White matter changes and neuropsychological changes in individuals with persistent post-concussion symptoms following mild traumatic brain injury

Abstract

Following a mild traumatic brain injury (mTBI) a number of individuals fail to recover within the normal time frame and experience persistent post-concussion symptoms (PPCS). Advances in neuroimaging, have provided a new technique known as Diffusion Tensor Imaging (DTI), capable of examining white matter changes following mTBI. The present study examined individuals who sustained a mTBI (n=46) 3-6 months previously and a control group matched for age, gender and education (n=20). The mTBI group were further subdivided into two groups of individuals reporting higher levels of persistent post-concussion symptoms (HPPCS), and those reporting lower levels of persistent post-concussion symptoms (LPPCS) based on their self-report on the Rivermead Post-Concussion Questionnaire (RPQ). Specific neuropsychological tests were used to assess cognitive domains (attention, information processing speed, and working memory) and mood (irritability, anxiety and depression) changes commonly reported by individuals with PPCS. Participants underwent magnetic resonance imaging scans including DTI. A whole-brain voxel-based analysis known as Tract-Based Statistics (TBSS) was used to measure white matter microstructure. Analyses were also conducted to examine whether cognitive performance was associated with white matter microstructural properties in the mTBI group. It was hypothesised that the HPPCS group would perform more poorly on cognitive tests trials with increased cognitive demands and complexity, but not on tests that measured simple cognitive functioning. It was also hypothesised that greater white matter disruption would be shown in the HPPCS group compared to the LPPCS group. Lastly, it was predicted that disrupted white matter microstructure in the whole mTBI group would be associated with poorer performance on selected cognitive tests.

Consistent with these predictions, the mTBI performed significantly worse compared to the control group in two out of the four cognitive tests, the Paced Auditory Serial Additions Test (PASAT) and the Symbol Digit Modalities Test. The HPPCS group also performed significantly worse compared to the LPPCS group in two out of four cognitive tests, including the PASAT and Computerised Topography Information Processing (CTIP), specifically on the last trial on the CTIP, which involves the greatest cognitive demand. TBSS analysis revealed that the mTBI group displayed significantly disrupted white matter microstructure as indicated by reduced Fractional Anisotropy (FA) and increased Mean Diffusivity (MD) and Radial Diffusivity (RD) compared to the control group. Strikingly, the HPPCS group also displayed significantly disrupted white matter compared to the LPPCS group, specifically reduced FA and increased RD. Finally, the regression analyses showed a number of regionally specific relationships between disrupted white matter microstructure and cognitive performance in the whole mTBI group. The results contribute to a better characterisation of the neuropsychological and neural changes that occur in individuals with PPCS, and suggest ongoing disruptions in neural functioning contribute to prolonged symptoms of mTBI.