Cortical substrates and functional correlates of auditory deviance processing deficits in schizophrenia.

Anthony J Rissling,Gregory A Light,David L Braff,Catherine A Sugar,Scott Makeig,Makoto Miyakoshi

doi:10.1016/j.nicl.2014.09.006

Abstract

Although sensory processing abnormalities contribute to widespread cognitive and psychosocial impairments in schizophrenia (SZ) patients, scalp-channel measures of averaged event-related potentials (ERPs) mix contributions from distinct cortical source-area generators, diluting the functional relevance of channel-based ERP measures. SZ patients (n = 42) and non-psychiatric comparison subjects (n = 47) participated in a passive auditory duration oddball paradigm, eliciting a triphasic (Deviant−Standard) tone ERP difference complex, here termed the auditory deviance response (ADR), comprised of a mid-frontal mismatch negativity (MMN), P3a positivity, and re-orienting negativity (RON) peak sequence. To identify its cortical sources and to assess possible relationships between their response contributions and clinical SZ measures, we applied independent component analysis to the continuous 68-channel EEG data and clustered the resulting independent components (ICs) across subjects on spectral, ERP, and topographic similarities. Six IC clusters centered in right superior temporal, right inferior frontal, ventral mid-cingulate, anterior cingulate, medial orbitofrontal, and dorsal mid-cingulate cortex each made triphasic response contributions. Although correlations between measures of SZ clinical, cognitive, and psychosocial functioning and standard (Fz) scalp-channel ADR peak measures were weak or absent, for at least four IC clusters one or more significant correlations emerged. In particular, differences in MMN peak amplitude in the right superior temporal IC cluster accounted for 48% of the variance in SZ-subject performance on tasks necessary for real-world functioning and medial orbitofrontal cluster P3a amplitude accounted for 40%/54% of SZ-subject variance in positive/negative symptoms. Thus, source-resolved auditory deviance response measures including MMN may be highly sensitive to SZ clinical, cognitive, and functional characteristics.

Highlights

There is growing evidence that sensory processing impairments contribute to cognitive and psychosocial deficits in schizophrenia (SZ) patients (Braff and Light, 2004; Javitt, 2009)
Even when the participant3s attention is drawn to another stimulus stream, average event-related potentials (ERPs) time-locked to presentations of deviant stimuli interspersed in a train of standard tones evoke a response complex dominated by three peaks, labeled mismatch negativity (MMN), P3a, and reorienting negativity (RON), that appears to index
This study aimed to identify the primary sources of the auditory deviance response complex in SZ and non-psychiatric comparison subjects (NCS), and to explore whether source-level ERP measures are more sensitive than standard scalp-channel measures to clinical, cognitive, and functional SZ characteristics

Summary

Introduction

There is growing evidence that sensory processing impairments contribute to cognitive and psychosocial deficits in schizophrenia (SZ) patients (Braff and Light, 2004; Javitt, 2009). Even when the participant3s attention is drawn to another stimulus stream (e.g., here an animated cartoon), average event-related potentials (ERPs) time-locked to presentations of deviant stimuli interspersed in a train of standard tones evoke a response complex dominated by three peaks, labeled mismatch negativity (MMN), P3a, and reorienting negativity (RON), that appears to index preattentive sensory discrimination and attention-related orienting processes (e.g., Näätänen, 1990; Rissling et al, 2012; Rissling et al, 2013). Studies use measures of the difference between responses evoked by infrequent Deviant versus Standard tones in a continuing sequence to avoid contamination by potentials indexing low-level auditory processes common to both responses.

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