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

Abstract

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.

Reductions in Complex Mismatch Negativity to Extra Tone Gestalt Pattern Deviance in First-Episode Schizophrenia

“…Alain et al (20) found no significant difference in cMMN to a repeat deviant in longterm schizophrenia, although there was a trend-level group difference when the nose electrode was used as the reference. The cMMN to a missing tone on a gestalt grouping task was significantly reduced in long-term schizophrenia (29) and in early-course schizophrenia (30). The cMMN to infrequent extra tones in a gestalt grouping task is reduced in long-term schizophrenia (23).…”

Neurophysiologic measures of target engagement predict response to auditory-based cognitive training in treatment refractory schizophrenia

“…MMN and P3a are reliable biomarkers of central auditory system plasticity and discriminability-key processes underlying TCT [27][28][29]. Schizophrenia patients often have large-effect size deficits in MMN and P3a [30,31] that are associated with (and perhaps contribute to) higher-order cognitive, clinical, and psychosocial functioning [12,14,18,[32][33][34]. Importantly, MMN and P3a also show strong relationships with elements of TCT.…”

Test–retest reliability of the magnetic mismatch negativity response to sound duration and omission deviants

“…MMN deficits in early and prodromal stages of ScZ are particularly robust to deviations in sound duration (Bodatsch et al, 2011;Nagai et al, 2013;Todd et al, 2008). However, only few studies have shown reduced sound omission responses in ScZ (Kreitschmann-Andermahr et al, 1999;Salisbury and McCathern, 2016), thought to reflect endogenous predictive mechanisms (Arnal and Giraud, 2012;Schröger et al, 2015;Wacongne et al, 2012).…”