On 15 December 2011, SRF hosted a Webinar event co-sponsored by the International Congress on Schizophrenia Research and moderated by Angus MacDonald III of the University of Minnesota. The presenters—Alice Medalia of Columbia University, Sophia Vinogradov of the University of California, Los Angeles, and Morris Bell of Yale University—gave brief slide presentations and participated in a panel discussion.
One of the most exciting developments in the treatment of schizophrenia in the past decade has been the rise of cognitive remediation. Cognitive remediation refers to a collection of approaches that share the goal of strengthening patients’ capacity to think. In this, it is distinct from cognitive behavior therapy (CBT), which emphasizes interpretations of experience. Cognitive remediation has grown in popularity largely because problems with thinking are a prominent aspect of the disorder, yet these symptoms are largely not addressed by available pharmaceuticals. Cognitive remediation is non-pharmacological, but it does affect the brain. Building on evidence from stroke, normal aging, and animal models, cognitive remediation is designed to leverage the brain’s own plasticity to build capacity. Several popular approaches to cognitive remediation emphasize drill and practice, in particular, the use of computer tasks to provide immediate feedback and adapt to people’s current abilities.
While a growing database suggests the promise of such techniques, the proverbial cognitive remediation jury is out. One of the reasons for this is that most studies have been of a limited scale; many are only beginning to incorporate double-blind, placebo-controlled designs and long-term follow-up. In this Webinar, we will address the question, What is the latest knowledge about the internal validity of cognitive remediation experiments?
Another challenge to cognitive remediation is generalization. While it is clear that patients can improve on the tasks for which they train, to what extent does training in one domain extend to other domains, and, most importantly, to functioning in life? Furthermore, how long should the effects of training endure?
Given the plurality of approaches, are we closer to knowing which are most effective from a cost-benefit standpoint? Do these various approaches affect brain systems differently? And is it possible to know beforehand who will have a positive response to the treatment?
Finally, and crucially, what are the vital questions that still need to be addressed, technologies that need to be developed, or policies that need to be implemented before cognitive remediation can become part of the comprehensive care for patients with schizophrenia?
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Medalia A, Choi J. Cognitive remediation in schizophrenia. Neuropsychol Rev . 2009 Sep 1 ; 19(3):353-64. Abstract
Bell MD, Zito W, Greig T, Wexler BE. Neurocognitive enhancement therapy with vocational services: work outcomes at two-year follow-up. Schizophr Res . 2008 Oct 1 ; 105(1-3):18-29. Abstract
Kurtz MM, Seltzer JC, Fujimoto M, Shagan DS, Wexler BE. Predictors of change in life skills in schizophrenia after cognitive remediation. Schizophr Res . 2009 Feb 1 ; 107(2-3):267-74. Abstract
McGurk SR, Mueser KT, DeRosa TJ, Wolfe R. Work, recovery, and comorbidity in schizophrenia: a randomized controlled trial of cognitive remediation. Schizophr Bull . 2009 Mar 1 ; 35(2):319-35. Abstract
Eack SM, Hogarty GE, Cho RY, Prasad KM, Greenwald DP, Hogarty SS, Keshavan MS. Neuroprotective effects of cognitive enhancement therapy against gray matter loss in early schizophrenia: results from a 2-year randomized controlled trial. Arch Gen Psychiatry . 2010 Jul 1 ; 67(7):674-82. Abstract
Vinogradov S, Fisher M, Holland C, Shelly W, Wolkowitz O, Mellon SH. Is serum brain-derived neurotrophic factor a biomarker for cognitive enhancement in schizophrenia? Biol Psychiatry . 2009 Sep 15 ; 66(6):549-53. Abstract
Haut KM, Lim KO, MacDonald A. Prefrontal cortical changes following cognitive training in patients with chronic schizophrenia: effects of practice, generalization, and specificity. Neuropsychopharmacology . 2010 Aug 1 ; 35(9):1850-9. Abstract
Comments on Online Discussion
Comment by: David Yates Submitted 1 December 2011
Posted 2 December 2011
I hope the presenters and discussants at the meeting take into account in their presentations the strong evidence for poor working memory capacity already at the onset of schizophrenia, and continuing thereafter (Schobel et al., 2009; Reif et al., 2006; Gold et al., 2010; van Raalten et al., 2008), which limits the ability to rehearse and practice in new situations. This becomes the block to further development in capability.
