The objective of this study was to evaluate group-by-time interactions between gray matter morphology of healthy controls and that of patients with mild traumatic brain injury (mTBI) as they transitioned from acute to chronic stages, and to relate these findings to long-term cognitive alterations to identify distinct recovery trajectories between good outcome (GO) and poor outcome (PO). High-resolution T1-weighted magnetic resonance images were acquired in 49 mTBI patients within 7 days and 1 year post-injury and at equivalent times in 49 healthy controls. Using linear mixed-effects models, we performed mass-univariate analyses and associated the results of the interaction with changes in cognitive performance. Morphological alterations indexed by increased or decreased cortical thickness have been expected mainly in frontal, parietal, and temporal brain regions. A significant interaction was found in cortical thickness, spatially restricted to bilateral structures of the prefrontal cortex, showing thickening in mTBI and normal developmental thinning in controls. A discrete thickness increase that can interpreted as the absence of cortical thinning typically seen in the healthy population was associated with cognitive recovery in the GO subgroup, while the exaggerated cortical thickening in the PO patients was linked to worsening cognitive performance. Thickness of the prefrontal cortex is subject to structural alterations during the first year after mTBI. Beside beneficial neuroplasticity, a prolonged state of neuroinflammation for symptomatic patients (maladaptive neuroplasticity) cannot be excluded. If the underlying cellular processes responsible for cortical thickening following mTBI have been determined, brain stimulation or even pharmacological intervention targeting the prefrontal cortex might promote endogenous neural restoration.
Keywords: cortical thickness; group-by-time interaction; longitudinal analysis; mild traumatic brain injury; recovery.