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Cognitive Training in Mental Disorders: Advancing the Science

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Meeting Summary
Bethesda, Maryland

Sponsored by:
National Institute of Mental Health (NIMH)

On April 9-10, 2012, NIMH convened a group of experts in cognitive training (CT, also often referred to as cognitive remediation (CR)), to review the current state of evidence for efficacy of CT approaches, discuss interventions currently in development, identify challenges to this line of research and research gaps, and learn of efforts to adopt CT interventions in clinical practice. The overarching theme of the presentations and discussions was the potential for CT approaches to add to the catalog of evidence-based treatments for people with mental disorders. Meeting participants expressed optimism that one day we may be able to identify the key neural system impairments unique to individual patients, and prescribe personalized programs of CT to target those impairments.

Much of the early work in this area involved the development of CT approaches to improve the cognitive impairment associated with schizophrenia. Recognizing that similar cognitive problems are found in other disorders as well, there has been increasing interest in applying these approaches to other populations, as well as extending them to other targets. Potential targets include neuroplasticity, brain circuit function, and cognitive processes linked to emotion regulation, clinical symptoms, and community functioning. Interventions in various stages of development were described for a variety of conditions, including schizophrenia, memory decline associated with aging, attention deficit hyperactivity disorder, anxiety, autism, velo-cardio-facial syndrome, and pediatric bipolar disorder. The modalities by which interventions are delivered vary as well, including paper-and-pencil tasks, computerized tasks/games, motor activities/games, and multimodal approaches. From these presentations and the ensuing discussions, several common themes and gap areas were identified.

Need for rigorously designed clinical trials

Recent reviews1-4 are encouraging in that they conclude that CT programs result in significant, albeit modest, improvements in performance on neuropsychological measures of specific cognitive skills (e.g., memory, attention, problem-solving). Evidence supporting the efficacy of CT interventions for improving clinical symptoms or everyday functioning, however, is inconsistent. Even the more extensively researched interventions would benefit from trials designed to address variability in treatment response. There is a need to understand mediators and moderators of treatment effect in order to move toward an ability to predict and enhance treatment response and prescribe treatments according to patient profiles. Other interventions are in earlier stages of development. Workshop participants emphasized the need for rigor in design and identified several critical research design elements. These include:

  • Detailed treatment protocols and fidelity assessments
  • Detailed subject characterization including baseline cognitive capacity/deficits
  • Attention to concomitant treatments
  • Appropriate control or comparison groups
  • Randomization and adequate masking of treatment assignment
  • Valid and reliable proximal and distal outcome measures, including:
    • Cognitive outcomes that are distinct from training tasks effects
    • Functional outcomes
    • Control for practice effects
  • Assessment and reporting of retention/completion rate
  • Evaluation of hypothesized mechanisms of treatment effects
  • Assessment of adverse effects
  • State of the art statistical methods for data analysis, and
  • Replication of treatment effects derived from single site trials in larger multi-site trials.

Value of combined approaches

There may be added value in combining intervention approaches. A meta-analysis suggested that CT for schizophrenia may be more effective when administered within the context of a psychosocial rehabilitation program.1 Other approaches that are currently being explored include multimodal interventions to address different components of a disorder (e.g., CT in combination with group social skills training for autism); and adjunctive “priming” interventions (e.g., direct brain stimulation or aerobic exercise) to enhance effects of CT. Relatedly, there was a discussion about whether, or when, CT should be delivered within a social context (e.g., via an individual practitioner, in a group, or with a peer); this remains an empirical question.

Understanding mechanisms of treatment effects

There is need for a better understanding of relationships between neurophysiology/neurocircuitry, cognition, symptoms/behavior, and functioning. We do not know if these relationships are the same across development, nor do we know if the relationships between neural circuits and cognition are the same within the context of different symptom clusters or disorders. A better understanding of these relationships can lead to testable hypotheses about mechanisms of treatment effects, as well as potential predictors or early indicators of treatment response. It was suggested that intervention development is not linear, from proof of principle to efficacy to effectiveness, but in actuality is more synergistic. Basic neuroscience can suggest appropriate intervention targets, and interventions can be a probe to test hypothesized relationships between neurocircuitry and behavior.

Communication and sharing of resources

Given the rapid proliferation of new and adapted CT approaches, and the need for rigorous testing, investigators expressed enthusiasm for opportunities to share experiences and resources. It was suggested that a toolkit or web-based site for sharing assessment tools, treatment protocols, and “lessons learned” would facilitate standardization of interventions and assessments, and prevent redundancy.

The Tel Aviv University – NIMH Attention Bias Modification Treatment Initiative was presented as one attempt to facilitate a standardized approach to intervention, assessment, and trial design. Data from participating clinical trials will be pooled for future mega-analyses. More information can be found at http://www.tau.ac.il/~yair1/index.html .

Dissemination, policy, and regulation

Meeting participants discussed the barriers to widespread adoption and dissemination of CT interventions. The New York State Office of Mental Health, for example, has incorporated cognitive remediation as one of the Medicaid reimbursable services allowed in its Personalized Recovery-Oriented Services (PROS) program for adults with serious mental illness and functional impairments. The discussions with policy makers and administrators highlighted that data regarding the degree to which these interventions translate into functional gains and cost savings will ultimately be most helpful in informing decisions regarding whether and when to adopt and implement CT interventions. It was noted that State policy makers look to the federal government for guidance in determining whether an intervention has sufficient evidence of efficacy.

Next steps

Participants discussed their views on advancing research on the efficacy of CT for individuals with mental disorders. Opportunities will be sought to disseminate guidelines for rigor in research design. NIMH will utilize existing Funding Opportunity Announcements to guide the field. It was noted that increased opportunities for communication, standardization and sharing of resources, as well as pooling of data, will move the field forward. As research on the efficacy of CT develops, issues about regulation and widespread dissemination are becoming more pressing, and there will be a need for continuing dialogue between developers/investigators, and the federal agencies funding research, regulatory agencies, and agencies guiding policy.

References

1Wykes T et al. A meta-analysis of cognitive remediation for Schizophrenia: Methodology and effect sizes. Am J Psychiatry 168, 2011.
2Cicerone KD et al. Evidence-based cognitive rehabilitation: Updated review of the literature from 2003 through 2008. Arch Phys Med Rehabil 92, 2011.
3Cramer SC et al. Harnessing neuroplasticity for clinical applications. Brain 134, 2011.
4Hakamata Y et al. Attention bias modification treatment: A meta-analysis towards the establishment of novel treatment for anxiety. Biol Psychiatry 68, 2010.