Altered functional connectivity between sub-regions in the thalamus and cortex in schizophrenia patients measured by resting state BOLD fMRI at 7T

Abstract

The thalamus is a small brain structure that relays neuronal signals between subcortical and cortical regions. Abnormal thalamocortical connectivity in schizophrenia has been reported in previous studies using blood-oxygenation-level-dependent (BOLD) functional MRI (fMRI) performed at 3T. However, anatomically the thalamus is not a single entity, but is subdivided into multiple distinct nuclei with different connections to various cortical regions. We sought to determine the potential benefit of using the enhanced sensitivity of BOLD fMRI at ultra-high magnetic field (7T) in exploring thalamo-cortical connectivity in schizophrenia based on subregions in the thalamus. Seeds placed in thalamic subregions of 14 patients and 14 matched controls were used to calculate whole-brain functional connectivity. Our results demonstrate impaired thalamic connectivity to the prefrontal cortex and the cerebellum, but enhanced thalamic connectivity to the motor/sensory cortex in schizophrenia. This altered functional connectivity significantly correlated with disease duration in the patients. Remarkably, comparable effect sizes observed in previous 3T studies were detected in the current 7T study with a heterogeneous and much smaller cohort, providing evidence that ultra-high field fMRI may be a powerful tool for measuring functional connectivity abnormalities in schizophrenia. Further investigation with a larger cohort is merited to validate the current findings.

Keywords: Biomarker; High field; Imaging; Psychosis; Thalamus.

Figure 1.

Oxford thalamic connectivity atlas. The thalamus is segmented into seven sub-regions based on white matter diffusion tractography. Each sub-region has a primary connection to a cortical area as listed in the Figure.

Figure 2.

Map of thalamic functional connectivity changes between schizophrenia patients and control subjects overlaid on MNI normalized anatomical images. Only voxels that show significant difference between the two groups are highlighted (red: schizophrenia > control; blue: schizophrenia < control). Significant results from all sub-thalamic seed regions in Tables 2 and 3 are shown on the same figure.

Figure 3.

Correlations analysis. Scatter plots showing correlations between the disease duration in schizophrenia patients, and the thalamic functional connectivity to the sensory/motor cortex (a) and the prefrontal cortex (b), respectively. R²: adjusted R² from linear regression. Age, smoking status and medication dosage were included as covariates in the correlation analysis. All sub-thalamic regions that showed significant difference in functional connectivity with the sensory/motor or the prefrontal cortex in the group comparisons were combined in the correlation analysis.

Figure 4.

Correlation between thalamic functional connectivity to the sensory/motor cortex and the prefrontal cortex. R²: adjusted R² from linear regression. All sub-thalamic regions that showed significant difference in functional connectivity with the sensory/motor or the prefrontal cortex in the group comparisons were combined in the correlation analysis.