Lexical and semantic priming deficits in patients with Alzheimer's disease

Two experiments utilizing priming procedures examined the status of semantic memory in demented and amnesic patients. In the first investigation, lexical priming was assessed in patients with dementia of the Alzheimer type (DAT), Huntington's Disease (HD), alcoholic Korsakoff's syndrome (KS), and in intact control subjects. Subjects were first exposed to a list of words in a rating task and then required to complete three-letter stems with the "first word that comes to mind". Half of the stems could be completed with the previously presented words and the other half were used to assess baseline guessing rates. Recall and recognition of incidentally exposed words was also assessed. Although all three patient groups were impaired on tests of recall and recognition, only the DAT patients exhibited a priming deficit on the stem-completion task. In the second experiment, DAT, HD, and intact control subjects were administered a semantic priming test which required the subject to "free associate" to the first words of previously presented semantically associated word pairs. The results for this association task showed that DAT patients were significantly less likely to produce the second word of the semantically related pair than were the other subject groups. The results of these two experiments suggest that the memory capacities of DAT patients are characterized by a breakdown in the structure of semantic memory and that this impairment is evident on some "automatic" as well as "effortful" processing tasks.     

Cross-modal semantic and homograph priming in healthy young, healthy old, and in Alzheimer's disease individuals.

Two experiments are reported that explore the influence of strength of the prime-target relationship on the observed priming effects in young, healthy old, and individuals diagnosed with dementia of the Alzheimer type (DAT). In Experiment 1, participants were auditorily presented primes (FURNITURE) and after varying delays presented visual targets that were (1) high-strength related (e.g., SOFA), (2) low-strength related (e.g., RUG), or (3) unrelated control words (e.g., COW or DEER). The results indicated that the DAT individuals produced relatively larger priming effects that both the young and the healthy old, but these data could be accommodated by increases in effect size due to general slowing of response latencies. In Experiment 2, the same cross-modal priming paradigm was used with ambiguous words presented as primes (e.g., BANK) and either high-dominant (e.g., MONEY) or low-dominant (e.g., RIVER) words as targets. The results of Experiment 2 produced a qualitatively distinct pattern of priming that indicated DAT individuals only produced priming for high-dominant targets and not for low-dominant targets, whereas, the healthy control groups produced equivalent priming for both high- and low-dominant targets. The discussion focuses on the implication that these results have for the interpretation of semantic priming effects, in general, along with implications for the apparent semantic memory loss in DAT individuals.     

Electrophysiological evidence for primary semantic memory functional organization deficits in schizophrenia

N400, an event-related brain potential (ERP) waveform elicited by meaningful stimuli, is normally reduced by stimulus repetition (N400 repetition priming), and relatedness between the eliciting stimulus and preceding ones (relatedness priming). Schizophrenia patients' N400 relatedness priming deficits suggest impairment in using meaningful prime stimuli to facilitate processing of related concepts in semantic memory. To examine whether this deficiency arises from difficulty activating the prime concept per se, as indexed by reduced N400 repetition priming; or from impaired functional connections among concepts in semantic memory, as reflected by reduced relatedness priming but normal repetition priming; we recorded ERPs from 16 schizophrenia patients and 16 controls who viewed prime words each followed at 300- or 750-ms stimulus-onset asynchrony (SOA) by an unrelated, related or repeated target word, or a nonword, in a lexical-decision task. In both groups, N400s were largest (most negative) for unrelated, intermediate for related, and smallest for repeated targets. Schizophrenia patients exhibited subnormal N400 relatedness priming at the 300-ms SOA, but normal repetition priming at both SOAs, suggesting that their impairment in using prime words to activate related concepts results from abnormal functional connections among concepts within semantic memory, rather than inability to activate the prime concept itself.     

