Rule learning in a serial reaction time task: an fMRI study on patients with early Parkinson's disease.

In the present study, we investigated implicit rule learning in patients with Parkinson's disease (PD) and healthy participants. Functional magnetic resonance imaging (fMRI) and a variant of the serial reaction time task were employed to examine the performance of previously learned regular sequences. Participants responded to successively appearing visual stimuli by pressing spatially corresponding keys. Unbeknownst to them, a cycling 12-item sequence was presented. In order to measure rule learning independently from initial visuomotor learning, participants were trained with the sequence prior to scanning. In the fMRI session, alternating blocks of regular and random stimuli were performed. Imaging revealed activations in the frontomedian and posterior cingulate cortex during performance of sequence blocks as opposed to random blocks. The magnitude of activations in these two areas was correlated with the behavioral index for rule learning. As has been reported earlier, the frontomedian cortex may be involved in the prediction of future stimuli and anticipation of corresponding actions, whereas the posterior cingulate activation may rather be related to memory retrieval. Additional activations of the right putamen and the inferior frontal sulcus were not related to behavioral performance. In patients with early PD, the behavioral data showed reduced training effects during pretraining, but intact rule learning during the fMRI session. Imaging revealed highly similar frontomedian and posterior cingulate activations in patients and controls, in the absence of significant striatal and inferior frontal activations in patients. Our findings support the view that in early PD, with the lateral striatofrontal dopaminergic projections being affected, medial dopaminergic projections involved in the application of previously learned rules may still be spared.