16.1 Brainstem, Organization and External Structure
a Anterior view. The sites of entry and emergence of the ten pairs of true cranial nerves (III—XII) are particularly well displayed in this view.
Note: Cranial nerve II (optic nerve) is a derivative of the diencephalon. Note also the site below the pyramids where the pyramidal fibers cross over the midline from each side (decussation of the pyramids). Most of the axons of the large motor pathway for the trunk and limbs cross to the opposite side at this level.
b Posterior view. Since the cerebellum has been removed, we can see the rhomboid fossa, which forms the floor of the fourth ventricle. The surface of the fossa is raised by several cranial nerve nuclei, which bulge into the fourth ventricle. The cerebellum is connected to the brainstem by three cerebellar peduncles on each side:
• Superior cerebellar peduncle
• Middle cerebellar peduncle
• Inferior cerebellar peduncle
The superior and inferior cerebellar peduncles border portions of the rhomboid fossa and thus contribute to the boundaries of the fourth ventricle.
c Left lateral view. In addition to the cerebellar peduncles, this view displays the superior and inferior colliculi. Together with their counterparts on the right side, the colliculi form the quadrigeminal plate (see b), which is a prominent structure of the mesencephalon. The two superior colliculi are part of the visual pathway, while the inferior colliculi are part of the auditory pathway. The trochlear nerve (CN IV) runs forward below the inferior colliculus, and is the only cranial nerve that emerges from the dorsal side of the brainstem. The olive appears as a prominence on the side of the medulla oblongata. The nuclei within the olive function as a relay station for the motor system (see p.342).
A Cranial nerve nuclei in the brainstem
a Posterior view with the cerebellum removed, exposing the rhomboid fossa; b Midsagittal section of the right half of the brainstem viewed from the left side.
The diagrams show the nuclei themselves and the course of the tracts leading to and away from them (to save space, the vestibular and cochlear nuclei are not shown).
The arrangement of the cranial nerve nuclei is easier to understand when we divide them into functional nuclear columns. The motor nuclei,
В Overview of the nuclei of cranial nerves III—XII which give rise to the efferent fibers, are shown on the left side of diagram a, and the sensory nuclei, where the afferent fibers terminate, are shown in b. The arrangement of these nuclei can be derived from the arrangement of the nuclei in the spinal cord (see p. 68). The function and connections of some of these cranial nerves can be clinically evaluated by testing the brainstem reflexes (whose relay centers are located in the brainstem). These reflexes are important in the evaluation of comatose patients. A prime example is the pupillary reflexes, which are described more fully on p. 363.
Motor nuclei: give rise to efferent (motor) fibers, left in Aa
Sensory nuclei: where afferent (sensory) fibers terminate, right in Aa
Somatic efferent or somatic motor nuclei (red):
• Nucleus of oculomotor nerve (CN III)
• Nucleus of trochlear nerve (CN IV)
• Nucleus ofabducent nerve (CN VI)
• Nucleus of accessory nerve (CN XI)
• Nucleus of hypoglossal nerve (CN XII)
Somatic afferent (somatic sensory) and vestibulocochlear nuclei (yellow):
Sensory nuclei associated with the trigeminal nerve (CN V):
• Mesencephalic nucleus of trigeminal nerve (special feature: pseudounipolar ganglion cells (“displaced sensory ganglion”), provide direct sensory innervation for muscles of mastication)
• Principal (pontine) sensory nucleus of trigeminal nerve
• Spinal nucleus of trigeminal nerve
Visceral efferent (visceral motor) nuclei:
Nuclei associated with the parasympathetic nervous system
• Visceral oculomotor (Edinger-Westphal) nucleus (CN III)
• Superior salivatory nucleus (facial nerve, CNVII)
• Inferior salivatory nucleus (glossopharyngeal nerve, CN IX)
• Dorsal vagal nucleus (CNX)
Nuclei of the vestibulocochlear nerve (CN VIII):
о Vestibular part:
• Medial vestibular nucleus • Lateral vestibular nucleus
• Superior vestibular nucleus • Inferior vestibular nucleus о Cochlear part:
• Anterior cochlear nucleus • Posterior cochlear nucleus
Nuclei of the branchial arch nerves (dark blue):
• Trigeminal motor nucleus (CN V)
• Facial nucleus (CNVII)
• Nucleus ambiguus (glossopharyngeal nerve, CN IX; vagus nerve, CN X; accessory nerve, CN XI, cranial root)
Visceral afferent (visceral sensory) nuclei (green):
• Nucleus of the solitary tract (nuclear complex):
о Superior part:
• Special visceral afferents (taste) from facial (CN VII), glossopharyngeal (CN IX), and vagus (CN X) nerves
о Inferior part:
• General visceral afferents from glossopharyngeal (CN IX) and vagus (CN X) nerves
16.2 Brainstem: Cranial Nerve Nuclei, Red Nucleus, and Substantia nigra
D Cross-sectional structure of the brainstem at different levels
Transverse sections through the a mesencephalon, b pons, and c medulla oblongata, viewed from above.
