Functional networks in motor sequence learning: Abnormal topographies in Parkinson's disease

We examined the neural circuitry underlying the explicit learning of motor sequences in normal subjects and patients with early stage Parkinson's dise ase (PD) using O-15-water ((H2O)-O-15) positron emission tomography (PET) a nd network analysis. All subjects were scanned while learning motor sequenc es in a task emphasizing explicit learning, and during a kinematically cont rolled motor execution reference task. Because different brain networks are thought to subserve target acquisition and retrieval during motor sequence learning, we used separate behavioral indices to quantify these aspects of learning during the PET experiments. In the normal cohort, network analysi s of the PET data revealed a significant covariance pattern associated with acquisition performance. This topography was characterized by activations in the left dorsolateral prefrontal cortex (PFdl), rostral supplementary mo tor area (preSMA), anterior cingulate cortex, and in the left caudate/putam en. A second independent covariance pattern was associated with retrieval p erformance. This topography was characterized by bilateral activations in t he premotor cortex (PMC), and in the right precuneus and posterior parietal cortex. The normal learning-related topographies failed to predict acquisi tion performance in PD patients and predicted retrieval performance less ac curately in the controls. A separate network analysis was performed to iden tify discrete learning-related topographies in the PD cohort. In PD patient s, acquisition performance was associated with a covariance pattern charact erized by activations in the left PFdl, ventral prefrontal, and rostral pre motor regions, but not in the striatum. Retrieval performance in PD patient s was associated with a covariance pattern characterized by activations in the right PFdl, and bilaterally in the PMC, posterior parietal cortex, and precuneus. These results suggest that in early stage PD sequence learning n etworks are associated with additional cortical activation compensating for abnormalities in basal ganglia function. (C) 2001 Wiley-Liss, Inc.