Effects of word frequency on semantic memory in schizophrenia: electrophysiological evidence for a deficit in linguistic access.

Background: Abnormal storage and/or access are among the hypothesized causes of semantic memory deficit in schizophrenia. Neuropsychological and connectionist models have emphasized functional systems that serve the processing of word meaning and frequency: semantic storage disturbance is presumed to result from weak representations of word meaning; defective access is assumed to result from compromises to pathways that activate word frequency knowledge. Candidate biological systems include neuromodulatory pathways that normally function to enhance neural signals (e.g., cholinergic system). Electrophysiological responding may be informative regarding the storage-access distinction for schizophrenia.

Methods: Visual event-related potentials were recorded for 14 schizophrenia outpatients receiving atypical antipsychotics, and 14 healthy controls group-matched to patients on age, gender, and demographics. N400 was elicited using an incidental semantic priming paradigm, in which semantic relatedness and word frequency were varied, and a letter probe task.

Results: Compared to controls, patients showed reduced N400 (microV) discrimination of semantic relatedness. Groups also showed different patterns of N400 to word frequency. Controls' N400 increased in negativity as words decreased in frequency of occurrence, while patients did not show a linear relationship between N400 and word frequency. Groups also differed for N400 to frequently occurring words. Patients exhibited increased negativity to high and very high frequency words, compared to controls. A subgroup of patients receiving antipsychotics with known affinity binding for muscarinic receptors (clozapine and olanzapine) showed significant albeit limited N400 priming, but their N400 to word frequency remained nonsignificant.

Conclusions: Results suggest a deficit in semantic access for schizophrenia, as well as an influence of neuromodulators on the activation of connections among semantic representations. Cumulative findings indicating only limited N400 priming for patients receiving either typical or atypical antipsychotics support the hypothesis that semantic memory deficit represents a trait marker for schizophrenia.