Van Raalten et al. (van Raalten et al., 2008) suggest that a simplified setting can be successfully managed with a reduced working memory capacity, by simplifying, as in chunking, and by rehearsal and by mentoring, but that meeting more complicated demands fails.
It seems to me that the results from cognitive remediation in practice so far are better explained as obtained by reducing the demands upon memory capacity—by simplifying the setting—than by showing an outcome of better coping with the kind of demand that is nearer normal expectation.
What follows the conclusion of the "therapy" and the simplified routine will be the test of the outcome. Finding a setting of outside participation, with much reduced expectation, was previously part of the treatment for schizophrenia, creating a routine of engagement that reduced relapsing. It used to be called "rehabilitation."
Schobel SA, Lewandowski NM, Corcoran CM, Moore H, Brown T, Malaspina D, Small SA. Differential targeting of the CA1 subfield of the hippocampal formation by schizophrenia and related psychotic disorders. Arch Gen Psychiatry . 2009 Sep 1 ; 66(9):938-46. Abstract
Reif A, Fritzen S, Finger M, Strobel A, Lauer M, Schmitt A, Lesch KP. Neural stem cell proliferation is decreased in schizophrenia, but not in depression. Mol Psychiatry . 2006 May 1 ; 11(5):514-22. Abstract
Gold JM, Hahn B, Zhang WW, Robinson BM, Kappenman ES, Beck VM, Luck SJ. Reduced capacity but spared precision and maintenance of working memory representations in schizophrenia. Arch Gen Psychiatry . 2010 Jun 1 ; 67(6):570-7. Abstract
van Raalten TR, Ramsey NF, Jansma JM, Jager G, Kahn RS. Automatization and working memory capacity in schizophrenia. Schizophr Res . 2008 Mar 1 ; 100(1-3):161-71. Abstract
The possibility of drill and practice influencing brain plasticity has little support. The most recent (and most rigorous) meta-analysis showed that the cognitive remediation evidence is most supportive of strategy training to influence functioning outcomes, and the difference compared with drill and practice was significant. So even if drill and practice influences brain plasticity (and at the moment we have no strong support for this), it is strategy type training that influences recovery. More recent drill and practice studies have also shown no improvement in drill and practice.
In terms of the internal validity of the cognitive remediation studies, this was investigated in the same meta-analysis. Despite previous findings that poor internal validity inflated effect sizes, this was not the case for cognitive remediation, and this was probably because the outcome measures in terms of cognitive tests were designed not to be influenced by such factors as rater bias. So methodological rigor (internal and external validity) does not seem to have an influence on cognitive remediation outcomes.
So what does? One factor is metacognition, and this may be the one area for future investigation. Metacognition is the ability to be aware of problem-solving strategies and to use these strategies in new situations. It has been shown to influence exam success, learning math, etc. Interestingly, it has also recently been shown to be vital in cognitive rehabilitation for people with brain injury. A recent meta-analysis suggests that this has the most influence on recovery (as it might in schizophrenia). Despite the comments in the introduction to this discussion, the effects of drill and practice are not overwhelming in traumatic brain injury, and the clinical recommendations are not to use such types of training in preference to strategy training.
No doubt cognitive rehabilitation of any kind does influence the brain rather than the liver, but if we are to have a beneficial effect on people's lives, then perhaps we should look at how our cognitive test improvements might transfer to real life.
Wykes T, Huddy V, Cellard C, Mcgurk SR, Czobor P. A Meta-Analysis of Cognitive Remediation for Schizophrenia: Methodology and Effect Sizes. American Journal of Psychiatry 2011 May;168(5):472-85. Abstract
Cicerone K, Langenbahn D, Braden C, et al. Evidence-based cognitive rehabilitation: Updated review of the literature from 2003 through 2008. Arch Phys Med Rehabil 2011; 92: 519-530. Abstract