INTRODUCTION
One of the most dramatic developmental changes of the central nervous system is that seen in the limbic system. Various structures of the adult limbic system encompass every lobe as well as the brainstem with interconnections via fiber tracks that at times travel almost circumferential distances. The embryologic development of the human limbic system is evolutionarily old and has remained remarkably consistent over time and across most mammalian species. The formation of various structures of the limbic system in conjunction with the surrounding brain development helps explain the form and function of the adult limbic system. A thorough understanding of the limbic embryologic development is critical to the neurosurgeon's ability to operate safely within its structures.
STRUCTURE AND DEVELOPMENT OF LIMBIC SYSTEM
The limbic system extends from the medial surface of the frontal lobe to the temporal lobe, comprising a series of four C-shaped structures that are separated by sulci or remnants (Fig. 1.1). The outermost “C” arch is formed sequentially by the subcallosal area, cingulate gyrus, parahippocampal gyrus, and uncus. The inner arch is formed by the paraterminal gyrus, indusium griseum, tail of hippocampus, dentate gyrus, and Ammon's horn.1-4 A long sulcus between these two arches, the callosal sulcus and the hippocampal fissure, defines the third arch. The fourth and final arch is formed by the fimbria and fornix.2,4,5 The anatomic complexity of the limbic structures is reflected by their embryological development and an overview is presented in the following text.
Developmentally, the limbic system arises from the telencephalon and diencephalon.4-6 Examination of the gray matter architecture reveals that most structures have a three layered cortex. The dentate gyrus and Ammon's horn have a trilaminar type of cortex which gradually transitions to a neocortical six layer cortex in the entorhinal area of the parahippocampal gyrus.4,7
Hippocampus
The hippocampus first appears at the dorsomedial wall of the cerebral hemisphere adjacent to the lamina terminalis at around day 37 of gestation4-6,8,9 and is the first cortical area to differentiate.8-10
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Fig. 1.1: Mesial surface of brain demonstrating the adult pathway of the four limbic arches. The outermost arch is formed by the cingulate gyrus, which merges with and becomes the parahippocampal gyrus. The inner arch is formed by the indusium griseum, which is the adult remnant of the hippocampus. This structure is continuous with the tail of hippocampus, dentate gyrus, and Ammon's horn. The callosal sulcus, which becomes the hippocampal fissure, defines the third arch. The fourth and final arch is formed by the fimbria and fornix (white arrowheads).
This structure forms a continuous bulge into the inferomedial wall of the lateral ventricle as it extends in crescent fashion into the temporal tip where the temporal lobe forms. At week 10 of gestation, the hippocampus forms a large part of the cerebral hemisphere.11
As the corpus callosum begins to develop around 14 weeks’ gestation, the anterior hippocampus regresses and the temporal portion remains as the most developed part.8,11 By 17 weeks, the paraterminal gyrus and indusium griseum are the only remnants of the anterior hippocampus. In the temporal lobe, the anterior tip of the hippocampus is separated from the developing amygdala by the uncal recess of the temporal horn. The body of the hippocampus forms the inferomedial border of the temporal horn with its subependymal superior surface covered by the alveus (Figs. 1.2A to D). The hippocampal tail extends around the splenium of the corpus callosum and forms the indusium griseum.3,12,13 The indusium griseum and its associated white matter bundles (medial and lateral longitudinal striae) are intimately applied to the surface of the corpus callosum.4,14 Anteriorly, the indusium griseum extends around the genu of the corpus callosum to merge with the paraterminal gyrus.3,4,13,15
The hippocampal fissure is first seen at about 55 days’ gestation but is not well formed until 10 weeks.8,16 It forms as a result of the differential growth of Ammon's horn compared to the dentate gyrus.10,11,16 By 15 weeks (Figs. 1.2A to D), the most developed part of the fissure is in the temporal lobe.8,11 With continued growth of the dentate gyrus, the hippocampal fissure deepens and eventually fuses together. A remnant cavity of this can be seen in 10% of the normal population in MRI studies.7,17 The medial hemispheric part of the fissure eventually becomes the callosal sulcus separating the indusium griseum from the cingulate gyrus.2,5 In the temporal lobe, the hippocampal fissure runs parallel to the choroidal fissure5 and merges into the uncal sulcus.17
The parahippocampal gyrus forms the inferomedial surface of the temporal lobe in the adult form. Developmentally, the hippocampal fissure forms the superior border of the parahippocampal gyrus. On the lateral side, the collateral sulcus separates it from the occipitotemporal gyrus. Beginning at 13 weeks and soon after, the parahippocampal gyrus undergoes rapid growth and expansion, essentially causing it to rotate in the inferomedial direction, covering the hippocampus and hippocampal fissure.
Fornix and Mammillary Body
The fornix is the main efferent fiber tract from the hippocampus. The majority of fibers arise from the subiculum and Ammon's horn,13,18 travel over the subependymal ventricular surface as the alveus and merge as the fimbria.
