The Cortico-Limbo-Thalamo-Cortical Circuits: An Update to the Original Papez Circuit of the Human Limbic System

Abstract

The Papez circuit, first proposed by James Papez in 1937, is a circuit believed to control memory and emotions, composed of the cingulate cortex, entorhinal cortex, parahippocampal gyrus, hippocampus, hypothalamus, and thalamus. Pursuant to James Papez, Paul Yakovlev and Paul MacLean incorporated the prefrontal/orbitofrontal cortex, septum, amygdalae, and anterior temporal lobes into the limbic system. Over the past few years, diffusion-weighted tractography techniques revealed additional limbic fiber connectivity, which incorporates multiple circuits to the already known complex limbic network. In the current review, we aimed to comprehensively summarize the anatomy of the limbic system and elaborate on the anatomical connectivity of the limbic circuits based on the published literature as an update to the original Papez circuit.

Keywords: Brain networks; Diffusion-weighted imaging; Limbic; Papez circuit; Tractography; White matter connections.

Fig. 1

A 3-D reconstruction of the major gray and white matter structures of the limbic system including the Papez circuit. Frontal (cyan), parietal (red), and temporal (creamy color) cortices are shown in the background. Major gray matter nuclei of the limbic system are also shown, including the thalamus (TH in pink), hippocampus (brown), and amygdala (Amyg in red). Please note that the hypothalamus including the mammillary bodies is not shown, however, the mammillo-hypothalamic tract is shown by an arrowhead connecting the hypothalamus to the ventral thalamus. Major white matter pathways of the limbic system are shown, including the cingulum bundle (Cing in green), fornix (FX in blue), and uncinate fasciculus (UF in yellow). The Papez circuit is shown in yellow curved lines including the two parallel loops of cingulum loop and forniceal loop (FX loop). The two loops communicate with one another mediated by the thalamus via the mammillothalamic tract (shown by yellow arrowhead) and the thalamo-cortical fibers (TC). The Papez circuit consists of the frontoparietal connectivity with the parahippocampal gyrus/hippocampal formations via the cingulum bundle, hippocampal formations to mammillary bodies via the fornix, mammillary bodies to the thalamus via the mammillothalamic tract, and the thalamus to the frontoparietal lobes and cingulum bundle via the thalamocortical fibers (TC)

Fig. 2

Axial (A) and 3-D (B) views of the high spatial resolution diffusion weighted imaging of brain parenchyma are shown. 2A shows the axial view of the thalami (TH) demonstrating three major colors. The anterior third of the thalamus contains the green fibers (green arrow), which run in anterior–posterior or posterior-anterior orientation, named the anterior thalamic radiations (ATR), shown as green fiber tracts in B. The ATR mostly project from the thalamus to the prefrontal cortex. The middle third of the thalamus contains the blue fibers (blue arrow), which are the cranio-caudally oriented fibers, named the superior thalamic radiations (STR). The STR is shown as blue projection fibers (B), projecting from the thalamus to the posterior frontal and parietal cortices (B). The posterior third of the thalamus includes the red fibers (red arrow) which course in latero-lateral direction, called the posterior thalamic radiations (PTR). The PTR fibers are shown in red (B) and are mostly projecting from the thalamus to the occipital cortex

Fig. 3

A-D represents the 3-D fiber tract reconstructions of the fornix, cingulum bundle, amygdalothalamic, and dorsal thalamo-hypothalamic tract. 3A. shows the relationship between the fornix (yellow) and the amygdalothalamic tract (ATT in red). Forniceal arms, crura, body, and columns are shown. 3B shows the relationship of the fornix (blue) and cingulum bundle (green). 3C illustrates the ATT (in cyan), arising from the dorsomedial thalamus and inserting into the amygdala. 3D illustrates the dorsal thalamo-hypothalamic tract (DTH in yellow) arising from the dorsomedial thalamus and inserting into the anterior hypothalamic nuclei. ATT, amygdalothalamic tract; Cing, cingulum bundle; DTH, dorsal thalamo-hypothalamic tract; Third vent, third ventricle; TH, thalamus

Fig. 4

represents the 3-D fiber reconstruction of the fornix (yellow), stria terminalis (black), amygdalofugal tract (AFT in pink), and uncinate fasciculus (UF in green). The stria terminalis is shown connecting the amygdala to the region of septal nuclei (Septal N). The amygdalofugal tract is shown connecting the amygdala to the hypothalamic nuclei (HN) and septal nuclei (Septal N). The uncinate fasciculus is shown connecting the amygdala to the orbitofrontal cortex and ventromedial prefrontal cortex (VMPFC). The white arrows demonstrate the medial projections of the UF to the VMPFC. Diagonal band of Broca (DBB) are shown as the mustache like yellow fibers arising from the septal nuclei and course toward the Para olfactory regions bilaterally

