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BACKGROUND: Altered gamma-band connectivity has been shown across all stages of schizophrenia (SZ) and for persons at High Risk for Psychosis (HRP). Oscillations in the gamma-band frequency range are suggested to play a crucial role for both local and long-range synchronization within the brain during perceptual and cognitive processes. Structural connectivity in the brain is provided by white matter (WM) tracts connecting these areas. Reduced WM integrity is also a feature of SZ that has often been described. The aim of this study is to investigate the relationship between altered gamma-band connectivity and WM structural connectivity in Clinical High Risk for Psychosis (HRP) patients using Electroencephalography (EEG) and Diffusion Tensor Imaging (DTI) to achieve a better understanding of which factors could predict a transition to SZ considering functional and structural connectivity. The identification of those biomarkers would be a further step toward understanding the causes of SZ and could contribute to a more individualized and targeted therapy to achieve a better outcome in patients. METHODS: The study includes a total of 26 HRP patients, 7 converted to schizophrenia after one year (HRP-C) and 13 healthy controls (HC). High density EEG (64 channels) was recorded during the performance of a cognitively demanding auditory choice reaction task. Source estimation and analysis of the functional gamma-band connectivity was done using eLORETA. We defined Regions of Interest (ROIs) that were known to be generators of the auditory evoked Gamma-Band Response (aeGBR) from a previous combined EEG-fMRI study of this population – the dorsal anterior cingulate cortex (dACC) and the bilateral auditory cortices. MRI data acquisition was done with a 3T Siemens scanner (Trio). We generated whole-brain 2-Tensor-Tractography for all subjects in order to analyze the integrity of the underlying WM fiber bundles implicated in this functional network, namely the Cingulum Bundle (CB), the Medial Longitudinal Fasciculus (MdLF), the Arcuate Fasciculus (AF) and the Extreme Capsule (EC).The primary outcome measure is the fractional anisotropy of the tissue (FAt), which is corrected for free water (FW) in the brain. RESULTS: Our preliminary results show a lower aeGBR in HRP-C patients compared to HC with the HRP-NC at an intermediate level. We found longer reaction times for HRP compared to HC. The study is presently on-going. Based on previous work in this sample, we hypothesize that the CB, MdLF, AF and EC of the HRP-C will exhibit decreased FAt and increased FW compared to HC. DISCUSSION: The combination of EEG with its high temporal resolution and DTI with its high spatial resolution allows for detailed insight into the possible disturbances in HRP patients compared to HC. Alterations in both modalities have been shown before, however, in this study we aim to link functional connectivity alterations in the previously described networks to their structural correlate to achieve a better insight into their interaction. Taken together, the quantification of those possible biomarkers might help to detect a transition to SZ earlier and thus allow an early intervention.

Background: Schizophrenia has long been suggested to represent a disorder with prominent neural dysconnectivity. Gamma-band oscillations are highly relevant in this context, due both to their proposed involvement in neuronal synchronization and to their association with neurotransmitter systems relevant for schizophrenia. Several task-related studies have confirmed reduced power and synchronization of gamma-band oscillations in schizophrenia, but it has been suggested that these findings might not apply to the resting state. The present study aimed to investigate resting-state gamma-band connectivity in patients with schizophrenia. Methods: Sixty-four channel resting-state electroencephalography (eyes closed) was recorded in 22 patients with first-episode schizophrenia and 22 healthy controls matched for age and gender. Orthogonalized power envelope correlation was used as a measure of connectivity across 80 cortical regions at 40 Hz. Mean connectivity at each region was compared across groups using the nonparametric randomization approach. Additionally, the network-based statistic was applied to identify affected networks in patients. Results: Patients displayed increased mean functional gamma-band connectivity compared to controls in the left rolandic operculum. Network-based analyses indicated increased connectivity in patients within a strongly lateralized network consisting mainly of left inferior frontal/orbitofrontal, lateral and medial temporal, and inferior parietal areas. Within this network, gamma-band connectivity was higher in patients with low positive and disorganization symptom levels. Conclusions: The present study provides a link between resting-state gamma-band connectivity and the core symptoms of schizophrenia. The observed findings are different than those reported by task-related studies, suggesting that resting-state studies might reveal new aspects in the pathophysiology of schizophrenia.

Objectives. Abnormalities of oscillatory gamma activity are supposed to reflect a core pathophysiological mechanism underlying cognitive disturbances in schizophrenia. The auditory evoked gamma-band response (aeGBR) is known to be reduced across all stages of the disease. The present study aimed to elucidate alterations of an aeGBR-specific network mediated by gamma oscillations in the high-risk state of psychosis (HRP) by means of functional magnetic resonance imaging (fMRI) informed by electroencephalography (EEG). Methods. EEG and fMRI were simultaneously recorded from 27 HRP individuals and 26 healthy controls (HC) during performance of a cognitively demanding auditory reaction task. We used single trial coupling of the aeGBR with the corresponding blood oxygen level depending response (EEG-informed fMRI). Results. A gamma-band–specific network was significantly lower active in HRP subjects compared with HC (random effects analysis, P < .01, Bonferroni-corrected for multiple comparisons) accompanied by a worse task performance. This network involved the bilateral auditory cortices, the thalamus and frontal brain regions including the anterior cingulate cortex, as well as the bilateral dorsolateral prefrontal cortex. Conclusions. For the first time we report a reduced activation of an aeGBR-specific network in HRP subjects brought forward by EEG-informed fMRI. Because the HRP reflects the clinical risk for conversion to psychotic disorders including schizophrenia and the aeGBR has repeatedly been shown to be altered in patients with schizophrenia the results of our study point towards a potential applicability of aeGBR disturbances as a marker for the prediction of transition of HRP subjects to schizophrenia.