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Updated: Jul 20, 2026
High-resolution In Vivo Manual Segmentation Protocol for Human Hippocampal Subfields Using 3T Magnetic Resonance Imaging
Published on: November 10, 2015
Hippocampal atrophy confounds template-based functional MR imaging measures of hippocampal activation in patients
C K Sandstrom1, S Krishnan, M J Slavin
1Department of Radiology, Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC, USA.
Background And Purpose:
Functional MR imaging has been used to study patterns of hippocampal activation that distinguish pathologic from normal memory loss in the elderly population. Our objective was to assess whether hippocampal atrophy confounds measurements of hippocampal activation in subjects with mild cognitive impairment (MCI).
Methods:
Twenty subjects with MCI and 20 elderly control subjects with objectively normal memory were studied at 4T during a face-name paradigm designed to activate the hippocampus. Hippocampal activation was measured using 2 separate approaches: applying a preset region of interest (ROI) in standardized template space and applying a manually drawn ROI in native subject space. Pearson correlation coefficients were calculated to compare group-dependent relationships between hippocampal volume and activation. Analysis of covariance (ANCOVA) was performed to assess group differences in hippocampal activation during encoding and retrieval. Age and hippocampal volume were included as covariates, as was a term for the interaction between hippocampal volume and group.
Results:
When hippocampal activation was measured by the template-based method, the correlation coefficient in the right hippocampus of subjects with MCI but not control subjects during retrieval differed significantly from zero. There was a significant (P < .05) group-by-volume interaction in the ANCOVA model. No significant correlations or interactions were demonstrated when activation was measured in native subject space with manually drawn ROIs.
Conclusion:
Our findings suggest a potential confounding relationship between hippocampal volume and activation for subjects with MCI in template-based analyses. Template-based measures of hippocampal activation that do not adequately account for hippocampal atrophy should be used with caution in patients with MCI.
Insights
Hippocampal atrophy may confound functional MRI activation measurements in mild cognitive impairment (MCI) when using template-based methods. Researchers recommend caution with these template-based analyses in MCI patients.
Area of Science:
- Neuroimaging
- Cognitive Neuroscience
- Gerontology
Background:
- Functional magnetic resonance imaging (fMRI) is used to study hippocampal activation patterns differentiating pathological from normal memory loss in the elderly.
- Hippocampal atrophy, a common feature in aging and neurodegenerative diseases, may influence fMRI activation measurements.
Purpose of the Study:
- To assess whether hippocampal atrophy confounds hippocampal activation measurements in individuals with mild cognitive impairment (MCI).
- To investigate the impact of hippocampal volume on activation patterns during memory tasks in MCI patients compared to healthy controls.
Main Methods:
- fMRI at 4T was used during a face-name association task in 20 MCI subjects and 20 elderly controls.
- Hippocampal activation was measured using both template-based regions of interest (ROIs) and manually drawn ROIs in native space.
- Analysis of covariance (ANCOVA) examined group differences in activation, with age and hippocampal volume as covariates.
Main Results:
- Template-based analysis revealed a significant correlation between hippocampal volume and activation in MCI subjects during retrieval, but not in controls.
- A significant group-by-volume interaction was observed in the ANCOVA model for template-based measures (P < .05).
- No significant correlations or interactions were found when using manually drawn ROIs in native subject space.
Conclusions:
- Hippocampal volume and activation show a potential confounding relationship in MCI subjects when using template-based fMRI analyses.
- Template-based hippocampal activation measures that do not account for atrophy may yield inaccurate results in MCI patients.
- Manual ROI analysis in native space may provide more reliable activation estimates in the presence of hippocampal atrophy.
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