Disruption to higher order processes in Friedreich ataxia

Friedreich ataxia (FRDA), the most common of the genetically inherited ataxias, is characterised by ocular motor deficits largely reflecting disruption to brainstem-cerebellar circuitry. These deficits include fixation instability, saccadic dysmetria, disrupted pursuit, and vestibular abnormalities. Whether higher order or cognitive control processes involved the generation of more volitional eye movements are similarly impaired, has not been explored previously. This research examined antisaccade and memory-guided saccade characteristics in 13 individuals with genetically confirmed FRDA, and contrasted performance with neurologically healthy individuals. We demonstrate, for the first time, a broad range of deficits in FDRA consistent with disruption to higher order processes involved in the control of saccadic eye movement. Significant differences between FDRA and control participants were revealed across all movement parameters (latency, gain, velocity, position error), and across all saccade types, including alterations to velocity profiles. FDRA participants also generated significantly more erroneous responses to non-target stimuli in both saccade paradigms. Finally, a number of correlations between ocular motor and clinical measures were revealed including those between contrast acuity and saccadic latency (all saccade types), disease duration and measures of response inhibition (errors and relative latencies for antisaccades), and neurological scores and error latencies, arguably a reflection of difficulty resolving response conflict. These results suggest a role for the cerebellum in higher order cognitive control processes, and further support the proposal that eye movement markers, which can be measured with accuracy and reliability, may be a useful biomarker in FDRA. (C) 2009 Elsevier Ltd. All rights reserved.