Microstructural abnormalities in deep and superficial white matter in youths with mild traumatic brain injury

Stojanovski, Sonja; Nazeri, Arash; Lepage, Christian; Ameis, Stephanie H.; Voineskos, Aristotle N.; Wheeler, Anne L.

doi:10.1016/j.nicl.2019.102102

Cited by 14 publications

(11 citation statements)

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“…These findings support the vulnerability of white matter to chronic effects of concussion, 33,80 and support current literature that reports differences relative to controls, and changes over time in diffusion measures in white matter after concussion in childhood. 36,81–83 Moreover, we observed stronger and more robust differences in superficial white matter than in deep white matter as these remained significant for comparisons with both the closely matched comparison group as well as the subset of children scanned on the Siemens Prisma scanners in our sensitivity analyses. This may be due to the protracted time course of superficial white matter myelination making it more vulnerable to childhood injury.…”

Section: Discussionmentioning

confidence: 69%

“…24,84,85 Damage to superficial white matter fibers has been reported in post-mortem studies of traumatic brain injury, 86,87 and diffusion differences in superficial white matter related to concussion were recently described by our group in another large pediatric population cohort with a wider age range. 36 The complex patterns of crossing fibers in these short tracts are likely more accurately captured in the current study due to the use of RSI over the simpler DTI model. 85…”

Section: Discussionmentioning

confidence: 90%

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Premature white matter microstructure in female children with a history of concussion

Nishat

Stojanovski

Scratch

et al. 2021

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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.

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Section: Discussionmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 90%

Premature white matter microstructure in female children with a history of concussion

Nishat

Stojanovski

Scratch

et al. 2021

Preprint

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“…Prior studies have attempted to address heterogeneity in white matter structure in concussions. 13-15 Using different approaches, these studies generated point summaries that accounted for the high-dimensional variability of white matter structure to better distinguish patients from controls. Our approach offers an important advantage.…”

Section: Discussionmentioning

confidence: 99%

“…10-12 Other studies aim instead to account for heterogeneity in white matter structure alterations. 13-15 Ware et al 15 built individualized maps of white matter abnormalities which revealed substantial inter-subject variability in traumatic axonal injury and minimal consistency of subject-level effects. Taylor et al 14 computed a multivariate summary measure of white matter structure across 22 major white matter bundles which achieved better classification accuracy of concussed patients from healthy controls compared to single tract measures.…”

Section: Introductionmentioning

confidence: 99%

Multi-tract multi-symptom relationships in pediatric concussion

Stojanovski

Nishat

et al. 2021

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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.

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“…First, limitations of DTI should be recognized; complex white matter fiber configurations and diverse intra‐voxel tissue organization (e.g., partial volume effects) are known to affect the accuracy of DTI measurements (Alexander et al., 2001; Tuch et al., 2002; Vos et al., 2011; Wiegell et al., 2000), precluding definitive conclusions of the potential for the collar to modulate and preserve these metrics. Future research should consider incorporating other diffusion MRI approaches with more novel and specific sequences (e.g., HARDI, Edlow & Wu, 2013) and complementary analytic techniques (e.g., neurite orientation and dispersion density imaging, Zhang, Schneider, Wheeler‐Kingshott, & Alexander, 2012), quantifying superficial (i.e., short association or “U” fibers) rather than primarily deep (e.g., long association fibers, commissural fibers) white matter (Stojanovski et al., 2019), and measures of structural connectivity (Xiao, Yang, Xi, & Chen, 2015) and/or graph theory (Bullmore & Sporns, 2009). Another limitation of DTI is that it fails to measure cerebral blood flow—which is affected by repetitive, sub‐concussive head impacts (Slobounov et al., 2017) and potentially modulated by JVC—warranting future multimodal MRI approaches to supplement the present DTI findings (e.g., arterial spin labeling, Koretsky, 2012).…”

Section: Discussionmentioning

confidence: 99%

The effects of internal jugular vein compression for modulating and preserving white matter following a season of American tackle football: A prospective longitudinal evaluation of differential head impact exposure

Diekfuss

Yuan

Foss

et al. 2020

J of Neuroscience Research

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The purpose of this clinical trial was to examine whether internal jugular vein compression (JVC)-using an externally worn neck collar-modulated the relationships between differential head impact exposure levels and pre-to postseason changes in diffusion tensor imaging (DTI)-derived diffusivity and anisotropy metrics of white matter following a season of American tackle football. Male high-school athletes (n = 284) were prospectively assigned to a non-collar group or a collar group. Magnetic resonance imaging data were collected from participants pre-and postseason and head impact exposure was monitored by accelerometers during every practice and game throughout the competitive season. Athletes' accumulated head impact exposure was systematically thresholded based on the frequency of impacts of progressively higher magnitudes (10 g intervals between 20 to 150 g) and modeled with pre-to postseason changes in DTI measures of white matter as a function of JVC neck collar wear. The findings revealed that the JVC neck collar modulated the relationships between greater high-magnitude head impact exposure (110 to 140 g) and longitudinal changes to white matter, with each group showing associations that varied in directionality. Results also revealed that the JVC neck collar group partially preserved longitudinal changes in DTI metrics. Collectively, these data indicate that a JVC neck collar can provide a mechanistic response to the diffusion and anisotropic properties of brain white matter following the highly diverse exposure to repetitive head impacts in American tackle football. Clinicaltrials.gov: NCT# 04068883.

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Microstructural abnormalities in deep and superficial white matter in youths with mild traumatic brain injury

Abstract: HighlightsDeep and superficial white matter structure was altered in youths with mild TBI.Slower processing speed was associated with superficial white matter structure in TBI.Some abnormalities were more pronounced in superficial compared to deep white matter.

Cited by 14 publications

References 59 publications

Premature white matter microstructure in female children with a history of concussion

Premature white matter microstructure in female children with a history of concussion

Multi-tract multi-symptom relationships in pediatric concussion

The effects of internal jugular vein compression for modulating and preserving white matter following a season of American tackle football: A prospective longitudinal evaluation of differential head impact exposure

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