White matter structural network abnormalities underlie executive dysfunction in amyotrophic lateral sclerosis.

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.

Dimond D ，Ishaque A ，Chenji S ，Mah D ，Chen Z ，Seres P ，Beaulieu C ，Kalra S ... -  《-》

Executive deficits, not processing speed relates to abnormalities in distinct prefrontal tracts in amyotrophic lateral sclerosis.

Pettit LD ，Bastin ME ，Smith C ，Bak TH ，Gillingwater TH ，Abrahams S ... -  《-》

Additional resources and the default mode network: Evidence of increased connectivity and decreased white matter integrity in amyotrophic lateral sclerosis.

Heimrath J ，Gorges M ，Kassubek J ，Müller HP ，Birbaumer N ，Ludolph AC ，Lulé D ... -  《-》

Gray matter and white matter changes in non-demented amyotrophic lateral sclerosis patients with or without cognitive impairment: A combined voxel-based morphometry and tract-based spatial statistics whole-brain analysis.

Christidi F ，Karavasilis E ，Riederer F ，Zalonis I ，Ferentinos P ，Velonakis G ，Xirou S ，Rentzos M ，Argiropoulos G ，Zouvelou V ，Zambelis T ，Athanasakos A ，Toulas P ，Vadikolias K ，Efstathopoulos E ，Kollias S ，Karandreas N ，Kelekis N ，Evdokimidis I ... -  《-》

Reduced structural connectivity within a prefrontal-motor-subcortical network in amyotrophic lateral sclerosis.

To investigate white matter structural connectivity changes associated with amyotrophic lateral sclerosis (ALS) using network analysis and compare the results with those obtained using standard voxel-based methods, specifically Tract-based Spatial Statistics (TBSS). MRI data were acquired from 30 patients with ALS and 30 age-matched healthy controls. For each subject, 85 grey matter regions (network nodes) were identified from high resolution structural MRI, and network connections formed from the white matter tracts generated by diffusion MRI and probabilistic tractography. Whole-brain networks were constructed using strong constraints on anatomical plausibility and a weighting reflecting tract-averaged fractional anisotropy (FA). Analysis using Network-based Statistics (NBS), without a priori selected regions, identified an impaired motor-frontal-subcortical subnetwork (10 nodes and 12 bidirectional connections), consistent with upper motor neuron pathology, in the ALS group compared with the controls (P = 0.020). Reduced FA in three of the impaired network connections, which involved fibers of the corticospinal tract, correlated with rate of disease progression (P ≤ 0.024). A novel network-tract comparison revealed that the connections involved in the affected network had a strong correspondence (mean overlap of 86.2%) with white matter tracts identified as having reduced FA compared with the control group using TBSS. These findings suggest that white matter degeneration in ALS is strongly linked to the motor cortex, and that impaired structural networks identified using NBS have a strong correspondence to affected white matter tracts identified using more conventional voxel-based methods.

Buchanan CR ，Pettit LD ，Storkey AJ ，Abrahams S ，Bastin ME ... -  《-》