A feature common to all three sections is the dorsally situated tegmentum (“hood,” medium gray), the phylogenetical ly old part of the brainstem. The tegmentum of the adult brain contains the brainstem nuclei. Anterior to the tegmentum are the large ascending and descending tracts that run to and from the telencephalon. This region is called the cerebral peduncle (crus cerebri) in the mesencephalon, the basilar part (foot) of the pons at the pontine level, and the pyramids in the medulla oblongata. The tegmentum is covered dorsally by the tectum (= “roof”) only in the region of the mesencephalon. In the mature brain pictured here, this structure forms the quadrigeminal plate containing the superior and inferior colliculi (“little hills”), shown faintly in Da. The brainstem is covered by the cerebellum at the level of the medulla oblongata and pons and therefore lacks a tectal covering at those levels.
C Location of the substantia nigra and red nucleus in the mesencephalon
Both of these nuclei, like the cranial nerve nuclei, are well-defined structures that belong functionally to the extrapyramidal motor system. Anatomically, the substantia nigra is part of the cerebral peduncles and therefore is not located in the tegmentum of the mesencephalon (see A, p. 234). Owing to their high respective contents of melanin and iron, the substantia nigra and red nucleus appear brown and red, respectively, in sections of fresh brain tissue. Both nuclei extend into the diencephalon and are connected to its nuclei by fiber tracts (see E).
E Afferent (blue) and efferent (red) connections of the red nucleus and substantia nigra
These two nuclei are important relay stations in the motor system. The red nucleus consists of a larger neorubrum and a smaller paleorubrum. It receives afferent axons from the dentate nucleus (dentatorubral tract), superior colliculi (tectorubral tract), inner pallidum (pallidorubral tract), and cerebral cortex (corticorubral tract). The red nucleus sends its axons to the olive (rubro-olivary fibers and reticulo-olivary fibers, part of the central tegmental tract) and to the spinal cord (rubrospinal tract). It coordinates muscle tone, body position, and gait. A lesion of the red nucleus produces resting tremor, abnormal muscle tone (tested as involuntary muscular resistance of the joints in the relaxed patient), and choreoathetosis (involuntary writhing movements, usually involving the distal parts of the limbs). The substantia nigra consists of a compact part (dark, contains melanin) and a reticular part (reddish, contains iron; for simplicity, the entire substantia nigra appears dark in the drawing). Most of its axons project diffusely to other brain areas and are not collected into tracts. Axons from the caudate nucleus (striatonigral fibers), anterior cerebral cortex (corticonigral fibers), putamen, and precentral cortex terminate in the substantia nigra.
16.3 Brainstem: Reticular Formation
A Structural-functional relationships in the reticular formation
Midsagittal section of the brainstem viewed from the left side. While the cranial nerve nuclei, substantia nigra, and red nucleus have well-defined boundaries, as we have seen, the reticular formation (light green) is a relatively diffuse network of nerve cells and fibers in the brainstem, ocupying the areas between the cranial nerve nuclei described above. It can be roughly divided into two main groups of nuclei:
• Medial group (specific nuclei labeled in the diagram): nuclei containing large neurons whose axons form long ascending and descending tracts (see E).
• Lateral group (not individually labeled in the diagram): nuclei containing small neurons whose axons usually stay within the brainstem. They are therefore called “association areas.”
Besides respiratory and circulatory regulation, the diffuse neuronal network of the reticular formation performs many other important autonomic functions that are mapped in the diagram neurotransmitters. Diagram В shows several nuclear regions and their neurotransmitters in some detail.
