Date Published: May 9, 2019
Publisher: Public Library of Science
Author(s): Eiji Kirino, Yayoi Hayakawa, Rie Inami, Reiichi Inoue, Shigeki Aoki, Manuel S. Malmierca.
Functional magnetic resonance imaging (fMRI), electroencephalogram (EEG), and diffusion tensor imaging (DTI) recording have complementary spatiotemporal resolution limitations but can be powerful methods when used together to enable both functional and anatomical modeling, with each neuroimaging procedure used to maximum advantage. We recorded EEGs during event-related fMRI followed by DTI in 15 healthy volunteers and 12 patients with schizophrenia using an omission mismatch negativity (MMN) paradigm. Blood oxygenation level-dependent (BOLD) signal changes were calculated in a region of interest (ROI) analysis, and fractional anisotropy (FA) in the white matter fibers related to each area was compared between groups using tract-specific analysis. Patients with schizophrenia had reduced BOLD activity in the left middle temporal gyrus, and BOLD activity in the right insula and right parahippocampal gyrus significantly correlated with positive symptoms on the Positive and Negative Syndrome Scale (PANSS) and hostility subscores. BOLD activation of Heschl’s gyri also correlated with the limbic system, including the insula. FA values in the left anterior cingulate cortex (ACC) significantly correlated with changes in the BOLD signal in the right superior temporal gyrus (STG), and FA values in the right ACC significantly correlated with PANSS scores. This is the first study to examine MMN using simultaneous fMRI, EEG, and DTI recording in patients with schizophrenia to investigate the potential implications of abnormalities in the ACC and limbic system, including the insula and parahippocampal gyrus, as well as the STG. Structural changes in the ACC during schizophrenia may represent part of the neural basis for the observed MMN deficits. The deficits seen in the feedback/feedforward connections between the prefrontal cortex and STG modulated by the ACC and insula may specifically contribute to impaired MMN generation and clinical manifestations.
Functional magnetic resonance imaging (fMRI) and electroencephalogram (EEG) imaging have complementary spatiotemporal resolution limitations and can be powerful methods when used together to understand brain function. However, functional connectivity analyses using fMRI and EEG require anatomical model-based hypotheses. Diffusion tensor imaging (DTI) measures the diffusion direction of water molecules, allowing the visualization of axonal projections in the white matter and fiber connectivity. Adding DTI to simultaneous magnetic resonance imaging (MRI) and EEG recordings enables both functional and anatomical modeling, with each neuroimaging procedure used to maximum advantage.
The left STG was activated by the omission deviant in the controls in accordance with previous reports identifying the MMN generator in that locus [1, 9, 14, 15, 57]. Patients with schizophrenia exhibited reduced BOLD activity in the left MTG relative to controls, which is also in line with previous reports of attenuated MMN in schizophrenia [8, 58–62]. The significant correlation between BOLD activity in the right STG and MMN amplitudes suggests that the phenomenon seen on fMRI may be a counterpart to the MMN component recorded on the EEG.
This is the first study to examine MMN using simultaneous fMRI, EEG, and DTI recording in patients with schizophrenia to determine the implications of abnormalities in the ACC, STG, and limbic system, including the insula and parahippocampal gyrus, and understand their dysfunctions as reflected by MMN. The ACC structural changes occurring in schizophrenia may be part of the neural basis underlying MMN deficits, and deficits in the feedback/feed-forward connection between the prefrontal cortex and STG modulated by the ACC and insula may specifically contribute to impaired MMN generation and clinical manifestations.