White matter damage and cognitive impairment after traumatic brain injury

Abstract

White matter disruption is an important determinant of cognitive impairment after brain injury, but conventional neuroimaging underestimates its extent. In contrast, diffusion tensor imaging provides a validated and sensitive way of identifying the impact of axonal injury. The relationship between cognitive impairment after traumatic brain injury and white matter damage is likely to be complex. We applied a flexible technique—tract-based spatial statistics—to explore whether damage to specific white matter tracts is associated with particular patterns of cognitive impairment. The commonly affected domains of memory, executive function and information processing speed were investigated in 28 patients in the post-acute/chronic phase following traumatic brain injury and in 26 age-matched controls. Analysis of fractional anisotropy and diffusivity maps revealed widespread differences in white matter integrity between the groups. Patients showed large areas of reduced fractional anisotropy, as well as increased mean and axial diffusivities, compared with controls, despite the small amounts of cortical and white matter damage visible on standard imaging. A stratified analysis based on the presence or absence of microbleeds (a marker of diffuse axonal injury) revealed diffusion tensor imaging to be more sensitive than gradient-echo imaging to white matter damage. The location of white matter abnormality predicted cognitive function to some extent. The structure of the fornices was correlated with associative learning and memory across both patient and control groups, whilst the structure of frontal lobe connections showed relationships with executive function that differed in the two groups. These results highlight the complexity of the relationships between white matter structure and cognition. Although widespread and, sometimes, chronic abnormalities of white matter are identifiable following traumatic brain injury, the impact of these changes on cognitive function is likely to depend on damage to key pathways that link nodes in the distributed brain networks supporting high-level cognitive functions.

Serum insulin‐like growth factor‐I levels are associated with improved white matter recovery after traumatic brain injury

“…We have previously shown that after TBI, FA measurements in particular WM tracts relate to multiple neuropsychological domains 10, 11, 46. In a separate cross‐sectional cohort of patients after moderate–severe TBI and controls who were scanned once, we confirmed both lower SPCC FA and lower immediate verbal memory recall in patients after TBI compared to controls.…”

Microglia/Macrophage Polarization Dynamics in White Matter after Traumatic Brain Injury

“…However, TBI can also elicit severe white matter injury (WMI) that correlates with long-term deficits in motor and cognitive function. 5,6 Complications after TBI involve more than the initial tissue damage induced directly by mechanical trauma. 1,7,8 Delayed secondary events, such as ischemia, lipid degradation, free radical formation, excitotoxicity, and protease release can be equally devastating.…”

HDAC inhibition prevents white matter injury by modulating microglia/macrophage polarization through the GSK3β/PTEN/Akt axis

“…traumatic brain injury | oligodendrocyte | microglial polarization | myelination | inflammation T raumatic brain injury (TBI) often leads to catastrophic neurological disabilities and sometimes ends in death (1). TBI results not only in gray matter damage, but also in severe white matter injury (WMI), thereby disrupting signal transmission and eliciting poor functional outcomes (2,3). WMI in TBI patients is strongly correlated with neurological deficits, and diffusion tensor imaging of white matter offers prognostic value for neurological status (2)(3)(4).…”