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. 2022 Aug 11;14:923673. doi: 10.3389/fnagi.2022.923673

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Copyright © 2022 Liu, Zhu, Sun, Zhang, Feng, Gjerswold-Selleck, Sikka, Zhu, Liu, Nuriel, Wei, Wu, Vaughan, Laine, Provenzano, Small and Guo.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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DeepContrast maps differential anatomical patterns of dysfunction in the hippocampal formation. (A) A three-dimensional rendering of the bilateral hippocampal formation (left panel) consisting of the hippocampus (HC) and the entorhinal cortex (EC) and axial, sagittal, and coronal slices from a group-wise T1-weighted MRI template cutting through the hippocampal formation (right three panels). The hippocampal formation is displayed along the anterior-to-posterior axis. (B) A voxel-based analysis of the synthesized CBV maps of 177 individuals ranging from 20 to 72 years of age reveals that the greatest age-related decline occurred in the body of the hippocampal circuit (color-coded by the degree of significance). (C) A coronal slice, onto which the hippocampal formation mask is applied, reveals that age-related decline primarily localizes to the dentate gyrus. The voxel-based analysis is conducted using a multiple regression model in SPM12 using sex as a covariate and age as the regressor, and the age-related differences are contrasted using Student's t test. Multiple comparisons are corrected for, yielding voxel-wise p < 0.005 and cluster-wise p < 0.05 (refer to methods). (D) A scatter plot shows the association between age and mean synthesized CBV values in the dentate gyrus after the removal of gender effects (β_age = −6.36e-4, t_age = −4.64, p_age = 6.85e-6). The shaded area surrounding the regression line indicates the 95% CI. (E) A voxel-based analysis of the synthesized CBV maps of 50 Alzheimer's disease (AD) patients compared with 50 age-matched normal controls, each with two back-to-back scans, reveals AD-related reduction in the entorhinal cortex (color-coded by the degree of significance). (F) A coronal slice, onto which the hippocampal formation mask is applied, reveals that AD-related decline localizes primarily to the transentorhinal cortex. The voxel-based analysis is conducted using a multiple regression model in SPM12 using age, sex, and participant identity as covariates and diagnostic class (i.e., cognitive normal vs. dementia) as the regressor and the AD-related difference are contrasted using Student's t-test. Multiple comparisons are corrected for, yielding voxel-wise p < 0.005 and cluster-wise p < 0.05 (refer to methods). (G) A box plot showing individual-participant mean synthesized CBV values in the right transentorhinal cortex indicates a significant difference between patients with Alzheimer's disease and healthy controls (two sample t-test one-tailed p = 0.031). Center line: median; box limits: upper and lower quartiles; whiskers: 1.5× interquartile range; points: outliers. HC: hippocampus; EC: entorhinal cortex; DG: dentate gyrus; CA3: cornu Ammonis 3; CA1: cornu Ammonis 1; Sub: subiculum; Prs: presubiculum; PaS: parasubiculum.