Associations between regional brain atrophy, executive control, and saccadic latency in Parkinson's disease and healthy aging

Background: Both sub-cortical and cortical brain regions related to saccadic control are affected by Parkinson's disease pathology, and a relationship between saccade alterations and cognitive features of Parkinson's disease has been suggested. The mechanisms of the neuronal decision process for saccades and the patterns of saccade latencies have been characterised by the LATER model. The analysis of individual latency distributions reveals important information about how neural decision is affected by disease or medication. Methods: We used a head-mounted saccadometer and LATER model to determine the latency parameters in 18 patients with Parkinson's disease in relative dopaminergic on and off states and 17 age-matched control subjects. We correlated latency parameters with tests of motor and cognitive function, and voxelwise cerebral grey matter volume (voxel based morphometry). Results: There were no significant differences in any of the latency parameters between controls and patients, whether in the on or the off state; or between the patients in the on and the off state. However, there was a negative correlation between letter fluency and the variability of saccade latency, whereas no correlation was found between overall motor function and any of the latency parameters. Voxel-wise grey matter volume estimates correlated with the latency parameters in several brain areas in patients and controls (p < 0.05 FWE corrected for multiple comparisons). Shorter saccade latency positively correlated with grey matter volume in regions of the prefrontal cortex, the cerebellar vermis, and the fusiform gyrus. The variability of saccade latency negatively correlated with grey matter volume in the frontal eye fields in patients; in controls, there was a negative correlation between the variability of latency and grey matter volume of the frontal and parietal eye fields, the premotor cortex, and the lateral prefrontal cortex. Conclusions: The behavioural and imaging findings point to an association between saccade latency, executive function and the prefrontal cortex. Our findings also suggest that saccadic latency and variability are associated with atrophy within a known oculomotor network. Therefore, saccadometry may provide important information on the severity of executive dysfunction and at the same time offer a rapid and non-invasive correlate of focal brain atrophy in healthy ageing and neurodegeneration. [Copyright Elsevier B.V.]