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Daniel H. Mathalon, PhD, MD; William O. Faustman, PhD; Judith M. Ford, PhD

Arch Gen Psychiatry. 2002;59:641-648.

Background  One factor hypothesized to underlie thinking disturbance in patients with schizophrenia is abnormal or disinhibited automatic spreading activation of semantic networks, which can be assessed using the N400 event-related potential. N400 is a negative-going component elicited at about 400 milliseconds following semantic stimuli that are not primed by the preceding context. Semantic priming refers to facilitated semantic processing gained through preexposure to semantic context, which can happen automatically or strategically. Using N400, inferences can be drawn regarding the extent to which a given context primes a word.

Methods  During a picture-word matching task, N400s to primed (exact match) and unprimed (remotely related) words were recorded from 18 healthy control subjects and 18 patients with schizophrenia performing a picture-word matching task. A short interval (325 milliseconds) between picture and word onset (stimulus-onset asynchrony) was used to optimize the role of automatic spreading semantic activation and to minimize the role of attention, expectancy, preparation, and working memory.

Results  Despite behavioral evidence of normal semantic priming, patients generated an abnormally small N400 (ie, less negative) to unprimed words. The N400 to primed words was neither larger nor smaller in patients than in controls, suggesting normal use of context.

Conclusions  A reduced N400 to unprimed words in patients with schizophrenia suggests that there was inappropriate priming of words by remotely related semantic contexts. This is consistent with an overly broad automatic spread of activation through semantic networks in patients with schizophrenia.

From the Department of Psychiatry, VA Connecticut Healthcare System, West Haven, and Yale University School of Medicine, New Haven (Dr Mathalon); the Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, Calif (Drs Faustman and Ford); and VA Palo Alto Health Care System, Palo Alto, Calif (Drs Faustman and Ford).

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