Abstract
Working memory impairment is one of the most troubling and persistent symptoms after mild traumatic brain injury (MTBI). Here we investigate how working memory deficits relate to detectable WM microstructural injuries to discover robust biomarkers that allow early identification of patients with MTBI at the highest risk of working memory impairment. Multi-shell diffusion MR imaging was performed on a 3T scanner with 5 b-values. Diffusion metrics of fractional anisotropy, diffusivity and kurtosis (mean, radial, axial), and WM tract integrity were calculated. Auditory-verbal working memory was assessed using the Wechsler Adult Intelligence Scale, 4th ed, subtests: 1) Digit Span including Forward, Backward, and Sequencing; and 2) Letter-Number Sequencing. We studied 19 patients with MTBI within 4 weeks of injury and 20 healthy controls. Tract-Based Spatial Statistics and ROI analyses were performed to reveal possible correlations between diffusion metrics and working memory performance, with age and sex as covariates. ROI analysis found a significant positive correlation between axial kurtosis and Digit Span Backward in MTBI (Pearson r = 0.69, corrected P = .04), mainly present in the right superior longitudinal fasciculus, which was not observed in healthy controls. Patients with MTBI also appeared to lose the normal associations typically seen in fractional anisotropy and axonal water fraction with Letter-Number Sequencing. Tract-Based Spatial Statistics results also support our findings. Differences between patients with MTBI and healthy controls with regard to the relationship between microstructure measures and working memory performance may relate to known axonal perturbations occurring after injury.
Highlights
BACKGROUND AND PURPOSEWorking memory impairment is one of the most troubling and persistent symptoms after mild traumatic brain injury (MTBI)
ROI analysis found a significant positive correlation between axial kurtosis and Digit Span Backward in MTBI (Pearson r ϭ 0.69, corrected P ϭ .04), mainly present in the right superior longitudinal fasciculus, which was not observed in healthy controls
Differences between patients with MTBI and healthy controls with regard to the relationship between microstructure measures and working memory performance may relate to known axonal perturbations occurring after injury
Summary
Multi-shell diffusion MR imaging was performed on a 3T scanner with 5 b-values. Diffusion metrics of fractional anisotropy, diffusivity and kurtosis (mean, radial, axial), and WM tract integrity were calculated. We studied patients with MTBI within 4 weeks of injury and healthy controls. Tract-Based Spatial Statistics and ROI analyses were performed to reveal possible correlations between diffusion metrics and working memory performance, with age and sex as covariates. Inclusion criteria were the following: 1) adult individuals in the age range of 18 – 65 years; 2) diagnostic MTBI criteria defined by the American Congress of Rehabilitation Medicine,[26] including either loss of consciousness of Ͻ30 minutes or altered consciousness at time of the accident and a Glasgow Outcome Score of 13–15; and 3) injury within 4 weeks. Formal neurocognitive tests including the WAIS-IV working memory subtests were performed, and MR images were acquired within 1 day of neurocognitive tests. Subgroups of the subjects in this study were previously included in 2 works with nonoverlapping hypotheses.[24,27]
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