Mismatch negativity: An index of a preattentive processing deficit in schizophrenia

Shelley, Anne-Marie; Ward, Philip B.; Catts, Stanley V.; Michie, Patricia T.; Andrews, Sally; McConaghy, Nathaniel

doi:10.1016/0006-3223(91)90126-7

Cited by 379 publications

(232 citation statements)

References 17 publications

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“…Visual inspection of these waveforms indicates that healthy controls showed an early differential response (ie the MMN) between standard and deviant stimuli, whereas patients did not. This pattern is in keeping with what would be expected from prior investigations of the MMN in schizophrenia patients (Catts et al, 1995;Javitt et al, 1993Javitt et al, , 1998Shelley et al, 1991;Shutara et al, 1996). To statistically assess whether our cohort of patients exhibited a deficient MMN, area measures (vs the 0 mV baseline) were taken from these electrodes over the 70-155 ms interval and submitted to a 2 Â 2 Â 4 repeated measures ANOVA, using diagnosis for schizophrenia as the between-subject factors and stimulus condition and electrode as within-subject factors.…”

Section: Baseline Measurements: Controls Vs Patientssupporting

confidence: 91%

“…The first followed a between-subject designs and was carried out to verify that our cohort of patients exhibited impaired MMN relative to healthy controls at the onset of the protocol, as has been repeatedly demonstrated in prior studies of schizophrenic patients (Catts et al, 1995;Javitt et al, 1993Javitt et al, , 1998Shelley et al, 1991;Shutara et al, 1996). The second followed a within-subject designs and was carried out to assess whether 2 months of NAC administration restored MMN generation relative to the administration of placebo.…”

Section: Eeg Recordings and Analysesmentioning

confidence: 97%

“…NMDA receptor antagonists block MMN generation in both primates (Javitt et al, 1996) and humans (Umbricht et al, 2000), suggesting that the MMN reflects current flow through NMDA channels. The amplitude of MMN is known to be decreased in schizophrenia (Catts et al, 1995;Javitt et al, 1993Javitt et al, , 1998Shelley et al, 1991;Shutara et al, 1996; for review see Turetsky et al, 2007), further implicating impaired NMDA function in such patients.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Glutathione Precursor, N-Acetyl-Cysteine, Improves Mismatch Negativity in Schizophrenia Patients

Lavoie

Murray

Deppen

et al. 2007

Neuropsychopharmacol

328

222

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In schizophrenia patients, glutathione dysregulation at the gene, protein and functional levels, leads to N-methyl-D-aspartate (NMDA) receptor hypofunction. These patients also exhibit deficits in auditory sensory processing that manifests as impaired mismatch negativity (MMN), which is an auditory evoked potential (AEP) component related to NMDA receptor function. N-acetyl-cysteine (NAC), a glutathione precursor, was administered to patients to determine whether increased levels of brain glutathione would improve MMN and by extension NMDA function. A randomized, double-blind, cross-over protocol was conducted, entailing the administration of NAC (2g/day) for 60 days and then placebo for another 60 days (or vice versa). 128-channel AEPs were recorded during a frequency oddball discrimination task at protocol onset, at the point of cross-over, and at the end of the study. At the onset of the protocol, the MMN of patients was significantly impaired compared to sex-and age-matched healthy controls (p ¼ 0.003), without any evidence of concomitant P300 component deficits. Treatment with NAC significantly improved MMN generation compared with placebo (p ¼ 0.025) without any measurable effects on the P300 component. MMN improvement was observed in the absence of robust changes in assessments of clinical severity, though the latter was observed in a larger and more prolonged clinical study. This pattern suggests that MMN enhancement may precede changes to indices of clinical severity, highlighting the possible utility AEPs as a biomarker of treatment efficacy. The improvement of this functional marker may indicate an important pathway towards new therapeutic strategies that target glutathione dysregulation in schizophrenia.

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Section: Baseline Measurements: Controls Vs Patientssupporting

confidence: 91%

Section: Eeg Recordings and Analysesmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Glutathione Precursor, N-Acetyl-Cysteine, Improves Mismatch Negativity in Schizophrenia Patients

Lavoie

Murray

Deppen

et al. 2007

Neuropsychopharmacol

328

222

View full text Add to dashboard Cite

show abstract

“…Out of 15 studies in schizophrenia, deficits in MMN generation were found in 13 studies (Alain et al, 1998;Catts et al, 1995;Hirayasu et al, 1998;Javitt et al, 1993Javitt et al, , 1995Javitt et al, , 2000Kreitschmann-Andermahr et al, 1999;Oades et al, 1997;Shelley et al, 1991;Shutara et al, 1996;Umbricht et al, 1998Umbricht et al, , 1999 demonstrating deficits in context-dependent information processing of auditory stimuli at a preattentive automatic level. Schizophrenic patients also exhibit deficient performance in complex tasks that engage the prefrontal cortex (Barch et al, 2001) and require utilization of contextual information for correct task performance (Cohen et al, 1999;Javitt et al, 2000;Servan-Schreiber et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Effects of the 5-HT2A Agonist Psilocybin on Mismatch Negativity Generation and AX-Continuous Performance Task: Implications for the Neuropharmacology of Cognitive Deficits in Schizophrenia

