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Title: Fronto-cerebellar dysfunction and dysconnectivity underlying cognition in friedreich ataxia: the IMAGE-FRDA study
Austin Authors: Harding, Ian H;Corben, Louise A;Storey, Elsdon;Egan, Gary F;Stagnitti, Monique R;Poudel, Govinda R;Delatycki, Martin B ;Georgiou-Karistianis, Nellie
Affiliation: School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia
Bruce Lefroy Centre, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia
Friedreich Ataxia Clinic, Monash Medical Centre, Monash Health, Melbourne, Victoria, Australia
Department of Medicine, Monash University, Melbourne, Victoria, Australia
Monash Biomedical Imaging, Monash University, Melbourne, Victoria, Australia
Department of Clinical Genetics, Austin Health, Heidelberg, Victoria, Australia
Issue Date: Jan-2016 2015-10
Publication information: Human Brain Mapping 2016; 37(1): 338-350
Abstract: Friedreich ataxia (FRDA) is a progressive neurodegenerative disorder defined by pathology within the cerebellum and spinal tracts. Although FRDA is most readily linked to motor and sensory dysfunctions, reported impairments in working memory and executive functions indicate that abnormalities may also extend to associations regions of the cerebral cortex and/or cerebello-cerebral interactions. To test this hypothesis, 29 individuals with genetically confirmed FRDA and 34 healthy controls performed a verbal n-back working memory task while undergoing functional magnetic resonance imaging. No significant group differences were evident in task performance. However, individuals with FRDA had deficits in brain activations both in the lateral cerebellar hemispheres, principally encompassing lobule VI, and the prefrontal cortex, including regions of the anterior insular and rostrolateral prefrontal cortices. Functional connectivity between these brain regions was also impaired, supporting a putative link between primary cerebellar dysfunction and subsequent cerebral abnormalities. Disease severity and genetic markers of disease liability were correlated specifically with cerebellar dysfunction, while correlations between behavioural performance and both cerebral activations and cerebello-cerebral connectivity were observed in controls, but not in the FRDA cohort. Taken together, these findings support a diaschisis model of brain dysfunction, whereby primary disease effects in the cerebellum result in functional changes in downstream fronto-cerebellar networks. These fronto-cerebellar disturbances provide a putative biological basis for the nonmotor symptoms observed in FRDA, and reflect the consequence of localized cerebellar pathology to distributed brain function underlying higher-order cognition.
DOI: 10.1002/hbm.23034
PubMed URL:
Type: Journal Article
Subjects: Friedreich ataxia
Functional connectivity
Psychophysiological interaction
Working memory
Appears in Collections:Journal articles

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