The lifetime of automatic semantic priming effects may exceed two seconds

The N400 component of event-related potentials (ERPs) was obtained in a modified version of the Neely [J.H. Neely, Semantic priming and retrieval from lexical memory: Roles of inhibitionless spreading activation and limited-capacity attention, Journal of Experimental Psychology: General, Vol. 106 (1977), pp. 226-254.] paradigm which permits unconfounding of semantic priming effects due to automatic and attentional processes. It was found that a short stimulus onset asynchrony (SOA) of 250 ms between the prime and the target was associated with automatic but not expectancy effects on the amplitude of N400. At a long SOA of 2000 ms between prime and target, semantic priming effects on N400 were obtained associated with both automatic and expectancy processes. Moreover, there was no significance difference in the magnitude of the automatic effects at the two SOAs, suggesting that automatic processing had not decayed within the 2000 ms interval between the prime and target. The results support the two-processing interpretation of semantic priming advanced by Posner and Synder [M.I. Posner, C.R.R. Snyder, Attention and cognitive control, in: R.L. Solso (Ed.), Information Processing and Cognition: The Loyola Symposium, Erlbaum, Hillsdale, NJ (1975).] and concur with the results of Neely [J.H. Neely, Semantic priming and retrieval from lexical memory: Roles of inhibitionless spreading activation and limited-capacity attention, Journal of Experimental Psychology: General, Vol. 106 (1977), pp. 226-254], with the exception of indicating a longer persistence of automatic processes.     

Semantic memory is impaired in both dementia with Lewy bodies and dementia of Alzheimer's type: a comparative neuropsychological study and literature review

OBJECTIVE: To test the hypothesis that semantic impairment is present in both patients with dementia with Lewy bodies (DLB) and those with dementia of Alzheimer's type (DAT). METHODS: A comprehensive battery of neuropsychological tasks designed to assess semantic memory, visuoperceptual function, verbal fluency, and recognition memory was given to groups of patients with DLB (n=10), DAT (n=10) matched pairwise for age and mini mental state examination (MMSE), and age matched normal controls (n=15). RESULTS: Both DLB and DAT groups exhibited impaired performance across the range of tasks designed to assess semantic memory. Whereas patients with DAT showed equivalent comprehension of written words and picture stimuli, patients with DLB demonstrated more severe semantic deficits for pictures than words. As in previous studies, patients with DLB but not those with DAT were found to have impaired visuoperceptual functioning. Letter and category fluency were equally reduced for the patients with DLB whereas performance on letter fluency was significantly better in the DAT group. Recognition memory for faces and words was impaired in both groups. CONCLUSIONS: Semantic impairment is not limited to patients with DAT. Patients with DLB exhibit particular problems when required to access meaning from pictures that is most likely to arise from a combination of semantic and visuoperceptual impairments.     

Depth-of-processing effects on semantic activation deficits in schizophrenia: an electrophysiological investigation

N400, an event-related brain potential (ERP) waveform elicited by meaningful stimuli, is normally reduced (made less negative) by relatedness between the eliciting stimulus and preceding ones (N400 semantic priming). Schizophrenia patients' N400 semantic priming deficits suggest impairment in using meaningful context to activate related concepts in semantic memory. We aimed to examine the degree to which this impairment can be ameliorated by task instructions that more explicitly require processing of stimulus meaning. We recorded ERPs from 16 schizophrenia patients and 16 controls who viewed prime words each followed at 750-ms stimulus-onset asynchrony by an unrelated or related target word, or a nonword, in a non-semantic task (indicating whether a letter occurred in the target) compared to an explicit semantic task (judging prime-target relatedness). Consistent with previous work, controls exhibited greater N400 semantic priming (larger amplitude reductions for related versus unrelated targets) in the semantic task than in the orthographic task. Schizophrenia patients showed this same pattern, although their N400 semantic priming effects were smaller than controls' across tasks. Nevertheless, patients' priming effects increased as much as did controls' from the orthographic to the semantic task. Thus, connections among related concepts in schizophrenia patients' semantic memory appear grossly intact, such that, given a meaningful stimulus, they can make use of explicit cues to activate related concepts at a neurophysiological level, although their ability to do so remains less than normal. These data provide support for further research on semantic-cueing strategies for cognitive remediation of verbal memory in schizophrenia.     

Automatic activation of the semantic network in schizophrenia: evidence from event-related brain potentials.

