Sex differences in hippocampal connectivity during spatial long-term memory.

Sex differences in brain activity have been reported across various types of long-term memory. To our knowledge, sex differences in functional connectivity during long-term memory have not been investigated. A previous study on the structural connectome identified that female brains have a greater degree of interhemispheric connectivity than males, whereas males have a greater degree of intrahemispheric connectivity than females. The aim of the current investigation was twofold: (a) identify which brain regions were functionally connected to the hippocampus during spatial long-term memory, and (b) determine if there were sex differences in the functionally connected regions. During the study phase, abstract shapes were presented to the left or right of fixation. During the test phase, abstract shapes were presented at fixation and participants classified each item as previously on the "left" or "right". A hippocampal region of interest (ROI) was identified by contrasting spatial memory hits and misses. The peak coordinate from this ROI was used to define the center of a sphere that was used as the seed for the functional connectivity analysis. The connectivity analysis produced many connected activations including the medial posterior frontal cortex, lateral posterior frontal cortex, left inferior frontal gyrus, posterior cingulate cortex, and caudate/putamen. Although there were no regions with greater connectivity in females than males, the male versus female comparison produced connected activations in the medial posterior frontal cortex, anterior prefrontal cortex, precuneus, and cingulate sulcus. Females also had greater interhemispheric connectivity than males. The current findings suggest collapsing across sex in cognitive neuroscience studies may not be warranted.