Neurophysiological Targets for Cognitive Training in Schizophrenia

Schizophrenia is recognized as one of the leading causes of medical disability worldwide,
ranked 9th overall by the World Health Organization, and affects more than 2 million
Americans per year. There is considerable evidence to suggest that disability status in
schizophrenia relates more directly to cognitive Impairment, involving attention, reasoning,
and memory, than to characteristic symptoms of psychosis. Accordingly, the evaluation and
advancement of interventions designed to restore cognitive function, generally termed
cognitive remediation, is of critical importance to our rehabilitation mission. Recent
randomized controlled trials of cognitive remediation in schizophrenia have found moderate
gains in cognitive function and improved outcomes in important areas of community living.
However, despite these encouraging findings, there remains sparse evidence in support of
assumptions that (1) cognitive outcomes represent benefits of training-induced adaptive
learning, (2) that training effects are specific to method of intervention, or (3) that
change in cognitive test performance occurs through restoration of impaired neural circuitry
in schizophrenia. This project will begin to address these issues by examining
modality-specific effects of computer-based cognitive training on psychophysiological
measures of sensory information processing. Training will be administered using two
commercially available computer-based software packages, separately targeting auditory and
visually-mediated processes using principles of bottom-up perceptual learning. Two
psychophysiological paradigms, mismatch negativity (MMN) and P300 generation, will be
administered as tests of early visual and auditory processing. MMN and P300 have been studied
extensively in human neuroscience as probes of sensory echoic memory and attention engagement
to contextually relevant information. Furthermore, reductions in MMN and P300 generation are
reliably observed in schizophrenia, follow the course of a progressive neuropathological
process, and correlate with severity of cognitive impairment. The specific aims of this study
are to determine: (1) whether training selectively influences bottom-up (MMN) or top-down
(P300) information processing, (2) whether training effects are modality (auditory vs.
visual) specific, (3) whether baseline MMN and P300 predict, or rate-limit, training
progress, and (4) whether pre-post change in cognitive test performance is mediated by
neural-level change in MMN and P300 generation. Answers to these questions will provide
information needed to structure cognitive training for maximum benefit in schizophrenia.

Inclusion Criteria:

- DSM-IV diagnosis of schizophrenia or schizoaffective disorder

- Age between 18 & 70

- minimum of 30 days since discharge from last hospitalization

- minimum of 30 days since last change in psychiatric medications

- receiving mental health services

- no housing changes in the past 30 days

Exclusion Criteria:

- current diagnosis of alcohol or substance abuse

- history of brain trauma or neurological disease

- chart diagnosis of mental retardation or premorbid intelligence < 70 based on Wechsler
Test of Adult Reading (WTAR) full-scale estimated IQ

- auditory or visual impairment that would interfere with study procedures

- a sample of 20 healthy community volunteers was also recruited according to these
criteria and tested, without intervention, as a normative reference sample for
MMN and P300 measures