As maturation of the brain continues throughout development, there is a risk of interference from concussions which are common in childhood. A concussion can cause widespread disruption to axons and inflammation in the brain and may influence emerging cognitive abilities. Females are more likely to experience persistent problems after a concussion, yet the sex-specific impact of concussions on brain microstructure in childhood is not well understood.In children from a large population sample, this study (1) investigated differences in white matter and cortical microstructure between children with and without a history of concussion, and (2) examined relationships between altered brain microstructure and cognitive performance.Neurite density measures from diffusion weighted magnetic resonance imaging were examined in 9-to 10-year-old children in the Adolescent Brain Cognitive Development Study with (n = 336) and without (n = 7368) a history of concussion. (1) Multivariate regression models were used to investigate the relationships between concussion history, sex, and age in the deep white matter, superficial white matter, subcortical structures, and cortex. (2) Principal component analysis was performed on neurite density, and components were examined in relation to performance on the Flanker Inhibitory Control and Attention Task and the Pattern Comparison Processing Speed Task to investigate the relationship between altered neurite density and cognitive performance.Neurite density in all tissue types demonstrated robust positive relationships with age reflecting maturation of brain microstructure. (1) Comparisons between children with and without a history of concussion revealed higher neurite density in deep and superficial white matter in females with concussion. No group differences were observed in subcortical or cortical neurite density. (2) Higher neurite density in superficial white matter beneath the frontal and temporal cortices was associated with lower scores on the processing speed test in females with concussion, and higher scores on the processing speed test in males with concussion.These findings suggest that concussion in childhood leads to premature white matter maturation in females and that this may be associated with slower processing speed. These sex-specific effects on the developing brain may contribute to the enhanced vulnerability to persistent symptoms after concussion in females.

The heterogeneity of white matter damage and symptoms in concussions has been identified as a major obstacle to therapeutic innovation. In contrast, the vast majority of diffusion MRI studies on concussion have traditionally employed group-comparison approaches. Such studies do not consider heterogeneity of damage and symptoms in concussion. To parse concussion heterogeneity, the present study combines diffusion MRI (dMRI) and multivariate statistics to investigate multi-tract multi-symptom relationships. Using dMRI data from a sample of 306 children ages 9 and 10 with a history of concussion from the Adolescent Brain Cognitive Development Study (ABCD study), we built connectomes weighted by classical and emerging diffusion measures. These measures were combined into two informative indices, the first capturing a mixture of patterns suggestive of microstructural complexity, the second representing almost exclusively axonal density. We deployed pattern-learning algorithms to jointly decompose these connectivity features and 19 behavioural measures that capture well-known symptoms of concussions. We found idiosyncratic symptom-specific multi-tract connectivity features, which would not be captured in traditional univariate analyses. Multivariable connectome-symptom correspondences were stronger than all single-tract/single-symptom associations. Multi-tract connectivity features were also expressed equally across different sociodemographic strata and their expression was not accounted for by injury-related variables. In a replication dataset, the expression of multi-tract connectivity features predicted adverse psychiatric outcomes after accounting for other psychopathology-related variables. By defining cross-demographic multi-tract multi-symptom relationships to parse concussion heterogeneity, the present study can pave the way for the development of improved stratification strategies that may contribute to the success of future clinical trials and the improvement of concussion management.

Background: Response inhibition engages the cortico-striato-thalamo-cortical (CSTC) circuit, which has been implicated in children, and youth with obsessive compulsive disorder (OCD). This study explored whether CSTC engagement during response inhibition, measured using magnetoencephalography (MEG), differed in a sample of medication-naïve youth with OCD, compared to typically developing controls (TDC).Methods: Data was analyzed in 17 medication-naïve children and youth with OCD (11.7 ± 2.2 SD years) and 13 TDC (12.6 ± 2.2 SD years). MEG was used to localize and characterize neural activity during a Go/No-Go task. Task performance on Go/No-Go conditions and regional differences in amplitude of activity during Go and No-Go condition between OCD vs. TDC were examined using two-sample t-tests. Post-hoc analysis with Bayesian t-tests was used to estimate the certainty of outcomes.Results: No differences in Go/No-Go performance were found between OCD and TDC groups. In response to the visual cue presented during the Go condition, participants with OCD showed significantly increased amplitude of activity in the primary motor (MI) cortex compared to TDC. In addition, significantly reduced amplitude of PCu was found following successful stopping to No-Go cues in OCD vs. TDC during No-Go task performance. Bayesian t-tests indicated high probability and large effect sizes for the differences in MI and PCu amplitude found between groups.Conclusion: Our preliminary study in a small medication-naïve sample extends previous work indicating intact response inhibition in pediatric OCD. While altered neural response in the current study was found during response inhibition performance in OCD, differences localized to regions outside of the CSTC. Our findings suggest that additional imaging research in medication-naïve samples is needed to clarify regional differences associated with OCD vs. influenced by medication effects, and suggest that MEG may be sensitive to detecting such differences.

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Some children that experience a concussion exhibit long-lasting emotional and behavioral problems post injury, with greater rates of persistent problems in females. Establishing the contribution of (1) pre-existing behavioral problems and (2) disrupted maturation of the brain′s vulnerable white matter, to long-lasting behavioral problems has been a challenge due to a lack of pre-injury behavioral and imaging data. From the Adolescent Brain Cognitive Development Cohort, this study examined 204 11-12-year-old children who experienced a concussion after baseline data collection at age 9-10-years-old. Internalizing and externalizing behavioral problems were assessed with the Child Behavior Checklist. In 99 of these children with MRI data available, white matter microstructure was characterized in deep and superficial white matter by neurite density from restriction spectrum image modeling of diffusion MRI. Linear regressions modeled 1) post-concussion behavior symptoms controlling for pre-injury behavior, 2) the impact of concussion on white matter maturation, and 3) the contribution of deviations in white matter maturation to post-concussion behavior symptoms. When controlling for pre-injury scores, post-injury internalizing and externalizing scores were higher in female but not male children with concussion compared to children with no concussion. Group comparisons of change in neurite density over two years reflecting white matter maturation demonstrated an age-dependent effect whereby younger female children had less change in neurite density over time than younger children with no concussion. In female children with concussion, less change in superficial white matter neurite density over time was associated with more internalizing behavior problems. These results suggest that in female children, concussions are associated with behavior problems beyond those that exist pre-injury, and injury to the brain's vulnerable white matter may be a biological substrate underlying persistent internalizing behaviors.

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