How specific are deficits in mismatch negativity generation to schizophrenia?

Department of Psychiatric Research, University of Zurich, Zurich, Switzerland.
Biological Psychiatry (Impact Factor: 9.47). 07/2003; 53(12):1120-31. DOI: 10.1016/S0006-3223(02)01642-6
Source: PubMed

ABSTRACT Mismatch negativity (MMN) is an auditory event-related potential that provides an index of auditory sensory memory. Deficits in MMN generation have been repeatedly demonstrated in chronic schizophrenia. Their specificity to schizophrenia has not been established.
Mismatch negativity to both duration and frequency deviants was investigated in gender- and age-matched patients with schizophrenia or schizoaffective disorder (n = 26), bipolar disorder (n = 16), or major depression (n = 22) and healthy control subjects (n = 25).
Only patients with schizophrenia demonstrated significantly smaller mean MMN than did healthy control subjects. Detailed analyses showed significantly smaller MMN to both duration and frequency deviants in patients with schizophrenia than in healthy control subjects; however, the reduction of frequency MMN in patients with schizophrenia was not significant in the comparison across all groups. Mismatch negativity topography did not differ among groups. No consistent correlations with clinical, psychopathologic, or treatment variables were observed.
Mismatch negativity deficits, and by extension deficits in early cortical auditory information processing, appear to be specific to schizophrenia. Animal and human studies implicate dysfunctional N-methyl-D-aspartate receptor functioning in MMN deficits. Thus MMN deficits may become a useful endophenotype to investigate the genetic underpinnings of schizophrenia, particularly with regard to the N-methyl-D-aspartate receptor.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cognition is often affected in a variety of neuropsychiatric, neurological, and neurodevelopmental disorders. The neural discriminative response, reflected in mismatch negativity (MMN) and its magnetoencephalographic equivalent (MMNm), has been used as a tool to study a variety of disorders involving auditory cognition. MMN/MMNm is an involuntary brain response to auditory change or, more generally, to pattern regularity violation. For a number of disorders, MMN/MMNm amplitude to sound deviance has been shown to be attenuated or the peak-latency of the component prolonged compared to controls. This general finding suggests that while not serving as a specific marker to any particular disorder, MMN may be useful for understanding factors of cognition in various disorders, and has potential to serve as an indicator of risk. This review presents a brief history of the MMN, followed by a description of how MMN has been used to index auditory processing capability in a range of neuropsychiatric, neurological, and neurodevelopmental disorders. Finally, we suggest future directions for research to further enhance our understanding of the neural substrate of deviance detection that could lead to improvements in the use of MMN as a clinical tool.
    Brain Topography 05/2014; DOI:10.1007/s10548-014-0374-6 · 2.52 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cognitive impairment is an important predictor of functional outcome in patients with schizophrenia, yet its neurobiology is still incompletely understood. Neuropathological evidence of impaired synaptic connectivity and NMDA receptor-dependent transmission in superior temporal cortex motivated us to explore the correlation of in vivo mismatch negativity (MMN) with cognitive status in patients with schizophrenia. MMN elicited in a roving stimulus paradigm displayed a response proportional to the number of stimulus repetitions (memory trace effect). Preliminary evidence in patients with chronic schizophrenia suggests that attenuation of this MMN memory trace effect was correlated with the degree of neuropsychological memory dysfunction. Here we present data from a larger confirmatory study in patients with schizophrenia, bipolar disorder, probable Alzheimer’s disease and healthy controls. We observed that the diminution of the MMN memory trace effect and its correlation with memory impairment was only found in the schizophrenia group. Recent pharmacological studies using the roving paradigm suggest that attenuation of the MMN trace effect can be understood as abnormal modulation of NMDA receptor-dependent plasticity. We suggest that the convergence of the previously identified synaptic pathology in supragranular cortical layers with the intracortical locus of MMN generation accounts for the remarkable robustness of MMN impairments in schizophrenia. We further speculate that this layer-specific synaptic pathology identified in supragranular neurons plays a pivotal computational role, by weakening the encoding and propagation of prediction errors to higher cortical modules. According to predictive coding theory such breakdown will have grave implications not only for perception, but also for higher-order cognition and may thus account for the MMN - cognition correlations observed here. Finally, MMN is a sensitive and specific biomarker for detecting the early prodromal phase of schizophrenia and is well suited for the exploration of novel cognition-enhancing agents in humans.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Phenomenological research indicates that disturbance of the basic sense of self may be a core phenotypic marker of schizophrenia spectrum disorders. Basic self-disturbance refers to disruption of the sense of ownership of experience and agency of action and is associated with a variety of anomalous subjective experiences. Little is known about the neurocognitive underpinnings of basic self-disturbance. In these two theoretical papers (of which this is Part 2), we review some recent phenomenological and neurocognitive research and point to a convergence of these approaches around the concept of self-disturbance. Specifically, we propose that subjective anomalies associated with basic self-disturbance may be associated with: 1. source monitoring deficits, which may contribute particularly to disturbances of "ownership" and "mineness" (the phenomenological notion of presence or self-affection) and 2. aberrant salience, and associated disturbances of memory, prediction and attention processes, which may contribute to hyper-reflexivity, disturbed "grip" or "hold" on perceptual and conceptual fields, and disturbances of intuitive social understanding ("common sense"). In this paper (Part 2) we focus on aberrant salience. Part 1 (this issue) addressed source monitoring deficits. Empirical studies are required in a variety of populations in order to test these proposed associations between phenomenological and neurocognitive aspects of self-disturbance in schizophrenia. An integration of findings across the phenomenological and neurocognitive "levels" would represent a significant advance in the understanding of schizophrenia and possibly enhance early identification and intervention strategies.
    Schizophrenia Research 07/2013; 152(1). DOI:10.1016/j.schres.2013.06.033 · 4.43 Impact Factor