Joint principles of motor and cognitive dysfunction in Parkinson's disease.

Traditionally, the lateral premotor cortex (PM) is assigned a role in stimulus-driven rather than memory-driven motor control, whereas the opposite holds for the mesial premotor cortex (supplementary motor area, SMA). Consistently, patients with Parkinson's Disease (PD), in which a specific functional degradation of the mesial loop (i.e., SMA-Striatum) occurs, show impaired memory-driven but relatively preserved stimulus-driven motor control. However, both parts of the premotor cortex are involved in perceptual prediction tasks as well. Here we tested whether the functional bias described on the motor level (i.e., memory-driven/mesial versus stimulus-driven/lateral) can also be detected in perceptual prediction tasks thereby suggesting that PD patients exhibit the same pattern of impaired memory-driven and preserved stimulus-driven control in the cognitive domain. To this end, we investigated 20 male PD-patients "on" and "off" dopaminergic medication while performing a serial prediction task (SPT). A specific modification was implemented to the classical SPT (SPT0) that caused shifts from stimulus- to memory-based prediction (SPT+). As a result, PD patients showed a significantly impaired performance "off" compared to "on" medication for SPT+, whereas no significant "on"/"off"-effects were found for SPT0. Descriptively, the "off"-performance decreased gradually with increasing demands on memory-based prediction. Furthermore, the severity of motor deficits according to the UPDRS III correlated significantly with impaired performance in SPT0 "on" medication. Importantly, an even stronger dependency was found for UPDRS III and SPT+. These findings point to a role of the SMA-striatal loop in memory-driven serial prediction beyond the motor domain.