The Forebrain in Relation to the Brainstem. c. 2011 John LaMuth

Research concerning the embryological development of the human forebrain and spinal cord prove significant in explaining the fundamental differences in forebrain organization. At the most elementary level of development, the primitive laminar arrangement of gray matter in the human spinal cord occurs by way of cellular migrations from broad plates of undifferentiated neuroblast cells. The dorsal (alar) plate of the neuraxis gives rise to the dorsal sensory horns of the spinal cord, whereas the ventral (basal) plate leads to the formation of the ventral (motor) spinal horns.

The spinal cord and medulla oblongata, in contrast to more rostra] brain structures, retain the basic neuraxial organization exhibited by protochordates such as Amphioxus, The spinal cord of the primitive chordate Amphioxus as well as all other vertebrates displays a segmented organization coexisting with a similar serial arrangement of somatic musculature. Each spinal segment in vertebrates consists of paired dorsal and ventral nerve roots as well as interconnective gray and white matter intrinsic to each segment. The num¬ber of spinal segments varies widely over the phylogenetical scale. The sharks, at one extreme, may have over 100 spinal segments while adult frogs possess only 10 segments after metamorphosis.

The human spinal cord is made up of 31 segments grouped into 8 cervical, 12 thoraicic, 5 lumbar, 5 sacral and I caudal classifications. The medulla oblongata of vertebrates coincides roughly with the series of segments that innervate the branchial clefts of fishes or their subsequently modified form in terrestrial vertebrates. The medulla has undergone modification in vertebrates by way of a flexure in the basic neuraxial pattern forming an expansive fourth ventricle from the much smaller central canal. The reorganization in the medulla caused by this flexure is most readily discussed in terms of the fundamental pattern retained unmodified in the spinal cord of vertebrates.

A cross section through a spinal segment of any representative chordate reveals the same basic organization of gray and white matter. In Am¬phioxus, the gray matter (cell bodies) immediately lines the central canal, while the white matter (nerve fibers) is located peripherally in the cord, In the primitive lamprey eel this arrangement is maintained, however the gray matter migrates laterally away from the central canal and becomes subdivided into dorsally located sensory cells and ventrally located motor cells with connective interneurons located intermediately. In sharks as well as in all other vertebrates, a similar arrangement is observed, however, with the gray matter migrating more extensively to form laterally located dorsal and ventral horns, In higher vertebrates the dorsal horn is identified as a column of gray matter extending from region of the central canal to the dorso-lateral surface of the cord connecting with the dorsal spinal root. Similarly, the ventral horn consists of the span of gray matter extending to meet the spinal origin of the ventral spinal root. At the thoraicic and lumbar levels of many vertebrates, a lateral horn is also observed, the cells of which give rise to sympathetic connections in the autonomic nervous system.

The arrangement of spinal gray matter into dorsal, ventral and lat¬eral horns is loosely correlated to subdivisions made according to func¬tional criteria. The dorsal horn is the major terminus of fibers from the sensory dorsal root. The dorsomedial portion of the dorsal horn receives sensory fibers concerning the body wall and is termed ‘the somatic sensory column’, The ventro-lateral portion of dorsal horn receives sensory fibers concerning the body cavity and is termed ‘the visceral sensory column’, The dorsal horn is incompletely separated from the ventral horn by an amorphous band of gray matter surrounding the central canal termed ‘the spinal reticular matter’ in regard to its loosely structured cellular matrix. The gray matter of the ventral horn is the principal origin of fibers traveling outward in the ventral root to motor endplates or autonomic ganglia. The ventro-medial portion of the ventral horn gives rise to motor fibers controlling striated muscle and is therefore termed the somatic motor column. The dorso-latera] portion of the ventral horn gives rise to motor fibers controlling smooth muscle and visceral organs and is therefore termed ‘the visceral motor column’. The great expansion of the visceral motor column within the intermediate spinal segments is termed ‘the lateral horn’ and is composed of a specialized intermedio-lateral gray column which gives rise to the white communicating ramus of the sympathetic autonomic nervous system.