BACKGROUND: Language disorder associated with schizophrenia might be due to disturbances in both automatic activation and mechanisms of controlled attention. The contribution of each process to semantic memory dysfunction has not been determined for schizophrenia, and the semantic priming paradigm is well-suited for addressing this question. In the present report, event-related potentials (ERPs) elicited under conditions assumed to reveal automatic activation (short prime-target interval and low proportion of related words) are compared directly with ERPs elicited under conditions associated with controlled processing (long prime-target interval and high proportion of related words). METHODS: Visual ERPs were recorded during a lexical decision task, in which semantic relationship (associated and unassociated words), expectancy (relatedness proportions), and prime-target interval (250- and 850-msec inter-stimulus intervals [ISIs]) were varied. Diagnosis and expectancy were between-subjects factors; semantic relationship and ISI were repeated measures. The N400 priming effect (enhanced negativity to unassociated words) was compared between 34 male normal control subjects tested once and 37 male schizophrenia inpatients evaluated during their participation in a double-blind haloperidol maintenance therapy and placebo replacement protocol. RESULTS: The N400 priming effect for patients was significantly reduced during both pharmacologic phases, compared with controls. During haloperidol treatment, however, patients showed a significant N400 priming effect over the anterior scalp region and additionally under the automatic activation condition. The N400 priming effect was enhanced under the controlled processing condition for control subjects; this effect was not observed for patients. N400 amplitude elicited under the rapid presentation rate (250-msec ISI) differed between medicated patients and controls; groups did not differ for the 850-msec ISI. CONCLUSIONS: Findings suggest that automatic activation and mechanisms of controlled attention are both disrupted during semantic memory access for schizophrenia patients. Pharmacologic agents, such as haloperidol, might enhance automatic activation of the semantic network in this patient population, as indexed by the N400 component of the ERP.     

The anatomy and time course of semantic priming investigated by fMRI and ERPs

We combined complementary non-invasive brain imaging techniques with behavioural measures to investigate the anatomy and time course of brain activity associated with semantic priming in a lexical-decision task. Participants viewed pairs of stimuli, and decided whether the second item was a real word or not. There were two variables, the semantic relationship between the prime and the target (related or unrelated) and the interval between the onset of prime and target (200 or 1000 ms), to vary the degree of semantic expectancy that was possible during task performance. Behavioural results replicated the well-established finding that identification of the target is facilitated by a preceding semantically related prime. Event-related functional magnetic resonance imaging (efMRI) identified two brain areas involved in the semantic-priming effect. Activity in the anterior medial temporal cortex was diminished when target words were primed by semantically related words, suggesting involvement of this brain region during active semantic association or integration. In contrast, activity in the left supramarginal gyrus in the temporal-parietal junction was enhanced for target words primed by semantically related words. Brain areas influenced by the interval between prime and target words, and by the interaction between word interval and semantic priming were also identified. A parallel experiment using event-related potentials (ERPs) unveiled a striking difference in the time course of semantic priming as a function of expectancy. In line with previous reports, the primary effect of semantic priming on ERPs was the attenuation of the N400 component, in both short- and long-interval conditions. However, the priming effect started significantly earlier in the long-interval condition. Activity in the anterior medial temporal cortex has previously been shown to contribute to the N400 component, a finding that links the priming results obtained with efMRI and ERP methods.     

Cross-modal semantic priming in schizophrenia.

Work on implicit memory in normal subjects has demonstrated the influence of stimulus modality on the retrieval of semantic information. The present study examined the effects of auditory and visual semantic priming on the recognition of visual words using a lexical decision task. Performance was studied in a group of 20 patients with DSM-IV schizophrenia and 26 normal volunteers of similar age and sex. There were two versions of the task: ipsimodal, in which the word or nonword visual target followed 400 ms after the onset of a visual word prime which may or may not be semantically related to the target; and cross-modal, in which the visual target followed 400 ms after the onset of an auditory word prime. Both groups showed significant priming in both modality conditions, although the schizophrenia patients exhibited significantly greater priming in the cross-modal condition. Priming effects in the ipsimodal condition did not differ substantially between patients and controls. The priming effects in the two conditions correlated with each other in the schizophrenia patients only. The results suggest that priming may occur through amodal semantic representations. In schizophrenia, there appears to be increased cross-modal connectivity (reduced modality modularity and informational encapsulation) between lexical representations that could result in impaired language, particularly speech, processing.     

