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

Affiliations

¹ The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA. Electronic address: jhua@mri.jhu.edu.
² Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
³ F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
⁴ The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
⁵ Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York, USA; Department of Psychiatry, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA.
⁶ Department of Psychiatry and Behavioral Sciences and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁷ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Department of Psychiatry and Behavioral Sciences and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁹ Department of Psychiatry and Behavioral Sciences and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 30409697
PMCID: PMC6500777
DOI: 10.1016/j.schres.2018.10.016

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

Jun Hua et al. Schizophr Res. 2019 Apr.

. 2019 Apr:206:370-377.

doi: 10.1016/j.schres.2018.10.016. Epub 2018 Nov 6.

Authors

Affiliations

¹ The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA. Electronic address: jhua@mri.jhu.edu.
² Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, USA.
³ F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
⁴ The Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research, The Johns Hopkins University School of Medicine, Baltimore, MD, USA; F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD, USA.
⁵ Center for Psychiatric Neuroscience, Feinstein Institute for Medical Research, Manhasset, New York, USA; Department of Psychiatry, Zucker School of Medicine at Hofstra/Northwell, Hempstead, New York, USA.
⁶ Department of Psychiatry and Behavioral Sciences and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁷ Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Department of Psychiatry and Behavioral Sciences and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience and Pharmacology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁹ Department of Psychiatry and Behavioral Sciences and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

PMID: 30409697
PMCID: PMC6500777
DOI: 10.1016/j.schres.2018.10.016

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.

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Conflict of interest statement

Conflict of interest

Equipment used in the study was manufactured by Philips. Peter C.M. van Zijl receives grant support from Philips, is a paid lecturer for Philips, and is the inventor of technology that is licensed to Philips. This arrangement has been approved by Johns Hopkins in accordance with its conflict of interest policies.

Figures

**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.

See this image and copyright information in PMC

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

Affiliations

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

Authors

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Conflict of interest statement

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