Sex differences in volume and structural covariance of the anterior and posterior hippocampus

Sex differences in episodic and spatial memory are frequently observed, suggesting that there may be sex-related structural differences in the hippocampus (HC). Earlier findings are inconsistent, possibly due to a known variability along the hippocampal longitudinal axis. Here, we assessed potential sex differences in hippocampal volume and structural covariance with the rest of the brain in young men and women (N=76), considering the anterior (aHC) and posterior (pHC) hippocampus separately. Women exhibited a larger pHC than men adjusted for brain size. Using partial least squares, we identified two significant patterns of structural covariance of the aHC and pHC. The first included brain areas that covaried positively and negatively in volume with both the aHC and pHC in men, but showed greater covariance with the aHC than pHC in women. The second pattern revealed distinct structural covariance of the aHC and pHC that showed a clear difference between men and women: in men the pHC showed reliable structural covariance with the medial and lateral parietal lobes and the prefrontal cortex, whereas in women the aHC showed reliable structural covariance with the anterior temporal lobe bilaterally. This pattern converges with resting state functional connectivity of the aHC and pHC and suggests that these hippocampal sections interact with different brain regions, consistent with a division of labor with regards to episodic and spatial memory. Our findings lend support to a division of the HC into an anterior and posterior part and identify sex as a potential moderating factor when investigating hippocampal structure and connectivity.