Modulation of language processing in schizophrenia: effects of context and haloperidol on the event-related potential.

BACKGROUND: Disturbances in language associations were among the first clinical symptoms reported for individuals described as schizophrenic (Bleuler 1911/1950). Currently, associative language disturbance is a diagnostic feature of schizophrenia (American Psychiatric Association 1994); however, the mechanisms that produce this symptom remain unknown. In the present study, two candidate psychological functions were examined: sensitivity to semantic context and expectancy (attention). METHODS: Visual event-related potentials were recorded during a lexical decision task in which semantic relationship and expectancy (relatedness proportions) were varied. Semantic priming processes were compared between 34 male normal control subjects tested once and 37 male schizophrenic inpatients evaluated during their participation in a double-blind haloperidol maintenance therapy and placebo replacement protocol. RESULTS: Schizophrenic patients failed to discriminate between associated and unassociated words, as measured by the amplitude of the N400 component (i.e., absence of the N400 priming effect); however, the overall mean amplitude of N400 did not differ between patients and control subjects. In addition, patients and control subjects did not differ significantly in the amplitude of N400 elicited to associated words or to unassociated words. Finally, the effect of expectancy-based processing on the magnitude of the N400 priming effect did not differ between patients and control subjects. CONCLUSIONS: On the basis of these findings, a tentative hypothesis is suggested that schizophrenic patients are characterized by a pattern of indiscriminate or random spread of activation in their semantic network during the processing of single-word semantic contexts.     

Differentiating frontal and temporal variant frontotemporal dementia from Alzheimer's disease

OBJECTIVE/BACKGROUND: To determine whether difficulty in the early differentiation between frontotemporal dementia (FTD) and AD may arise from a failure to discriminate between the temporal and frontal variants of FTD. METHODS: Neuropsychological profiles of patients with early dementia of Alzheimer type (DAT; n = 10), the temporal variant of FTD (tv-FTD or semantic dementia; n = 5), and the frontal variant of FTD (fv-FTD; n = 10) were compared to each other and normal controls (n = 10). Structural MRI demonstrated temporal lobe atrophy in the tv-FTD patients and frontal lobe atrophy in the fv-FTD group. RESULTS: Subjects with tv-FTD showed severe deficits in semantic memory with preservation of attention and executive function. Subjects with fv-FTD showed the reverse pattern. Attention and executive function impairment separated the fv-FTD patients from the early DAT subjects, who were densely amnesic. CONCLUSION: The double dissociation in performance on semantic memory and attention/executive function clearly separated the temporal and frontal variants of FTD and aids the early differentiation of FTD from AD. The characteristic cognitive profiles reflect the distribution of pathology within each syndrome and support the putative role of the inferolateral temporal neocortex in semantic memory, the medial temporal lobe structures of the hippocampal complex in episodic memory, and the frontal lobes in executive function.     

The underlying mechanisms of semantic memory loss in Alzheimer's disease and semantic dementia

Patients with Alzheimer's disease (AD) and patients with semantic dementia (SD) both exhibit deficits on explicit tasks of semantic memory such as picture naming and category fluency. These deficits have been attributed to a degradation of the stored semantic network. An alternative explanation attributes the semantic deficit in AD to an impaired ability to consciously retrieve items from the semantic network. The present study used an implicit lexical-decision priming task to examine the integrity of the underlying semantic network in AD and SD patients matched for degree of impairment on explicit semantic memory tasks. The AD (n=11) and SD (n=11) patient groups were matched for age, education, level of dementia and impairment on four explicit semantic memory tasks. Healthy elderly participants (n=22) were matched for age and education. Semantic priming effects were evaluated for three types of semantic relationships (attributes, category coordinates, and category superordinates) and compared to lexical associative priming. Healthy controls showed significant priming across all conditions. In contrast, AD patients showed normal superordinate priming, and significant (although somewhat reduced) coordinate priming, but no attribute priming. SD patients showed no priming effect for any semantic relationship. All groups showed significant associative priming. The results indicate that SD patients do indeed have substantial degradation of semantic memory, while AD patients have a partially intact network, accounting for priming in superordinate and coordinate conditions. These findings suggest that AD patients' impairment on explicit semantic tasks is the product of deficient explicit retrieval in combination with a partially degraded semantic network.     

