Large Processes with Small Targets: Rarity and Pollination in Rain Forests

Abstract

Background: Amyotrophic lateral sclerosis (ALS) is a rare multi-system degenerative disease characterised by motor symptoms and, additionally, by cognitive impairments and behavioural abnormalities (Goldstein LH et al, 2013). So far, only a few imaging studies have explicitly related cognitive-behavioural symptoms to structural brain changes in ALS. The current study aimed to determine the association of cognitive-behavioural symptoms with the integrity of fiber tracts using DTI. We investigated a wide range of diffusion indices to comprehensively characterise the microstructural integrity of the white matter (Metwalli NS et al. 2010). Methods: We assessed 74 ALS patients and 65 matched healthy control subjects employing a comprehensive neuropsychological test battery and 3 Tesla-MRI. Using tract-based spatial statistics (TBSS), maps of fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were compared among ALS patients with and without cognitive impairment and healthy controls. Statistical analysis was conducted using ANCOVAs. Further, a region of interest (ROI) approach was employed with αpriori defined white matter tracts based on the ICBM-DTI-81-WM labels atlas. The averaged diffusivity values of the ROIs were correlated with neuropsychological tests using linear regression. Results: Patients without cognitive impairment demonstrated white matter changes predominantly in motor tracts. Cognitively impaired patients (ca. 30%) presented, additionally, significant white matter alterations in extra-motor regions, particularly the frontal lobe areas (see figure 1). RD-maps, reflecting a loss of integrity of the axonal wall, revealed the most pronounced effects. Specific correlations between executive tasks, memory tasks, and behavioural measures were found with fiber tract integrity in the large association tracts. The majority of cognitive scores correlated with RD. Conclusions: Our findings indicate that white matter changes, predominantly in the long association fibre bundles, are related to disturbances of executive and memory functions. In particular, correlations between executive tasks and their functionally corresponding white matter structures suggest that cognitive impairment is related to structural white matter changes in ALS patients. Eventually, our study demonstrates that the integration of different DTI-metrics is useful investigating neurodegenerative disorders such ALS . Our results highlight radial diffusivity as the most sensitive marker of neurodegeneration in ALS, especially of extra-motor brain areas.