Schizophrenia patients who underwent 80 hours of computerized training showed significant and sustained improvements in the ability to distinguish between internal experience and outside reality, a group of researchers has shown.

Improvements in reality monitoring – in which patients can distinguish a self-generated image, sound, or written phrase from one presented to them – corresponded to improvements in activation of the medial prefrontal cortex (mPFC), as confirmed by functional magnetic resonance imaging (fMRI).

The findings suggest that it is possible to improve brain function even among people who have lived decades with their disease.

The researchers, led by Karuna Subramaniam, Ph.D., of the San Francisco VA Medical Center, also recorded improved mPFC activity corresponding with behavioral improvements 6 months after the intervention had ended, suggesting a broader benefit to the training (Neuron 2012;73:842-53).

For their research, Dr. Subramaniam and colleagues recruited 31 clinically stable, persistently ill, volunteer schizophrenia patients, five of whom were women. The mean age of all subjects was 40 years, and mean illness duration was 19.4 years. A separate group of 16 healthy controls was recruited.

All underwent a baseline reality monitoring experiment in which brain activation patterns were recorded. The 16 schizophrenia subjects who were randomly assigned to the invention group received targeted training involving auditory, verbal, visual, and social cognitive processes, whereas 14 randomly assigned schizophrenia controls were given commercial computer games, such as Hangman, Tic-Tac-Toe, and Tetris, for 5 hours a week over 16 weeks in the laboratory.

After 16 weeks, 15 schizophrenia subjects in the intervention group, 14 in the games group, and 12 healthy controls participated in another fMRI reality-monitoring experiment. And 6 months later, 25 of the schizophrenia subjects returned for a reassessment of their clinical and functional status, reported Dr. Subramaniam, also of the University of California, San Francisco.

Intervention subjects showed significant improvement on delayed verbal memory recall at 16 weeks, compared with baseline (P = .02), whereas computer games subjects showed no significant improvement in this measure (P = .30). Intervention subjects also showed significant improvement performing a complex reality-monitoring task that was not part of the training exercises at 16 weeks, compared to baseline (P = .03), whereas games subjects showed no significant improvement in this measure (P = .89).

Compared with patients who played computer games, the trained patients showed a significant improvement in their accuracy when they performed a complex task, as well as a significant increase in mPFC activation during performance; a significant relationship was seen between mPFC activation after training and better social functioning after 6 months, Dr. Subramaniam and colleagues found.

“To our knowledge, this is the first time that a complex higher-order cognitive process in a serious neuropsychiatric illness – in this case, the ability to distinguish the source of information generated by the ‘self’ from information generated by the ‘other’ – has been the targeted outcome of a neuroscience-informed cognitive training strategy,” the researchers wrote in their analysis.

The findings show, they wrote, that “it is possible to significantly improve brain function in schizophrenia, even in patients who have been ill for an average of 20 years, and it appears that these improvements set the stage for an enduring improvement in social functioning that occurs even in the absence of other psychosocial therapies.”

Dr. Subramaniam reported no relevant financial disclosures. The study was funded by the National Institute of Mental Health. Two coauthors, Gregory V. Simpson, Ph.D., and Dr. Sophia Vinogradov, disclosed employment and consulting relationships, respectively, with the Brain Plasticity Institute, which has a financial interest in computerized cognitive training programs.