Verbal Association for Simple Common Words in High-Functioning Autism

We investigated conceptual relationships in semantic memory using an indirect priming technique in high-functioning autistic adolescents and their controls who were matched for age, verbal IQ, performance IQ, and nonverbal reasoning ability. The prime was a single word and the target task was completing a word fragment that was semantically related or unrelated to the prime word. The autistic subjects and controls showed similar semantic priming effects, indicating intact conceptual relationships for simple common words in those with autism. Only in the autistic group was a significant correlation found between performance for the related items and two nonverbal cognitive measures, which suggests a possibility that semantic processing in individuals with autism might be qualitatively different from that in controls.     

Abnormally increased semantic priming in children with symptomatic HIV-1 disease: evidence for impaired development of semantics?

Language deficits are a major characteristic of neurobehavioral dysfunction in pediatric HIV disease. An object decision task, which assessed reaction time facilitation following a semantic or identical prime in comparison to an unrelated prime, was used to investigate whether semantic processing abnormalities could be responsible, in part, for these deficits. Thirty children with vertically acquired HIV infection (M age 9.0 years; range 6-13) participated. Either a picture of the same object (repetition prime), a semantically related object (semantic prime), a semantically unrelated object, or a nonsense object preceded a target picture, which in 50% of the cases was a real object. Brain scans of children were rated and used together with neurobehavioral functioning to classify children as having HIV-related CNS abnormalities (n = 13) or not (n = 17). Increased semantic priming but not repetition priming was associated with a greater degree of cortical atrophy. Furthermore, CNS compromised children had significantly faster reaction times following a semantic prime compared to an unrelated prime than non-compromised patients. This facilitation following semantic priming for the CNS compromised patients (13.3%) almost equaled the facilitation following repetition priming (15.3%) while for the non-compromised patients facilitation following semantic priming (7.9%) was clearly smaller than following repetition priming (14.6%). These data suggest that HIV infection in children may result in a reduced neural network leading to impoverished semantic representations characterized by poor differentiation between closely related objects.     

Repetition Priming in Dementia of Alzheimer's Type in Japanese

Background : Memory is profoundly impaired in patients with dementia of Alzheimer's type (DAT). However, the study of priming, which is thought to be implicit memory, is relatively scarce in DAT. In Japan there is only one study, which investigated repetition priming in DAT and the relationship between the severity of dementia and repetition priming in DAT has never been examined. Therefore, we studied repetition priming in patients with various severity of DAT from the standpoint of familiarity of words.
Method : A new repetition priming task, which is constructed of 3 syllable Japanese Kana nouns and which contains high familiarity words and low familiarity words according to Chihara was used for an implicit memory task. The task was carried out by normal controls and patients with DAT. Each group was matched by age, sex, and educational level.
Results : A clear repetition priming effect was found among the control and dementia groups both in low and high familiarity words. The priming effects of a high familiarity task demonstrated no statistical differences among the control and dementia group. However, the priming effect of the low familiarity task in the severe dementia group was revealed to be significantly low compared with that of the control group (p<0.01), mild (p<0.01) and moderate group (p<0.05), and there was also statistical significance between the normal control and moderate dementia group (p<0.05).
Conclusion : These results indicate that dementia severity and word familiarity influences repetition priming in DAT.     

Verbal learning and memory deficits in Mild Cognitive Impairment

Criteria for amnestic MCI rely on the use of delayed recall tasks to establish the presence of memory impairment. This study applied the California Verbal Learning Test to detail memory performance in MCI patients (n=70), as compared to control subjects (n=92) and AD patients (n=21). Learning across the 5 trials was different among the 3 groups. Learning strategy was also different, the MCI group showing less semantic clustering than the control group. However, both MCI patients and controls could benefit from semantic cueing. This study showed that beyond consolidation deficits, MCI patients have marked difficulties in acquisition and recall strategies.     

