Introduction

Conventional structural neuroimaging methods can identify changes in cortical thickness but cannot relate these changes to specific cortical layers due to a lack of sensitivity. However, several indirect measures sensitive to changes specifically occurring in supragranular cortical layers were developed recently (github.com/kwagstyl/schizophrenia_gyral_sulcal).

Objectives

The aim was to assess the ability of these novel measures to detect cortical layers thickness characteristics potentially associated with risk or resilience to developing schizophrenia.

Methods

43 first-episode schizophrenia (FES) male patients, 29 non-converted individuals at ultra-high risk of psychosis (ncUHR, mean follow-up period – 6.5 years), and 43 matched healthy controls (HC) underwent structural MRI at 3T Philips scanner. Images were processed via FreeSurfer and MATLAB to derive two markers specific to supragranular thickness change: gyral-sulcal thickness differences (GSTD) and gyral-sulcal intrinsic curvature differences on pial surface (GSCD).

Results

GSCD measures were increased in temporal, parietal and occipital cortices, whereas both GSTD and GSCD were increased in the right frontal cortex in FES compared to HC. No GSTD or GSCD were changed in ncUHR compared to HC, and GSCD was decreased in the frontal cortex compared to FES.

Conclusions

Our findings from the indirect measures indicate a potential predominance of supragranular thinning in FES and suggest that a supragranular thinning in the right frontal lobe might be associated with precipitating risk and/or illness effects of schizophrenia. At the same time, no clear supragranular markers directly associated with resilience or risk mechanisms were identified.

The work was supported by RFBR grant 20-013-00748.

Introduction

Schizophrenia patients with auditory verbal hallucinations (AVH) demonstrate impaired functional connectivity (FC) between brain regions, involved in executive functions and language. However, as most studies compare patients to healthy controls, the specificity of these findings either for schizophrenia in general or for AVH is unclear.

Objectives

We aimed to compare whole-brain resting-state FC of main language brain regions between schizophrenia patients with and without history of AVH and healthy controls.

Methods

Schizophrenia male patients with (n=31; mean age 29,8±11,6) or without history of AVH (n=16; 29±12,4) and 39 healthy male controls (30±8,9) underwent resting-state fMRI on 3T Philips scanner. No between-group differences in age, illness duration, and severity of clinical symptoms except AVH were revealed. Regions of interest (ROIs) were taken from the independent fMRI study with conventional language localizer and included left inferior frontal gyrus (l_IFG) and superior temporal gyri (STG) bilaterally. Whole-brain FC of each ROI was compared between groups (ANCOVA; p<.005 voxelwise; p(FDR)<.017 clusterwise, corrected for number of ROIs) with post hoc tests.

Results

Decreased FC between each STG (left and right) and anterior cingulate cortex (ACC) was revealed in all patients, compared to healthy controls. Patients with history of AVH, compared to other groups, showed decreased FC between l_IFG and ACC.

Conclusions

Disrupted fronto-temporal FC is non-specific for AVH and characterizes all schizophrenia patients. Patients with history of AVH have impaired FC between the l_IFG, underlying language production, and ACC, involved in differentiation between language production and comprehension.

The study was supported by RFBR grant 18-013-01214.

Introduction

Machine learning has increasingly been applied to classification of psychosis spectrum in neuroimaging research. However, a number of multimodal studies using MRI and electroencephalography (EEG) is quite limited.

Objectives

To assess the power of multimodal structural MRI (sMRI) and EEG data to provide pairwise discrimination between first-episode schizophrenia (FES) patients, individuals at ultra-high-risk of psychosis (UHR), and healthy controls (HC) using machine learning algorithms.

Methods

46 FES male patients, 39 UHR individuals, and 54 matched HC underwent sMRI (3T Philips scanner) and electroencephalography. T1-weighted images were processed via FreeSurfer to obtain cortical and subcortical measures. L2 regularized logistic regression was used to evaluate the efficacy of diagnostic prediction.

