F173. PITCH AND DURATION MISMATCH NEGATIVITY, AUDITORY CORTEX GRAY MATTER, AND PRODROMAL ROLE FUNCTIONING IN THE FIRST EPISODE SCHIZOPHRENIA SPECTRUM

Background. The mismatch negativity (MMN) brainwave indexes novelty detection. MMN to infrequent pitch (pMMN) and duration (dMMN) deviants is reduced in long-term schizophrenia. Although not reduced at first psychosis, pMMN is inversely associated with left hemisphere Heschl’s gyrus (HG) gray matter volume within 1 year of first hospitalization for schizophrenia-spectrum psychosis, consistent with pathology of left primary auditory cortex early in disease course. We examined whether the relationship was present earlier, at first psychiatric contact for psychosis, and whether the same structural-functional association was apparent for dMMN. Method. Twenty-seven first-episode schizophrenia-spectrum (FESz) and 27 matched healthy comparison (HC) individuals were compared. EEG-derived pMMN and dMMN were measured by subtracting the standard tone waveform (80%) from the pitch- and duration-deviant waveforms (10% each). HG volumes were calculated from T1-weighted structural magnetic resonance imaging using Freesurfer. Results. In FESz, pMMN amplitudes at Fz were inversely associated with left HG (but not right) gray matter volumes, and dMMN amplitudes were associated significantly with left HG volumes and at trend-level with right HG. There were no structural-functional associations in HC. Conclusions. pMMN and dMMN index gray matter reduction in left hemisphere auditory cortex early in psychosis, with dMMN also marginally indexing right HG volumes. This suggest conjoint functional and structural pathology that affects the automatic detection of novelty with varying degrees of penetrance prior to psychosis. These brainwaves are sensitive biomarkers of pathology early in the psychotic disease course, and may serve as biomarkers of disease progression and as therapeutic outcome measures.

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Pitch and Duration Mismatch Negativity Are Associated with Distinct Auditory Cortex and Inferior Frontal Cortex Volumes in the First-Episode Schizophrenia Spectrum

Schizophrenia Bulletin Open ◽

10.1093/schizbullopen/sgab005 ◽

2021 ◽

Author(s):

Mark T Curtis ◽

Brian A Coffman ◽

Dean F Salisbury

Keyword(s):

Auditory Cortex ◽

Frontal Cortex ◽

Gray Matter ◽

Mismatch Negativity ◽

First Episode ◽

The Novel ◽

Inferior Frontal Cortex ◽

Heschl’S Gyrus ◽

First Episode Schizophrenia ◽

Gray Matter Volumes

Abstract Background Pitch and duration mismatch negativity (pMMN/dMMN) are related to left Heschl’s gyrus gray matter volumes in first-episode schizophrenia (FESz). Previous methods were unable to delineate functional subregions within and outside Heschl’s gyrus. The Human Connectome Project multimodal parcellation (HCP-MMP) atlas overcomes this limitation by parcellating these functional subregions. Further, MMN has generators in inferior frontal cortex, and therefore, may be associated with inferior frontal cortex pathology. With the novel use of the HCP-MMP to precisely parcellate auditory and inferior frontal cortex, we investigated relationships between gray matter and pMMN and dMMN in FESz. Methods pMMN and dMMN were measured at Fz from 27 FESz and 27 matched healthy controls. T1-weighted MRI scans were acquired. The HCP-MMP atlas was applied to individuals, and gray matter volumes were calculated for bilateral auditory and inferior frontal cortex parcels and correlated with MMN. FDR correction was used for multiple comparisons. Results In FESz only, pMMN was negatively correlated with left medial belt in auditory cortex and area 47L in inferior frontal cortex. Duration MMN negatively correlated with the following auditory parcels: left medial belt, lateral belt, parabelt, TA2, and right A5. Further, dMMN was associated with left area 47L, right area 44, and right area 47L in inferior frontal cortex. Conclusions The novel approach revealed overlapping and distinct gray matter associations for pMMN and dMMN in auditory and inferior frontal cortex in FESz. Thus, pMMN and dMMN may serve as biomarkers of underlying pathological deficits in both similar and slightly different cortical areas.

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