Cognitive deficits in Friedreich ataxia correlate with micro-structural changes in dentatorubral tract

Atrophy of the dentate nucleus is one of the major neuropathological changes in Friedreich ataxia (FRDA). Neuroimaging studies demonstrated white matter (WM) degeneration in FRDA. In this study, we used advanced tractography techniques to quantitatively measure WM changes in the dentato-thalamic and dentato-rubral tracts, and correlated these changes with cognitive profiles of FRDA. We also analysed diffusivity changes of the thalamo-cortical tract to assess whether neurological degeneration of WM extends beyond the primary site of involvement in FRDA. Twelve genetically proven individuals with FRDA and 14 controls were recruited. Sixty directions diffusion tensor images were acquired. The WM bundles from the dentate nucleus were estimated using a constrained spherical deconvolution method and the diffusivity characteristics measured. The Simon task was used to assess cognitive profile of FRDA. The dentato-rubral, dentato-thalamic and thalamo-cortical tracts manifested significantly lower fractional anisotropy, higher mean diffusivity and increased radial diffusivity in FRDA compared with controls. There was no difference in axial diffusivity between the two groups. The mean and radial diffusivity of the dentato-rubral tract was positively correlated with choice reaction time, congruent reaction time, incongruent reaction time and Simon effect reaction time and negatively with the larger GAA repeat. Significant changes in diffusivity characteristics were observed in the dentato-thalamic and thalamo-cortical tracts, suggesting extensive WM degeneration and affected WM structures in FRDA. Correlation of WM changes in the dentato-rubral tract with the cognitive assessment suggested that this tract is an important contributor to cognitive disturbances in FRDA.