Clinical trial NCT00923078: Neurophysiological Targets for Cognitive Training in Schizophrenia
Official title: Neurophysiological Targets for Cognitive Training in Schizophrenia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Schizophrenia
Keywords: schizophrenia
cognitive remediation
rehabilitation
electrophysiology
neuropsychology
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2009-06-18
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether computer-based training of auditory and visual processing results in corresponding improvement in brain function in individuals with schizophrenia.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Visual Target Detection (P300 Event-related Potential Amplitude) Change
timeFrame: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
measure: Auditory Mismatch Negativity (MMN) Amplitude Change
timeFrame: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
measure: MCCB Cognitive Composite Score Change
timeFrame: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
Secondary outcomes:
measure: Visual Learning (BVMT-R) Change
timeFrame: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
measure: Verbal Learning (HVLT-R) Change
timeFrame: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
measure: Visual Working Memory (Spatial Span) Change
timeFrame: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
measure: Auditory Working Memory (LNS) Change
timeFrame: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
Other outcomes:
Locations:
city: West Haven
country: United States
facility: VA Connecticut Health Care System (West Haven)
state: Connecticut
Study officials:
affiliation: VA Connecticut Health Care System (West Haven)
name: Jason K Johannesen, PhD
role: PRINCIPAL_INVESTIGATOR
References: