Pitch and Duration Mismatch Negativity and Heschl’s Gyrus Volume in First-Episode Schizophrenia-Spectrum Individuals

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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F205. Mismatch Negativity Correlates With Auditory Cortex Gray Matter and Prodromal Role Functioning in First Episode Schizophrenia Spectrum Individuals

Biological Psychiatry ◽

10.1016/j.biopsych.2018.02.819 ◽

2018 ◽

Vol 83 (9) ◽

pp. S318-S319

Author(s):

Anna Shafer ◽

Timothy K. Murphy ◽

Brian A. Coffman ◽

Dean Salisbury

Keyword(s):

Auditory Cortex ◽

Gray Matter ◽

Mismatch Negativity ◽

First Episode ◽

Role Functioning ◽

Schizophrenia Spectrum ◽

First Episode Schizophrenia

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

Schizophrenia Bulletin ◽

10.1093/schbul/sby017.704 ◽

2018 ◽

Vol 44 (suppl_1) ◽

pp. S288-S288

Author(s):

Dean Salisbury ◽

Anna Shafer ◽

Brian Coffman ◽

Timothy Murphy

Keyword(s):

Auditory Cortex ◽

Gray Matter ◽

Mismatch Negativity ◽

First Episode ◽

Role Functioning ◽

Schizophrenia Spectrum ◽

First Episode Schizophrenia

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S137. LEFT HEMISPHERE MEG DEFICIT IN PITCH AND DURATION MISMATCH NEGATIVITY IN FIRST EPISODE PSYCHOSIS

Schizophrenia Bulletin ◽

10.1093/schbul/sbaa031.203 ◽

2020 ◽

Vol 46 (Supplement_1) ◽

pp. S87-S88

Author(s):

Erin Duricy ◽

Brian Coffman ◽

Mark Curtis ◽

Rebekah Farris ◽

Vanessa Fishel ◽

...

Keyword(s):

Auditory Cortex ◽

Left Hemisphere ◽

Mismatch Negativity ◽

Time Window ◽

Time Windows ◽

First Episode ◽

Oddball Paradigm ◽

Late Time ◽

Disease Course ◽

Eeg Recordings

Abstract Background Mismatch negativity (MMN) is an event-related potential (ERP) that is severely impaired in long-term schizophrenia. However, though largely debated, numerous electroencephalography (EEG) studies suggest that MMN is less reduced in individuals at their first episode of psychosis (FEP). Pitch MMN (pMMN) is not reduced, although duration MMN (dMMN) may be reduced compared to healthy controls (HC), and may show left hemisphere deficits early on. Few MMN studies in FEP have utilized magnetoencephalography (MEG). MEG could potentially be more sensitive to circumscribed differences, given its ability to more effectively localize MMN sources within the auditory cortex. Using MEG, we compared pMMN and dMMN between FEP and HC to identify potential source location- and timing-dependent differences in early disease course. Methods Simultaneous MEG and EEG recordings of pMMN and dMMN were obtained with an oddball paradigm from 15 FEP and 19 HC. Of those, 12 FEP and 11 HC had usable EEG recordings, with the remainder lost due to a circuit board failure. MMN was calculated by subtraction of the sensor-space average to the standard tones from the average to the deviant tones. For EEG, mean amplitudes across fronto-central electrodes (F1, Fz, F2, FC1, FCz, FC2) were calculated over a 30 msec window at group peak latency. For MEG data, source activity was determined in Brainstorm using minimum norm estimation, multisphere head models, and individual MRI cortical surface reconstructions. Using the HCP Brain Atlas, regions of interest (ROIs) were determined based on areas of peak activity at two time windows for each task: an Early time window of 105–115 ms for both pMMN and dMMN, and a Late time window of 125–135 ms for pMMN and 155–165 ms for dMMN. Mean amplitudes were calculated over six auditory cortex ROIs: A1, Brodmann’s Area 43, Brodmann’s Area 52, Lateral Belt, Medial Belt, and Parabelt. Mixed-model ANOVA was then used to compare groups, regions, hemispheres, time windows, and tasks using SPSS software. Results For EEG peak MMNs, there were no significant differences between groups in pMMN or dMMN (p’s > 0.1). For MEG sources, however, ANOVA indicated a Region x Hemisphere x Group interaction (p = 0.038), but no significant regional differences between Pitch and Duration or for either Early or Late time windows (p’s > 0.1). When ROI data were averaged across tasks and time windows, the right hemisphere showed no difference between groups, whereas the left hemisphere showed a trend for reduced MMN activity in FEP (p = 0.069). Post-hoc comparisons of the six left hemisphere ROIs revealed that all regions but Brodmann’s Area 43 showed significant reduction in FEP (p’s < 0.05). Discussion These findings support previous literature that indicate relatively preserved EEG scalp measures of MMN in FEP. However, the MEG source data indicate a deficit in the left hemisphere auditory cortex of FEP. This left hemisphere reduction was observed in 5 out of 6 source regions and at both time windows. This suggests broad left hemisphere auditory cortex pathophysiology early in disease course to which EEG may be relatively less sensitive by comparison with MEG. In conclusion, FEP may be associated with a selective left hemisphere MMN deficit in auditory regions on the superior temporal plane, but not the opercular cortex (i.e. Brodmann’s Area 43).

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