В Nuclear regions and neurotransmitters in the reticular formation
Posterior view of the brainstem (cerebellum removed). Reticular formation shown in green. Several nuclear regions and neurotransmitters are shown here. Left side: classification of the nuclear regions; right side: distribution of neurotransmitters in the nuclear regions. The nuclear regions of the reticular formation can be classified by their location (medial or lateral groups of nuclei, see A) or by the neurotransmitters they contain:
• Serotonergic (purple = serotonin)
• Cholinergic (red = acetylcholine)
• Noradrenergic (light blue = norepinephrine)
• Dopaminergic (orange = dopamine)
• Adrenergic (yellow = epinephrine)
The nuclei that flank the midline are called the raphe nuclei (shown in purple, raphe = “seam”). They contain the neurotransmitter seratonin, and their neurons project to the hypothaloamus, limbic system, and neocortex. The locus ceruleus (shown in blue, caeruleus = “blue”) is a region that actually appears blue in the fresh brain. This nucleus contains noradrenergic neurons which send axons to the cerebellum, hypothalo- mus, and cerebral cortex.
C Respiratory center in the reticular formation
a Posterior view with the cerebellum removed. b Transverse section at the level indicated, showing that the two nuclear groups in a do not lie in the same vertical plane.
An important autonomic function of the reticular formation is the regulation of breathing. The neurons controlling respiration are divided into an inspiratory group (red) and an expiratory group (blue). Their size is only approximate (as shown here) due to the extensive arborization of the axons and dendrites of these neurons. Respiratory rhythm is controlled by a group of cells in the ventral medulla called the pre-Bôtzinger complex. When portions of the rhythmogenic neurons in this complex are destroyed in the rat, periods of apnea may be observed even during the day when activity normally peaks. It is believed that the loss of more than 60% of these cells (which number in the thousands) is responsible forthe development of sleep apnea in elderly patients.
D Circulatory center in the reticular formation of the cat (after Kahle)
a Dorsal view, b transverse sections at the levels indicated.
Another important function of the reticular formation is circulatory regulation. The neurons responsible for this function have a diffuse arrangement similar to that of the respiratory neurons. Stimulating certain regions (dark red) via electrodes inserted into the reticular formation will cause the blood pressure to rise while stimulating other regions (pale red, depressor center) will cause it to fall.
E Branching pattern of a neuron in the reticular formation of the rat brainstem (after Scheibel)
Midsagittal section viewed from the left side. Neurons can be selectively visualized by the silver-impregnation (Golgi) staining method. The axon of the neuron shown here divides into an ascending branch, which comes into contact with the diencephalic nuclei (shown in brown) and a descending branch, which establishes connections with cranial nerve nuclei (green) in the pons and medulla oblongata. This extensive arborization allows neurons of the reticular formation to have widespread effects on multiple brain regions.
16.4 Brainstem: Descending and Ascending Tracts
A Descending tracts in the brainstem
a Midsagittal section viewed from the left side, b Posterior view with the cerebellum removed.
The descending tracts shown here begin in the telencephalon and terminate partly in the brainstem but mostly in the spinal cord. The most prominent tract that descends through the brainstem, the corticospinal tract, terminates in the spinal cord. Its axons a rise from large pyramidal neurons of the primary motor cortex and terminate on or near alpha motor neurons in the anterior horn of the spinal cord. Most of the axons cross to the opposite side (decussate) at the level of the pyramids. The fibers in this part of the pyramidal tract that descend through the brainstem are called corticospinal fibers. Those fibers in the pyramidal tract that terminate in the brainstem are called corticonuclear fibers. Corticonuclear axons connect the motor cortex to the brainstem motor nuclei of the cranial nerves.
Note: Direct cortical projections to the brainstem nuclei are predominantly:
• bilateral for:
- the trigeminal motor nucleus (CN V)
- neurons in the facial nucleus (CN VII) that innervate muscles in the forehead
- nucleus ambiguus (CNX)
• contralateral (crossed) for:
- the nucleus of the abducent nerve (CN VI)
- neurons in the facial nucleus (CN VII) that innervate muscles in the lower face
- the nucleus of the hypoglossal nerve (CN XII)
• ipsilateral for:
- neurons in the nucleus of the accessory nerve (CN XI) that innervate the sternocleidomastoid muscle
The pattern of corticonuclear innervation is important in the diagnosis of different lesions, particularly involving the facial nerve (CN VII; see D, p. 79). Most cortical projections to the brainstem motor nuclei, however, are indirect, involving intermediate neurons, many of which are located in the surrounding reticular formation. Direct cortical control of brainstem motor neurons, specifically for the tongue and face, seems to be a recent evolutionary development, present in primates but not in other mammals. The nuclei of the oculomotor (CN III) and trochlear (CN IV) nerves, which do not receive direct cortical projections, are synaptically connected with the abducent nucleus through the medial longitudinal fasciculus (see D, p. 321), a brainstem tract that contains both ascending and descending fibers.
