Microstructural correlates of Edinburgh Cognitive and Behavioural ALS Screen (ECAS) changes in amyotrophic lateral sclerosis

Edinburgh Cognitive and Behavioural ALS Screen (ECAS) was designed for testing patients with amyotrophic lateral sclerosis (ALS), a multi-system neurodegenerative disease characterized by progressive physical disability. In this study, we aim to explore the potential brain microstructural substrates associated with performance on ECAS in the early stages of ALS, using a whole-brain tract-based spatial statistics diffusion tensor imaging approach. Thirty-six non-demented ALS patients, assessed using ECAS, and 35 age-, sex- and education-matched healthy controls underwent magnetic resonance imaging at 3 Tesla. The ALS patients showed decreased fractional anisotropy (FA) in the cortico-spinal tracts and corpus callosum (CC) and significant association between verbal fluency score, among ALS-specific ECAS scores, and FA measures in several long association fiber tracts in the frontal, temporal and parietal lobes. Furthermore, the ALS non-specific total score was inversely related to axial diffusivity (AD) in the mediodorsal nucleus of the thalamus, with more extended areas of correlation in the CC, when considering only the memory subscore. Our results point towards microstructural degeneration across motor and extra-motor areas in ALS, underlining that alterations in verbal fluency performances may be related to impairment of frontotemporal connectivity, while alterations of memory may be associated with damage of thalamocortical circuits.