Rudolf Nieuwenhuys

The insular cortex: a review.

The human insular cortex forms a distinct, but entirely hidden lobe, situated in the depth of the Sylvian fissure. Here, we first review the recent literature on the connectivity and the functions of this structure. It appears that this small lobe, taking up less than 2% of the total cortical surface area, receives afferents from some sensory thalamic nuclei, is (mostly reciprocally) connected with the amygdala and with many limbic and association cortical areas, and is implicated in an astonishingly large number of widely different functions, ranging from pain perception and speech production to the processing of social emotions. Next, we embark on a long, adventurous journey through the voluminous literature on the structural organization of the insular cortex. This journey yielded the following take-home messages: (1) The meticulous, but mostly neglected publications of Rose (1928) and Brockhaus (1940) are still invaluable for our understanding of the architecture of the mammalian insular cortex. (2) The relation of the insular cortex to the adjacent claustrum is neither ontogenetical nor functional, but purely topographical. (3) The insular cortex has passed through a spectacular progressive differentiation during hominoid evolution, but the assumption of Craig (2009) that the human anterior insula has no homologue in the rhesus monkey is untenable. (4) The concept of Mesulam and Mufson (1985), that the primate insula is essentially composed of three concentrically arranged zones, agranular, dysgranular, and granular, is presumably correct, but there is at present much confusion concerning the more detailed architecture of the anterior insular cortex. (5) The large spindle-shaped cells in the fifth layer of the insular cortex, currently known as von Economo neurons (VENs), are not only confined to large-brained mammals, such as whales, elephants, apes, and humans, but also occur in monkeys and prosimians, as well as in the pygmy hippopotamus, the Atlantic walrus, and Florida manatee. Finally, we point out that the human insula presents a unique opportunity for performing an in-depth comparative analysis of the relations between structure and function in a typical sensory and a typical cognitive cortical domain.

The Forebrain of Actinopterygians Revisited

The forebrain of actinopterygian fishes differs from that of other vertebrates in that it consists of a pair of solid lobes. Lateral ventricles surrounded by nervous tissue are entirely lacking. Comparative anatomical and embryological studies have shown that the unusual configuration of the forebrain in actinopterygians results from an outward bending or eversion of the dorsal portions of its lateral walls. Due to this eversion, the telencephalic roof plate is transformed into a wide, membranous structure which surrounds the dorsal and lateral parts of the solid lobes and is attached to their lateral or ventrolateral aspects. The taeniae, i.e. the lines of attachment of the widened roof plate, represent important landmarks in actinopterygian forebrains. In the present paper, the process of eversion is specified and quantified. It is pointed out that recent suggestions to modify the original eversion concept lack an empirical basis. Eversion is the antithesis of the inward bending or inversion that occurs in the forebrains of most other vertebrates. The forebrain lobes in actinopterygians, like those in other vertebrates, comprise a pallium and a subpallium, both of which include a number of distinct cell masses. The morphological interpretations of these cell masses over the past 130 years are reviewed and evaluated in light of a set of carefully selected criteria for homologous relationships. Special attention is paid to the interpretation of a cell mass known as Dp, situated in the caudolateral portion of the pallium in teleosts (by far the largest clade of living actinopterygians). Based on its position close to the taenia, and given the everted condition of the pallium in teleosts, this cell mass clearly corresponds with the medial pallium in inverted forebrains; however, Dp receives a dense olfactory input, and it shares this salient feature with the lateral pallium, rather than with the medial pallium of inverted forebrains. There is presently no consensus regarding the homology of Dp. Several recent authors [Wullimann and Mueller, 2004; Yamamoto et al., 2007] consider the lateral pallium in inverted forebrains and Dp in teleosts to be homologous because they believe that these cell masses originate from the same germinative zones, but that Dp attains its ultimate position only through migration. On the other hand, the present author believes that Dp is situated in the immediate vicinity of its germinative zone and that it represents a specialized part of the lateral pallial zone in teleosts, a zone that can be homologized topologically with the medial pallium in inverted forebrains. Further, it is proposed that the lateral olfactory tract in teleosts, which supplies most of the olfactory fibers to Dp, is not homologous to the same-named tract in the inverted forebrains of most other vertebrates.

The development and general morphology of the telencephalon of actinopterygian fishes: synopsis, documentation and commentary.

