Functional MRI Studies in Friedreich's Ataxia: A Systematic Review

Marinela Vavla, Filippo Arrigoni, Denis Peruzzo, Domenico Montanaro, Francesca Frijia, Silvia Pizzighello, Alberto De Luca, Emma Della Libera, Federica Tessarotto, Paola Guerra, Ian H. Harding, Andrea Martinuzzi

Research output: Contribution to journalReview ArticleResearchpeer-review

Abstract

Friedreich's ataxia (FRDA) is an inherited neurodegenerative movement disorder with early onset, widespread cerebral and cerebellar pathology, and no cure still available. Functional MRI (fMRI) studies, although currently limited in number, have provided a better understanding of brain changes in people with FRDA. This systematic review aimed to provide a critical overview of the findings and methodologies of all fMRI studies conducted in genetically confirmed FRDA so far, and to offer recommendations for future study designs. About 12 cross-sectional and longitudinal fMRI studies, included 198 FRDA children and young adult patients and, 205 healthy controls (HCs), according to the inclusion criteria. Details regarding GAA triplet expansion and demographic and clinical severity measures were widely reported. fMRI designs included motor and cognitive task paradigms, and resting-state studies, with widespread changes in functionally activated areas and extensive variability in study methodologies. These studies highlight a mixed picture of both hypoactivation and hyperactivation in different cerebral and cerebellar brain regions depending on fMRI design and cohort characteristics. Functional changes often correlate with clinical variables. In aggregate, the findings provide support for cerebro-cerebellar loop damage and the compensatory mechanism hypothesis. Current literature indicates that fMRI is a valuable tool for gaining in vivo insights into FRDA pathology, but addressing that its limitations would be a key to improving the design, interpretation, and generalizability of studies in the future.

Original languageEnglish
Article number802496
Number of pages13
JournalFrontiers in Neurology
Volume12
DOIs
Publication statusPublished - 10 Mar 2022

Keywords

  • clinical study
  • fMRI protocol
  • Friedreich's ataxia
  • functional magnetic resonance imaging
  • study design
  • systematic review

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