An Event-Related Brain Potential Study of Direct and Indirect Semantic Priming in Schizophrenia

Objective: Following a meaningful prime stimulus, schizophrenia patients have been hypothesized to exhibit impaired neurophysiological activation of related concepts in general, and/or supranormal activation of weakly related concepts in particular, within semantic memory. The former abnormality may occur at longer intervals, and the latter at shorter intervals, after the prime. The authors tested these hypotheses using the N400 event-related brain potential as a probe of activation of concepts in semantic memory. Method: Event-related potentials were recorded in 16 schizophrenia patients and 16 normal comparison subjects who viewed prime words, each followed by a target that was a directly (strongly) related word, indirectly (weakly) related word, unrelated word, or nonword, in a lexical-decision task. Equal numbers of each target type were presented 300 and 750 msec after the prime. Results: In the comparison subjects, N400 amplitude was largest (most negative) following unrelated targets, intermediate after indirectly related targets, and smallest after directly related targets. In contrast, patients’ N400 amplitudes did not differ between these target types, reflecting larger amplitudes following both directly and indirectly related targets in patients than in comparison subjects; these findings held regardless of prime-to-target stimulus-onset asynchrony. Within patients, at the longer asynchrony, larger N400 amplitudes after directly and indirectly related targets correlated with positive psychotic symptoms. Conclusions: The results suggest hypoactivation of strongly and weakly related concepts following a meaningful stimulus, regardless of interval, in schizophrenia. An N400 index of this hypoactivation correlated with severity of delusions, suggesting a role for abnormal semantic processing in their pathogenesis.