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Frontal white matter connections and cognitive change in amyotrophic lateral sclerosis: a DTI-tractography study

Frontal white matter connections and cognitive change in amyotrophic lateral sclerosis: a DTI-tractography study

Tsermentseli, S., Dell'Acqua, F., Landau, S., Williams, S.C.R., Jones, D.K., Leigh, P.N., Catani, M. and Goldstein, L.H. (2012) Frontal white matter connections and cognitive change in amyotrophic lateral sclerosis: a DTI-tractography study. Journal of Neurology, Neurosurgery & Psychiatry, 83 (10). e1. ISSN 0022-3050 (Print), 1468-330X (Online) (doi:

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Objective: Traditionally considered a motor-neuron disorder, cognitive and behavioural impairments in a subset of non-demented amyotrophic lateral sclerosis (ALS) patients are now well-acknowledged. This study aimed to define the structural basis of cognitive abnormalities in ALS, by clarifying the involvement of specific cognitive domains and the respective contribution of white matter damage to the integrity of the uncinate (UF), inferior longitudinal (ILF) and inferior-frontal occipital (IFOF) fasciculi.

Method: 26 ALS patients and 27 healthy controls underwent a detailed neuropsychological assessment and a whole brain diffusion tensor imaging (DTI) scan. The two groups were matched for age, IQ, years of education, and anxiety and depression scores. Individual neuropsychological test scores were converted into four composite scores, measuring executive functions, language, memory and visuospatial ability. Changes in fractional anisotropy (FA) and mean diffusivity (MD) were measured along the UF, ILF, and the IFOF using a two-region of interest approach.

Results: ALS patients were found to exhibit impaired performance on the executive and language composite test scores, but not on memory and visuospatial composite test scores. DT-MRI investigations of the white matter association tracts (ie, UF, ILF and IFOF) identified no significant differences in ALS-patients compared to healthy controls with respect to mean FA values, indicating that water diffusion within these tracts still followed the main axonal direction. MD values however were found to be significantly increased within the uncinate fasciculus of ALS-patients compared to healthy controls. This is associated with neurodegeneration, as an increased MD typically arises from reduced barriers of diffusion, indicating weak axonal myelination. Correlational analysis did not find significant relationships between white matter tracts and neuropsychological composite scores.

Conclusion: The findings confirm the presence of executive dysfunction in ALS patients and also suggest that language deficits maybe more extensive and prevalent than has been suggested by previous research. These results suggest involvement of the UF within the disease-profile of ALS, however correlations to significant deficits remain to be found. If confirmed in a larger study this frontal white matter change could represent an important biomarker for trials in ALS.

Item Type: Article
Additional Information: [1] P20, in Poster abstracts from the BNPA 2012 AGM. [2] The British Neuropsychiatry Association 25th AGM, took place 9-10 February 2012, at The Institute of Child Health, Guilford Street, London, UK. Abstracts also available at:
Uncontrolled Keywords: amyotrophic lateral sclerosis, cognitive change, diffusion tenson imaging
Subjects: B Philosophy. Psychology. Religion > BF Psychology
Faculty / School / Research Centre / Research Group: Faculty of Education, Health & Human Sciences
Related URLs:
Last Modified: 14 Oct 2016 09:22

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