Dramatic impairment of prediction due to frontal lobe degeneration.

Prediction is essential for motor function in everyday life. For instance, predictive mechanisms improve the perception of a moving target by increasing eye speed anticipatively, thus reducing motion blur on the retina. Subregions of the frontal lobes play a key role in eye movements in general and in smooth pursuit in particular, but their precise function is not firmly established. Here, the role of frontal lobes in the timing of predictive action is demonstrated by studying predictive smooth pursuit during transient blanking of a moving target in mild frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD) patients. While control subjects and AD patients predictively reaccelerated their eyes before the predicted time of target reappearance, FTLD patients did not. The difference was so dramatic (classification accuracy >90%) that it could even lead to the definition of a new biomarker. In contrast, anticipatory eye movements triggered by the disappearance of the fixation point were still present before target motion onset in FTLD patients and visually guided pursuit was normal in both patient groups compared with controls. Therefore, FTLD patients were only impaired when the predicted timing of an external event was required to elicit an action. These results argue in favor of a role of the frontal lobes in predictive movement timing.