Working memory dysfunction in schizophrenia: An event-related potential study

There is considerable evidence to support an integral relationship between pre-frontal cortex (PFC) function and working memory (WM). Recently PFC and WM have been implicated as structures and functions respectively, that may underlie some of the cognitive deficits and symptomatology observed in schizophrenia. The present study employed a test of auditory-verbal WM (i.e., Letter Number Span) and tests of visual-verbal WM (i.e., Continuous performance tasks). The continuous performance tasks (CPTs) taxed the WM system, manipulating load in two dimensions; (1) rule complexity and (2) delay. The CPTs were administered while concurrently obtaining event-related potentials (ERPs). ERPs were employed to index the registration of sensory stimuli (N1), and the time course of subsequent cognitive analysis (P3), allowing for identification of the information processing stage, or stages, where WM dysfunction became manifest. Sixteen clinically and diagnostically stable outpatients and sixteen well matched healthy controls participated. Multimodal WM dysfunction in schizophrenic subjects was evident in the present study. Behavioral measures proved sensitive to WM dysfunction in schizophrenics revealing reduced accuracy and slowed reaction time (RT). Auditory-verbal WM showed clear deficits in the patient group. In the visual-verbal modality, patients consistently displayed reduced accuracy and increased RT across the CPT tasks. However, patient performance did not worsen when task complexity and delay intervals were increased, suggesting a generalized cognitive deficit, not a dysfunction specific to WM processes. ERP measures were specific in elucidating the stages of WM where dysfunction manifested. N1 amplitude in response to target stimuli was larger in the patient group, suggesting altered sensory processing of stimuli during CPT tasks. The increased N1 amplitude findings suggested that dysfunction in the WM system was present as early as the stage of sensory registration, and is consistent with hypotheses of an early processing imprecision in schizophrenia. (N1), latency and P3 latency did not reveal significant differences between groups, therefore, processing speed appeared normal up to P3. The finding of normal P3 latency in schizophrenic subjects with concurrently delayed RTs, indicated slowed response selection and execution in the patient group. Response inhibition deficits suggested by more FAs, along with a possible frontal shift in P3 distribution suggestive of greater recruitment of frontal cortex, provided evidence that frontal structures contributed to the deficits observed in the schizophrenic group.