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Research paper
Regional thalamic MRI as a marker of widespread cortical pathology and progressive frontotemporal involvement in amyotrophic lateral sclerosis
  1. Sicong Tu1,2,3,
  2. Ricarda A L Menke2,3,
  3. Kevin Talbot3,
  4. Matthew C Kiernan1,
  5. Martin R Turner2,3
  1. 1 Brain and Mind Centre, Sydney Medical School, University of Sydney, Sydney, New South Wales, Australia
  2. 2 Wellcome Centre for Integrative Neuroimaging, University of Oxford, Oxford, UK
  3. 3 Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, UK
  1. Correspondence to Dr Sicong Tu, Wellcome Centre for Integrative Neuroimaging, John Radcliffe Hospital, Oxford, OX3 9DU, UK; sicong.tu{at}sydney.edu.au; Professor Martin R Turner, West Wing Level 6, John Radcliffe Hospital, Oxford, OX3 9DU, UK; martin.turner{at}ndcn.ox.ac.uk

Abstract

Background The thalamus is a major neural hub, with selective connections to virtually all cortical regions of the brain. The multisystem neurodegenerative syndrome amyotrophic lateral sclerosis (ALS) has pathogenic overlap with frontotemporal dementia, and objective in vivo markers of extra-motor pathological spread are lacking. To better consider the role of the thalamus in neurodegeneration, the present study assessed the integrity of the thalamus and its connectivity to major cortical regions of the brain in a longitudinal manner.

Methods Diffusion-based MRI tractography was used to parcellate the thalamus into distinct regions based on structural thalamo-cortical connectivity in 20 patients with ALS, half of whom were scanned at two time points, and 31 matched controls scanned on a single occasion.

Results At baseline, widespread diffusivity alterations in motor- and extramotor-associated thalamic parcellations were detectable. Longitudinal decline selectively affected thalamic regions associated with frontal and temporal lobe connectivity. Diffusivity measures were significantly correlated with clinical measures of disease burden. Progression of functional disability, as indicated by change on the ALS functional rating scale, was associated with longitudinal change in mean diffusivity of the right frontal lobe thalamic parcellation (r=0.59, p=0.05).

Conclusions Regional thalamic connectivity changes mirror the progressive frontotemporal cortical involvement associated with the motor functional decline in ALS. Longitudinal MRI thalamic parcellation has potential as a non-invasive surrogate marker of cortical dysfunction in ALS.

  • amyotrophic lateral sclerosis
  • motor neuron disease
  • diffusion tensor imaging
  • tractography
  • thalamus

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Footnotes

  • Contributors ST contributed to design, analysis and manuscript preparation. RAM contributed to design, data acquisition, analysis and manuscript preparation. KT contributed to data acquisition and manuscript preparation. MCK contributed to manuscript preparation. MRT contributed to design, data acquisition and manuscript preparation.

  • Funding ST is funded by the Australian National Health and Medical Research Council CJ Martin Early Career Fellowship (APP1121859). MCK was supported by the Australian National Health and Medical Research Council Program Grant (Forefront #1037746). MRT is funded by the Medical Research Council and Motor Neurone Disease Association Lady Edith Wolfson Senior Clinical Fellowship (MR/K01014X/1). The Oxford MND Centre (MRT, KT) receives funding from the Motor Neurone Disease Association.

  • Competing interests None declared.

  • Patient consent Not required.

  • Ethics approval Ethical approval for this study was obtained from South Central Oxford Ethics Committee B (08/H0605/85).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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