Emotional Resilience Predicts Preserved White Matter Microstructure Following Mild Traumatic Brain Injury

Abstract

Background: Adult patients with mild traumatic brain injury (mTBI) exhibit distinct phenotypes of emotional and cognitive functioning identified by latent profile analysis of clinical neuropsychological assessments. When discerned early after injury, these latent clinical profiles have been found to improve prediction of long-term outcomes from mTBI. The present study hypothesized that white matter (WM) microstructure is better preserved in an emotionally resilient mTBI phenotype compared with a neuropsychiatrically distressed mTBI phenotype.

Methods: The present study used diffusion magnetic resonance imaging to investigate and compare WM microstructure in major association, projection, and commissural tracts between the two phenotypes and over time. Diffusion magnetic resonance images from 172 patients with mTBI were analyzed to compute individual diffusion tensor imaging maps at 2 weeks and 6 months after injury.

Results: By comparing the diffusion tensor imaging parameters between the two phenotypes at global, regional, and voxel levels, emotionally resilient patients were shown to have higher axial diffusivity compared with neuropsychiatrically distressed patients early after mTBI. Longitudinal analysis revealed greater compromise of WM microstructure in neuropsychiatrically distressed patients, with greater decrease of global axial diffusivity and more widespread decrease of regional axial diffusivity during the first 6 months after injury compared with emotionally resilient patients.

Conclusions: These results provide neuroimaging evidence of WM microstructural differences underpinning mTBI phenotypes identified from neuropsychological assessments and show differing longitudinal trajectories of these biological effects. These findings suggest that diffusion magnetic resonance imaging can provide short- and long-term imaging biomarkers of resilience.

Keywords: DTI; Diffusion MRI; Neuroimaging; Neuropsychology; Resilience; Traumatic brain injury.

Figure 1:

Hypothesized roles of resilience versus DAI on WM microstructural integrity and clinical outcomes after mTBI. Solid boxes represent observed variables; dashed boxes represent unobserved variables. Red arrows and boxes denote negative effects; green arrows/boxes denote positive effects; gold arrows/boxes reflect transitions between observed variables. Larger arrows signify a larger effect. A. What the injury brings to the brain: The ER and ND patients are assumed to have no difference in preinjury resilience. Differing intensities of DAI are postulated to cause the LPA cluster segregation of the two phenotypes as well as the expected DTI differences (red arrows) that gradually increase between 2 weeks and 6 months postinjury due to group differences in axonal degeneration (red box) that impact clinical outcome. B. What the brain brings to the injury: The ER and ND patients are assumed to be different in preinjury resilience, but not DAI severity. In this scenario, the initial differences of DTI metrics at 2 weeks are largely due to premorbid differences in resilience and the enlarging differences expected at 6 months are due to adaptive versus maladaptive responses to the mTBI among the ER versus ND patients (green box).

Figure 2:

Global axial diffusivity (AD) comparison between the ER patients (blue dots) and the ND patients (orange dots). The black bars show the mean and its 95% confidence intervals for the group of dots. A. ER (1.112 ± 0.045 × 10⁻³ mm·s⁻¹) had higher AD than ND (1.098 ± 0.047 × 10⁻³ mm·s⁻¹) at 2 weeks after mTBI. B. ER (1.111± 0.044 × 10⁻³ mm·s⁻¹) had higher AD than ND (1.091 ± 0.046 × 10⁻³ mm·s⁻¹) at 6 months after mTBI. C. The longitudinal change of global AD computed as the value at 6 months minus the value at 2 weeks. ND (−0.671 ± 1.944 × 10⁻⁵ mm·s⁻¹) showed more negative changes than ER (−0.124 ± 1.582 × 10⁻⁵ mm·s⁻¹, not significantly different from zero).

Figure 3:

The longitudinal change of AD computed as the value at the second timepoint minus the value at the first timepoint. A red star on the abscissa denotes a significant longitudinal change after FDR correction. Association tracts: SS - sagittal stratum. Projection tracts: PCR - posterior corona radiata; PLIC - posterior limb internal capsule; PTR - posterior thalamic radiation. Commissural tracts: BCC/GCC - body/genu of corpus callosum. Brainstem and cerebellar tracts: CP - cerebral peduncle; ICP/MCP/SCP -inferior/middle/superior cerebellar peduncle; PCT - pontine crossing tract.

Figure 4:

Voxelwise statistics of AD comparison between ER and ND at 2 weeks (A at the top) and 6 months (B at the bottom). The colorbar on the right shows the range of p-values from 0.05 to 0 corrected for multiple voxelwise comparisons: red is marginally significant while yellow is highly significant. The statistical significance represents ER patients with higher AD than ND patients in a given WM voxel. In each row, nine slices of the axial view of brain lay out sequentially, with the z-coordinate labeled at the bottom.

Figure 5:

Histograms of outcomes of Glasgow Outcome Scale Extended (GOSE) measure of disability and Rivermead Postconcussion Questionnaire (RPQ) measure of TBI symptoms at six months postinjury, stratified by clinical phenotypes identified at two weeks postinjury. Blue represents the ER cohort and orange the ND cohort.