Over the course of evolution, the brain network formed by the amygdala and the medial prefrontal cortex underwent distinct structural transformations in the lineages of Old World monkeys and humans. This network plays a central role in behavioral adaptation: when facing an uncertain environment, an individual must rapidly detect salient information—interactions with conspecifics, resource availability, the presence of danger—while integrating its own internal state, whether emotional, motivational, or physiological. Both the amygdala and the medial prefrontal cortex are heterogeneous structures: the amygdala comprises several interconnected nuclei (lateral, basolateral, basomedial, and central), whereas the medial prefrontal cortex includes ventromedial and cingulate regions involved in stimulus evaluation and decision monitoring. Notable structural differences distinguish the two species: in humans, the amygdala is ten times larger than in the macaque, largely owing to an expansion of the lateral nucleus, and the cortical regions located at the interface between the ventromedial cortex and the mid-cingulate cortex have also expanded. It remained to be determined whether, and how, these anatomical rearrangements translate into a different functional organization.
To address this question, the authors used resting-state functional magnetic resonance imaging, a method reproducible across species, in twenty awake human subjects and three awake macaques. The use of the awake state is important, because anesthesia alters functional connectivity within the frontal cortex. The analysis focused on ipsilateral functional connectivity between the four main amygdaloid nuclei, taken as seed regions, and sixteen regions of the medial prefrontal cortex, carefully positioned according to subject-specific sulcal landmarks and adjusted to the respective size of each brain in order to ensure proportionate comparisons.
In humans, the connectivity between the amygdala and the medial prefrontal cortex describes a rostro-caudal U-shaped profile along the corpus callosum: positive with the ventromedial prefrontal cortex and the anterior cingulate cortex, negative with the anterior part of the mid-cingulate cortex, and then positive again with its posterior part. In the macaque, although a U-shaped organization is also observed, the negative connectivity is shifted more ventrally, at the junction between the ventromedial cortex and the anterior cingulate cortex. The authors further show that this profile is carried by all of the amygdaloid nuclei and that the physical distance between regions does not predict the strength of the connectivity.
This divergence in the functional organization of the amygdala–medial prefrontal cortex network between humans and macaques could help shed light on the differences in behavioral adaptation capacities specific to the respective socio-ecological niches of the two species.