Human subsystems of medial temporal lobes extend locally to amygdala nuclei and globally to an allostatic-interoceptive system

In mammals, the hippocampus, entorhinal, perirhinal, and parahippocampal cortices (i.e., core regions of the human medial temporal lobes, MTL) are locally interlaced with the adjacent amygdala nuclei at the structural and functional levels. At the global brain level, the human MTL has been described as part of the default mode network and amygdala nuclei as parts of the salience network, with both networks collectively forming a large-scale brain system supporting allostatic-interoceptive functions. We hypothesized (i) that intrinsic functional connectivity of slow activity fluctuations would reveal human MTL subsystems locally extending to the amygdala; and (ii) that these extended local subsystems would be globally embedded in large-scale brain systems supporting allostatic-interoceptive functions. Capitalizing on resting-state fMRI data of three independent samples of cognitively healthy adults (one main and two replication samples: N ​= ​101, 60, and 29, respectively), we analyzed the functional connectivity of fluctuating ongoing BOLD-activity within and outside the amygdala-MTL in a data-driven way using masked independent component and dual-regression analyses. We found that at the local level, MTL subsystems extend to the amygdala and are functionally organized along the longitudinal amygdala-MTL axis. These subsystems are characterized by consistent involvement of amygdala, hippocampus, and entorhinal cortex, but variable participation of perirhinal and parahippocampal regions. At the global level, amygdala-MTL subsystems selectively connect to salience, thalamic-brainstem, and default mode networks - the major cortical and subcortical components of the allostatic-interoceptive system. These findings provide evidence for integrated amygdala-MTL subsystems in humans, which are embedded within a larger allostatic-interoceptive system.