Patterns of change in cortical morphometry following traumatic brain injury in adults

Abstract

Progressive cortical volumetric loss following moderate-severe traumatic brain injury (TBI) has been observed; however, regionally specific changes in the structural determinants of cortical volume, namely, cortical thickness (CT) and cortical surface area (CSA), are unknown and may inform the patterns and neural substrates of neurodegeneration and plasticity following injury. We aimed to (a) assess differences in CT and CSA between TBI participants and controls in the early chronic stage postinjury, (b) describe longitudinal changes in cortical morphometry following TBI, and (c) examine how regional changes in CT and CSA are associated. We acquired magnetic resonance images for 67 participants with TBI at up to 4 time-points spanning 5 months to 7 years post-injury, and 18 controls at 2 time-points. In the early chronic stage, TBI participants displayed thinner cortices than controls, predominantly in frontal regions, but no CSA differences. Throughout the chronic period, TBI participants showed widespread CT reductions in posterior cingulate/precuneus regions and moderate CT increase in frontal regions. Additionally, CSA showed a significant decrease in the orbitofrontal cortex and circumscribed increase in posterior regions.No changes were identified in controls. Relationships between regional cortical changes in the same morphological measure revealed coordinated patterns within participants, whereas correlations between regions with CT and CSA change yielded bi-directional relationships. This suggests that these measures may be differentially affected by neurodegenerative mechanisms such as transneuronal degeneration following TBI and that degeneration may be localized to the depths of cortical sulci.These findings emphasize the importance of dissecting morphometric contributions to cortical volume change.

Interaction of Alzheimer Disease and Traumatic Brain Injury on Cortical Thickness

“…These microscopic changes, which are typically identified post-TBI, are also part of AD pathology. Furthermore, studies examining the long-term effects of TBI, have found cortical thinning and volumetric reductions in frontotemporal regions 15,16 . These findings indicate a partial overlap of TBI-related regions and those identified in the AD literature, but also some key differences in the brain regions most affected by AD and TBI.…”

“…[38][39][40] In addition, thinning may at least partly be counteracted by neuroplastic change and compensatory mechanisms of injury. 16,38 The effects may cause apparent increases in cortical thickness. Although cardiovascular factors, depression, and APOE status were investigated in relation to the observed effects of TBI on cortical thickness, they added negligible explanatory power to our models.…”

“…Clinical decline in the AD+TBI group may be driven by the pathology burden of chronic TBI beyond gray matter loss in frontotemporal areas, but future research is needed. In addition to focal damage due to impact-acceleration forces, 16,29 TBI causes long-lasting inflammatory effects that may cause changes in gray matter in regions distal from the expected primary sites of impact, including the middle temporal lobes and postcentral gyrus 15,16,30 . Persisting inflammation and white matter damage may also contribute to clinical impairments in TBI 31,32 .…”

“…The reduced cortical thinning of the AD+TBI group should be interpreted cautiously, however, as this measure is sensitive to multiple microstructural changes in response to chronic TBI including glial activation due to inflammatory response and altered cell morphology 38–40 . In addition, thinning may at least partly be counteracted by neuroplastic change and compensatory mechanisms of injury 16,38 . The effects may cause apparent increases in cortical thickness.…”

Spatiotemporal profile of atrophy in the first year following moderate‐severe traumatic brain injury

“…The temporospatial distribution of atrophy in TBI is therefore necessary to measure as it may highlight specific pathophysiological mechanisms underlying brain atrophy (Green et al, 2014) and aid in the identification of optimal timing for therapeutic interventions following injury (Bramlett & Dietrich, 2015;Wilde et al, 2022). We have successfully identified such a spatiotemporal profile utilizing our state-of-the-art morphometry processing pipeline which aligns with the previously established time course of atrophy in the cortex (Mazaharally et al, 2021) while extending the profile to also include the subcortex and white matter.…”