Longitudinal changes following acute brain injuries

Abstract

Although it is known the human brain can recover after a brain lesion, the response mechanisms of recovery are not yet fully understood. Using longitudinal data, our aim was first to characterise the ways in which brain networks change after an acute brain lesion either as a result of trauma/insult or following brain surgery. Secondly, we investigated if those changes are associated with recovery or disease progression. In this thesis, we analyse longitudinal structural changes in mild TBI, and epilepsy patients following temporal lobe resection using graph theory and connectometry. Alterations in brain structure were later related with cognitive recovery or seizure freedom using regression models. In addition, we analysed longitudinal, functional changes following moderate to severe TBI using clustering algorithms. We investigated the network flexibility over functional connectivity patterns/states by calculating the entropy of time spent in these states. Shifts in entropy were compared with longitudinal white matter integrity and blood biomarkers using linear models. In patients who underwent temporal lobe resection, we found alterations in structural connectivity and in the density of anisotropic diffusing water over time. Some of the observed changes were related with seizure freedom. Similarly, we found that a set of alterations in structural connectivity following mild TBI were related with changes in cognitive trajectory. When investigating longitudinal functional changes in moderate to severe TBI patients, we found a set of cognitive functional connectivity patterns. Changes in entropy after TBI were related to alterations in the concentration of plasma tau. Our studies suggest that early alterations in brain structure and function occur following acute brain lesions such as TBI or those as result of temporal lobe resection. While some of these alterations are the result of the injury itself in the network, other alterations may be a result of brain reorganisation and promote patient recovery.