus in older children (d [95% confidence interval] = -0.61 [-1.15 to -0.08]); and in the basal forebrain (-0.47 [-0.94 to -0.01]), subcallosal area (-0.55 [-1.01 to -0.08]), and the posterior orbital gyrus (-0.55 [-1.02 to -0.08]) in females. Cortical thinning was demonstrated for frontal and occipital regions 3 months postinjury in males with mTBI with persistent symptoms vs without persistent symptoms (-0.80 [-1.55 to -0.05] to -0.83 [-1.56 to -0.10]) and 6 months postinjury in females and younger children with mTBI with persistent symptoms relative to mTBI without persistent symptoms and OI (-1.42 [-2.29 to -0.45] to -0.91 [-1.81 to -0.01]). DISCUSSION: These findings signal little diagnostic and prognostic utility of postacute gray matter macrostructure in pediatric mTBI. However, mTBI altered the typical course of cortical gray matter thinning up to 6 months postinjury, even after symptoms typically abate in most children. Collapsing across symptom status obscured the neurobiological heterogeneity of discrete clinical outcomes after pediatric mTBI. The results illustrate the need to examine neurobiology in relation to clinical outcomes and within a neurodevelopmental framework.
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Concussão Encefálica , Lesões Encefálicas , Feminino , Humanos , Masculino , Criança , Concussão Encefálica/diagnóstico por imagem , Estudos Longitudinais , Estudos Prospectivos , Substância Cinzenta/diagnóstico por imagem , Afinamento Cortical CerebralRESUMO
Advanced diffusion-weighted imaging techniques have increased understanding of the neuropathology of paediatric mild traumatic brain injury (i.e. concussion). Most studies have examined discrete white-matter pathways, which may not capture the characteristically subtle, diffuse and heterogenous effects of paediatric concussion on brain microstructure. This study compared the structural connectome of children with concussion to those with mild orthopaedic injury to determine whether network metrics and their trajectories across time post-injury differentiate paediatric concussion from mild traumatic injury more generally. Data were drawn from of a large study of outcomes in paediatric concussion. Children aged 8-16.99 years were recruited from five paediatric emergency departments within 48â h of sustaining a concussion (n = 360; 56% male) or mild orthopaedic injury (n = 196; 62% male). A reliable change score was used to classify children with concussion into two groups: concussion with or without persistent symptoms. Children completed 3â T MRI at post-acute (2-33 days) and/or chronic (3 or 6 months, via random assignment) post-injury follow-ups. Diffusion-weighted images were used to calculate the diffusion tensor, conduct deterministic whole-brain fibre tractography and compute connectivity matrices in native (diffusion) space for 90 supratentorial regions. Weighted adjacency matrices were constructed using average fractional anisotropy and used to calculate global and local (regional) graph theory metrics. Linear mixed effects modelling was performed to compare groups, correcting for multiple comparisons. Groups did not differ in global network metrics. However, the clustering coefficient, betweenness centrality and efficiency of the insula, cingulate, parietal, occipital and subcortical regions differed among groups, with differences moderated by time (days) post-injury, biological sex and age at time of injury. Post-acute differences were minimal, whereas more robust alterations emerged at 3 and especially 6 months in children with concussion with persistent symptoms, albeit differently by sex and age. In the largest neuroimaging study to date, post-acute regional network metrics distinguished concussion from mild orthopaedic injury and predicted symptom recovery 1-month post-injury. Regional network parameters alterations were more robust and widespread at chronic timepoints than post-acutely after concussion. Results suggest that increased regional and local subnetwork segregation (modularity) and inefficiency occurs across time after concussion, emerging after post-concussive symptom resolve in most children. These differences persist up to 6 months after concussion, especially in children who showed persistent symptoms. While prognostic, the small to modest effect size of group differences and the moderating effects of sex likely would preclude effective clinical application in individual patients.
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Introduction: Prenatal alcohol exposure (PAE) contributes to widespread neurodevelopmental challenges, including reading, and has been associated with altered white matter. Here, we aimed to investigate whether arcuate fasciculus (AF) development is associated with pre-reading language skills in young children with PAE. Methods: A total of 51 children with confirmed PAE (25 males; 5.6 ± 1.1 years) and 116 unexposed controls (57 males; 4.6 ± 1.2 years) underwent longitudinal diffusion tensor imaging (DTI), for a total of 111 scans from participants with PAE and 381 scans in the unexposed control group. We delineated the left and right AF and extracted mean fractional anisotropy (FA) and mean diffusivity (MD). Pre-reading language ability was assessed using age-standardized phonological processing (PP) and speeded naming (SN) scores of the NEPSY-II. Linear mixed effects models were run to determine the relationship between diffusion metrics and age, group, sex, and age-by-group interactions, with subject modeled as a random factor. A secondary mixed effect model analysis assessed the influence of white matter microstructure and PAE on pre-reading language ability using diffusion metric-by-age-by-group interactions, with 51 age- and sex-matched unexposed controls. Results: Phonological processing (PP) and SN scores were significantly lower in the PAE group (p < 0.001). In the right AF, there were significant age-by-group interactions for FA (p < 0.001) and MD (p = 0.0173). In the left AF, there was a nominally significant age-by-group interaction for MD that failed to survive correction (p = 0.0418). For the pre-reading analysis, a significant diffusion-by-age-by-group interaction was found for left FA (p = 0.0029) in predicting SN scores, and for the right FA (p = 0.00691) in predicting PP scores. Discussion: Children with PAE showed altered developmental trajectories for the AF, compared with unexposed controls. Children with PAE, regardless of age, showed altered brain-language relationships that resembled those seen in younger typically developing children. Our findings support the contention that altered developmental trajectories in the AF may be associated with functional outcomes in young children with PAE.
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BACKGROUND: The prevalence of prenatal depressive symptoms has more than doubled during the COVID-19 pandemic, raising substantial concerns about child outcomes including sleep problems and altered brain development. The objective of this work was to determine relationships between prenatal depressive symptoms, infant brain network structure, and infant sleep. METHODS: Pregnant individuals were recruited as part of the Pregnancy during the Pandemic (PdP) study. Maternal depressive symptoms were measured in pregnancy and postpartum. When infants of those participants were 3 months of age (n=66; 26 females), infants underwent diffusion magnetic resonance imaging and infant sleep was evaluated. Using tractography, we calculated structural connectivity matrices for the default mode (DMN) and limbic networks. We examined associations between graph theory metrics of infant brain networks and prenatal maternal depressive symptoms, with infant sleep as a moderator. RESULTS: Prenatal depressive symptoms were negatively related to average DMN clustering coefficient and local efficiency in infant brains. Infant sleep duration was related to DMN global efficiency and moderated the relationship between prenatal depressive symptoms and density of limbic connections such that infants who slept less had a more negative relationship between prenatal depressive symptoms and local brain connectivity. CONCLUSIONS: Prenatal depressive symptoms appear to impact early topological development in brain networks important for emotion regulation. In the limbic network, sleep duration moderated this relationship, suggesting sleep may play a role in infant brain network development.