Direct and indirect pathways from the amygdala to the frontal lobe in rhesus monkeys

To elucidate the anatomical relationships between the frontal association cortex and the limbic system in primates, projections from the amygdala to frontal cortex were studied in the rhesus monkey using retrograde and anterograde tracing methods. Following injections of horseradish peroxidase (HRP) into the orbital prefrontal cortex, the gyrus rectus, the superior frontal gyrus, and the anterior cingulate gyrus of the frontal lobe, labeled neurons were found in the basolateral, basomedial, or basal accessory nuclei of the amygdala. None of these nuclei contained labeled neurons following HRP injections into the principal sulcus or the lateral inferior convexity of the frontal lobe. This selective distribution of amygdala connections was confirmed by injection tritiated amino acids into the amygdala. Silver grains were present only over the orbital cortex and gyrus rectus on the ventral surface of the frontal lobe and over the superior prefrontal gyrus and anterior cingulate gyrus on the medial wall of the hemisphere, while the dorsolateral prefrontal cortex was free of radioactivity. The isotope injection of the amygdala also revealed a projection to the magnocellular moiety of the mediodorsal nucleus (MDmc) which is known to innervate the same ventromedial regions of the frontal lobe that receive direct connections from the amygdala. Although MDmc and amygdala project to the same cortical regions, their terminal fields are different. The direct amygdala input terminates in layer 1 in orbital cortex and gyrus rectus and layer 2 in the dorsomedial cortex and cingulate gyrus, while the thalamic input is primarily to layer 3 and, in some areas, also the superficial half of layer 1. These findings indicate that the frontal lobe of rhesus monkeys can be subdivided into two separable cortical regions: 1) A ventromedial region including the anterior cingulate gyrus which receives both direct (amygdalo-cortical) and indirect (amygdalo-thalamo-cortical) input from the amygdala; and 2) a dorsolateral frontal region which is essentially devoid of either direct or indirect amygdalofugal axons. On the basis of its selective relationship with the amygdala, the ventromedial region may be considered the "limbic" portion of the frontal association cortex.