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

Karuna Subramaniam, Tracy L. Luks, Coleman Garrett, Cleo Chung, Melissa Fisher, Srikantan Nagarajan, Sophia Vinogradov

Research output: Contribution to journalArticlepeer-review

83 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)281-292
Number of pages12
StatePublished - Oct 1 2014

Bibliographical note

Funding Information:
This work was supported by NIMH grant R01MH081051, which was administered by the Northern California Institute for Research and Education, and with resources of the Department of Veterans Affairs Medical Center, San Francisco, California. Its contents are solely the responsibility of the authors.

Funding Information:
A portion of the cognitive training software used in this study was supplied to the senior author free of charge by Posit Science Inc. Dr. Vinogradov is a consultant to Posit Science Inc., a company with a commercial interest in cognitive training software. None of the other authors have any financial interest in Posit Science. Drs. Subramaniam, Luks, Chung, Garrett, Fisher and Nagarajan report no competing interests. Drs. Vinogradov, Luks, and Nagarajan have received grants or research support from the National Institute of Mental Health.


  • Cognitive training
  • FMRI
  • Prefrontal cortex
  • Schizophrenia
  • Working memory

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