Neuropsychological and functional brain correlates of procedural learning in schizophrenia

Resumen

Background Neuropsychological studies of procedural learning in schizophrenia have been inconsistent, sometimes finding it to be preserved and sometimes impaired. Three factors which could account for the variability among findings were identified: type of task, presence of general intellectual impairment and the extrapyramidal side-effects of neuroleptic treatment. Additionally, functional imaging studies have found reduced basal ganglia activation in schizophrenia during performance of procedural learning tasks. However, the extent to which this finding might reflect or be confounded by some or all these factors has not been examined. Methods A sample of patients with schizophrenia and matched healthy controls were examined using different behavioural paradigms, the pursuit rotor, mirror reading and probabilistic learning (`weather prediction¿), aimed to engage different aspects of procedural learning. Additionally, different samples of schizophrenic patients and matched healthy controls underwent functional magnetic resonance while they performed a motor skill learning task. A measure of linear changes in intensity within block was used to model fMRI correlates of learning on this task. Comparisons between subgroups of intellectually preserved patients and patients with and without parkinsonism and with and without tardive dyskinesia were also conducted at both, the behavioural and the functional neuroimaging level. Results At the behavioural level, the schizophrenic patients showed comparable learning to the controls on the pursuit rotor and mirror reading, but were impaired on the probabilistic learning task. However, this last difference disappeared when a subgroup of intellectually preserved patients was compared to a subgroup of matched controls. Patients with and without tardive dyskinesia or parkinsonism showed similar learning on all three tasks. At the brain functional level, the schizophrenic patients showed, compared to the healthy controls, reduced activation in regions which included the putamen and pallidum bilaterally, as well as the hippocampus and parahippocampus, the right sensorimotor cortex, and parts of the frontal cortex. When intellectually preserved patients were compared to controls, the clusters of reduced activation in the prefrontal cortex were no longer seen. In addition, when patients without parkinsonism were compared to controls all differences in activation disappeared. Conclusions Procedural learning tends to be preserved in schizophrenia across a range of different tasks; when impairment is found, differences in the overall level of intellectual function may be the determining factor. Additionally, changes in the functional imaging correlates of procedural learning performance in schizophrenia may reflect factors other than intrinsic brain functional abnormality. Extrapyramidal side-effects of neuroleptic drug treatment appear to be a particular cofounding factor.