Neuroplastic changes in patients with schizophrenia undergoing cognitive remediation: triple-blind trial

Abstract

BackgroundPatients with schizophrenia have shown cognitive improvements following cognitive remediation, but the neuroplastic changes that support these processes are not fully understood.AimsTo use a triple-blind, placebo-controlled trial to examine neural activation before and after cognitive remediation or a computer skills training (CST) placebo (trial registration: NCT00995553)).MethodTwenty-seven participants underwent functional magnetic resonance imaging before and after being randomised to either cognitive remediation intervention or CST. Participants completed two variants of the N-back task during scanning and were assessed on measures of cognition, functional capacity, community functioning and symptoms.ResultsWe observed a group × time interaction in the left prefrontal cortex, wherein the cognitive remediation group showed increased activation. These changes correlated with improved task accuracy within the cognitive remediation group, whereas there was no relationship between changes in activation in untrained cognitive measures. Significant changes were not observed in other hypothesised areas for the cognitive remediation group.ConclusionsWe replicated the finding that cognitive remediation increases left lateral prefrontal activation during a working memory task in patients with schizophrenia, suggesting this may be an important neural target for these types of interventions.

Fig. 1

Picture N-Back task behavioural findings. Patients in the cognitive remediation intervention group showed an increase in d′ from time 1 (T_1, mean 2.62, s.d. = 0.60) to time 2 (T₂, mean 3.15, s.d. = 0.82) on the 2-back trials of the picture N-back task (results using %-correct can be found in online Table DS2), whereas those in the computer skills training group (CST group) showed no change from T₁ (mean 2.54, s.d. = 0.88) to T₂ (mean 2.47, s.d. = 0.86).

Fig. 2

Group × time interaction in the left dorsolateral prefrontal cortex (DLPFC) region of interest (ROI) for 2-back v. 0-back blocks (2Bv0B). We observed a voxel-wise group × time interaction in the left DLPFC ROI during the 2Bv0B condition in the cognitive remediation intervention group (a) driven by increases from pre- to post-training in the cognitive remediation group but not the computer skills training group (CST group) (b). (c) Change in per cent signal change extracted from the significant voxels in the left DLPFC were positively correlated with changes in d' on the picture N-back task (r = 0.51, P(hypothesised)<0.05). This relationship held when using a robust linear estimator to control for the effects of outliers (r = 0.56, P(hypothesised)<0.05).