Evaluating Two Types of Cognitive Training in Veterans With Schizophrenia

Cognitive dysfunction is a major contributor to the poor community outcome of individuals with schizophrenia. Developing more effective cognitive remediation interventions is imperative to improve the daily lives of affected subjects and reduce the disability of this illness. The goal of this clinical trial is to evaluate two types of cognitive training approaches to determine which one is more beneficial for individuals with schizophrenia. This study also uses electrophysiological techniques to gain a better understanding of the mechanisms involved in cognitive remediation. Findings from this study will provide information about how to design the most optimally efficient cognitive training intervention to improve the cognitive and social functioning of patients with severe mental illness.

Schizophrenia is a disorder that affects both higher-level neurocognitive operations (e.g., verbal memory, executive functioning) and lower-level perceptual processes (e.g., auditory processing). These deficits contribute to the poor community outcome and severe functional disability seen in patients. Effectively treating the cognitive dysfunction associated with this illness is important to achieve improvements in daily functioning. Recent meta-analytic studies report that cognitive training in schizophrenia has a moderate effect-size impact on cognitive functioning and a lower impact on daily functioning. However, most training interventions for schizophrenia have only targeted higher-order cognitive processes. A few recent interventions have targeted basic perceptual processing and shown that auditory and visual perceptual abilities can be trained and improved in patients with schizophrenia. These findings suggest that basic perceptual processing may be an ideal target for intervention. At this point, it is still unclear whether a neuroplasticity-based, bottom-up intervention is more effective than an intervention that targets top-down functions like attention, working memory, and executive functioning. This clinical trial will contrast a bottom-up intervention targeting basic auditory processes and a top-down intervention targeting higher-order cognitive functions, compared with a control condition, in Veterans with schizophrenia. These interventions will be assessed by their effects on representative measures from three outcome domains: 1) neurocognition, 2) electroencephalography (EEG), and 3) functional capacity. Participants will be randomly assigned to the bottom-up auditory training, top-down cognitive training, or control treatment (commercial computer games). All treatments will be administered three times a week (1 hour each) for 12 weeks. A comprehensive battery of cognitive, electrophysiological, and functional measures will be administered at baseline, 6 weeks, and at completion of treatment. The investigators will enroll 120 Veterans with schizophrenia or schizoaffective disorder across the 5 years of the study. This study will determine which training approach leads to the largest magnitude of improvement in neurocognition, functional capacity, and neural functioning measured with EEG. Moreover, it will shed light on the neural mechanisms underlying the response to training. By determining whether it is more beneficial to treat lower-level perceptual processes or higher-level cognitive functions, the results of this project will inform future recovery-based cognitive remediation interventions for Veterans with schizophrenia.

In each session, participants will work on 4 of the 6 BFP exercises (15 min per exercise). Duration of training is 1 hour per day, 3 days per week, for 12 weeks, for a total of 36 hours.

In each session, participants will work on a different subset of 4 to 6 Cogpack exercises. Duration of training is 1 hour per day, 3 days per week, for 12 weeks, for a total of 36 hours.

In each session, participants will play between 8 and 16 games (1 to 15 min per game). Duration of training is 1 hour per day, 3 days per week, for 12 weeks, for a total of 36 hours.

This computerized "bottom-up" cognitive intervention is designed to improve the speed and accuracy of auditory information processing through increasingly more difficult stimulus recognition, discrimination, sequencing, and memory tasks under conditions of close attentional control, high reward, and novelty. BFP consists of 6 exercises. Stimuli across the exercises are chosen such that they span the acoustic and organizational structure of speech, from very simple acoustic stimuli and tasks to complex manipulations of continuous speech. The exercises adaptively progress based on the subject's individual performance during a training session and become more challenging as the subject's abilities improve. Participants will work with 4 of the 6 exercises (15 min per exercise) in each session.

This computerized "top-down" cognitive intervention is designed to provide training across a broad range of cognitive functions. Cogpack consists of domain-specific exercises aimed at training specific cognitive areas (attention, working memory, verbal and visual memory, executive functioning, reasoning, language) and non-domain-specific exercises that require the use of several functions at a time. Cogpack includes low-level cognitive exercises (i.e., scanning, hand-eye coordination, and psychomotor speed) that will not be included in this protocol to better separate bottom-up from top-down training interventions. There will be a total of 34 exercises and variants of the same exercises with different levels of difficulty. In each session, participants will work on a different subset of 4 to 6 exercises.

Sporcle computer games will be used as a "placebo" treatment to control for the effects of computer exposure, contact with research personnel, time spent being cognitively active, and financial compensation for participation. The games cover trivia-type questions about geography, entertainment, science, history, literature, sports, movies, etc. Subjects will receive the same amount of attention from staff members and the same monetary reinforcements as participants in the experimental treatment groups. They will also complete 3 hours of "training" per week over 12 weeks, for a total of 36 hours.

The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) was used to assess basic cognition. It includes tests representing 6 separable cognitive domains. The MCCB composite score (average of 6 domain t-scores) served as the primary cognitive outcome measure. Minimum and maximum values are 20 and 68. Higher scores mean a better outcome.

A Mismatch Negativity (MMN) Paradigm was used to assess basic auditory processing. MMN amplitude was measured as the mean voltage in the 145-200 ms latency range at pooled frontocentral electodes. Minimum and maximum values are -8 and +2 microvolts. More negative scores mean a better outcome.

The University of California San Diego (UCSD) Performance-based Skills Assessment (UPSA) was used to assess functional capacity. The UPSA total score served as a secondary functional outcome measure. Minimum and maximum values are 40 and 100. Higher scores mean a better outcome.

Inclusion Criteria: Veterans with a Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder Between 25 and 65 years of age Estimated premorbid inteIligence quotient (IQ) > 70 (based on reading ability) Understand spoken English sufficiently to comprehend the consent form Clinically stable (i.e., no inpatient hospitalization in the 3 months, no changes in psychiatric medications in the 6 weeks, and no changes in housing in the 2 months, prior to enrollment) Exclusion Criteria: Documented history of mental retardation or severe learning disability Clinically significant neurological disease as determined by medical history (e.g., epilepsy, stroke) History of serious head injury with loss of consciousness greater than 1 hour and concomitant neuropsychological sequelae Meeting DSM-IV criteria for drug or alcohol dependence during the 6 months, or abuse during the month preceding study enrollment

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