Associations of mismatch negativity with psychotic symptoms and functioning transdiagnostically across psychotic disorders.

Abstract

Mismatch negativity (MMN) amplitude has been widely shown to be diminished in schizophrenia and, more recently, in other psychotic disorders. Although there is considerable evidence linking MMN reduction to cognitive and functional deficits in schizophrenia, there is little evidence of associations with specific psychotic symptoms. Further, it is unclear if MMN reductions relate to specific symptoms, cognitive, and functional deficits transdiagnostically across different psychotic disorders. The present study examines MMN amplitude in a large cohort of cases diagnosed with psychotic disorders including schizophrenia and schizoaffective disorder (N = 116); bipolar disorder and major depressive disorder (N = 75); and other psychotic disorders (N = 25), as well as individuals with no psychotic disorder diagnoses (N = 248). Furthermore, we examined the association of MMN with symptoms, cognitive functioning, and real-world functioning to determine whether these relationships differ by diagnosis. Results showed that MMN amplitude was reduced in cases overall compared to never-psychotic individuals, with no differences between psychotic disorders. Furthermore, there were transdiagnostic associations of reduced duration MMN (MMN-D) with worse auditory hallucinations (r = .14) and disorganization (r = .14), frequency MMN (MMN-F) with real-word functioning (r = .20) and episodic memory (r = −.22), and both components with executive functioning (MMN-D: r = −.17; MMN-F: r = −.15). Our findings relating MMN reductions with cognitive and real-world functioning replicate earlier research in schizophrenia and extend these relationships to other psychotic disorders. Furthermore, our correlations with MMN-D are consistent with computational modeling research and theoretical proposals that view MMN reduction, cognitive dysfunction, and psychotic symptoms as reflecting underlying predictive coding deficits. However, differences in relationships with MMN-F suggest that additional work is warranted on this topic.

All grown up: Computational theories of psychosis, complexity, and progress.

“…They argue that the metanalysis may have failed to find significant associations between the MMN amplitude and positive symptoms because it considered only a broad positive symptom category instead of specific symptoms. Thus, in keeping with other articles in this issue-which seek to resolve specific details- Donaldson et al (2020) find that the duration MMN is associated with disorganization and hallucinations as well as measures of cognition. Furthermore, they note that this effect is transdiagnostic, appearing in psychosis, regardless of the specific disorder.…”

“…They also explore the importance of hierarchical organization, which has recently been modeled explicitly and verified empirically by fitting models to behavior and psychophysics (e.g., Powers, Mathys, & Corlett, 2017). The articles by Fryer et al (2020) and Donaldson et al (2020) demonstrate the utility of viewing neurophysiological data through the lens of predictive processing because they revisit the tried-and-true finding of attenuated mismatch negativity (MMN) in psychosis. They find that careful analysis can reveal key insights that might change our mechanistic interpretation of this putative biomarker.…”

“…In addition to supplementing the MMN, this putative biomarker of psychosis onset may help to stage patients in at-risk populations in treatment studies or longitudinal cohorts. The Donaldson et al (2020) article describes how different versions of the MMN are correlated with distinct positive and cognitive symptoms and functional outcomes. Taken together with the Fryer et al (2020) study, it appears that a battery of tests based on the MMN paradigm is emerging, which, given the practicality and reproducibility of the paradigm, may eventually enter clinical practice.…”

Volatility of subliminal haptic feedback alters the feeling of control in schizophrenia.

“…MMN reduction has been suggested to be related to premorbid functioning rather than with symptoms (Erickson et al, 2017). A recent meta-analysis has shown some relation with hallucinations specifically, but only marginally so (Donaldson et al, 2020). Here we take a different approach and consider temporal prediction.…”

What we think about when we think about predictive processing.

“…The current studies were also selected to determine how PPF reflects on transdiagnostic symptoms over-and-above diagnostic categories. Donaldson et al (2020) report that prediction errors in a popular perceptual task correspond to positive but not negative symptoms across people with schizophrenia and affective psychoses. If prediction errors are robust across diagnoses, they may also shed light on the transition to psychosis.…”