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

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.

MMN and P3a Elicited by a Novelty Oddball Paradigm Are Not Reduced in Early-Phase Psychosis

“…Based on several lines of study [52,53], duration MMN holds promise as a biomarker for schizophrenia as this deviant type is shown to be reduced in those with EPP, more so than other deviant types. However, our results, along with other studies [54][55][56], are not homogeneous to this, which speaks to the ambiguity and instability of MMN as a biomarker for schizophrenia. Specifically, it has been demonstrated that effect size of observed MMN reductions are smaller in EPP compared to the chronic illness [52]; this is somewhat mirrored by the small effect sizes between groups observed in the present study.…”

Attentional M100 gain modulation localizes to auditory sensory cortex and is deficient in first‐episode psychosis

“…Further, FEP were deficient in enhancing cortical activity with attention across these regions as well, suggesting that they have relatively widespread sensory and attention modulation deficits in auditory cortex, encompassing primary and nonprimary auditory cortex. The specificity of localizing this functional deficit in primary and auditory belt regions may provide insight to the emergence of psychosis, as specific temporal lobe abnormalities (e.g., Heschl's gyrus gray matter reduction) are present very early in the disorder (Curtis et al, 2021 ; Kasai et al, 2003 ) and show progressive pathology with disease duration (Salisbury et al, 2007 ). Understanding how the underlying progressive pathology relates to decline in functional abilities such as auditory attention modulation can provide a better understanding of this interplay at the emergence of psychosis.…”

Activity-State Dependent Reversal of Ketamine-Induced Resting State EEG Effects by Clozapine and Naltrexone in the Freely Moving Rat

“…We characterised how LFP and ECoG spectra are modulated during ketamine exposure with and without pre-administration of naltrexone or clozapine. We recorded drug-induced LFP/ECoG in freely moving rats from four brain structures relevant to schizophrenia and major depressive disorder: LFPs from the thalamus ( 54 – 60 ), prefrontal cortex (PFC) ( 61 – 64 ), the nucleus accumbens (NAc) ( 65 – 69 ), and ECoG above the auditory cortex (AC) ( 70 – 76 ). To control for behavioural states, data from head-mounted accelerometers were utilised to algorithmically define if the animal was active or passive in each LFP/ECoG window.…”