Structural Injuries Are Associated with Better Emotional Well-being after Traumatic Brain Injury

ABSTRACT Background Emotional disturbances are common after traumatic brain injury (TBI), yet the neuroanatomic basis of these sequalae remains unclear. We aimed to determine whether emotional wellbeing is associated with the extent and/or location of structural brain injury in individuals with chronic TBI. Methods We studied 188 adults with chronic (≥1 year post-injury) TBI enrolled in the multi-center Late Effects of TBI (LETBI) study. Participants underwent T1-weighted MRI to assess cortical lesion location and volume, and diffusion MRI to measure global mean white matter fractional anisotropy (FA), defined as the mean FA across 40 white matter tracts. The primary outcome was emotional wellbeing, measured as the RAND-36 emotional wellbeing subscale t score. To identify associations between structural injury and the primary outcome, we used multivariate linear models adjusted for age, sex, years of education, time since injury, history of psychiatric illness, and multiple indices of scan quality. Results The cohort was predominantly male (68%) and white (88%), with a mean age of 58 years (SD 15) and median time since injury of 8 years (IQR 14). The presence of cortical lesions was independently associated with greater emotional wellbeing scores (RAND-36 adjusted t score was 4.1; 95% CI: [1.0, 7.0] points higher in participants with versus without lesions; p=0.009). Right temporal and lateral orbitofrontal lesions associated with lower (worse) emotional wellbeing scores, and left hemispheric lesions associated with higher (better) scores. Lower global white matter FA was independently associated with greater emotional wellbeing scores (RAND-36 adjusted t score was 2.7 [0.8, 4.7] points higher per 1 SD decrease in FA; p = 0.008). The strongest associations between individual white matter tract integrity and emotional wellbeing were in the anterior (genu) corpus callosum (β = -3.0, [-1.3, -4.7]; pHolm=0.034) and the left cingulum bundle (β = -3.0, [-1.2, -4.8]; pHolm=0.048). Conclusions In a large cohort of participants with chronic TBI, structural brain injuries were associated with better emotional wellbeing scores. These findings challenge traditional interpretations of emotional disturbances after TBI and motivate future studies to determine whether specific structural brain injury locations may be causally associated with improvements in emotional wellbeing.