A new study determined that reduced cerebello-cerebral functional connectivity is directly associated with white matter damage and functional status in Friedreich ataxia (FA). The study, published in the Journal of Neurology, also found functional connectivity correlations with primary motor systems and nonmotor circuits.

“Using resting-state [functional magnetic resonance imaging (MRI)], we first quantify differences between people with [FA] and healthy controls in the functional connectivity of three distinct anatomical subregions of the cerebellar cortex,” the authors wrote. “We then investigate relationships between functional connectivity, disease severity, psychomotor function, and white matter integrity assessed by diffusion tensor imaging in the [FA] cohort.”

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The research team assessed 35 individuals with FA and 45 age- and sex-matched controls, all from Australia. The severity of FA was quantified, MRI data were collected, and cerebellar cortex connectivity maps were generated for all participants. Prior to scanning, the participants performed computerized finger-tapping tasks to assess psychomotor speed, timing, and coordination.

The results showed that the FA cohort had significantly poorer functional connectivity between the superior posterior cerebellum and the left dorsolateral prefrontal cortex than the healthy controls. Overall, the reduced functional connectivity in patients with FA was associated with disease severity, motor function, and white matter integrity.

Abnormalities in patients with FA were most prominent in the motor system, but they also affected whole-brain functional circuits and nonmotor circuits (superior posterior lobe), even in a task-free context, which suggests a general property of the pathophysiology of FA. However, connectivity between the nonmotor circuits and other areas of the cortex was not significantly impacted.

The authors conclude that the results suggest FA is a “whole-brain” disease and highlight the need for further studies on the correlations between cerebello-cerebral alterations and symptoms in FA. They speculate that these changes could represent important biomarkers for FA disease tracking.


Kerestes R, Cummins H, Georgiou-Karistianis N, et al. Reduced cerebello-cerebral functional connectivity correlates with disease severity and impaired white matter integrity in Friedreich ataxia. J Neurol. Published online March 1, 2023. doi:10.1007/s00415-023-11637-x