Amygdala and ventral tegmental area differentially interact with hippocampus and cortical medial temporal lobe during rest in humans.

Neuromodulatory regions that detect salience, such as amygdala and ventral tegmental area (VTA), have distinct effects on memory. Yet, questions remain about how these modulatory regions target subregions across the hippocampus and medial temporal lobe (MTL) cortex. Here, we sought to characterize how VTA and amygdala subregions (i.e., basolateral amygdala and central-medial amygdala) interact with hippocampus head, body, and tail, as well as cortical MTL areas of perirhinal cortex and parahippocampal cortex in a task-free state. To quantify these interactions, we used high-resolution resting state fMRI and characterized pair-wise, partial correlations across regions-of-interest. We found that basolateral amygdala showed greater functional coupling with hippocampus head, hippocampus tail, and perirhinal cortex when compared to either VTA or central-medial amygdala. Furthermore, the VTA showed greater functional coupling with hippocampus tail when compared to central-medial amygdala. There were no significant differences in functional coupling with hippocampus body and parahippocampal cortex. These results support a framework by which neuromodulatory regions do not indiscriminately influence all MTL subregions equally, but rather bias information processing to discrete MTL targets. These findings provide a more specified model of the intrinsic properties of systems underlying MTL neuromodulation. This emphasizes the need to consider heterogeneity both across and within neuromodulatory systems to better understand affective memory.