Emotion-Related Visual Mismatch Responses in Schizophrenia: Impairments and Correlations with Emotion Recognition.

BACKGROUND AND OBJECTIVES:Mismatch negativity (MMN) is an event-related potential (ERP) measure of preattentional sensory processing. While deficits in the auditory MMN are robust electrophysiological findings in schizophrenia, little is known about visual mismatch response and its association with social cognitive functions such as emotion recognition in schizophrenia. Our aim was to study the potential deficit in the visual mismatch response to unexpected facial emotions in schizophrenia and its association with emotion recognition impairments, and to localize the sources of the mismatch signals. EXPERIMENTAL DESIGN:The sample comprised 24 patients with schizophrenia and 24 healthy control subjects. Controls were matched individually to patients by gender, age, and education. ERPs were recorded using a high-density 128-channel BioSemi amplifier. Mismatch responses to happy and fearful faces were determined in 2 time windows over six regions of interest (ROIs). Emotion recognition performance and its association with the mismatch response were also investigated. PRINCIPAL OBSERVATIONS:Mismatch signals to both emotional conditions were significantly attenuated in patients compared to controls in central and temporal ROIs. Controls recognized emotions significantly better than patients. The association between overall emotion recognition performance and mismatch response to the happy condition was significant in the 250-360 ms time window in the central ROI. The estimated sources of the mismatch responses for both emotional conditions were localized in frontal regions, where patients showed significantly lower activity. CONCLUSIONS:Impaired generation of mismatch signals indicate insufficient automatic processing of emotions in patients with schizophrenia, which correlates strongly with decreased emotion recognition

Differentiation of Schizophrenia Patients from Healthy Subjects by Mismatch Negativity and Neuropsychological Tests

BACKGROUND: Schizophrenia is a heterogeneous disorder with diverse presentations. The current and the proposed DSM-V diagnostic system remains phenomenologically based, despite the fact that several neurobiological and neuropsychological markers have been identified. A multivariate approach has better diagnostic utility than a single marker method. In this study, the mismatch negativity (MMN) deficit of schizophrenia was first replicated in a Han Chinese population, and then the MMN was combined with several neuropsychological measurements to differentiate schizophrenia patients from healthy subjects. METHODOLOGY/PRINCIPAL FINDINGS: 120 schizophrenia patients and 76 healthy controls were recruited. Each subject received examinations for duration MMN, Continuous Performance Test, Wisconsin Card Sorting Test, and Wechsler Adult Intelligence Scale Third Edition (WAIS-III). The MMN was compared between cases and controls, and important covariates were investigated. Schizophrenia patients had significantly reduced MMN amplitudes, and MMN decreased with increasing age in both patient and control groups. None of the neuropsychological indices correlated with MMN. Predictive multivariate logistic regression models using the MMN and neuropsychological measurements as predictors were developed. Four predictors, including MMN at electrode FCz and three scores from the WAIS-III (Arithmetic, Block Design, and Performance IQ) were retained in the final predictive model. The model performed well in differentiating patients from healthy subjects (percentage of concordant pairs: 90.5%). CONCLUSIONS/SIGNIFICANCE: MMN deficits were found in Han Chinese schizophrenia patients. The multivariate approach combining biomarkers from different modalities such as electrophysiology and neuropsychology had a better diagnostic utility

Effects of NMDA receptor antagonist memantine on mismatch negativity

Mismatch negativity (MMN) and its magnetic counterpart (MMNm) have been shown to be altered in patients with various psychiatric and neurological disorders, e.g. Alzheimer's disease and schizophrenia, indicating deficits in involuntary attention. N-Methyl-d-aspartate (NMDA) receptor-mediated glutamate dysfunction is suggested to underlie these deficits. However, the role of NMDA receptors in involuntary attention is poorly understood. Memantine is an NMDA receptor antagonist that has been demonstrated to be effective in the treatment of patients with Alzheimer's disease. We aimed to investigate whether a single dose of memantine would affect MMN/MMNm in healthy subjects studied with simultaneous electroencephalography (EEG) and magnetoencephalography (MEG). Monaural left-ear auditory stimuli were presented in a passive oddball paradigm with infrequent deviant tones differing in frequency and duration. Neuronal activity was recorded in 13 healthy subjects after oral administration of 30 mg of memantine or placebo in a randomized, double-blind, cross-over design. MMNm was analyzed using equivalent current dipoles. MMN was evaluated from frontocentral electrodes. Memantine lowered subjects’ arousal level as measured by visual analog scales, and enhanced the amplitude of MMN in EEG. No differences in MMN latency were observed in MEG or EEG. Memantine did not affect the location, strength, amplitude or latency of MMNm, P1m, and N1m components. No changes in amplitude or latency were observed for P1 and N1 peaks. These results indicate that memantine affects involuntary attention without otherwise changing auditory processing of the stimuli. As memantine-induced changes in MMN were detected only in EEG, we suggest that the effect is mostly related to the frontal cortex