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

Emotional disturbances are common after traumatic brain injury (TBI), yet the neuroanatomic basis of these sequelae remains unclear. We aimed to determine whether emotional well-being is associated with the extent and/or location of structural brain injury in individuals with chronic TBI. We studied 188 adults with chronic (≥1 year postinjury) TBI enrolled in the multicenter Late Effects of TBI (LETBI) study. Participants underwent T1-weighted MRI to assess cortical lesion location and volume, and diffusion MRI to measure white matter fractional anisotropy (FA). The primary outcome was emotional well-being, measured as the RAND-36 emotional well-being subscale T score. To identify associations between structural injury and the primary outcome, we used multivariable linear models adjusted for age, sex, years of education, time since injury, history of seeking psychiatric care, and multiple indices of scan quality. 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 well-being scores (RAND-36 adjusted T score was 4.1; 95% CI: [1.0, 7.0] points higher in participants with vs without lesions; p = 0.009). Right temporal and lateral orbitofrontal lesions are associated with lower (worse) emotional well-being scores, and left hemispheric lesions are associated with higher (better) scores. Lower global white matter FA was independently associated with greater emotional well-being 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 well-being were in the anterior (genu) corpus callosum (β = -3.0, [-1.3, -4.7]; p_Holm = 0.034) and the left cingulum bundle (β = -3.0, [-1.2, -4.8]; p_Holm = 0.048). In a large cohort of participants with chronic TBI, structural brain injuries were associated with better emotional well-being 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 well-being.