Fig. 5

Different views of 3-D reconstructions of the prefronto-caudo-thalamic tract (PFCT in red) on T1 weighted backgrounds. 4A-D shows the connectivity of the PFCT with multiple gray matter nuclei, including the caudate head (CaudH), septal nuclei (SN), superior hypothalamic nuclei (SHN), lentiform nuclei (LN), and the thalamus (TH). The PFCT projects to the medial prefrontal cortex (PreFr). 4C shows the medial forebrain bundle (MFB in yellow), running side by side along the lateral and superior aspect of the PFCT inserting into the lateral prefrontal cortex (PreFr)

Fig. 6

Four consecutive coronal T1 weighted anatomical views demonstrating the trajectory of the PFCT (red) from posterior (A) to anterior (D). The trajectory of the PFCT is shown arising from the dorsomedial thalamus (TH), projecting laterally and anteriorly along the lateral aspect of the third ventricle toward the caudate head (CauH, white arrow in C). The PFCT passes through the bed nucleus of stria terminalis (BNST), septal nuclei (SN), nucleus accumbens (NAC), and caudate head before projecting into the medial prefrontal cortex. Along the way, the PFCT receives projections from the superior hypothalamic nuclei (SHN, arrowhead in A) and lentiform nuclei (LN, arrowhead in B). Ag, amygdala; Pu, putamen; Th, thalamus

Fig. 7

Different views of 3-D reconstructions of the prefronto-caudo-thalamic tract (PFCT in red) and the medial forebrain bundle (MFB in yellow) on T1 weighted imaging backgrounds. The MFB connects the midbrain's periaqueductal gray matter (PAG) to the ventral tegmental areas and the prefrontal cortex (PreFr). The MFB projects from the PAG anteriorly near the midline into the ventral tegmental area toward the interpeduncular cistern (marked by arrowhead in 7A-C). The MFB then courses superiorly toward the genu of the internal capsule (black arrow in 7D), where it enters the anterior limb of the internal capsule (ALIC). Unlike the MFB which courses through the ALIC into the prefrontal cortex, the PFCT courses outside the ALIC, more medially and through the caudate head before projecting to the medial prefrontal cortex (7B-D)

Fig. 8

A-C trajectory of the amygdalofugal tract (orange) on T1 weighted backgrounds. 8D. 3-D reconstruction of the AFT is demonstrated. The AFT originates from the amygdala and projects superiorly and medially toward the midline. While projecting toward the midline (8B), the AFT courses through the basal nucleus of Meynert (BNM, arrowheads in 8B) along the inferior aspect of the anterior commissure (AC). The AFT splits into three groups of fibers near the midline (8D). Two groups of fibers project cranially toward the septal nuclei (SN, superior anterior marked by white arrows in 8C-D) and the bed nucleus of stria terminals (BNST, superior posterior marked by black arrows in 8B-D). The third group of fibers projects caudally into the hypothalamic nuclei (HN, yellow arrow in 8A) and ventral tegmental area

Fig. 9

Schematic view of the major anterior neuronal circuits (fronto-temporal connectivity) of the limbic system mostly connected to the frontal and temporal cortices. The Papez circuit is shown by dotted box. The Papez circuit consists of the frontoparietal connectivity with the parahippocampal gyrus via the cingulum bundle, hippocampal formations to mammillary bodies via the fornix, mammillary bodies to the thalamus via the mammillothalamic tract (MTT), thalamus to the frontal lobe and cingulum bundle via the thalamocortical fibers (TC). By considering other limbic pathways such as the PFCT, ST, AFT, UF, ATT and DTH, several neuronal loops are added to the limbic system which were detailed in the text

Fig. 10

Schematic view of the major anterior (fronto-temporal connectivity) and posterior (parieto-occipito-cerebellar connectivity) neuronal circuits of the limbic system connected to the frontal, parietal, occipital and temporal cortices as well as cerebellar hemispheres. By introducing posterior limbic pathways such as POHT, cerebello-hypothalamic and cerebello-septal/BNST, DRTT and PTR, several additional neuronal circuits are added to the limbic network. This schematic view shows the tight connectivity of the limbic gray matter nuclei to the posterior cerebral and cerebellar cortices including the parietal, occipital lobes and cerebellar hemispheres. The circuits are detailed in the manuscript