Cognitive and functional connectivity alterations in Friedreich's ataxia

Abstract

ObjectiveThe aim of this study was to perform the first resting‐state functional MRI (RS‐fMRI) analysis in Friedreich's ataxia (FRDA) patients to assess possible brain functional connectivity (FC) differences in these patients, and test their correlations with neuropsychological performances.MethodsIn total, 24 FRDA patients (M/F: 15/9, mean age 31.3 ± 15.0) and 24 healthy controls (HC; M/F: 15/9, mean age 30.7 ± 15.5) were enrolled in this cross‐sectional study. All patients underwent a thorough neuropsychological battery, investigating different cognitive domains. RS‐fMRI data were analyzed using a seed‐based approach, probing the FC of cortical areas potentially referable to specific executive and cognitive functions compromised in FRDA.ResultsCompared to HC, FRDA patients showed overall worse neuropsychological scores in several domains, including global cognitive assessment, spatial memory, visuoperception and visuospatial functions, and executive functions. Analysis of RS‐fMRI data showed a higher FC in FRDA patients compared to HC between paracingulate gyri and the medial frontal gryrus, between the superior frontal gyrus and bilateral angular gyri, and between the middle temporal gyrus and the cingulate gyrus, with a reduced FC between the medial frontal gryrus and the cerebellum.InterpretationWe found a reduction in FC between frontal areas and the contralateral cerebellar cortex in FRDA, in line with the known alteration in cerebello‐cortical pathway in this condition. On the other hand, a higher FC between different cortical areas was shown, possibly reflecting a compensatory phenomenon. These results, in conjunction with clinical findings, may shed new light on the pattern of supratentorial and infratentorial involvement, and on dynamics of brain plasticity in this disease.

Longitudinal Study of Cognitive Functioning in Friedreich’s Ataxia

“…Therefore, the cognitive deficit reported in FDRA may be the consequences of these abnormalities in the cerebellar-cortical system (e.g. Cocozza et al, 2018;Selvadurai et al, 2020;Zalesky et al, 2014). In this same line, the cognitive changes observed in this research may be related to the longitudinal microstructural changes reported in diffusion tensor imaging studies (Mascalchi et al, 2016;Rezende et al, 2016).…”

Central Nervous System Therapeutic Targets in Friedreich Ataxia

“…On the microstructural level, changes in fractional anisotropy by diffusion MRI are consistently detected in the deep cerebellar white matter and in the dentatothalamic tracts, 39,40,[47][48][49][50] which appear to correlate with ataxia severity. Correspondingly, several studies detected impaired cerebellocerebral connectivity, 17,[51][52][53] which is essentially due to atrophy of dentatothalamic fibers. Overall, imaging confirms the presence and progression of cerebellar pathology in FRDA, mostly, but not exclusively, affecting the DN, and the consequent impairment in structural and functional connectivity.…”

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

“…Previous neuroimaging investigations suggested that the level of rsFC is linked with FRDA patients' neurological status. A resting‐state functional magnetic resonance imaging (rfMRI) study described that a higher level of rsFC between superior and medial frontal gyri, and angular and cingulate‐paracingulate gyri might be associated with better cognitive performances in FRDA patients (Cocozza et al, 2018). Furthermore, a previous magnetoencephalography (MEG) study from our group showed that FRDA patients with symptoms onset after age 12 had significantly higher levels of brain rsFC compared with matched healthy individuals and FRDA patients with symptoms onset before age 12 (Naeije et al, 2020b).…”