title: 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.
authors.affiliation: Melbourne Neuropsychiatry Centre, The University of Melbourne, Level 3, Alan Gilbert Building, Melbourne, VIC, 3010, Australia, azalesky@unimelb.edu.au.
authors.forename: Andrew
authors.initials: A
authors.lastname: Zalesky
authors.forename: Hamed
authors.initials: H
authors.lastname: Akhlaghi
authors.forename: Louise A
authors.initials: LA
authors.lastname: Corben
authors.forename: John L
authors.initials: JL
authors.lastname: Bradshaw
authors.forename: Martin B
authors.initials: MB
authors.lastname: Delatycki
authors.forename: Elsdon
authors.initials: E
authors.lastname: Storey
authors.forename: Nellie
authors.initials: N
authors.lastname: Georgiou-Karistianis
authors.forename: Gary F
authors.initials: GF
authors.lastname: Egan
mesh_terms: D000328:Adult; D001933:Brain Stem / Q000473:pathology*; D002531:Cerebellum / Q000473:pathology*; D005260:Female; D005621:Friedreich Ataxia / Q000473:pathology*; D006179:Gyrus Cinguli / Q000473:pathology*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000473:pathology*; D066127:White Matter / Q000473:pathology; D055815:Young Adult