Exploring semantic memory by investigating buildup and release of proactive interference in healthy older adults and individuals with dementia of the Alzheimer type.

There is debate regarding the integrity of semantic memory in dementia of the Alzheimer type (DAT). One view argues that DAT is associated with a breakdown in semantic memory; the other argues that DAT is associated with predominantly preserved semantic memory and a breakdown in retrieval. The classic release from proactive interference (RPI) paradigm was used to shed light on this debate. Individuals with early-stage DAT (n = 36) and healthy older adult controls (n = 45) participated in an RPI paradigm. Each trial was a Brown-Peterson task in which participants read three-word lists, counted (for 0, 3, 6, or 9 s), and recalled the words. Both groups showed significant proactive interference (PI), but the size of the PI was significantly smaller in the DAT group. The group difference in PI may be due to the faster forgetting rate in the DAT group. Both groups showed significant RPI and there was no group difference in size when RPI was considered in terms of PI levels. Both groups showed PI and RPI in prior list intrusions. The DAT group's significant buildup and release of PI based on semantic categories suggest predominantly preserved semantic memory activity, at least, in early-stage DAT individuals.     

The effects of prime visibility on ERP measures of masked priming

In two experiments, the effect of the duration (40, 80 and 120 ms) of pattern masked prime words on subsequent target word processing was measured using event-related potentials. In Experiment 1, target words were either repetitions of the prior masked prime (car-CAR) or were another unrelated word (job-CAR). In Experiment 2, primes and targets were either semantically related (cap-HAT) or were unrelated (car-HAT). Unrelated target words produced larger N400s than did repeated (Exp 1) or semantically related (Exp 2) words across the different prime durations and these N400 priming effects tended to be smaller overall for semantic than repetition priming. Moreover, there was only a modest decline in the size of N400 repetition priming at the shortest prime durations, and there was no relationship between this N400 effect and a measure of prime categorization performance. However, the size of semantic priming at the shortest durations was relatively smaller than at longer durations and was correlated with prime categorization performance. The findings are discussed in the context of the functional significance of the N400 as well as a model that argues for different mechanisms during masked repetition and semantic priming.     

An effect of priming task repetition on memory processes in an epileptic with amnesia

The purpose of this paper is to investigate memory processes in an epileptic with amnesia. Selective impairment of memory in organic amnesia has been reported in some clinical observations. They also demonstrated that organic amnesia can retain some aspects of learning experience, despite their inability to recollect them. We investigated an effect of priming task repetition on memory processes in a female with organic amnesia aged 28 (probable encephalitic patient) and eight control college students aged 20-26. In this paper, her memory processes were analyzed, using the same picture priming task, carried twelve times during the period of seven months. We used semantic priming paradigm. Three types of prime-target pair were used: identical, semantically related and unrelated. After a prime picture, a target picture appeared on the CRT display. She was asked to name each target as rapidly and accurately as possible. We analysed reaction time (RT) in naming the picture targets, error rate, and verbal reports of the priming task in the pre- and post-examination interview. In the first examination, priming effect was observed in her RT as in the controls'. This suggests that she retained some amount of semantic memory, and the structure of her semantic memory closely resembled that in the controls. Naming RT reduced and error rate decreased with repetition of the examination. This suggests that she acquired picture naming skill during early few examinations. However it was difficult for her to recognize and recollect the picture stimuli in this period. Further, she did not show any episodic memory of the examinations. There was dissociation between improved RT performance and poor verbal reports during early few examinations. When the same priming task was repeated in early few examinations, the priming effect became weaker in her RT. In the controls, on the contrary, the priming effect remained during the whole task repetition. Semantic strategy was apparently used in the controls, but not in the amnesic patient. She apparently used strategy of non-semantic association between the prime and target. In the last few examinations, her naming RT delayed and the priming effect was observed again as in the first examination. She seemed to use semantic strategy. In addition to this priming effect, she re-collected a few pictures and showed some episodic memory of the examination.(ABSTRACT TRUNCATED AT 400 WORDS)     

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.