How Specific Are Deficits in Mismatch Negativity Generation to Schizophrenia?

Department of Psychiatric Research, University of Zurich, Zurich, Switzerland.
Biological Psychiatry (Impact Factor: 10.26). 07/2003; 53(12):1120-31. DOI: 10.1016/S0006-3223(02)01642-6
Source: PubMed


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.

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Available from: Daniel Umbricht, Aug 20, 2015
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    • "MMN results in patients with BD have been equivocal (Domján et al. 2012; Umbricht et al. 2003; Salisbury et al. 2007). However, compared to schizophrenia, MMN studies on BD are scarce in number (Andersson et al. 2008; Catts et al. 1995; Domján et al. 2012; Hall et al. 2009; Salisbury et al. 2007; Takei et al. 2010; Umbricht et al. 2003). MMNm peak latencies have been reportedly prolonged for tone-duration increments (Takei et al. 2010), tone duration decrements (Andersson et al. 2008), and for frequency changes (Takei et al. 2010) in these patients, as well as smaller in amplitude MMN compared to control subjects (Andersson et al. 2008). "
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    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; 27(4). DOI:10.1007/s10548-014-0374-6 · 3.47 Impact Factor
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    • "First, our study was not designed to demonstrate MMN and cognitive impairment in bipolar disorder. The effect size of MMN reduction was 0.14 and of a similar magnitude to that reported by Umbricht et al. (2003). We would have required a sample of several hundred participants per group to confirm a difference with sufficient statistical power. "
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    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.
    International journal of psychophysiology: official journal of the International Organization of Psychophysiology 03/2014; 95(2). DOI:10.1016/j.ijpsycho.2014.03.008 · 2.88 Impact Factor
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    • "Additionally, Takei and colleagues [33] found that the magnetic global field power of pure-tone frequency and the duration MMNm, a magnetic counterpart of MMN, was significantly decreased in those with MDD compared with healthy volunteers. Although these researchers reported dysfunction in the automatic processing of all observed patients with MDD, Umbricht et al. [34] found that both frequency and duration deviance-elicited MMN were normal in MDD. Additionally, Lepisto et al. [35] employed a syllable deviance task and also found unchanged MMN amplitude but shorter MMN latency in children with MDD. "
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    ABSTRACT: Major depressive disorder (MDD) is an important and highly prevalent mental disorder characterized by anhedonia and a lack of interest in everyday activities. Additionally, patients with MDD appear to have deficits in various cognitive abilities. Although a number of studies investigating the central auditory processing of low-level sound features in patients with MDD have demonstrated that this population exhibits impairments in automatic processing, the influence of emotional voice processing has yet to be addressed. To explore the automatic processing of emotional prosodies in patients with MDD, we analyzed the ability to detect automatic changes using event-related potentials (ERPs). This study included 18 patients with MDD and 22 age- and sex-matched healthy controls. Subjects were instructed to watch a silent movie but to ignore the afferent acoustic emotional prosodies presented to both ears while continuous electroencephalographic activity was synchronously recorded. Prosodies included meaningless syllables, such as "dada" spoken with happy, angry, sad, or neutral tones. The mean amplitudes of the ERPs elicited by emotional stimuli and the peak latency of the emotional differential waveforms were analyzed. The sad MMN was absent in patients with MDD, whereas the happy and angry MMN components were similar across groups. The abnormal sad emotional MMN component was not significantly correlated with the HRSD-17 and HAMA scores, respectively. The data indicate that patients with MDD are impaired in their ability to automatically process sad prosody, whereas their ability to process happy and angry prosodies remains normal. The dysfunctional sad emotion-related MMN in patients with MDD were not correlated with depression symptoms. The blunted MMN of sad prosodies could be considered a trait of MDD.
    PLoS ONE 03/2014; 9(3):e91995. DOI:10.1371/journal.pone.0091995 · 3.23 Impact Factor
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