title: White matter structural network abnormalities underlie executive dysfunction in amyotrophic lateral sclerosis.
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.
authors: Neuroscience and Mental Health Institute, University of Alberta, 4-142 Katz Group Centre, 116 St. and 85 Ave, Edmonton, Alberta, T6G 2E1, Canada.
authors: Dennis
authors: D
authors: Dimond
authors: Neuroscience and Mental Health Institute, University of Alberta, 4-142 Katz Group Centre, 116 St. and 85 Ave, Edmonton, Alberta, T6G 2E1, Canada.
authors: Abdullah
authors: A
authors: Ishaque
authors: Neuroscience and Mental Health Institute, University of Alberta, 4-142 Katz Group Centre, 116 St. and 85 Ave, Edmonton, Alberta, T6G 2E1, Canada.
authors: Sneha
authors: S
authors: Chenji
authors: Division of Neurology, Department of Medicine, University of Alberta, 7-132F Clinical Sciences Building, 11350-83 Ave, Edmonton, Alberta, T6G 2G3, Canada.
authors: Dennell
authors: D
authors: Mah
authors: Department of Biomedical Engineering, University of Alberta, 1098 Research Transition Facility, 8308-114 St, Edmonton, Alberta, T6G 2V2, Canada.
authors: Zhang
authors: Z
authors: Chen
authors: Department of Biomedical Engineering, University of Alberta, 1098 Research Transition Facility, 8308-114 St, Edmonton, Alberta, T6G 2V2, Canada.
authors: Peter
authors: P
authors: Seres
authors: Neuroscience and Mental Health Institute, University of Alberta, 4-142 Katz Group Centre, 116 St. and 85 Ave, Edmonton, Alberta, T6G 2E1, Canada.|Department of Biomedical Engineering, University of Alberta, 1098 Research Transition Facility, 8308-114 St, Edmonton, Alberta, T6G 2V2, Canada.
authors: Christian
authors: C
authors: Beaulieu
authors: Neuroscience and Mental Health Institute, University of Alberta, 4-142 Katz Group Centre, 116 St. and 85 Ave, Edmonton, Alberta, T6G 2E1, Canada.|Division of Neurology, Department of Medicine, University of Alberta, 7-132F Clinical Sciences Building, 11350-83 Ave, Edmonton, Alberta, T6G 2G3, Canada.|Department of Biomedical Engineering, University of Alberta, 1098 Research Transition Facility, 8308-114 St, Edmonton, Alberta, T6G 2V2, Canada.
authors: Sanjay
authors: S
authors: Kalra
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000150:complications*; D001284:Atrophy / Q000473:pathology; D060825:Cognitive Dysfunction / Q000209:etiology*; D063132:Connectome; D056324:Diffusion Tensor Imaging; D056344:Executive Function / Q000502:physiology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D009483:Neuropsychological Tests; D066127:White Matter / Q000473:pathology*
keywords: amyotrophic lateral sclerosis; executive function; graph theory; motor neuron disease; structural connectivity; tract-based spatial statistics; white matter integrity