Figs. 1.2A to D: Photographs and MRI images of the medial surface of the embryological cerebral hemispheres. (A) The medial surface of an approximately 14-week-old embryo. The hippocampus (H) extends from the temporal lobe to the frontal lobe (small arrows). The prominent hippocampal sulcus is readily visible (large arrowheads). The uncus (U) has an anterior position but has not fully turned to cover the hippocampus medially. (Th: Thalamus;*: Area affected by dissection) (B) Reformatted sagittal oblique MRI image of the same specimen demonstrating the hippocampus (H) and the hippocampal sulcus (small arrows). (C) The medial surface of an approximately 17-week-old specimen. The corpus callosum (CC) is partially formed and the hippocampal remnant along the sulcus of the corpus callosum (arrowheads) is visible along the frontoparietal region. The cingulate gyrus (CG) is now visible. The hippocampal sulcus (small arrows) is less visible as the uncus (U) assumes a more medial position. Early formation of the parahippocampal gyrus (PHG) is also seen at this time. (D) Sagittal MRI image of the same specimen. The hippocampal remnant is seen (arrows) along the forming sulcus of the corpus callosum.
The fimbria lies superior to the dentate gyrus and is separated from it by the fimbriodentate fissure. Posteriorly, the fimbria increases in thickness, becoming the crura of fornix. Anteriorly, the crura form a triangular sheet of fibers called the commissure of the fornix. The crura then join to from the body of the fornix, which continue on to becoming the columns of the fornix before dividing proximal to the anterior commissure 5to the precommissural and postcommissural fibers. The precommissural fibers terminate in the septal area, diagonal band of Broca, lateral preoptic area, and anterior hypothalamus. The postcommissural fibers terminate in the mammillary bodies.
The fibers of the fornix appear at 8 weeks’ gestation. The commissure of the fornix begins to appear around 10 weeks and by 13.5 weeks, the alveus is visible in the subependymal surface, and the fimbriodentate fissure is present.8 The fornix and hippocampus can be seen as separate entities after 16 weeks gestational age.14 The mammillary bodies, which are diencephalic in origin, arise as a single rounded protuberance from the floor of the hypothalamus. Around the 3rd month of gestation, the mammillary bodies are divided by a median furrow, forming the left and right sides.4-6
Septal Area
The septal area is an important part of the limbic system and serves as an area of interconnection for various anatomic nuclei. The area includes the subcallosal gyrus, paraterminal gyrus, septal nuclei, olfactory stria, and the diagonal band of broca.5,13,15 This region is located on the medial surface of the frontal lobe, inferior to the corpus callosum and anterior to the lamina terminalis.4,15
The septal area is a telencephalic structure that first appears at 37 days’ gestational age.8 The septal nuclei and some of the fiber connections can be identified at about 47 days’ gestation. By the 3rd month of gestation, the septal nuclei are well-developed and lie below the corpus callosum and anterior to the septum pellucidum near their adult anatomic position.8
Amygdala
The amygdala is an almond-shaped collection of nuclei that have both olfactory and limbic functions.19 Although in the adult brain, the uncus which encompasses the amygdala and the hippocampus has an intimate anatomic relationship, as will be explained here, the two structures are distinct and develop separately during gestation. The amygdala arises from the corpus striatum embryologically and remains directly connected to the putamen superiorly and the tail of the caudate nucleus that ends in the amygdala.4,5,13,18 The amygdala is divided into two major masses of nuclei: (1) the corticomedial and (2) basolateral nuclear group.
Developmentally, the amygdala is the first part of the corpus striatum to appear as a thickening next to the primitive hippocampal formation at about 35 days’ gestation. As it develops, the amygdala migrates from being directly posterior to the lateral ventricle to its ventral and anterior temporal location; and it rotates medially such that nuclei that were originally lateral become basal and ventral in position.8,20,21 This parallels the development of the temporal horn and medial rotation of the temporal pole. This development continues until the adult uncus assumes its anteromedial temporal position.
Insula
The sylvian fold and insular region begin to develop by gestation week 18. This is followed by the development of the central insular sulcus, which is visible on the surface before the temporal and frontal lobes fold.
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Fig. 1.3: Lateral surface of the embryological hemisphere at 19-week gestation age. The frontoparietal central sulcus (small arrows) is visible and is aligned with the developing central insular sulcus (arrowheads). As the temporal lobe continues to fold and join the frontotemporal opercula (large arrows), the insula assumes its adult hidden position.
The central insular sulcus corresponds to the location and development of the central sulcus of the frontoparietal lobes (Fig. 1.3). As development continues by 22 weeks’ gestation, the insula becomes narrower and less visible due to the posterior-to-anterior folding of the temporal lobe against the parietal and frontal opercula. The Sylvian fissure becomes anatomically visible and completely closed by 27 weeks gestation, at which point the insula is no longer visible.
CONCLUSION
The developmental anatomy of the limbic system is complex. A detailed understanding of the sequential development of various structures allows for an understanding of the adult structures including the four C-shaped arches, lying in an oblique sagittal plane and extending from the temporal pole to the medial surface of the frontal lobe.
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