Pitch and Duration Mismatch Negativity and Premorbid Intellect in the First Hospitalized Schizophrenia Spectrum

Mismatch negativity (MMN) to deviant stimuli is robustly smaller in individuals with chronic schizophrenia compared with healthy controls (Cohen’s d > 1.0 or more), leading to the possibility of MMN being used as a biomarker for schizophrenia. However, there is some debate in the literature as to whether MMN is reliably reduced in first-episode schizophrenia patients. For the biomarker to be used as a predictive marker for schizophrenia, it should be reduced in the majority of cases known to have the disease, particularly at disease onset. We conducted a meta-analysis on the fourteen studies that measured MMN to pitch or duration deviants in healthy controls and patients within 12 months of their first episode of schizophrenia. The overall effect size showed no MMN reduction in first-episode patients to pitch-deviants (Cohen’s d < 0.04), and a small-to-medium reduction to duration-deviants (Cohen’s d = 0.47). Together, this indicates that pitch-deviant MMN is not a candidate biomarker for schizophrenia prediction, while duration-deviant MMN may hold some promise, albeit nearly a third as large an effect as in chronic schizophrenia. Potential causes for discrepancies between studies are discussed.

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“…Five studies measured MMN to pitch and duration deviants and so were included in both analyses. 51,54,56,57,61 …”

Section: Resultsmentioning

confidence: 99%

“…43-47 The SDs from 1 article could not be ascertained for the first-episode or control group. 48 The remaining 14 studies were included in the analysis, 7,49-61 and the results from these studies are summarized in Table 1.…”

Section: Methodsmentioning

confidence: 99%

Mismatch Negativity in First-Episode Schizophrenia

2016

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“…Simple pitch and duration deviant MMNs show large effect sizes (Cohen’s d = ~1) for reductions in long term schizophrenia (Salisbury et al 2002; Umbricht and Krljes 2005; Erickson et al 2016). MMN reductions at psychosis onset and their development during the early disease course remain controversial (Erickson et al 2016; Salisbury et al 2016; Haigh et al 2016; Todd et al 2008). …”

Section: Introductionmentioning

confidence: 99%

Abnormal Complex Auditory Pattern Analysis in Schizophrenia Reflected in an Absent Missing Stimulus Mismatch Negativity

Salisbury

McCathern

2016

Brain Topogr

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The simple mismatch negativity (MMN) to tones deviating physically (in pitch, loudness, duration, etc.) from repeated standard tones is robustly reduced in schizophrenia. Although generally interpreted to reflect memory or cognitive processes, simple MMN likely contains some activity from non-adapted sensory cells, clouding what process is affected in schizophrenia. Research in healthy participants has demonstrated that MMN can be elicited by deviations from abstract auditory patterns and complex rules that do not cause sensory adaptation. Whether persons with schizophrenia show abnormalities in the complex MMN is unknown. Fourteen schizophrenia participants and 16 matched healthy underwent EEG recording while listening to 400 groups of 6 tones 330 ms apart, separated by 800 ms. Occasional deviant groups were missing the 4th or 6th tone (50 groups each). Healthy participants generated a robust response to a missing but expected tone. The schizophrenia group was significantly impaired in activating the missing stimulus MMN, generating no significant activity at all. Schizophrenia affects the ability of “primitive sensory intelligence” and pre-attentive perceptual mechanisms to form implicit groups in the auditory environment. Importantly, this deficit must relate to abnormalities in abstract complex pattern analysis rather than sensory problems in the disorder. The results indicate a deficit in parsing of the complex auditory scene which likely impacts negatively on successful social navigation in schizophrenia. Knowledge of the location and circuit architecture underlying the true novelty-related MMN and its pathophysiology in schizophrenia will help target future interventions.

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“…in [3][4][5][6][7]. Moreover, MMN deficits correlate highly with level of function in established 5,8 , first-episode 9 and prodromal 10,11 schizophrenia, suggesting that it indexes core pathophysiological mechanisms.…”

Section: Introductionmentioning

confidence: 99%

“…In ERSP analysis, electrophysiological activity is divided conventionally into discrete delta (.5-4 Hz), theta (4-7 Hz), alpha (7)(8)(9)(10)(11)(12), beta (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24) and gamma (>24 Hz) bands, which reflect differential underlying local-circuit processes 20,[27][28][29] . Within these bands, stimulus-related activity is further differentiated into those that reflect alterations in phase reset mechanisms as reflected in intertrial coherence (ITC) vs. those that reflect alterations in single-trial power (e.g.…”

Section: Introductionmentioning

confidence: 99%