Results

The accuracies of pairwise discriminations were: 87% for FES vs HC (specificity 83%, sensitivity 91%); 77% for FES vs UHR (specificity 76%, sensitivity 79%); 75% for UHR vs HC (specificity 77%, sensitivity 73%).

Conclusions

Current findings suggest that the patterns of anatomical and functional variability have potential as biomarkers for discrimination between schizophrenia, UHR, and healthy subjects. Furthermore, results show that the selection and multimodality of feature types are important. Specifically, adding EEG data to morphometric measures improved accuracy rates in FES vs HC and FES vs UHR contrasts, whereas standalone EEG data provided higher accuracy compared with morphometric or multimodal data in UHR vs HC discrimination. Expectedly, predictive power for the UHR was smaller than for the FES due to its intermediate anatomical features, located between those observed in healthy controls and those found in patients.

The work was supported by RFBR grant 20-013-00748

Introduction

Schizophrenia patients with auditory verbal hallucinations (AVH) demonstrate impaired functional connectivity (FC) between brain regions, involved in executive functions and language. However, as most studies compare patients to healthy controls, the specificity of these findings either for schizophrenia in general or for AVH is unclear.

Objectives

We aimed to compare whole-brain resting-state FC of main language brain regions between schizophrenia patients with and without history of AVH and healthy controls.

Methods

Schizophrenia male patients with (n=31; mean age 29,8±11,6) or without history of AVH (n=16; 29±12,4) and 39 healthy male controls (30±8,9) underwent resting-state fMRI on 3T Philips scanner. No between-group differences in age, illness duration, and severity of clinical symptoms except AVH were revealed. Regions of interest (ROIs) were taken from the independent fMRI study with conventional language localizer and included left inferior frontal gyrus (l_IFG) and superior temporal gyri (STG) bilaterally. Whole-brain FC of each ROI was compared between groups (ANCOVA; p<.005 voxelwise; p(FDR)<.017 clusterwise, corrected for number of ROIs) with post hoc tests.

Results

Decreased FC between each STG (left and right) and anterior cingulate cortex (ACC) was revealed in all patients, compared to healthy controls. Patients with history of AVH, compared to other groups, showed decreased FC between l_IFG and ACC.

Conclusions

Disrupted fronto-temporal FC is non-specific for AVH and characterizes all schizophrenia patients. Patients with history of AVH have impaired FC between the l_IFG, underlying language production, and ACC, involved in differentiation between language production and comprehension.

The study was supported by RFBR grant 18-013-01214.

Introduction

Studies examining gamma-aminobutyric acid (GABA) or glutamate in ultra-high risk for psychosis (UHR) have shown conflicting results, and a number of multimodal studies examining associations between metabolite and structural characteristics is very limited.

Objectives

We aimed to investigate potential associations between GABA and glutamate levels and cortical thickness in the frontal lobe in UHR individuals and healthy controls (HC).

Methods

20 male UHR individuals and 19 healthy controls (HC) underwent structural MRI and MR spectroscopy at 3T Philips scanner. T1-weighted images were processed via FreeSurfer 6.0 to quantify cortical thickness for selected frontal regions labeled according to Desikan atlas. MEGA-PRESS acquisitions were analyzed with jMRUi (ver. 5.1 Alpha), levels of GABA and glutamate were calculated as ratios to creatine + phosphocreatine.

Results

The study revealed: 1) GABA/Cr ratios reduction in the left frontal lobe (p=0.001) which was not attributable to antipsychotic medication; 2) cortical thickness reductions in the left pars orbitalis (p=0.005) (the anterior part of the inferior frontal gyrus) in the UHR individuals compared to HC. No significant correlations between GABA/Cr ratios and cortical thickness were identified in both groups.

Conclusions

The findings indicate that the UHR state is associated with altered GABA levels and cortical thickness reductions in the prefrontal cortex. The results also show that GABA levels are not directly related to cortical abnormalities, suggesting that altered metabolite levels may be associated with a complex system of structural and functional impairments, rather than directly correlating with structural changes in separate cortical regions.

The work was supported by RFBR grant 19-29-10040.