Cerebello-cerebral connectivity deficits in Friedreich ataxia

Abstract

Brain pathology in Friedreich ataxia is characterized by progressive degeneration of nervous tissue in the brainstem, cerebellum and cerebellar peduncles. Evidence of cerebral involvement is however equivocal. This brain imaging study investigates cerebello-cerebral white matter connectivity in Friedreich ataxia with diffusion MRI and tractography performed in 13 individuals homozygous for a GAA expansion in intron one of the frataxin gene and 14 age- and gender-matched control participants. New evidence is presented for disrupted cerebello-cerebral connectivity in the disease, leading to secondary effects in distant cortical and subcortical regions. Remote regions affected by primary cerebellar and brainstem pathology include the supplementary motor area, cingulate cortex, frontal cortices, putamen and other subcortical nuclei. The connectivity disruptions identified provide an explanation for some of the non-ataxic symptoms observed in the disease and support the notion of reverse cerebellar diaschisis. This is the first study to comprehensively map white matter connectivity disruptions in Friedreich ataxia using tractography, connectomic techniques and super-resolution track density imaging.

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Acknowledgments

This work was supported by funding from the Friedreich Ataxia Research Association (Australasia), Friedreich Ataxia Research Alliance (USA) and Murdoch Childrens Research Institute. The authors were supported by the Australian Research Council (DP0986320 to A.Z.); the Melbourne Neuroscience Institute (Melbourne Neuroscience Institute Fellowship to A.Z.); the University of Melbourne (Melbourne International Fee Remission Scholarship and Melbourne International Research Scholarship to H.A.), the National Health and Medical Research Council (Early Career Fellowship to L.A.C., Practitioner Fellowship to M.B.D., Research Fellowship to G.F.E.).

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Zalesky, A., Akhlaghi, H., Corben, L.A. et al. Cerebello-cerebral connectivity deficits in Friedreich ataxia. Brain Struct Funct 219, 969–981 (2014). https://doi.org/10.1007/s00429-013-0547-1

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Keywords

  • Friedreich ataxia
  • Diffusion-weighted imaging
  • White matter
  • Connectome
  • Connectivity