Abstract
Friedreich ataxia (FRDA) is a progressive autosomal recessive disease. While motor dysfunction is the primary neurological hallmark, little is known about the underlying neurobiological changes associated with motor deficits over the course of disease. We investigated the hypothesis that progressive functional changes in both the cerebellum and cerebrum are related to longitudinal changes in performance on complex motor tasks in individuals with FRDA. Twenty-two individuals with FRDA and 28 controls participated over 24 months. The longitudinal investigation included finger tap** tasks with different levels of complexity (i.e., visually cued, multi-finger; self-paced, single finger), performed in conjunction with fMRI acquisitions, to interrogate changes in the neurobiology of motor and attentional brain networks including the cerebellum and cerebrum. We demonstrated evidence for significant longitudinal decreased cerebral fMRI activity over time in individuals with FRDA, relative to controls, during an attentionally-demanding motor task (visually cued tap** of multiple fingers) in six cerebral regions: right and left superior frontal gyri, right superior temporal gyrus, right primary somatosensory area, right anterior cingulate cortex, and right medial frontal gyrus. Importantly, longitudinal decreased activity was associated with more severe disease status at baseline, higher GAA1 repeat length and earlier age of onset. These findings suggest a dynamic pattern of neuronal activity in motor, attention and executive control networks over time in individuals with FRDA, which is associated with increased disease severity at baseline, increased GAA1 repeat length and earlier age at onset.
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The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions. Researchers interested in access to the Code for data cleaning and analysis may contact the corresponding author.
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Acknowledgements
We thank the individuals who participated in this study, Monique Stagnitti for participant recruitment and scanning, and Jasmine Baja for assistance with this research.
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The IMAGE-FRDA study was funded by the Australian National Health and Medical Research Council (Project Grant 1046037).
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Shishegar, R., Harding, I.H., Selvadurai, L.P. et al. Longitudinal investigation of brain activation during motor tasks in Friedreich ataxia: 24-month data from IMAGE-FRDA. Brain Struct Funct 227, 809–819 (2022). https://doi.org/10.1007/s00429-021-02413-6
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DOI: https://doi.org/10.1007/s00429-021-02413-6