MMN in  Psychosis

Auditory Mismatch Negativity (MMN) is an event related potential that is elicited by unexpected irregularities in a constant auditory stream, e.g. during an oddball paradigm, where repetitive standard sounds are interspersed with infrequent randomly presented deviants.

Reductions in MMN-responses are well established in chronic schizophrenia. However, evidence for MMN impairments in Clinical High Risk for Psychosis (CHR-P) and First Episode Psychosis (FEP) patients groups is less consistent. 

In this work, we examined recorded neuromagnetic responses to duration deviants to establish whether MMN responses are impaired during early stage psychosis. 

Contrary to our hypothesis, MMN-responses were intact, suggesting that MMN may not constitute a biomarker for early detection and diagnosis of psychosis. 

Here is my poster summarising this work

Relevant Publication

• Pradeep D, Tineke Grent-‘t-Jong, Ruchika Gajwani, Joachim Gross, Andrew I Gumley,  Rajeev Krishnadas, Stephen M Lawrie, Matthias Schwannauer, Frauke Schultze-Lutter, Peter J Uhlhaas, "Intact Mismatch Negativity Responses in Clinical High-Risk for Psychosis and First-Episode Psychosis: Evidence from Source-Reconstructed Event-Related Fields and Time-Frequency Data", Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, vol. 9 (1), pp.121-131, 2024 (pdf)  https://www.biologicalpsychiatrycnni.org/article/S2451-9022(23)00244-6/fulltext

Executive Summary: Mismatch negativity (MMN) is widely used as a biomarker of psychosis and is traditionally considered pre-attentive. However, evidence suggests MMN depends on attentional context. This review shows that MMN deficits in clinical high-risk (CHR) and first-episode psychosis (FEP) often disappear when participants perform demanding visual distractor tasks. We argue that active distractor tasks reduce reliance on impaired top-down processes, supporting MMN via preserved bottom-up processing. These findings highlight the importance of task design for using MMN in early psychosis (ESZ) research.

Title: "Attentional engagement reduces mismatch negativity (MMN) deficits in early-stage psychosis: A literature review of active visual distractor task paradigms"

Background

The auditory mismatch negativity (MMN) event-related potential (ERP) has long been regarded as a pre-attentive index of auditory sensory prediction. Traditionally considered largely automatic, MMN has been widely used as a biomarker of vulnerability to and presence of psychosis. However, emerging evidence indicates that MMN is not strictly pre-attentive; rather, it is shaped by task demands and influenced by top-down attentional processes.

Given the mixed evidence from passive MMN paradigms in early psychosis samples, the aim of this review was to examine MMN findings from studies incorporating an active visual distractor task.

Methods

We carried out a systematic search of Embase, Medline, and PubMed databases with the terms  ‘mismatch negativity’ combined with 'clinical high risk for psychosis (CHR-P)' or 'first-episode psychosis (FEP)' and related variations. A total of 208 studies were identified, and after removal of duplicates, 149 studies were screened manually. Nine studies that included an active visual distractor task were included in this review. 

Results

In six of nine reviewed studies, MMN deficits, commonly observed in chronic schizophrenia, failed to appear in CHR-P and FEP samples when participants performed an engaging visual task. Three studies reported MMN deficits: one included a concurrent auditory task, another did not measure task engagement with the visual task, while a third showed intact MMN in the overall CHR-P sample employed a colour change detection task that may have imposed relatively lower attentional demands. 

Discussion

We argue that active visual distractor tasks stabilize arousal, reduce variability in task engagement, and diminish the need for top-down allocation of auditory attention, thereby shifting reliance toward relatively preserved bottom-up auditory processes. These conditions may mitigate the expression of early predictive processing impairments, thereby reducing the likelihood of detecting MMN deficits in early-stage psychosis groups. In contrast, passive or weakly controlled incidental tasks (e.g., watching a silent video or reading a book) show mixed results due to differences in top-down resource allocation required for forming and updating the internal model of auditory regularities. This could result in passive attentional fluctuations being misinterpreted as primary sensory deficits.

Conclusions

These findings call for a reconceptualization of MMN as a context-dependent phenomenon rather than a purely pre-attentive response. Careful consideration of attentional design, particularly the inclusion and quantification of active visual distractor task engagement, is critical when using MMN as a biomarker in early psychosis research.

We investigated frequency deviant Mismatch Negativity (f-MMN) responses in the auditory cortex of Early Schizophrenia (ESZ) patients and matched healthy controls using high-field 7T fMRI. We aimed to assess differences in cortical laminar-specific microcircuits active during f-MMN. We also manipulated participant’s attention either towards (irrelevant auditory feature) or away (concurrent visual stimulation) from the auditory stimulation.