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Subramaniam K, Luks TL, Fisher M, Simpson GV, Nagarajan S, Vinogradov S. Computerized cognitive training restores neural activity within the reality monitoring network in schizophrenia. Neuron. 2012 Feb 23 ; 73(4):842-53. Pubmed Abstract

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Comment by:  Philip Harvey
Submitted 27 February 2012
Posted 27 February 2012

This is a fabulous study for several reasons.

The authors use cognitive training to enhance cognition and measure both cognitive functioning and the intactness of a neural network that they previous discovered. They find that they enhance cognition and improve regional brain activation. Further, social functioning is improved at a six-month follow-up.

Since the authors measured cognition and functionally relevant outcomes, these data again provide support for the usefulness of cognitive remediation for cognition and functioning, as well as show that these interventions directly impact critical neural networks. The integration of brain, cognition, and functioning makes a strong argument for the universal application of cognitive remediation in people with schizophrenia.

View all comments by Philip HarveyComment by:  James Gold, SRF Advisor
Submitted 27 February 2012
Posted 27 February 2012

Dr. Subramaniam and colleagues deserve congratulations on an impressive study demonstrating that an extensive computerized cognitive training intervention appears to have effects on both brain physiology and performance on an untrained reality monitoring task—important evidence that the training does not only “teach to the test.” Further, the training appears to normalize the relationship between medial frontal activity and reality monitoring in patients, suggesting that the training has resulted in a reorganization of how patients are able to mobilize neural systems to meet the cognitive challenge. This result is important and adds to the evidence that the Posit Science approach may be valuable for people with schizophrenia. Adding to the importance of this result is the fact that, to date, there is no compelling, replicated evidence that any available pharmacological approach provides effective treatment for the cognitive impairments of schizophrenia. Indeed, given the apparent exodus of multiple major pharmaceutical companies from psychiatric treatment development research, the need to better understand the utility of psychosocial interventions is increasing as we search for answers for today’s patients and likely tomorrow’s as well.

No study is without problems in interpretation, and some arise here. For example, is it possible that the larger effect on the recognition of self-generated items versus externally presented items might be the result of potential ceiling effects in the externally presented condition? In addition, the interpretation of the social functioning results might have been clearer if change in BOLD signal had been correlated with change in social functioning. The current result: no overall change in social function, but correlation between BOLD signal at the end of training and social functioning level at six months. This makes it hard to interpret training-related improvement in medial prefrontal activity as causing the changes in social functioning, basically missing the link that goes directly from treatment condition to outcome.

Lastly, it remains unclear exactly how the Posit Science program works at a neural level. Clearly the approach was designed to target lower-level sensory-perceptual processes with the goal of increasing the fidelity and precision of the inputs to higher-order systems. It would certainly make sense that the gradual training approach, which titrates difficulty level, does indeed work this way. Other non-incompatible possibilities deserve to be considered. Might the dense training approach serve as a kind of attentional and strategy training just as much as perceptual training? That is, patients learn how to get things “right.” One could imagine that this could occur because specific neural populations involved in task performance become more efficient, their task-relevant “receptive fields” become more precise. Alternatively, it is also be possible that higher-order attentional functions are also becoming trained to more efficiently modulate lower-level systems. And it might be easier to understand the type of generalization effects seen in this study if the training inadvertently also had benefits to task general cognitive systems that may be brought to bear on many untrained tasks. It remains for future work to see which understanding is more accurate.

In the meantime, the contribution of the Vinogradov team deserves recognition for an ambitious study, a potentially important and intriguing finding, and providing a ray of hope in an otherwise pretty dark treatment development landscape.

View all comments by James GoldComment by:  Robert McCarley
Submitted 7 March 2012
Posted 8 March 2012
  I recommend the Primary Papers

Very exciting and hopeful data, especially in this patient population who had been ill nearly 20 years. These data argue strongly for similar trials at other sites.

From a scientific point of view, it will be interesting to see if these functional changes will be accompanied by structural alterations of increased MRI gray matter, compatible with plasticity and increased dendritic and synaptic elements.

View all comments by Robert McCarley