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Cognitive Deficits In Friedreich Ataxia Correlate with Micro-structural Changes in Dentatorubral Tract

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Abstract

Atrophy of the dentate nucleus is one of the major neuropathological changes in Friedreich ataxia (FRDA). Neuroimaging studies demonstrated white matter (WM) degeneration in FRDA. In this study, we used advanced tractography techniques to quantitatively measure WM changes in the dentato-thalamic and dentato-rubral tracts, and correlated these changes with cognitive profiles of FRDA. We also analysed diffusivity changes of the thalamo-cortical tract to assess whether neurological degeneration of WM extends beyond the primary site of involvement in FRDA. Twelve genetically proven individuals with FRDA and 14 controls were recruited. Sixty directions diffusion tensor images were acquired. The WM bundles from the dentate nucleus were estimated using a constrained spherical deconvolution method and the diffusivity characteristics measured. The Simon task was used to assess cognitive profile of FRDA. The dentato-rubral, dentato-thalamic and thalamo-cortical tracts manifested significantly lower fractional anisotropy, higher mean diffusivity and increased radial diffusivity in FRDA compared with controls. There was no difference in axial diffusivity between the two groups. The mean and radial diffusivity of the dentato-rubral tract was positively correlated with choice reaction time, congruent reaction time, incongruent reaction time and Simon effect reaction time and negatively with the larger GAA repeat. Significant changes in diffusivity characteristics were observed in the dentato-thalamic and thalamo-cortical tracts, suggesting extensive WM degeneration and affected WM structures in FRDA. Correlation of WM changes in the dentato-rubral tract with the cognitive assessment suggested that this tract is an important contributor to cognitive disturbances in FRDA.

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Study funding

Friedreich Ataxia Research Association (Australasia), Friedreich Ataxia Research Alliance (USA) and Murdoch Childrens Research Institute. HA received a Melbourne International Fee Remission Scholarship and a Melbourne International Research Scholarship. GFE is an NHMRC Principal Research Fellow (#1003993).

Conflict of Interest

Dr. Hamed Akhlaghi reports no disclosures.

Mr. Johnson Yu reports no disclosures.

Dr Louise Corben reports no disclosures.

Associate Professor Nellie Georgiou-Karistianis reports no disclosures.

Emeritus Professor John L. Bradshaw reports no disclosures.

Professor Elsdon Storey has received honoraria (payable to his institution) from Pfizer for lecturing on non-drug related issues at an education course. He is a co-investigator on an NIH trial for which Merck is providing active drug (aspirin and placebo).

Professor Martin B. Delatycki is Associate Editor for BMC Neurology, he receives grants from NHMRC, Friedreich Ataxia Research Alliance, Friedreich Ataxia Research Association, and he is on the Pfizer Australia Neuroscience Grant Panel.

Professor Gary Egan reports no disclosures.

Author information

Authors and Affiliations

  1. Monash Biomedical Imaging, Monash University, Clayton, Melbourne, Victoria, 3800, Australia

    Hamed Akhlaghi & Gary F. Egan

  2. University of Melbourne, Melbourne, Australia

    Johnson Yu

  3. Bruce Lefroy Centre for Genetic Health Research, Murdoch Childrens Research Institute, Parkville, Melbourne, Victoria, Australia

    Louise Corben & Martin B. Delatycki

  4. Experimental Neuropsychology Research Unit, School of Psychology and Psychiatry, Monash University, Clayton, Melbourne, Victoria, 3800, Australia

    Louise Corben, Nellie Georgiou-Karistianis & John L. Bradshaw

  5. Department of Medicine (Neurosciences), Monash University (Alfred Hospital Campus), Melbourne, Victoria, Australia

    Elsdon Storey

  6. Department of Clinical Genetics, Austin Health, Heidelberg, Melbourne, Victoria, Australia

    Martin B. Delatycki

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  1. Hamed Akhlaghi
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Correspondence to Hamed Akhlaghi.

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Akhlaghi, H., Yu, J., Corben, L. et al. Cognitive Deficits In Friedreich Ataxia Correlate with Micro-structural Changes in Dentatorubral Tract. Cerebellum 13, 187–198 (2014). https://doi.org/10.1007/s12311-013-0525-4

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  • DOI: https://doi.org/10.1007/s12311-013-0525-4

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