Abstract WMP48: The Impact of Brain Health and Long Range Cortical Disconnection on Stroke Recovery

Abstract

White matter hyperintensities (WMH) are linked to poor brain health, cardiovascular risk factors, cognitive decline, and stroke. The cumulative effect of microangiopathic changes and perivascular lipohyalinosis is commonly associated with white matter changes in the brain. However, the pathomechanism linking small vessel disease, white matter network disruption, cognitive decline, and stroke recovery is not well understood. We hypothesized that WMH are associated with loss of long range cortical connections, and subsequent disorganization of the optimal topological structure of white matter networks leading to poor post-stroke aphasia recovery. Using post-processing methods of diffusion tensor imaging optimized for lesioned brains, we reconstructed the individual structural whole-brain connectome from 49 right handed participants with a single left hemisphere ischemic stroke (age 59.9±12.5). All participants underwent language assessment using the Western Aphasia Battery (mean 58.9±22.76). WMHs were determined in the right hemisphere aphasia using the Fazekas scale. We assessed the density of each subject’s right hemisphere connectome, and then calculated the Euclidean distance between each pair of node centroids in each connectome. All fibers with lengths above the 3 rd quartile (75% and above) were designated long range. We further quantified the white matter topological network organization using Newman’s modularity algorithm. We found that participants with high a Fazekas score (especially PWMH) had lower connectome density (r = -0.41, p = 0.003), and more severe aphasia (r = -0.42, p = 0.002). Participants with lower right hemisphere density also had more severe aphasia (r = 0.5, p < 10 -3 ). Furthermore, loss of long range cortical connections was associated with the fragmentation of the right hemisphere network topology quantified by the optimal modularity score (r = 0.76, p < 10 -9 ). Loss of long range fiber connections related to higher WMH, and was associated with deviations from the optimal topological architecture that signifies a healthy brain. We postulate a mechanism by which brain health is lost – via loss of energy demanding long range fibers resulting in the disorganization of residual brain networks.