Age of onset modulates resting-state brain network dynamics in Friedreich Ataxia

This magnetoencephalography (MEG) study addresses (i) how Friedreich ataxia (FRDA) affects the sub-second dynamics of resting-state brain networks, (ii) the main determinants of their dynamic alterations, and (iii) how these alterations are linked with FRDA-related changes in resting-state functional brain connectivity (rsFC) over long timescales. For that purpose, 5 min of resting-state MEG activity were recorded in 16 FRDA patients (mean age: 27 years, range: 12-51 years; 10 females) and matched healthy subjects. Transient brain network dynamics was assessed using hidden Markov modeling (HMM). Post hoc median-split, nonparametric permutations and Spearman rank correlations were used for statistics. In FRDA patients, a positive correlation was found between the age of symptoms onset (ASO) and the temporal dynamics of two HMM states involving the posterior default mode network (DMN) and the temporo-parietal junctions (TPJ). FRDA patients with an ASO <11 years presented altered temporal dynamics of those two HMM states compared with FRDA patients with an ASO > 11 years or healthy subjects. The temporal dynamics of the DMN state also correlated with minute-long DMN rsFC. This study demonstrates that ASO is the main determinant of alterations in the sub-second dynamics of posterior associative neocortices in FRDA patients and substantiates a direct link between sub-second network activity and functional brain integration over long timescales.