Cognitive and functional connectivity alterations in Friedreich's ataxia

Area of Science:

• Neuroscience
• Neurology
• Medical Imaging

Background:

• Friedreich's ataxia (FRDA) is a rare inherited neurodegenerative disorder.
• Cognitive impairments are increasingly recognized in FRDA patients.
• Brain functional connectivity (FC) alterations may underlie these deficits.

Purpose of the Study:

• To investigate resting-state functional MRI (RS-fMRI) based FC differences in FRDA patients.
• To correlate FC findings with neuropsychological performance in FRDA.
• To explore the neurobiological underpinnings of cognitive dysfunction in FRDA.

Main Methods:

• Cross-sectional study comparing 24 FRDA patients and 24 healthy controls (HC).
• Comprehensive neuropsychological assessment across multiple cognitive domains.
• Seed-based RS-fMRI analysis to evaluate cortical and cerebello-cortical FC.

Main Results:

• FRDA patients demonstrated significantly worse performance in global cognition, spatial memory, visuoperception, visuospatial functions, and executive functions compared to HC.
• Elevated FC was observed between paracingulate gyri and medial frontal gyrus, superior frontal gyrus and bilateral angular gyri, and middle temporal gyrus and cingulate gyrus in FRDA patients.
• A reduced FC was found between the medial frontal gyrus and the cerebellum in FRDA patients.

Conclusions:

• FRDA is associated with reduced functional connectivity between frontal areas and the contralateral cerebellar cortex, consistent with cerebello-cortical pathway alterations.
• Increased FC between cortical regions may represent a compensatory mechanism in response to neurodegeneration.
• These findings enhance understanding of supratentorial and infratentorial brain involvement and brain plasticity dynamics in FRDA.