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Impaired illness insight in schizophrenia is associated with non-adherence and worse outcomes. Schizophrenia patients also exhibit error-monitoring deficits, which have been proposed to cause poor insight. To test this hypothesis, we examined whether schizophrenia patients' deficits in neurophysiological error-monitoring indices, the error-related negativity (ERN) and error positivity (Pe) event-related potential (ERP) amplitudes, are associated with impaired insight. ERPs were recorded in 18 schizophrenia patients and 18 normal comparison participants during a Stroop task. Patients' subnormal ERN and Pe amplitudes did not correlate with insight, suggesting that impaired insight in schizophrenia stems from neurocognitive mechanisms other than deficient error monitoring.

Abstract:The N400 event-related brain potential (ERP), a negative voltage deflection occurring approximately 400 ms after onset of any meaningful stimulus, is reduced in amplitude when the stimulus is preceded by related context. Previous work has found this N400 semantic priming effect to be decreased in schizophrenia, suggesting impairment in using meaningful context to activate related concepts in semantic memory. Thus, N400 amplitude may be a useful biomarker of abnormal semantic processing and its response to treatment in schizophrenia. To help assess validity of N400 amplitude as a longitudinal measure in schizophrenia, we evaluated its testretest reliability. ERPs were recorded in sixteen schizophrenia patients who viewed prime words, each followed at 300-or 750-ms stimulus-onset asynchrony (SOA) by a target that was either a related or unrelated word, or nonword. Participants' task was to indicate whether or not the target was a real word. They were retested on the same procedure one week later. Test-retest reliability was assessed by calculating Pearson's r and intraclass correlation coefficients (ICCs) across timepoints for N400 amplitudes for related and unrelated targets, at each SOA. Consistent with previous results, there were no significant differences between patients' N400 amplitudes for related and unrelated targets, at any SOA/timepoint combination. Pearson's r and ICCs for N400 amplitudes at Fz across timepoints were significant for both target types at each SOA (ranges: r 0.52-0.64, ICC 0.52-0.63; all p < .04). The results suggest potential utility of N400 amplitude as a longitudinal neurophysiological biomarker of semantic processing abnormalities in schizophrenia.3 Test-retest reliability of N400 event-related brain potential measures in a word-pair semantic priming paradigm in patients with schizophrenia

Rationale-Frequent cannabis use is a risk marker for schizophrenia and delusions, but the neurocognitive mechanisms of this relationship remain unclear.Objectives-We sought evidence that cannabis users have deficits in processing relationships between meaningful stimuli, similar to abnormalities reported in schizophrenia, and that these deficits are associated with delusion-like ideation. We used the N400 event-related brain potential (ERP) waveform as a neurophysiological probe of activation of concepts in semantic memory. We hypothesized that cannabis users would exhibit larger (more negative) than normal N400 amplitudes in response to stimuli meaningfully related to a preceding prime-reflecting deficient activation of concepts related to the prime. We further hypothesized that the magnitude of this abnormality would correlate with severity of delusion-like ideation.Methods-We recorded ERPs in 24 frequent cannabis users and 24 non-using comparison participants who viewed prime words followed by targets which were either words related or unrelated to the prime or pronounceable non-words. The participants' task was to indicate whether the target was a word. Delusion-like ideation was measured via the Schizotypal Personality Questionnaire.Results-Contrary to our hypothesis, cannabis users exhibited smaller than normal N400s to both related and unrelated targets. These abnormalities correlated with delusion-like ideation in cannabis users only. Conclusions-The results are consistent with a generalized abnormality of activation within semantic memory neural networks in cannabis users. Further research is needed to investigate whether such an abnormality plays a role in the development of delusion-like ideation in cannabis users.

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