Intrinsic Activity Reductions and Cerebello-Cortical Diaschisis-Like Mechanism in Friedreich Ataxia: An fALFF Resting-State fMRI Study.
- 1Department of Neurology, Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B.), CUB Hôpital Erasme, Brussels, Belgium.
- 2UNI-ULB Neuroscience Institute, Laboratoire de Neuroanatomie et Neuroimagerie translationnelles (LN2T), Université Libre de Bruxelles (ULB), Brussels, Belgium.
- 3Department of Translational Neuroimaging, Université Libre de Bruxelles (ULB), Hôpital Universitaire De Bruxelles (H.U.B.), CUB Hôpital Erasme, Brussels, Belgium.
Abstract
Background
Friedreich ataxia (FA) is characterized by progressive degeneration of the cerebellum and its output pathways, particularly the dentato-thalamo-cortical system, leading to motor impairment and the cerebellar cognitive affective syndrome (CCAS). Resting-state fMRI studies in FA have focused on alterations of long-range functional connectivity, but little is known about how intrinsic regional neural activity is affected within cerebello-cortical networks.Methods
Twenty-eight adults with genetically confirmed FA and 28 age- and sex-matched healthy controls underwent resting-state functional MRI. Intrinsic brain activity was quantified using the fractional amplitude of low-frequency fluctuations (fALFF). Whole-brain comparisons were performed between controls and patients, and between patients with definite CCAS (FA-Cog) and cognitively preserved patients (FA-NoCog). Within the FA group, voxelwise regressions assessed associations between fALFF, motor severity (Scale for the Assessment and Rating of Ataxia [SARA]), and cognitive performance (Cerebellar Cognitive Affective Syndrome Scale [CCAS-S]), adjusting for age, sex, head motion, and cerebellar gray matter volume.Results
Compared with controls, patients exhibited reduced fALFF in medial and lateral prefrontal regions. Higher SARA scores were associated with lower fALFF in occipital, sensorimotor, posterior cingulate, and cerebellar regions, whereas higher CCAS-S scores correlated with higher fALFF in bilateral prefrontal and cerebellar cognitive networks. Compared with FA-NoCog, FA-Cog patients showed lower fALFF in bilateral frontal and insular regions.Conclusions
Resting-state fALFF reveals downstream dysfunction of distributed cerebello-cortical networks in FA. Associations with motor severity and cognition, together with additional fronto-insular dysfunction in patients with definite CCAS, support progressive cerebello-cortical disconnection consistent with a diaschisis-like mechanism.
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BibTeX
@article{gilles2026intrinsic,
title = {{Intrinsic Activity Reductions and Cerebello-Cortical Diaschisis-Like Mechanism in Friedreich Ataxia: An fALFF Resting-State fMRI Study.}},
author = {Naeije Gilles and Trotta Nicola and Rovai Antonin},
journal = {Brain and behavior},
year = {2026},
month = oct,
doi = {10.1002/brb3.71866},
url = {https://europepmc.org/article/MED/42949167},
note = {CC BY},
}
RIS
TY - JOUR
TI - Intrinsic Activity Reductions and Cerebello-Cortical Diaschisis-Like Mechanism in Friedreich Ataxia: An fALFF Resting-State fMRI Study.
AU - Naeije Gilles
AU - Trotta Nicola
AU - Rovai Antonin
PY - 2026
DA - 2026/10/28
JO - Brain and behavior
DO - 10.1002/brb3.71866
UR - https://europepmc.org/article/MED/42949167
AB - Background Friedreich ataxia (FA) is characterized by progressive degeneration of the cerebellum and its output pathways, particularly the dentato-thalamo-cortical system, leading to motor impairment and the cerebellar cognitive affective syndrome (CCAS). Resting-state fMRI studies in FA have focused on alterations of long-range functional connectivity, but little is known about how intrinsic regional neural activity is affected within cerebello-cortical networks.Methods Twenty-eight adults with genetically confirmed FA and 28 age- and sex-matched healthy controls underwent resting-state functional MRI. Intrinsic brain activity was quantified using the fractional amplitude of low-frequency fluctuations (fALFF). Whole-brain comparisons were performed between controls and patients, and between patients with definite CCAS (FA-Cog) and cognitively preserved patients (FA-NoCog). Within the FA group, voxelwise regressions assessed associations between fALFF, motor severity (Scale for the Assessment and Rating of Ataxia [SARA]), and cognitive performance (Cerebellar Cognitive Affective Syndrome Scale [CCAS-S]), adjusting for age, sex, head motion, and cerebellar gray matter volume.Results Compared with controls, patients exhibited reduced fALFF in medial and lateral prefrontal regions. Higher SARA scores were associated with lower fALFF in occipital, sensorimotor, posterior cingulate, and cerebellar regions, whereas higher CCAS-S scores correlated with higher fALFF in bilateral prefrontal and cerebellar cognitive networks. Compared with FA-NoCog, FA-Cog patients showed lower fALFF in bilateral frontal and insular regions.Conclusions Resting-state fALFF reveals downstream dysfunction of distributed cerebello-cortical networks in FA. Associations with motor severity and cognition, together with additional fronto-insular dysfunction in patients with definite CCAS, support progressive cerebello-cortical disconnection consistent with a diaschisis-like mechanism.
SN - 2162-3279
ER -