Early Sensory Contributions to Contextual Encoding Deficits in Schizophrenia

Context: The AX version of the visual continuous performance task (AX-CPT) is widely used for investigating visual working memory dysfunction in schizophrenia. Event-related potentials (ERP) provide an objective index of brain function and can be used to evaluate brain substrates underlying impaired cognition in schizophrenia. Objective: To assess the mechanisms that underlie visual working memory dysfunction in schizophrenia relative to impairment of early visual processing. Design: Case-control study. Setting: Inpatient and outpatient facilities associated with the Nathan Kline Institute for Psychiatric Research. Participants: A total of 30 individuals with schizophrenia and 17 healthy comparison subjects. Interventions: Three versions of the AX-CPT, with parametric variations in the proportions of trial types, were used to test performance and underlying neural activity during differential challenge situations. Contrast sensitivity measures were obtained from most subjects. Main Outcome Measures: Behavioral performance was assessed using d' context scores. Integrity of stimulus- and task-related cortical activation to both cue and probe stimuli was assessed using sensory (C1, P1, N1) and cognitive (N2, contingent negative variation [CNV]) ERP components. Early magnocellular/parvocellular function was assessed using contrast sensitivity. Linear regression and path analyses were used to assess relations between physiological and behavioral parameters. Results: Patients showed reduced amplitude of both early sensory (P1, N1) and later cognitive (N2, CNV) ERP components. Deficits in sensory (N1) and cognitive (N2) component activation to cue stimuli contributed independently to impaired behavioral performance. In addition, sensory deficits predicted impaired cognitive ERP generation. Finally, deficits in performance correlated with impairments in contrast sensitivity to low, but not high, spatial frequency stimuli. Conclusions: Working memory deficits in schizophrenia have increasingly been attributed to impairments in stimulus encoding rather than to failures in memory retention. This study provides objective physiological support for encoding hypotheses. Further, deficits in sensory processing contribute significantly to impaired working memory performance, consistent with generalized neurochemical models of schizophrenia.