Umbricht

Vollenweider

Schmid

et al. 2003

Neuropsychopharmacol

168

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Previously the NMDA (N-methyl-D-aspartate) receptor (NMDAR) antagonist ketamine was shown to disrupt generation of the auditory event-related potential (ERP) mismatch negativity (MMN) and the performance of an 'AX'-type continuous performance test (AX-CPT)Fmeasures of auditory and visual context-dependent information processingFin a similar manner as observed in schizophrenia. This placebo-controlled study investigated effects of the 5-HT 2A receptor agonist psilocybin on the same measures in 18 healthy volunteers. Psilocybin administration induced significant performance deficits in the AX-CPT, but failed to reduce MMN generation significantly. These results indirectly support evidence that deficient MMN generation in schizophrenia may be a relatively distinct manifestation of deficient NMDAR functioning. In contrast, secondary pharmacological effects shared by NMDAR antagonists and the 5-HT 2A agonist (ie disruption of glutamatergic neurotransmission) may be the mechanism underlying impairments in AX-CPT performance observed during both psilocybin and ketamine administration. Comparable deficits in schizophrenia may result from independent dysfunctions of 5-HT 2A and NMDAR-related neurotransmission.

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“…Moreover, progressive changes in schizophrenic subjects can be indexed using a MMN paradigm in the ERP environment (Salisbury et al, 2007). Indeed, ERP has certain advantages in testing auditory sensory processing in that tones can be played in sound-proof laboratories with little to no extraneous noise, experimental design allows for a large number of deviants, greater than 160 in most studies (Shelley et al, 1991;Javitt et al, 1995;Umbricht et al, 1998;Michie et al, 2000;Baldeweg et al, 2004;Brockhaus-Dumke et al, 2005) (exception, Kirino and Inoue, 1999) and allows for precise time recordings on the order of milliseconds at the expense of poor spatial resolution.…”

Section: Discussionmentioning

confidence: 99%

Auditory processing abnormalities in schizotypal personality disorder: An fMRI experiment using tones of deviant pitch and duration

Dickey

Mórocz

Niznikiewicz

et al. 2008

Schizophrenia Research

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Background-One of the cardinal features of schizotypal personality disorder (SPD) is language abnormalities. The focus of this study was to determine whether or not there are also processing abnormalities of pure tones differing in pitch and duration in SPD.Methods-Thirteen neuroleptic-naïve male subjects met full criteria for SPD and were groupmatched on age and parental socioeconomic status to 13 comparison subjects. Verbal learning was measured with the California Verbal Learning Test. Heschl's gyrus volumes were measured using structural MRI. Whole-brain fMRI activation patterns in an auditory task of listening to tones including pitch and duration deviants were compared between SPD and control subjects. In a Contributors Dickey: designed the study, collected the fMRI data, analyzed the clinical and fMRI data, and wrote the manuscript. Morocz: analyzed the fMRI data. Niznikiewicz: collected and analyzed the ERP data, and contributed to the manuscript. Voglmaier: collected and analyzed CVLT data, and performed SCID interview. Dreusicke: analyzed the fMRI data. Toner: aided in fMRI data collection. Yoo: aided in initial fMRI data collection. Khan: aided in final fMRI data presentation. Shenton: reviewed the manuscript. McCarley: reviewed the manuscript. Conflict of interestAll authors declare that they have no conflict of interest. Results-In the region of the STG, SPD subjects demonstrated more activation to pitch deviants bilaterally (p<0.001); and to duration deviants in the left hemisphere (p=0.005) (two-sample t). SPD subjects also showed more bilateral parietal cortex activation to duration deviants. In no region did comparison subjects activate more than SPD subjects in either experiment. Exploratory correlations for SPD subjects suggest a relationship between peak activation on the right for deviant tones in the pitch experiment with odd speech and impaired verbal learning. There was no difference between groups on Heschl's gyrus volume. NIH Public AccessConclusions-These data suggest that SPD subjects have inefficient or hyper-responsive processing of pure tones both in terms of pitch and duration deviance that is not attributable to smaller Heschl's gyrus volumes. Finally, these auditory processing abnormalities may have significance for the odd speech heard in some SPD subjects and downstream language and verbal learning deficits.

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Mismatch negativity: An index of a preattentive processing deficit in schizophrenia

Cited by 379 publications

References 17 publications

Glutathione Precursor, N-Acetyl-Cysteine, Improves Mismatch Negativity in Schizophrenia Patients

Glutathione Precursor, N-Acetyl-Cysteine, Improves Mismatch Negativity in Schizophrenia Patients

Effects of the 5-HT2A Agonist Psilocybin on Mismatch Negativity Generation and AX-Continuous Performance Task: Implications for the Neuropharmacology of Cognitive Deficits in Schizophrenia

Auditory processing abnormalities in schizotypal personality disorder: An fMRI experiment using tones of deviant pitch and duration

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