Enhancement of brain activation during trial-and-error sequence learning in early PD.
BACKGROUND: Although the pathophysiology remains unknown, most nondemented patients with PD have difficulty with frontal tasks, including trial-and-error sequence learning. If given time, they can perform cognitive tasks of moderate difficulty as well as controls. However, it is not known how brain function is altered during this time period to preserve higher cortical function in the face of PD pathology. METHOD: To evaluate this phenomenon, the authors matched sequence learning between PD and control subjects for the last 30 seconds of a PET scan. Learning during the initial 50 seconds of PET was unconstrained. RESULTS: Learning indices were equivalent between groups during the last 30 seconds of the scan, whereas rates of acquisition, correct movements, and forgetting differed in the first 30 seconds. In normal controls sequence learning was associated with activations in the right prefrontal, premotor, parietal, rostral supplementary motor area, and precuneus regions. To achieve equal performance, the PD group activated greater volume within these same regions, and also their left sided cortical homologs and the lateral cerebellum bilaterally. CONCLUSIONS: Mildly affected patients with PD demonstrated only modest impairment of learning during the first 30 seconds of the task and performed equivalently with controls thereafter. However, the mechanism by which they achieved equiperformance involved considerable changes in brain function. The PD group had to activate four times as much neural tissue as the controls, including recruiting brain from homologous cortical regions and bilateral lateral cerebellum.