Intrinsic functional connectivity of the human medial temporal lobe suggests a distinction between adjacent MTL cortices and hippocampus.

Functional connectivity analyses can offer insights into mechanisms of the brain that might not be revealed by traditional fMRI. These analyses compare seed voxels' activity over time to the activity of other voxels over time and identify correlations between regions. This study is the first to perform functional connectivity analyses in the human medial temporal lobe (MTL) at high enough resolution to resolve the hippocampal subfields. We calculated the average correlation coefficients between the MTL cortices, which include the entorhinal (ERC), perirhinal (PRC), and parahippocampal cortex (PHC), and the hippocampal subfields dentate gyrus/CA3, CA1, and subiculum. We found that the hippocampal subfields had relatively high correlations with each other both within and across hemispheres, but did not have exceptionally strong correlations with the MTL cortices. The opposite was also seen where there was a relatively high correlation coefficient between the ERC and PRC, but both regions had low correlation coefficients with the hippocampal subfields. We also found greater functional connectivity within a hemisphere than across hemispheres. These effects were replicated across multiple datasets which differed in task demands, participants' age, and scanner sequence/slice acquisition. Notably, all datasets were better correlated to these patterns of intrinsic functional connectivity than to a model based on anatomical constraints. This is consistent with evidence that functional connectivity is not a direct mapping of anatomical connectivity. These patterns of functional connectivity imply a distinction between the MTL cortices and the hippocampus and speak to our understanding of the organization of the MTL.