Impact of antipsychotic treatment on attention and motor learning systems in first-episode schizophrenia

Abstract

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.

Keywords: caudate; cognition; dorsolateral prefrontal cortex; fMRI; risperidone; saccades.

Fig. 1.

Right anatomical side shown on left. Pretreatment, patients had only reduced activation relative to controls during prosaccades (row A) and predictive saccades (row C). After treatment, patients had increased activation relative to pretreatment for both tasks (row B prosaccade; row D predictive saccade). For the predictive saccade task, patients also had reduced activation (green voxels) in right dorsolateral prefrontal cortex after treatment. Slices above (positive) or below (negative) anterior commissure (mm): (A) 56, 25, 10, −7; (B) 59, 44, 18, 0; (C) 56, 41, 8, 0; (D) 33, 11, −15.

Fig. 2.

(A) Higher risperidone dose was associated with higher activation in bilateral caudate posttreatment for prosaccades (r = .60, P < .05; red squares) and at a trend level for predictive saccades (r = .51, P = .11, green circles). (B) Mean (1 SD) proportion of anticipatory saccades during the predictive saccade task was reduced in patients prior to treatment, but improved to normal after treatment (*P < .05). Baseline differences were found for whole sample, but graph depicts data only from participants re-scanned (14 patients, 12 controls). (C and D) Activation changes (posttreatment mean activation minus pretreatment mean activation) correlated at trend levels of significance with changes in predictive saccade task performance. Fewer anticipatory saccades after treatment associated with greater reduction in right dorsolateral prefrontal cortex activation (C; r = .51, P = .07), and with greater increases in right caudate (D; r = .50, P = .08). These associations did not change when controlling for antipsychotic dose, shown for each case as chlorpromazine equivalents.