Abstract
ObjectiveFriedreich ataxia (FRDA) is the commonest hereditary ataxia in Caucasians. Most patients are homozygous for expanded GAA triplet repeats in the first intron of the frataxin (FXN) gene, involved in mitochondrial iron metabolism. Here, we used magnetoencephalography (MEG) to characterize the main determinants of FRDA‐related changes in intrinsic functional brain architecture.MethodsFive minutes of MEG signals were recorded at rest from 18 right‐handed FRDA patients (mean age 27 years, 9 females; mean SARA score: 21.4) and matched healthy individuals. The MEG connectome was estimated as resting‐state functional connectivity (rsFC) matrices involving 37 nodes from six major resting state networks and the cerebellum. Source‐level rsFC maps were computed using leakage‐corrected broad‐band (3–40 Hz) envelope correlations. Post hoc median‐split was used to contrast rsFC in FRDA patients with different clinical characteristics. Nonparametric permutations and Spearman rank correlation test were used for statistics.ResultsHigh rank correlation levels were found between rsFC and age of symptoms onset in FRDA mostly between the ventral attention, the default‐mode, and the cerebellar networks; patients with higher rsFC developing symptoms at an older age. Increased rsFC was found in FRDA with later age of symptoms onset compared to healthy subjects. No correlations were found between rsFC and other clinical parameters.ConclusionAge of symptoms onset is a major determinant of FRDA patients' intrinsic functional brain architecture. Higher rsFC in FRDA patients with later age of symptoms onset supports compensatory mechanisms for FRDA‐related neural network dysfunction and position neuromagnetic rsFC as potential marker of FRDA neural reserve.
Highlights
Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia in Caucasians.[1]
No significant difference in power, restingstate functional connectivity (rsFC), node strength, and global connectivity was found between FRDA patients and healthy subjects
This MEG study demonstrates that the age of symptoms onset is a major determinant of the intrinsic functional brain architecture in FRDA patients
Summary
Friedreich ataxia (FRDA) is the most common autosomal recessive ataxia in Caucasians.[1]. The study of resting state (i.e., in the absence of any explicit task) functional connectivity (rsFC) allows to noninvasively characterize brain interactions in FRDA using a task and performance bias-free approach. Functional Connectivity in Friedreich Ataxia in autosomal dominant spinocerebellar ataxias (SCAs, e.g., SCAs 2, 6, and 7) demonstrated significant changes in cerebello-cortical and cortico-cortical rsFC that correlated with to some extent with various clinical variables.[8,9,10,11,12] the pattern of cerebellar pathology in these SCAs is different from FRDA, with the cerebellar cortex being primarily affected. A single fMRI study performed in FRDA demonstrated increased rsFC between brain areas potentially involved in specific cognitive functions, and decreased rsFC of cerebello-prefrontal connections.[14] Increases in rsFC were considered to reflect compensatory mechanisms, as they tended to correlate with some neuropsychological scores. We searched for correlation between rsFC changes, genetic, and clinical parameters (i.e., the size of GAA1 triplet expansion, age of symptoms onset, disease duration, and severity of clinical symptoms)
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