Resting state functional connectivity of the hippocampus along the anterior-posterior axis and its association with glutamatergic metabolism

Animal and human studies suggest differing anatomical and functional connectivity patterns of the anterior and posterior hippocampus. The biochemical underpinnings of the hippocampal resting state connectivity along this anterior-posterior axis remain unclear. We investigated twenty-five healthy male subjects in a multimodal study. We aimed to examine the relationship between resting state functional connectivity (RSFC) of the left and right hippocampus separated along the anterior-posterior axis and the corresponding glutamatergic function assessed by proton magnetic resonance spectroscopy (1H-MRS) of the glutamate-glutamine (Glx) complex. We observed a clear functional differentiation of the hippocampal RSFC along this axis. Moreover, a highly significant correlation was observed between the concentration of Glx in the right anterior hippocampus and its corresponding functional connectivity, but not with the amplitude of local low frequency fluctuations. Lower Glx levels were associated with a higher functional connectivity to the medial prefrontal cortex, perigenual anterior cingulate cortex (pACC) and the left ventrolateral prefrontal cortex (VLPFC). In addition, the Glx concentration in the posterior hippocampus predicted the verbal memory performance, i.e., the degree of retroactive interference. The present findings demonstrate for the first time a modulation of the anterior hippocampal RSFC by Glx concentration.