В Ascending tracts in the brainstem
a Left lateral view, b posterior view.
Two major ascending fiber bundles, the posterior funiculus (violet) and the lateral spinothalamic tract (dark blue), carry sensory information from the spinal cord to the brainstem. The posterior funiculus consists of the medial fasciculus gracilis, from the lower limb and trunk, and the lateral fasciculus cuneatus, from thoracic and cervical levels. Many of the fibers in these tracts are the central processes of dorsal root ganglion cells whose peripheral processes are in muscle spindles and tendon stretch receptors (proprioception) and cutaneous touch receptors. The first synapse in this ascending pathway is in the nucleus gracilis or nucleus cuneatus; the neurons from these nuclei send their axons in the medial lemniscus (lemniskos = “ribbon,” Gr.) across the midline to the thalamus (see p. 216, 218). The lateral spinothalamic tract bears pain and temperature information from secondary neurons in the contralateral spinal cord, passing without an additional synaptic relay directly to the thalamus.
The other ribbon-like sensory tract in the brainstem - the lateral lemniscus -contains axons from the cochlear nuclei, some of which cross the midline in the trapezoid body, to synapse in the inferior colliculus of the quadrigeminal plate.
C Courses of the major cerebellar tracts through the brainstem
a Midsagittal section viewed from the left side,
b Posterior view with the cerebellum removed.
The cerebellum is involved in the coordination of movement. Descending tracts (red) and ascending tracts (blue) enter the cerebellum through the superior, middle, and inferior cerebellar peduncles.
• Superior cerebellar peduncle: contains most of the efferent axons from the cerebellum (see p. 242). The only major afferent axon tract entering the cerebellum through the superior peduncle is the anterior spinocerebellar pathway.
• Middle cerebellar peduncle: largest of the three peduncles, occupied mostly by afferent fibers from contralateral basal pontine nuclei. These afferent fibers are the second step of a massive descending cortico-pontine to ponto-cerebellar projection.
• Inferior cerebellar peduncle: contains the afferent posterior spinocerebellar and olivocerebellar tracts. The posterior spinocerebellar tract enters і psi laterally, the olivocerebellar tract from the contralateral (inferior) olivary nuclei.
16.5 Mesencephalon and Pons, Transverse Section
A Transverse section through the mesencephalon (midbrain)
Nuclei: The most rostral cranial nerve nucleus is the relatively small nucleus of the oculomotor nerve (see B, p.226). In the same transverse plane is the mesencephalic nucleus of the trigeminal nerve; other trigeminal nuclei can be identified in sections at lower levels (see C). Unique in the CNS, the mesencephalic nucleus of the trigeminal nerve contains displaced pseudounipolar sensory neurons, closely related to the PNS neurons of the trigeminal ganglion (both populations are derived embryon- ically from the neural crest). The peripheral processes of these mesencephalic neurons are proprioceptors in the muscles of mastication. The superior collicular nucleus is part of the visual system. The red nucleus and substantia nigra are involved incoordination of motor activity. The red nucleus and all of the cranial nerve nuclei are located in the tegmentum of the mesencephalon, the superior colliculus is in the tectum (roof) of the mesencephalon, and the substantia nigra is in the cerebral peduncle (see C, p. 229). Different parts of the reticular formation, a diffuse aggregation of nuclear groups (see p. 230,231), are visible here and in sections below.
Tracts: The tracts at this level run anterior to the nuclear regions. Prominent descending tracts seen at this level include the pyramidal tract and the corticonuclear fibers that branch from it. Ascending tracts visible at this level include the lateral spinothalamic tract and the
medial lemniscus, both of which terminate in the thalamus.
В Transverse section through the upper pons
Nuclei: The only cranial nerve nucleus appearing in this plane of section is the mesencephalic trigeminal nucleus. It can be seen that the fibers from the nucleus of the trochlear nerve (CN IV) cross to the opposite side (decussate) while still within the brainstem.
Tracts: The ascending and descending tract systems are the same as in A and C. The pyramidal tract appears less compact at this level compared with the previous section due to the presence of intermingled pontine nuclei. This section cuts the tracts (mostly efferent) that exit the cerebellum through the superior cerebellar peduncle. The lateral lemniscus at the dorsal surface of the section is part of the auditory pathway. The relatively large medial longitudinal fasciculus extends from the mesencephalon (see A) into the spinal cord. It interconnects the brainstem nuclei and contains a variety of fibers that enter and emerge at various levels (“highway of the brainstem nuclei”). The smaller dorsal longitudinal fasciculus connects hypothalamic nuclei with the parasym pathetic cranial nerve nuclei. The size and location of the nuclei of the reticular formation, which here are shown graphically within a compact area, vary with the plane of the section. This diagram indicates only the approximate location of the reticular formation, and other smaller nuclei and fibers may be found within these regions.
