Mismatch Negativity as an Index of Auditory Short-Term Plasticity: Associations with Cortisol, Inflammation, and Gray Matter Volume in Youth at Clinical High Risk for Psychosis
Bibliographic record
Abstract
Mismatch negativity (MMN) event-related potential (ERP) component reduction, indexing N-methyl-D-aspartate receptor (NMDAR)-dependent auditory echoic memory and short-term plasticity, is a well-established biomarker of schizophrenia that is sensitive to psychosis risk among individuals at clinical high-risk (CHR-P). Based on the NMDAR-hypofunction model of schizophrenia, NMDAR-dependent plasticity is predicted to contribute to aberrant neurodevelopmental processes involved in the pathogenesis of schizophrenia during late adolescence or young adulthood, including gray matter loss. Moreover, stress and inflammation disrupt plasticity. Therefore, using data collected during the 8-center North American Prodrome Longitudinal Study (NAPLS-2), we explored relationships between MMN amplitudes and salivary cortisol, gray matter volumes, and inflammatory cytokines. Participants included 303 CHR-P individuals with baseline electroencephalography (EEG) data recorded during an MMN paradigm as well as structural magnetic resonance imaging (MRI) and salivary cortisol, of which a subsample (n = 57) also completed blood draws. More deficient MMN amplitudes were associated with greater salivary cortisol and pro-inflammatory cytokine levels in future CHR-Converters, but not among those who did not convert to psychosis within the next two years. More deficient MMN amplitude was also associated with smaller total gray matter volume across participants regardless of future clinical outcomes, and with subcortical gray matter volumes among future CHR-Converters only. These findings are consistent with the theory that deficient NMDAR-dependent plasticity results in an overabundance of weak synapses that are subject to over-pruning during psychosis onset, contributing to gray matter loss. Further, MMN plasticity mechanisms may interact with stress, cortisol, and neuroinflammatory processes, representing a proximal influence of psychosis.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.002 |
| Scholarly communication | 0.000 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".