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Related Experiment Video

Updated: Dec 24, 2025

Sex Differences in Mouse Hippocampal Astrocytes after In-Vitro Ischemia
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Region-specific sex differences in the hippocampus.

Liza van Eijk1, Narelle K Hansell2, Lachlan T Strike2

  • 1Child Health Research Centre, Faculty of Medicine, University of Queensland, Brisbane, Australia; The Australian e-Health Research Centre, CSIRO, Brisbane, Australia.

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|April 13, 2020
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Summary

Males have larger hippocampal volumes in specific subfields like the parasubiculum and fimbria compared to females, independent of total hippocampal volume. These sex differences in brain structure may impact neuropsychiatric disorders.

Keywords:
Controlling methodsGenderHippocampal subfieldsHippocampusSexVolume

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Area of Science:

  • Neuroscience
  • Human Anatomy
  • Brain Imaging

Background:

  • The hippocampus is crucial for memory and learning, with known sex differences in neuropsychiatric disorders.
  • Previous studies show inconsistent sex differences in hippocampal volume, especially after adjusting for brain size.
  • Limited research exists on sex differences within specific hippocampal subfields and the impact of adjustment methods.

Purpose of the Study:

  • To investigate sex differences in 12 hippocampal subfield volumes across two independent cohorts.
  • To determine if sex differences persist after adjusting for total hippocampal volume (HPV) or brain segmentation volume (BSV).
  • To compare the efficacy of different statistical methods for controlling confounding variables in sex difference analyses.

Main Methods:

  • Utilized data from the Queensland Twin IMaging study (QTIM) and the Human Connectome Project (HCP).
  • Extracted volumes of 12 hippocampal subfields using FreeSurfer 6.0.
  • Applied four statistical methods (allometric, covariate, residual, matching) to adjust for HPV or BSV and analyzed sex differences using hierarchical general linear models.

Main Results:

  • Males exhibited larger volumes than females in the parasubiculum and fimbria, even after adjusting for HPV.
  • Sex differences were observed in the hippocampal fissure, presubiculum, and hippocampal tail in the HCP cohort and combined sample.
  • No significant sex differences were found in cornu ammonis (CA)2/3, CA4, Hippocampus-Amygdala Transition Area (HATA), or the granule cell layer of the dentate gyrus (GCDG).

Conclusions:

  • Regionally specific sex differences exist in hippocampal subfields, particularly the fimbria and parasubiculum, independent of total hippocampal volume.
  • Adjusting for total hippocampal volume (HPV) appears more robust for detecting sex differences than adjusting for overall brain size (BSV).
  • Understanding these subfield sex differences is vital for research into sex-specific behaviors and neuropsychiatric disorders.