Impact of Antipsychotic Treatment on Attention and Motor Learning Systems in First-Episode Schizophrenia

Background: Antipsychotic medications have established clinical benefit, but there are few neuroimaging studies before and after initiating antipsychotic medication to assess drug influence on brain circuitry. Attention and motor learning tasks are promising approaches for examining treatment-related changes in frontostriatal systems. Methods: Twenty-one unmedicated first-episode schizophrenia patients (14 antipsychotic-naïve) participated in functional imaging studies while performing visual attention (prosaccades) and motor learning tasks (predictive saccades). Posttreatment testing was completed in 14 patients after 4–6 weeks of antipsychotic treatment. Matched healthy controls were studied in parallel. Results: Pretreatment, patients had reduced activation in the dorsal neocortical visual attention network. Activation deficits were significantly reduced posttreatment. Higher medication dose was associated with greater caudate activation at follow-up. For the motor learning task, patients’ dorsolateral prefrontal cortex (DLPFC) was unimpaired prior to treatment but showed significantly reduced activation after treatment. Conclusion: Impairments in dorsal cortical attention networks are present in untreated first-episode schizophrenia patients. These impairments are reduced after antipsychotic treatment, suggesting a beneficial effect on neural systems for attention. Treatment-emergent decreases in DLPFC activation observed for the motor learning task are consistent with other clinical and preclinical evidence suggesting that antipsychotics can have adverse effects on prefrontal function.Key words: fMRI, cognition, dorsolateral prefrontal cortex, saccades, caudate, risperidone