Abstract
We combined magnetoencephalography (MEG), 7 T proton magnetic resonance spectroscopy (MRS), and 7 T fMRI during performance of a task in a group of 23 first episode psychosis (FEP) patients and 26 matched healthy controls (HC). We recorded both the auditory evoked response to 40 Hz tone clicks and the resting state in MEG. Neurometabolite levels were obtained from the anterior cingulate cortex (ACC). The fMRI BOLD response was obtained during the Stroop inhibitory control task. FEP showed a significant increase in resting state low frequency theta activity (p < 0.05; Cohen d = 0.69), but no significant difference in the 40 Hz auditory evoked response compared to HC. An across-groups whole brain analysis of the fMRI BOLD response identified eight regions that were significantly activated during task performance (p < 0.01, FDR-corrected); the mean signal extracted from those regions was significantly different between the groups (p = 0.0006; d = 1.19). In the combined FEP and HC group, there was a significant correlation between the BOLD signal during task performance and MEG resting state low frequency activity (p < 0.05). In FEP, we report significant alteration in resting state low frequency MEG activity, but no alterations in auditory evoked gamma band response, suggesting that the former is a more robust biomarker of early psychosis. There were no correlations between gamma oscillations and GABA levels in either HC or FEP. Finally, in this study, each of the three imaging modalities differentiated FEP from HC; fMRI with good and MEG and MRS with moderate effect size.
Highlights
Schizophrenia is associated with impairments in cognitive control, a neuropsychological process thought to contribute to a wide range of cognitive deficits in schizophrenia[1]
Studies have revealed abnormal GABA measurements in schizophrenia[32,33]. These findings raise the question whether, in schizophrenia, abnormal gamma oscillations are related to altered GABA levels
In a small combined EEG/magnetic resonance spectroscopy (MRS) study, a significant correlation was observed between gamma oscillation and dorsolateral prefrontal cortex (PFC) GABA levels in the combined group of patients with schizophrenia and controls, both at rest and across working memory stages[34]
Summary
Schizophrenia is associated with impairments in cognitive control, a neuropsychological process thought to contribute to a wide range of cognitive deficits in schizophrenia[1]. Using diverse brain imaging techniques on the same subject population might be especially valuable in the study of schizophrenia. Both functional MRI (fMRI) and magnetoencephalography (MEG) allow the measurement of brain function; these are complementary modalities that, respectively, provide high spatial and temporal resolution. Low frequency oscillations are thought to support synchronization between distant brain regions[6,7]. This is important as functional connectivity between remote brain regions measured with fMRI has been shown to be altered in schizophrenia[8]
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