Post-acute white matter microstructure predicts post-acute and chronic post-concussive symptom severity following mild traumatic brain injury in children

ObjectiveTo determine the utility of fractional amplitude of low frequency fluctuations (fALFF) during resting state fMRI (rs-fMRI) as an advanced neuroimaging biomarker for Mild Traumatic Brain Injury (mTBI).BackgroundmTBI is defined by a constellation of functional rather than structural deficits. As a measure of functional connectivity, fALFF has been implicated in long-term outcomes post-mTBI. It is unclear however, how longitudinal changes in fALFF may relate to the clinical presentation of mTBI.Design/Methods111 patients and 32 controls (15–50 years old) were enrolled acutely after mTBI and followed with up to 4 standardized serial assessments. Patients were enrolled at either Encounter 1 (E1), within 72 hours, or Encounter 2 (E2), 5–10 days post-injury, and returned for Encounter 3 (E3) at 15–29 days and Encounter 4 (E4) at 83–97 days. Each encounter included a clinical exam, neuropsychological assessment, as well as rs-fMRI imaging. fALFF was analyzed independently in 14 functional networks and, in grey and white matter as a function of symptom severity. Symptom severity scores (SSS) ranged from 0–132 as defined by the SCAT2 symptom evaluation.ResultsIn mTBI patients, fALFF scores across 5 functional brain networks (language, sensorimotor, visuospatial, higher-order visual, and posterior salience) differed between mTBI patients with low versus high SSS (SSS <5 and >30, respectively). Overall, greater SSS were indexed by reduced connectivity (p < 0.03, Bonferroni corrected). Further analysis also identified corresponding network pairs which were most predictive of increased SSS. White matter fALFF was not correlated with symptom severity, however, decreased grey matter fALFF was significantly correlated with greater SSS (r = −0.25, p = 0.002).ConclusionsGrey matter fALFF was correlated with mTBI symptom burden suggesting that patterns of neural connectivity relate directly to the clinical presentation of mTBI. Furthermore, differences in functional network connectivity as a function of SSS may reflect which networks are implicated in recovery of mTBI.

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Elevated Intraindividual Variability in Executive Functions and Associations with White Matter Microstructure in Veterans with Mild Traumatic Brain Injury

Journal of the International Neuropsychological Society ◽

10.1017/s1355617720000879 ◽

2020 ◽

pp. 1-10

Author(s):

Scott F. Sorg ◽

Victoria C. Merritt ◽

Alexandra L. Clark ◽

Madeleine L. Werhane ◽

Kelsey A. Holiday ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Executive Functions ◽

Mild Traumatic Brain Injury ◽

Diffusion Tensor ◽

Intraindividual Variability ◽

Ptsd Symptoms ◽

White Matter Microstructure ◽

History Of

Abstract Objective: We examined whether intraindividual variability (IIV) across tests of executive functions (EF-IIV) is elevated in Veterans with a history of mild traumatic brain injury (mTBI) relative to military controls (MCs) without a history of mTBI. We also explored relationships among EF-IIV, white matter microstructure, and posttraumatic stress disorder (PTSD) symptoms. Method: A total of 77 Veterans (mTBI = 43, MCs = 34) completed neuropsychological testing, diffusion tensor imaging (DTI), and PTSD symptom ratings. EF-IIV was calculated as the standard deviation across six tests of EF, along with an EF-Mean composite. DSI Studio connectometry analysis identified white matter tracts significantly associated with EF-IIV according to generalized fractional anisotropy (GFA). Results: After adjusting for EF-Mean and PTSD symptoms, the mTBI group showed significantly higher EF-IIV than MCs. Groups did not differ on EF-Mean after adjusting for PTSD symptoms. Across groups, PTSD symptoms significantly negatively correlated with EF-Mean, but not with EF-IIV. EF-IIV significantly negatively correlated with GFA in multiple white matter pathways connecting frontal and more posterior regions. Conclusions: Veterans with mTBI demonstrated significantly greater IIV across EF tests compared to MCs, even after adjusting for mean group differences on those measures as well as PTSD severity. Findings suggest that, in contrast to analyses that explore effects of mean performance across tests, discrepancy analyses may capture unique variance in neuropsychological performance and more sensitively capture cognitive disruption in Veterans with mTBI histories. Importantly, findings show that EF-IIV is negatively associated with the microstructure of white matter pathways interconnecting cortical regions that mediate executive function and attentional processes.

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White matter microstructure is associated with functional, cognitive and emotional symptoms 12 months after mild traumatic brain injury

Scientific Reports ◽

10.1038/s41598-017-13628-1 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 12

Author(s):

Torgeir Hellstrøm ◽

Lars T. Westlye ◽

Tobias Kaufmann ◽

Nhat Trung Doan ◽

Helene L. Søberg ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Mild Traumatic Brain Injury ◽

Emotional Symptoms ◽

White Matter Microstructure

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Brain white matter after pediatric mild traumatic brain injury: a diffusion tensor and neurite orientation and dispersion imaging study

10.1101/2021.09.09.21263356 ◽

2021 ◽

Author(s):

Ayushi Shukla ◽

Ashley L Ware ◽

Sunny Guo ◽

Bradley Gooodyear ◽

Miriam H Beauchamp ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

White Matter ◽

Mild Traumatic Brain Injury ◽

Diffusion Tensor ◽

Univariate Analysis ◽

Significant Group ◽

Brain White Matter ◽

Orthopedic Injury ◽

White Matter Microstructure

Background: Pediatric mild traumatic brain injury (mTBI) affects millions of children annually. Diffusion tensor imaging (DTI) is sensitive to axonal injuries and white matter microstructure and has been used to characterize the brain changes associated with mild traumatic brain injury (mTBI). Neurite orientation dispersion and density imaging (NODDI) is a diffusion model that can provide additional insight beyond traditional DTI metrics, but has not been examined in pediatric mTBI. The goal of this study was to employ DTI and NODDI to gain added insight into white matter alterations in children with mTBI compared to children with mild orthopedic injury (OI). Methods: Children (mTBI n=320, OI n=176) aged 8-16.99 years (12.39 ± 2.32 years) were recruited from emergency departments at five hospitals across Canada and underwent 3T MRI on average 11 days post-injury. DTI and NODDI metrics were calculated for seven major white matter tracts and compared between groups using univariate analysis of covariance controlling for age, sex, and scanner type. False discovery rate (FDR) was used to correct for multiple comparisons. Results: Univariate analysis revealed no significant group main effects or interactions in DTI or NODDI metrics. Fractional anisotropy and neurite density index in all tracts exhibited a significant positive association with age and mean diffusivity in all tracts exhibited a significant negative association with age in the whole sample. Conclusions: Overall, there were no differences between mTBI and OI groups in brain white matter microstructure from either DTI or NODDI in the seven tracts. This indicates that mTBI is associated with only relatively minor white matter differences, if any, at the post-acute stage. Brain differences may evolve at later stages of injury, so longitudinal studies with long-term follow-up are needed.

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