Longitudinal functional brain imaging study in early course schizophrenia before and after cognitive enhancement therapy

•Neural underpinnings of therapeutic benefits in the early course of schizophrenia have not been clearly delineated.•Functional magnetic resonance (fMRI) studies were conducted in early course schizophrenia randomized to cognitive enhancement therapy (CET) or enriched supportive therapy (EST) for two years.•CET patients showed increases in right dorsolateral prefrontal activity and decreased frontocingulate connectivity whereas EST patients showed no change during treatment.•Changes in prefrontal activity and connectivity may be related to therapeutic change with CET.

ObjectiveSchizophrenia is characterized by impaired -social and non social cognition both of which lead to functional deficits. These deficits may benefit from cognitive remediation, but the neural underpinnings of such improvements have not been clearly delineated.MethodsWe conducted a functional magnetic resonance (fMRI) study in early course schizophrenia patients randomly assigned to cognitive enhancement therapy (CET) or enriched supportive therapy (EST) and treated for two years. Imaging data over three time points including fMRI blood oxygen level dependent (BOLD) data were acquired during performance of a cognitive control paradigm, the Preparing to Overcome Prepotency (POP) task, and functional connectivity data, were analyzed.ResultsDuring the two years of treatment, CET patients showed a continual increase in BOLD activity in the right dorsolateral prefrontal cortex (DLPFC), whereas EST patients tended to show no change in prefrontal brain function throughout treatment. Increases in right DLPFC activity were modestly associated with improved neurocognition (β = .14, p = .041), but not social cognition. Functional connectivity analyses showed reduced connectivity between the DLPFC and the anterior cingulate cortex (ACC) in CET compared to EST over the two years of treatment, which was associated with neurocognitive improvement. Conclusions. These findings suggest that CET leads to enhanced neural activity in brain regions mediating cognitive control and increased efficiency in prefrontal circuits; such changes may be related to the observed therapeutic effects of CET on neurocognitive function.