C Transverse section through the midportion of the pons
Nuclei: The trigeminal nerve leaves the brainstem at the midlevel of the pons, its various nuclei dominating the pontine tegmentum. The principal sensory nucleus of the trigeminal nerve relays afferents for touch and discrimination, while its spinal nucleus relays pain and temperature fibers. The trigeminal motor nucleus contains the motor neurons for the muscles of mastication.
Tracts: This section cuts the anterior spinocerebellar tract, which passes to the cerebellum, immediately dorsal to the pons.
CSF space: At this level the cerebral aqueduct has given way to the fourth ventricle, which appears in cross section. It is covered dorsally by the medullary velum.
D Transverse section through the lower pons
Nuclei: The lower pons contains a number of cranial nerve nuclei including the nuclei of the vestibulocochlear and abducent nerves, and the facial (motor) nucleus. The rhomboid fossa is covered dorsally by the cerebellum, whose nuclei also appear in this section—the fastigial nucleus, emboliform nucleus, globose nucleus, and dentate nucleus.
Tracts: The trapezoid body with its subnuclei is an important relay station and crossing point in the auditory pathway (see p. 366). The central tegmental tract is an important pathway in the motor system.
16.6 Medulla oblongata, Transverse Section
A Transverse section through the upper medulla oblongata
Nuclei: The nuclei of the hypoglossal nerve, vagus nerve, vestibulocochlear nerve, and the spinal nucleus of the trigeminal nerve appear in the dorsal part of the medulla oblongata. The inferior olivary nucleus, which belongs to the motor system, is located in the ventral part of the medulla oblongata. The reticular formation is interposed between the cranial nerve nuclei and the inferior olivary nucleus. It appears in all the transverse sections of this unit.
Tracts: Most of the ascending and descending tracts are the same as in the previous unit. A new structure appearing at this level is the inferior cerebellar peduncle, through which afferent tracts pass to the cerebellum (see p.242).
CSF space: The floor of the fourth ventricle is the rhomboid fossa, which marks the dorsal boundary of this section.
В Transverse section just above the middle of the medulla oblongata
Nuclei: The only cranial nerve nuclei visible at this level are those of the hypoglossal nerve, vagus nerve, and trigeminal nerve, appearing in the dorsal medulla. The lower portion of the inferior olivary nucleus appears in the ventral medulla.
Tracts: The ascending and descending tracts are the same as in the previous unit. Ascending sensory tracts (from nuclei gracilis and cuneatus, see p. 233,326) decussate in the medial lemniscus. The solitary tract carries the gustatory fibers of cranial nerves V, VII, and X. Dorsolateral to it is the nucleus of the solitary tract (not shown). The pyramidal tract again appears as a compact structure at this level due to the absence of interspersed nuclei and decussating fibers.
C Transverse section just below the middle of the medulla oblongata
Nuclei: The nuclei of the hypoglossal, vagus, and trigeminal nerves appear at this level. The irregular outline of the inferior olivary nucleus is still just visible in the ventral medulla. The nuclei that relay signals from the posterior funiculus—the nucleus cuneatus and nucleus gracilis—appear prominently in the dorsal part of the section. The tracts that arise from these nuclei decussate in the medial lemniscus (see above).
Tracts: The ascending and descending tracts correspond to those in the previous diagrams. The rhomboid fossa, which is the floor of the fourth ventricle, has narrowed substantially at this level to become the central canal.
D Transverse section through the lower medulla oblongata
The medulla oblongata is continuous with the spinal cord at this level, showing no distinct transition.
Nuclei: The cranial nerve nuclei visible at this level are the spinal part of the trigeminal nerve and the nucleus of the accessory nerve. This section passes through the caudal ends of the nuclei in the relay station of the posterior funiculus—the nucleus cuneatus and nucleus gracilis.
Tracts: The ascending and descending tracts correspond to those in the previous diagrams of this unit. The section passes through the decussation of the pyramids, and we can now distinguish the anterior pyramidal tract (uncrossed) from the lateral pyramidal tract (crossed; see p. 338). CSF space: This section passes through a portion of the central canal, which is markedly smaller at this level than in C. It may even be obliterated at some sites, but this has no clinical significance.