Altered lateralization of the cingulum in deployment‐related traumatic brain injury: An ENIGMA military‐relevant brain injury study

Abstract

Traumatic brain injury (TBI) in military populations can cause disruptions in brain structure and function, along with cognitive and psychological dysfunction. Diffusion magnetic resonance imaging (dMRI) can detect alterations in white matter (WM) microstructure, but few studies have examined brain asymmetry. Examining asymmetry in large samples may increase sensitivity to detect heterogeneous areas of WM alteration in mild TBI. Through the Enhancing Neuroimaging Genetics Through Meta‐Analysis Military‐Relevant Brain Injury working group, we conducted a mega‐analysis of neuroimaging and clinical data from 16 cohorts of Active Duty Service Members and Veterans (n = 2598). dMRI data were processed together along with harmonized demographic, injury, psychiatric, and cognitive measures. Fractional anisotropy in the cingulum showed greater asymmetry in individuals with deployment‐related TBI, driven by greater left lateralization in TBI. Results remained significant after accounting for potentially confounding variables including posttraumatic stress disorder, depression, and handedness, and were driven primarily by individuals whose worst TBI occurred before age 40. Alterations in the cingulum were also associated with slower processing speed and poorer set shifting. The results indicate an enhancement of the natural left laterality of the cingulum, possibly due to vulnerability of the nondominant hemisphere or compensatory mechanisms in the dominant hemisphere. The cingulum is one of the last WM tracts to mature, reaching peak FA around 42 years old. This effect was primarily detected in individuals whose worst injury occurred before age 40, suggesting that the protracted development of the cingulum may lead to increased vulnerability to insults, such as TBI.

Dopaminergic mesolimbic structural reserve is positively linked to better outcome after severe stroke

“…For additional sensitivity analyses, we re-computed the two winning models while considering several potentially confounding variables. First, possible hemispheric specialization of basal ganglia 48-50 and possible lateralization effects 51 and differential plasticity rates 52 known from traumatic brain injury patients were addressed by including the interaction lesion side × regional volume. This interaction was not significant, neither for the nucleus accumbens ( P = 0.78), not for the amygdala ( P = 0.53) which argues against side effects regarding both the mesolimbic network assessed and the affected stroke hemisphere.…”

“…Significances are indicated by asterisks. For sensitivity analyses, surviving correlative outcome models were re-computed while iteratively taking various potentially confounding factors into account: (i) side of the lesion including its interaction with the regional volume to account for hemispheric specialization of basal ganglia 48-50 and possible lateralization effects 51 and differential plasticity rates 52 known from traumatic brain injury patients; (ii) peak width of skeletonized mean diffusivity (PSMD) of the unaffected hemisphere as a marker of cerebral small vessel disease burden 53 ; and (iii) influence of initial symptom severity onto volumetry–outcome relationship as operationalized by the interaction between NIHSS (dichotomized by median split into higher and lower NIHSS scores) and regional volume. For specificity analyses, we computed additional outcome models which included only global—and not regional—parameters of structural reserve that are (i) TIV; (ii) averaged grey subcortical matter volume; and (iii) averaged cortical grey matter volume of the unaffected hemisphere.…”