White matter structural network abnormalities underlie executive dysfunction in amyotrophic lateral sclerosis |
| |
| Authors: | Dennis Dimond Abdullah Ishaque Sneha Chenji Dennell Mah Zhang Chen Peter Seres Christian Beaulieu Sanjay Kalra |
| |
| Affiliation: | 1. Neuroscience and Mental Health Institute, University of Alberta, Edmonton, Alberta, Canada;2. Division of Neurology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada;3. Department of Biomedical Engineering, University of Alberta, Edmonton, Alberta, Canada |
| |
| Abstract: | Research in amyotrophic lateral sclerosis (ALS) suggests that executive dysfunction, a prevalent cognitive feature of the disease, is associated with abnormal structural connectivity and white matter integrity. In this exploratory study, we investigated the white matter constructs of executive dysfunction, and attempted to detect structural abnormalities specific to cognitively impaired ALS patients. Eighteen ALS patients and 22 age and education matched healthy controls underwent magnetic resonance imaging on a 4.7 Tesla scanner and completed neuropsychometric testing. ALS patients were categorized into ALS cognitively impaired (ALSci, n = 9) and ALS cognitively competent (ALScc, n = 5) groups. Tract‐based spatial statistics and connectomics were used to compare white matter integrity and structural connectivity of ALSci and ALScc patients. Executive function performance was correlated with white matter FA and network metrics within the ALS group. Executive function performance in the ALS group correlated with global and local network properties, as well as FA, in regions throughout the brain, with a high predilection for the frontal lobe. ALSci patients displayed altered local connectivity and structural integrity in these same frontal regions that correlated with executive dysfunction. Our results suggest that executive dysfunction in ALS is related to frontal network disconnectivity, which potentially mediates domain‐specific, or generalized cognitive impairment, depending on the degree of global network disruption. Furthermore, reported co‐localization of decreased network connectivity and diminished white matter integrity suggests white matter pathology underlies this topological disruption. We conclude that executive dysfunction in ALSci is associated with frontal and global network disconnectivity, underlined by diminished white matter integrity. Hum Brain Mapp 38:1249–1268, 2017. © 2016 Wiley Periodicals, Inc. |
| |
| Keywords: | motor neuron disease amyotrophic lateral sclerosis white matter integrity graph theory tract‐based spatial statistics executive function structural connectivity |
|
|
