Trait aspects of auditory mismatch negativity predict response to auditory training in individuals with early illness schizophrenia

Bruno Biagianti, Brian J Roach, Melissa Fisher, Rachel Loewy, Judith M Ford, Sophia Vinogradov, Daniel H Mathalon, Bruno Biagianti, Brian J Roach, Melissa Fisher, Rachel Loewy, Judith M Ford, Sophia Vinogradov, Daniel H Mathalon

Abstract

Background: Individuals with schizophrenia have heterogeneous impairments of the auditory processing system that likely mediate differences in the cognitive gains induced by auditory training (AT). Mismatch negativity (MMN) is an event-related potential component reflecting auditory echoic memory, and its amplitude reduction in schizophrenia has been linked to cognitive deficits. Therefore, MMN may predict response to AT and identify individuals with schizophrenia who have the most to gain from AT. Furthermore, to the extent that AT strengthens auditory deviance processing, MMN may also serve as a readout of the underlying changes in the auditory system induced by AT.

Methods: Fifty-six individuals early in the course of a schizophrenia-spectrum illness (ESZ) were randomly assigned to 40 h of AT or Computer Games (CG). Cognitive assessments and EEG recordings during a multi-deviant MMN paradigm were obtained before and after AT and CG. Changes in these measures were compared between the treatment groups. Baseline and trait-like MMN data were evaluated as predictors of treatment response. MMN data collected with the same paradigm from a sample of Healthy Controls (HC; n = 105) were compared to baseline MMN data from the ESZ group.

Results: Compared to HC, ESZ individuals showed significant MMN reductions at baseline (p = .003). Reduced Double-Deviant MMN was associated with greater general cognitive impairment in ESZ individuals (p = .020). Neither ESZ intervention group showed significant change in MMN. We found high correlations in all MMN deviant types (rs = .59-.68, all ps < .001) between baseline and post-intervention amplitudes irrespective of treatment group, suggesting trait-like stability of the MMN signal. Greater deficits in trait-like Double-Deviant MMN predicted greater cognitive improvements in the AT group (p = .02), but not in the CG group.

Conclusions: In this sample of ESZ individuals, AT had no effect on auditory deviance processing as assessed by MMN. In ESZ individuals, baseline MMN was significantly reduced relative to HCs, and associated with global cognitive impairment. MMN did not show changes after AT and exhibited trait-like stability. Greater deficits in the trait aspects of Double-Deviant MMN predicted greater gains in global cognition in response to AT, suggesting that MMN may identify individuals who stand to gain the most from AT.

Trial registration: NCT00694889. Registered 1 August 2007.

Keywords: Biomarkers; Cognitive training; Mismatch negativity; Neuroplasticity; Schizophrenia.

Conflict of interest statement

Competing interests BB is a post-doctoral research fellow partially funded by Posit Science. The auditory training software used in this study was supplied free of charge by Posit Science. SV is a site PI on an SBIR grant to Posit Science, a company with a commercial interest in the training software used in these studies. None of the other authors have any financial interest in Posit Science. All authors declare no other conflicts of interest.

Figures

Fig. 1
Fig. 1
Mismatch Negativity (MMN) Amplitude For Each Group And Deviant Type. Ear-referenced ERP difference waveforms averaged across electrodes Fz, Fz, F4, C3, Cz, C4 for Duration, Double (duration + frequency), and Frequency MMN are given for each group (top). Healthy Controls (HC) are shown in blue, and individuals with Early Illness Schizophrenia (ESZ) in red. Scalp voltage topography maps of MMN amplitudes are shown for HC (middle) and ESZ (bottom) for each deviant type. MMN topography maps show the group means of MMN amplitudes around the grand average peak latency ±10 ms (indicated by gray bars in ERP difference waveform plots). Red dots on scalp topography maps indicate the 6 channels used in group comparisons and plotted in grand average waveforms. MMN is reduced in ESZ relative to HC across deviant types. Plotted data reflect group averages prior to any standardization based on the HC group
Fig. 2
Fig. 2
Mismatch Negativity (MMN) Amplitudes For Each Treatment Group And Deviant Type Before And After The Intervention. Ear-referenced ERP difference waveforms averaged across electrodes Fz, Fz, F4, C3, Cz, C4 for Duration, Double (duration + frequency), and Frequency MMN are given for Auditory Training (AT) participants (top) and Computer Games (CG) participants (bottom). Baseline MMN amplitudes are shown in blue, post-intervention MMN amplitude are shown in black
Fig. 3
Fig. 3
Scatter plots of the relationships between Change in Global Cognition and Trait-like Double-Deviant Mismatch Negativity (MMN) for Participants With Schizophrenia Who Received Computerized Auditory Training (left) and Participants Who Played Computer Games (right)

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