The Actinopterygii or ray-finned fishes comprise, in addition to the large superorder of teleosts, four other superorders, namely the cladistians, the chondrosteans, the ginglymodes, and the halecomorphs, each with a limited number of species. The telencephalon of actinopterygian fishes differs from that in all other vertebrates in that it consists of a pair of solid lobes. Lateral ventricles surrounded by nervous tissue are entirely lacking. At the end of the nineteenth century, the theory was advanced that the unusual configuration of the forebrain in actinopterygians results from an outward bending or eversion of its lateral walls. This theory was accepted by some authors, rejected or neglected by others, and modified by some other authors. The present paper is based on the data derived from the literature, complemented by new observations on a large collection of histological material comprising specimens of all five actinopterygian superorders. The paper consists of three parts. In the first, a survey of the development of the telencephalon in actinopterygian fishes is presented. The data collected show clearly that an outward bending or eversion of the pallial parts of the solid hemispheres is the principal morphogenetic event in all five actinopterygian superorders. In all of these superorders, except for the cladistians, eversion is coupled with a marked thickening of the pallial walls. In the second part, some aspects of the general morphology of the telencephalon in mature actinopterygians are highlighted. It is pointed out that (1) the degree of eversion varies considerably among the various actinopterygian groups; (2) eversion leads to the transformation of the telencephalic roof plate into a wide membrane or tela choroidea, which is bilaterally attached to the lateral or ventrolateral aspect of the solid hemispheres; (3) the lines of attachment or taeniae of the tela choroidea form the most important landmarks in the telencephalon of actinopterygians, indicating the sites where the greatly enlarged ventricular surface of the hemispheres ends and its reduced meningeal surface begins; (4) the meningeal surface of the telencephalon shows in most actinopterygians bilaterally a longitudinally oriented sulcus externus, the depth of which is generally positively correlated with the degree of eversion; (5) a distinct lateral olfactory tract, occupying a constant topological position close to the taenia, is present in all actinopterygians studied; and (6) this tract is not homologous to the tract of the same name in the evaginated and inverted forebrains of other groups of vertebrates. In the third and final section, the concept that the structural organization of the pallium in actinopterygians can be fully explained by a simple eversion of its walls, and the various theories, according to which the eversion is complicated by extensive shifts of its constituent cell groups, are discussed and evaluated. It is concluded that there are no reasons to doubt that the pallium of actinopterygian fishes is the product of a simple and complete eversion.

The Structural, Functional, and Molecular Organization of the Brainstem

According to His (1891, 1893) the brainstem consists of two longitudinal zones, the dorsal alar plate (sensory in nature) and the ventral basal plate (motor in nature). Johnston and Herrick indicated that both plates can be subdivided into separate somatic and visceral zones, distinguishing somatosensory and viscerosensory zones within the alar plate, and visceromotor and somatomotor zones within the basal plate. To test the validity of this “four-functional-zones” concept, I developed a topological procedure, surveying the spatial relationships of the various cell masses in the brainstem in a single figure. Brainstems of 16 different anamniote species were analyzed, and revealed that the brainstems are clearly divisible into four morphological zones, which correspond largely with the functional zones of Johnston and Herrick. Exceptions include (1) the magnocellular vestibular nucleus situated in the viscerosensory zone; (2) the basal plate containing a number of evidently non-motor centers (superior and inferior olives). Nevertheless the “functional zonal model” has explanatory value. Thus, it is possible to interpret certain brain specializations related to particular behavioral profiles, as “local hypertrophies” of one or two functional columns. Recent developmental molecular studies on brains of birds and mammals confirmed the presence of longitudinal zones, and also showed molecularly defined transverse bands or neuromeres throughout development. The intersecting boundaries of the longitudinal zones and the transverse bands appeared to delimit radially arranged histogenetic domains. Because neuromeres have been observed in embryonic and larval stages of numerous anamniote species, it may be hypothesized that the brainstems of all vertebrates share a basic organizational plan, in which intersecting longitudinal and transverse zones form fundamental histogenetic and genoarchitectonic units.

The structural organization of the forebrain: a commentary on the papers presented at the 20th Annual Karger Workshop 'Forebrain evolution in fishes'.

During the 2008 Karger Workshop considerable progress was made towards defining a model or structural plan, valid for the prosencephalon of all vertebrates. The presentations demonstrated that the following features, which are valid for tetrapods, also hold true for most groups of fish: (1) The diencephalon proper is clearly composed of three neuromeres, p1–p3; (2) in the pallium four, rather than three, fundamental longitudinal zones can be distinguished; (3) during ontogenesis, numerous GABA-ergic elements migrate tangentially from the subpallium to the pallium.

Analysis of the structure of the brain stem of mammals by means of a modified D'Arcy Thompson procedure.

In his famous book, ‘On Growth and Form’, D’Arcy Thompson demonstrated that the shapes of related animals, or parts thereof, can be transformed into each other by a simple graphical procedure, called the method of coordinates. In this procedure, an object is inscribed in a net of Cartesian coordinates. It appeared that the shape of related objects could be characterized by means of simple, harmonious deformations of the initial orthogonal system of coordinates. Here, I demonstrate that: (1) the central nervous system contains a built-in, natural coordinate system; (2) differences in shape and proportion of cross sections through the brain stem of various mammals can be easily analyzed with the aid of this coordinate system, and (3) sets of structures in the mammalian brain stem, which are closely related to the neocortex, but form part of entirely different functional systems, form spatially constrained complexes, and have the capacity to expand jointly and harmoniously within these complexes.