The white matter surrounding the gray matter in the cord is com¬posed peripherally of ascending and descending fiber tracts and more centrally of short connections between proximal segments. Many types of sensory fibers also branch at the level of entry, traveling in the centrally located fasciculus proprii before terminating in adjacent spinal segments. Fibers from cell bodies in the dorsal root ganglion pass directly up the spinal cord in the white matter between the paired dorsal horns. Those direct fibers travel in the dorsal column tract to reach the cuneate and gracile nuclei in the medulla. Another less dir¬ect somatosensory pathway is the spinothalamic tract, which reaches the diencephalon after an initial synapse in the spinal gray matter. Most descending spinal tracts descend from levels anterior to the medulla. The cortico-spinal tract emanates from the telencephalon while the rubro-spinal and interstitio-spinal tracts are derived from midbrain nuclei. These tracts synapse with interneurons in the spinal cord rather than the actual motor neurons, Several nuclei from the medulla proper also give rise to descending tracts including, but not limited to, the deep cerebellar nuclei and the lateral vestibular nucleus of Dieters. These more ancient tracts synapse in the motor-neuron region of the ventral horn. Generally the descending tracts travel ventrally while the ascending tracts pass dorsally in the spinal white matter. The predominance of white matter is greatest at the cervical level due to the additive inflow and outflow through this region.

This pattern fully extends into the brainstem, where the alar and basal plates contribute to the respective formation of the sensory and motor columns serving the identical functional components of the cranial nerves. The medulla oblongata, which is rostrally continuous with the spinal cord, accordingly, displays a similar longitudinal arrangement of functional columns. However, the brain stem flexure which forms the fourth ventricle of the medulla imposes a gaping open of the neuraxial format so that the homologues of both the dorsal and ventral horns subsequently come to lie in the floor of the fourth ventricle. This radical modification, in addition, modifies the relationship between the gray and white matter into an interlaced arrangement lacking the sharp boundary evident in the spinal cord. The orientation of the functional columns in the rhomboid fossa of the ventricle are from dorsal to ventral defined as 1) somatic sensory column, 2) visceral sensory column, 3) visceral motor column, and 4) somatic motor column, The visceral motor column of the medulla is distinguished as containing the cranial nerve nuclei that give rise to parasympathetic nervous system. The dorsal and ventral nerve roots of the medulla do not unite into a single mixed cranial nerve, in contrast to the arrangement seen in the spinal cord. The dorsal and ventral spinal roots in Amphioxus and the lamprey eel, however, are segmented similar to the cranial nerve arrangement, suggesting that this orientation is most fundamental. This alar plate/ basal plate pattern of organization shows fundamental differences when the neuraxial levels anterior to the brainstem are analyzed. The basal plate only superficially extends into the diencephalon, giving rise to the ventrally situated hypothalamic group of nuclei. The somato-motor component of the basal plate actually stops short of extending into the diencephalon, explaining its lack of a corresponding cranial motor component. The hypothalamus rather appears to have been formed exclusively from the continuation of the viscero-motor component of the basal plate, corroborated this region's well documented autonomic functions of thermal and circulatory regulation, as well as hunger and thirst expression mediated through hormonal control. The hypothalamus has significantly been described as the head ganglion of the autonomic nervous system (Mac Lean, 1949), suggesting exactly this type of visceral the motor control. The vast remaining upper regions of the human diencephalon are alternately derived from continuities with the sensory alar plate. The alar plate origins of the dorsal thalamus impart a purely sensory mode of function to this most highly developed subdivision within the diencephalon.

Human embryological examinations further demonstrate that the cerebrum hemispheres comprising the telencephalon (or endbrain) alternately arise as laterally-symmetric outpouchings that bud off each side of the diencephalon. This formation of the telencephalic hemisphere's from the dorsal alar plate region of the diencephalon gives the hemisphere regions of the forebrain as well their purely sensory functional characteristics. A general overview of these significant embryological findings leads to the logical conclusion that both the human cerebral hemispheres and the thalamus are derived from the same the variety of alar plate primordium that similarly gave rise to the dorsal horn gray matter of the brain stem and spinal cord.

The forebrain is split into two major subdivisions corresponding to the functional specificity of the visual and olfactory sets of cranial nerves. The first cranial (olfactory) nerve is functionally specific to the paired cerebral hemispheres which collectively comprise what is termed the telencephalon. The paired telencephalic hemispheres arise as bilateral outpouchings of the other major subdivision of the forebrain, the diencephalon. The diencephalon represents the major termination site for the second cranial (optic) nerve. The olfactory nerve connects to the paired olfactory bulbs within the telencephalon, whereas the optic nerve links the retina of each eye with the thalamus of the diencephalon. They is highly specialized nerve bundles differ fundamentally from those of the rest of the neuraxis with respect to the total lack of an associated motor component. Both the First and Second cranial nerves relay strict olfactory or optic sensibility without any counter-directed component to the musculature of either the head or the body. Research concerning the embryological development of the human forebrain and spinal cord significantly explains these functional differences in the organization of the forebrain cranial nerves.

