Altered Intracerebellar Functional Connectivity in Friedreich’s Ataxia: A Graph-Theory Functional MRI Study

Abstract

Historically, Friedreich’s Ataxia (FRDA) has been linked to a relatively preserved cerebellar cortex. Recent advances in neuroimaging have revealed altered cerebello-cerebral functional connectivity (FC), but the extent of intra-cerebellar FC changes and their impact on cognition remains unclear. This study investigates intra-cerebellar FC alterations and their cognitive implications in FRDA. In this cross-sectional, single-center study, resting-state functional MRI data from 17 patients with FRDA (average age 27.7 ± 13.6 years; F/M = 6/11) and 20 healthy controls (HC) (average age 29.4 ± 9.7 years; F/M = 9/11), all of whom underwent neuropsychological testing, were analyzed. From functional connectivity matrices, graph measures were computed at both the network and node levels using two complementary parcellations. FRDA patients exhibited decreased global efficiency ( p = 0.04), nodal degree ( p = 0.001) and betweenness centrality ( p = 0.04) in the vermal portion of lobule VIII, along with reduced global efficiency in cerebellar regions belonging to the Control-A network ( p = 0.02), one of the three subdivisions of the Frontoparietal network. Verbal memory deficits correlated with global efficiency in both the vermal portion of lobule VIII ( r = 0.53, p = 0.02) and the cerebellar regions of the Control-A network ( r = 0.49, p = 0.05). Graph analysis revealed regional intra-cerebellar FC changes in FRDA, marked by reduced functional centrality in cerebellar regions of the vermis and responsible for executive functions. These changes correlated with cognitive alterations, highlighting the role of the cerebellar cortex in the cognitive impairment observed in FRDA.

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