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Is curvature a biomarker for major depressive disorder? A morphological study using 7T MRI1Staten Island Technical High School, New York, NY, United States, 2Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States, 3Biomedical Engineering and Imaging Institute, Icahn School of Medicine at Mount Sinai, New York, NY, United States, 4Diagnostic, Molecular and Interventional Radiology, Icahn School of Medicine at Mount Sinai, New York, NY, United States
Synopsis
Numerous studies have analyzed morphological measurements to better understand how depression alters the brain, but few studies have explored curvature as a potential biomarker. By analyzing data from 7T MRI scans, we aimed to determine whether curvature measurements can differentiate between MDD patients and controls. We performed generalized linear models to analyze the relationship between participants’ status and measurements for intrinsic curvature index, Gaussian curvature, mean curvature, and folding index in thirty-four brain regions. Six regions showed significantly higher measures of curvature in MDD patients: the inferior temporal, pars triangularis, supramarginal, lateral orbitofrontal, isthmus cingulate, and entorhinal.
Introduction
Major depressive disorder (MDD) is a chronic psychiatric disorder ranked by the World Health Organization as one of the leading causes of disability worldwide1. Numerous studies have analyzed brain morphological measures such as volume and cortical thickness in an effort to identify biomarkers and improve understanding of the neurobiological mechanisms of depression2-5. Curvature, measured at the centimeter and millimeter scales, is a metric that quantifies the folds and intrinsic curvature shapes created during the expansion of the cortical surface6. It can be a sensitive biomarker because it is small-scale, less affected by confounding variables, such as normalization to other brain regions, and can detect subtle changes in brain connectivity6-8. However, few studies include curvature in their analysis9-14, 15, and to our knowledge, only three found significant curvature differences in MDD16, 17, 5. However, most of these studies used 1.5T and 3T MRI scanners. Ultra-high field 7T MRI offers improved spatial resolution, enabling more accurate measurement of mean curvature and better differentiations between subtle morphological features relevant to MDD18, 19. By analyzing data from 7T MRI scans, we aim to determine whether curvature measurements can be a significant differentiator between MDD patients and healthy controls.Materials & Methods
Forty-two patients diagnosed with major depressive disorder by a practicing psychiatrist, and forty-six healthy controls were scanned using a Siemens 7T whole-body scanner (Siemens Healthineers, Erlangen, Germany) and Nova 1-channel transmit, 32-channel receive head coil (Nova Medical, Wilimington, MA). T1-weighted magnetization prepared rapid gradient echo (MPRAGE) was acquired with the following parameters: TE/TR = 1.95/3000ms, TI = 1050ms, FOV = 225x183mm, 320x260x224 voxels, 0.7x0.7x0.7 mm3 isotropic resolution, 7 minutes scan time with GRAPPA 2 acceleration factor. Imaging data was automatically segmented using the FreeSurfer 6.0 algorithm. All subject recruitment and scanning was performed with approval of the local institutional review board, all data were de-identified to comply with HIPPA guidelines for protected health information.We performed generalized linear models to analyze the relationship between participants’ status as MDD patients or controls and the measurements for intrinsic curvature index, Gaussian curvature, mean curvature, and folding index in the left and right hemispheres of thirty-four cortical regions of the brain. Age and gender covariation was performed for the analysis using the R statistical software. Some statistical analysis, data analysis and data visualization was performed in Matlab (The Mathworks, Natick, MA).
Results
Figure 1 shows each of the brain regions for which significant differences were found in a curvature metric between patients and controls. Six regions showed significantly higher measures of curvature in MDD patients at the p<.05 level. The inferior temporal, pars triangularis, and supramarginal gyrus each showed higher values for Gaussian curvature, mean curvature, and intrinsic curvature index. The lateral orbitofrontal region, isthmus cingulate, and entorhinal were each significant for one measure of curvature. Figure 2 shows a violin plot showing the intrinsic curvature in the left inferior temporal lobe, showing significant difference between patients and controls, as well as greater variation among the patient cohort. Greater variation in curvature was observed in general for MDD patients compared to controls. Figure 3 shows a volumetric map of the cortex. Brain regions in which between-group differences were observed among the Gaussian curvature measure are highlighted in red.Discussion
We speculate that these regions showed significant curvature differences between MDD patients and HC because of their relevant associations with depression. When the inferior temporal, the pars triangularis, and the lateral orbitofrontal are impaired, MDD patients are less likely to respond to happy facial expressions, more likely to frown, and more likely to use language connected to negative self-thinking and low self-esteem20-22. Changes in the isthmus cingulate are related to difficulties in handling emotional memories23. The supramarginal gyrus is activated during periods of lucid dreaming, nightmares, and recurring visions24, 25. Lastly, the entorhinal cortex may be linked to rumination, a major symptom of MDD26.Conclusion
This study represents a preliminary analysis on a cohort of 88 total subjects, and identifies brain regions which may be of interest in future studies with larger cohort size, and therefore greater statistical power. In this study, curvature measurements identified six regions that may be linked to depression symptoms. These results show that curvature has the potential to differentiate MDD patients from healthy individuals. Even so, they provide stronger evidence that analyzing curvature can expand our knowledge of depression and how it alters the brain. Future studies can explore how curvature changes in these regions affect their functions and study the relationship between curvature and other morphological measures in MDD.Acknowledgements
Mariella Reynoso and Tara Lago jointly contributed to this work and are co-first authors.
The authors would like to acknowledge funding from NIH R01 MH109544.
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