The human brainstem has preserved much of its primordial segmental organization, despite the many modifications of the cranium that have occurred over the course of vertebrate evolution. Although the spinal nerves have consistently innervated the evolutionarily stable vertebral column, the cranial nerves of the brainstem originally served the primordial function of innervating the branchial gill clefts in man's filter feeding, aquatics ancestors. The branchial clefts our bilaterally symmetrical outpouchings of the pharnyx in both ancestral filter feeders and modern jaw-bearing fishes. The branchial clefs are supported by bony branchial arches, rather then vertebrae. The branchial clefts in modern fishes evolved into gas-exchanging gills, surplanting the outmoded nutrient function of ancestral forms. The further vertebrate transition to a terrestrial habitat resulted in the radical modification of the gill clefts into alternate structures subserving terrestrial specializations.

The human complement of brainstem-cranial nerves represents highly modified adaptations of the original branchial nerve format of the fishes. The human cranial nerves are still structured around the basic sensorimotor format of functional components previously demonstrated for the spinal nerves. The nerve cell bodies of the cranial sensory component lie entirely within the chain of cranial nerve ganglia within the brainstem. The primary motor-neuron divisions of the cranial nerves are alternately concentrated in a separate functional gray column within the central brainstem. The cranial nerves further differ from the spinal nerves in that each cranial nerve became specialized during evolution in the development of one or more of its sensory or motor components at the expense of its remaining features. In this regard, each cranial nerve became functionally unique during the final stages of vertebrate evolution.

The specialized nature of each cranial nerve brought about a radical reorganization of the mammalian brainstem. The nerve fibers within each branchial nerve underwent rearrangement according to function, rather than their level of entry into the brainstem. For instance, the cutaneous sensory distribution of the fifth (trigeminal) cranial nerve this progressively expanded to cover most of the head region, while the skin sense components of the rest of the cranial nerves become greatly diminished (Sarnat and Netsky, 1974). The long rosto-caudal extent of the sensory nucleus of the trigeminal nerve seems to facilitate the incorporation of functionally homologous fibers from adjacent brachial nerves. The eighth (auditory) cranial nerve is similarly cited as being derived from the special sensory components of the seventh, ninth, and tenth cranial nerves. The cranial motor nuclei are, in similar fashion, prolonged along the longitudinal axis of the brainstem in order to secure a reasonable amount of somatomotor continuity. This functional reorganization of the brainstem undoubtedly has interrupted much of the continuity that was primordially in evidence within the neuraxial column. In terms of the more regular spinal cord, this continuity serves to unite each neuromere segments with ones that are next in line. For the brainstem, however, the cells within the sensory and motor columns migrate to form elongated clumps of nuclei rather than remaining in continuous columns. This radical modification of the brainstem effectively obscures any obvious sequence of connectivity of the type demonstrated between the adjacent laminae of the dorsal spinal horn. It is instead necessary to inspect the higher forebrain levels of the human nervous system for clues to the continuity of this pattern at these higher levels.

The forebrain is split into two major subdivisions corresponding to the functional specificity of the visual and olfactory sets of cranial nerves. The first cranial (olfactory) nerve is functionally specific to the paired cerebral hemispheres which collectively comprise what is termed the telencephalon. The paired telencephalic hemispheres arise as bilateral outpouchings of the other major subdivision of the forebrain, the diencephalon. The diencephalon represents the major termination site for the second cranial (optic) nerve. The olfactory nerve connects to the paired olfactory bulbs within the telencephalon, whereas the optic nerve links the retina of each eye with the thalamus of the diencephalon. They is highly specialized nerve bundles differ fundamentally from those of the rest of the neuraxis with respect to the total lack of an associated motor component. Both the First and Second cranial nerves relay strict olfactory or optic sensibility without any counter-directed component to the musculature of either the head or the body. Research concerning the embryological development of the human forebrain and spinal cord significantly explains these functional differences in the organization of the forebrain cranial nerves.

The human forebrain significantly departs from the orderly pattern of neuraxial segmentation already cited for the brainstem and spinal cord. The human forebrain actually dwarfs the entire remainder of the brain, yet only two of the total complement of twelve cranial nerves actually enter into the forebrain. These two cranial nerves respectively deal with the special vertebrates senses of sight and smell. The senses are regarded as special because they arise later in neural evolution than the more phylogenetically ancient skin and body senses conveyed by the cranial and spinal nerves. For instance, in the ancient vertebrate filter feeding ancestor such as Amphioxus, the neuraxis already shows a complete complement of spinal and branchial nerves, although there is not a trace of any of the special senses of vision or olfaction. Amphioxus correspondingly exhibits very little of what can be classified as a forebrain, the neuraxis essentially ends at the upper limit of the brainstem. It is only at the vertebrate stage of development but the visual and olfactory senses come into prominence with the expansion of the rostral end of the neural tube to form the forebrain.