Evaluating Two Types of Cognitive Training in Veterans With Schizophrenia

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.

Inclusion Criteria:

- Veterans with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder

- Between 25 and 65 years of age

- Estimated premorbid 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