On old and new comparative neurological sinners: The evolutionary importance of the membranous parts of the actinopterygian forebrain and their sites of attachment

The forebrain of actinopterygian fishes differs from that of other vertebrates in that it consists of a pair of solid lobes. Lateral ventricles surrounded by nervous tissue are entirely lacking. This peculiar configuration of the actinopterygian forebrain results from an outward bending or eversion of its lateral walls during ontogenesis. Due to this eversion, the telencephalic roof plate is transformed into a wide, membranous structure that surrounds the dorsal and lateral parts of the solid lobes and is attached to their lateral or ventrolateral aspects. Another effect of the eversion is that the ventricular surface of the telencephalic lobes is very extensive, whereas their meningeal surface is small. In many recent publications on the forebrain of actinopterygian fishes, these structures are presented as solid lobes, without any reference to the fact that they are the product of an eversion process, and without any indication concerning the location and extent of their ventricular and meningeal surfaces. It is explained here that, in light of current concepts concerning the histogenesis of the brain, these omissions are intolerable. It is also strongly recommended that the location and extent of these surfaces should always be clearly indicated in brain sections in general, because the simple notion that in the brain of vertebrates the ventricular surface is on the inside and the meningeal surface on the outside has numerous and notable exceptions. J. Comp. Neurol. 513:87–93, 2009.

Blood Supply, Meninges and Cerebrospinal Fluid Circulation

The vascularization and the circulation of the cerebrospinal fluid (liquor cerebrospinalis, CSF) of the brain and the spinal cord are of great clinical importance. The main vascular syndromes are summarized in Table 4.1. In this chapter, the anatomy of blood vessels, meninges and circumventricular organs will be discussed. The central nervous system, which is of ectodermal origin (Chap. 2), is surrounded by mesodermal structures. A system of three connective tissue layers, the meninges, and a fluid compartment containing CSF are located between the bony skull and vertebral column and the nervous tissue of the brain and the spinal cord. Blood vessels, themselves of mesodermal origin, are surrounded by derivatives of the meninges over their full extent, until the interface between the capillary wall and the glial basal membrane makes exchange of substances possible. CSF is produced by the choroid plexus of the ventricles. It circulates from the interstitial spaces of the nervous tissue and the choroid plexus, through the ventricles and their apertures in the roof of the fourth ventricle, to the CSF compartment of the subarachnoid space and its exit through the arachnoid villi to the venous system. The nervous tissue of the central nervous system and the CSF spaces remain segregated from the rest of the body by barrier layers in the meninges (the barrier layer of the arachnoid), the choroid plexus (the blood-CSF barrier) and the capillaries (the blood-brain barrier). The circulation of the CSF plays an important role in maintaining the environment of the nervous tissue; moreover, the subarachnoidal space forms a bed that absorbs external shocks.

Principles of Current Vertebrate Neuromorphology

Causal analysis of molecular patterning at neural plate and early neural tube stages has shown that the central nervous system (CNS) of vertebrates is essentially organized into transverse neural segments or neuromeres and longitudinal zones which follow the curved axis of the brain. The intersection of the longitudinal and transverse patterning processes in the embryonic brain leads to the formation of a checkerboard pattern of distinct progenitor domains called “fundamental morphological units” (FMUs). The topologically invariant pattern formed by the ventricular surfaces of the FMUs of a given taxon represents the “Bauplan” or “blueprint” of the brain of that taxon. The FMUs initially represent thin epithelial fields; during further development they are transformed into three-dimensional radial units, extending from the ventricular surface to the meningeal surface. It is of note that the boundaries of the neuromeres, longitudinal zones, and radial units all strictly adhere to a non-Cartesian coordinate system inherent to the CNS of all vertebrates. The major neural histogenetic processes, including cellular proliferation, radial migration, and differentiation, as well as the formation of grisea (cell masses, nuclei, and cortices), occur principally within the confines of the FMUs, although tangential migration may also take cells to distant sites. Hence, recognition and delimitation of these units is essential for the identification and interpretation of grisea. An outline of the procedure to be followed in these processes of identification and interpretation is presented, and a list of the pertinent homology criteria is provided.

Sezioni dell’encefalo

Questo capitolo descrittivo presenta quattro serie di sezioni dell’encefalo condotte secondo i seguenti piani: 13 sezioni coronali 4 sezioni perpendicolari all’asse del tronco encefalico 6 sezioni sagittali 9 sezioni orizzontali