Intensive cognitive training in schizophrenia enhances working memory and associated prefrontal cortical efficiency in a manner that drives long-term functional gains

We investigated whether intensive computerized cognitive training in schizophrenia could improve working memory performance and increase signal efficiency of associated middle frontal gyri (MFG) circuits in a functionally meaningful manner. Thirty schizophrenia participants and 13 healthy comparison participants underwent fMRI scanning during a letter N-back working memory task. Schizophrenia participants were then randomly assigned to either 80 h (16 weeks) of cognitive training or a computer games control condition. After this intervention, participants completed a second fMRI N-back scanning session. At baseline, during 2-back working memory trials, healthy participants showed the largest and most significant activation in bilateral MFG, which correlated with task performance. Schizophrenia participants showed impaired working memory, hypoactivation in left MFG, and no correlation between bilateral MFG signal and task performance. After training, schizophrenia participants improved their 2-back working memory performance and showed increased activation in left MFG. They also demonstrated a significant association between enhanced task performance and right MFG signal, similar to healthy participants. Both task performance and brain activity in right MFG after training predicted better generalized working memory at 6-month follow-up. Furthermore, task performance and brain activity within bilateral MFG predicted better occupational functioning at 6-month follow-up. No such findings were observed in the computer games control participants. Working memory impairments in schizophrenia and its underlying neural correlates in MFG can be improved by intensive computerized cognitive training; these improvements generalize beyond the trained task and are associated with enduring effects on cognition and functioning 6 months after the intervention.