Reduced magnetic mismatch negativity: a shared deficit in psychosis and related risk

Abstract

Background Abnormal auditory processing of deviant stimuli, as reflected by mismatch negativity (MMN), is often reported in schizophrenia (SCZ). At present, it is still under debate whether this dysfunctional response is specific to the full-blown SCZ diagnosis or rather a marker of psychosis in general. The present study tested MMN in patients with SCZ, bipolar disorder (BD), first episode of psychosis (FEP), and in people at clinical high risk for psychosis (CHR). Methods Source-based MEG activity evoked during a passive auditory oddball task was recorded from 135 patients grouped according to diagnosis (SCZ, BD, FEP, and CHR) and 135 healthy controls also divided into four subgroups, age- and gender-matched with diagnostic subgroups. The magnetic MMN (mMMN) was analyzed as event-related field (ERF), Theta power, and Theta inter-trial phase coherence (ITPC). Results The clinical group as a whole showed reduced mMMN ERF amplitude, Theta power, and Theta ITPC, without any statistically significant interaction between diagnosis and mMMN reductions. The mMMN subgroup contrasts showed lower ERF amplitude in all the diagnostic subgroups. In the analysis of Theta frequency, SCZ showed significant power and ITPC reductions, while only indications of diminished ITPC were observed in CHR, but no significant decreases characterized BD and FEP. Conclusions Significant mMMN alterations in people experiencing psychosis, also for diagnoses other than SCZ, suggest that this neurophysiological response may be a feature shared across psychotic disorders. Additionally, reduced Theta ITPC may be associated with risk for psychosis.

Is source‐resolved magnetoencephalographic mismatch negativity a viable biomarker for early psychosis?

“…Despite the causes behind the exacerbated left vs. right structural abnormalities in SZ are outside the scope of the present study, we speculate that the different cytoarchitectonic organization of left and right auditory cortex (Harrison et al, 2010) may result in a differential sensitivity to the underlying pathophysiology and link with language‐related symptoms such as auditory hallucinations and impaired verbal cognition (Heidrich & Strik, 1997). On the other hand, our results contrast with the few other EEG dipole‐fitting (Oades et al, 2006; Randau et al, 2019) and MEG source‐localization (Valt et al, 2022) studies in FE that found right (Randau et al, 2019) or bilateral dMMN reductions, suggesting further research is necessary to account for the variability of the source‐reconstruction techniques applied in different studies.…”

“…Smaller grey matter volumes in HG of SZ but not BD were also found by Kasai et al (2003). Conversely, other studies comparing FE sz and affective‐spectrum disorder have found similar MMN reductions (Kaur et al, 2011; Valt et al, 2022). Future studies tracking MMN deficits in FE sz and FE Aff longitudinally and with larger samples should resolve the specificity of the deficit.…”

“…Shin et al (2009) investigated individuals with clinical high risk for psychosis and found reduced MMN in right STG. Valt et al (2022) reported reduced MMN sources in STG and bilateral transverse temporal sulcus and gyrus in FEP. Braeutigam et al (2018) applied dynamic causal modeling in MEG data from 16 FE sz adolescents to find different inter‐hemispheric connectivity patterns in FE sz and controls.…”