BARR'S The Human Nervous System: An anatomical viewpoint, 9th Edition

PART 2 - Regional Anatomy of the Central Nervous System

Chapter 7

Brain Stem: Nuclei And Tracts

Important Facts

  • The brain stem contains ascending and descending tracts, cranial nerves and other nuclei, and fibers connecting with the cerebellum.
  • The spinothalamic tract, which crosses into the spinal cord, is laterally located throughout the length of the brain stem.
  • The medial lemniscus is formed from axons that arise in the contralateral gracile and cuneate nuclei. The lemniscus is near the midline in the medulla, shifts laterally in the pons, and is laterally situated in the tegmentum of the midbrain.
  • Corticopontine and corticospinal fibers occupy the basis pedunculi. Corticopontine fibers end in the pontine nuclei. Corticospinal fibers continue caudally, forming the pyramid. Most pyramidal fibers decussate at the caudal end of the medulla.
  • The inferior olivary complex of nuclei and the pontine nuclei project across the midline to the cerebellum into the inferior and middle cerebellar peduncles, respectively.
  • The superior cerebellar peduncles consist largely of fibers leaving the cerebellum. These decussate at the level of the inferior colliculi, and some end in the red nucleus at the level of the superior colliculus.
  • The substantia nigra and the periaqueductal gray matter are present at all levels of the midbrain.
  • The seven motor nuclei of cranial nerves are the oculomotor and trochlear nuclei in the midbrain, trigeminal motor nucleus in the pons, facial motor and abducens nuclei at the pontomedullary junction, and nucleus ambiguus and hypoglossal nucleus in the medulla.
  • Preganglionic parasympathetic nuclei include the Edinger-Westphal nucleus, the dorsal nucleus of the vagus, and some of the neurons in the nucleus ambiguus.
  • The only general somatic sensory nuclei are the three components (spinal, pontine, and mesencephalic) of the trigeminal nuclear complex. The only visceral sensory nucleus is the solitary nucleus, the most rostral part of which is the gustatory nucleus (for taste).
  • The two cochlear and four vestibular nuclei receive special somatic sensory fibers. The lateral lemniscus extends for the length of the pons. The medial longitudinal fasciculus maintains its dorsomedial position throughout the brain stem.
  • The level of a lesion in the brain stem is indicated by involvement of cranial nerves and their nuclei. The position of the lesion at a particular level is indicated by disordered function of ascending or descending tracts.

The principal nuclei and fiber tracts of the brain stem are described and illustrated in this chapter. Long tracts that traverse the brain stem are noted successively in the medulla, pons, and midbrain. Some pathways are also reviewed as functional systems in Chapters 19 and 23. The nuclei of cranial nerves are included among the cell groups identified, but systematic descriptions of the functional components of the cranial nerves are reserved for Chapter 8.

Sections stained by Weigert's method are used as illustrations; the levels of the sections are shown in Figure 7-1. Some tracts do not stand out as distinct entities in such sections; their locations and functions have been established from clinicopathological correlations in humans and from experimental work with laboratory animals.

The reticular formation is mentioned briefly here because the term is used in several contexts in this chapter. The reticular formation is a region in the dorsal parts of the medulla and pons, and it extends rostrally into the tegmentum of the midbrain. It is traversed by small bundles of myelinated axons that course in all directions, and it contains overlapping populations of neurons


that are not easily classified into groups, although numerous nuclei are recognized. The reticular formation has several functions of primary importance, including an influence on levels of consciousness and degrees of alertness (ascending reticular activating system); a role in the control of movement through efferents to the spinal cord and to motor nuclei of cranial nerves; and contributions to visceral and other involuntary activities through groups of neurons that function as cardiovascular and respiratory “centers.” In view of its special histological characteristics and functional importance, the reticular formation is discussed separately in Chapter 9, along with several smaller nuclei of the brain stem.


FIGURE 7-1 Key to the levels of the series of Weigert-stained sections of the brain stem that illustrate this chapter.


At the level of the pyramidal decussation, there is an extensive rearrangement of gray matter and white matter in the transitional zone between the spinal cord and the medulla. Theventral gray horns continue into the region of the decussation, where they include motor cells for the first cervical nerve and the spinal root of the accessory nerve. There, the gray matter is traversed obliquely by bundles of fibers that pass from the pyramids to the lateral corticospinal tracts (Figs. 7-2 and 7-3). The dorsal gray horns of the spinal cord are replaced by the spinal trigeminal nuclei. At the rostral ends of the dorsal funiculi, at the level of the pyramidal decussation, are the caudal ends of the gracile and cuneate nuclei.Above the decussation, the medulla has a complex structure that is entirely different from that of the spinal cord (Figs. 7-4, 7-5, 7-6, and 7-7).The inferior olivary nucleus, which is dorsal and lateral to the pyramid, is the most prominent feature of the rostral half of the medulla, and the base of the inferior cerebellar peduncle appears as a prominent area of white matter in the dorsolateral part of the medulla (see Fig. 7-7).


Medial Lemniscus System

The dorsal funiculus of the spinal cord transmits impulses for ipsilateral discriminative touch and proprioception. The gracile fasciculus is concerned with sensations from the leg and lower trunk, and the cuneate fasciculus carries signals from the upper trunk, arm, and neck. The gracile nucleus, in which fibers of the corresponding fasciculus terminate, is present throughout the closed portion of the medulla. The fibers of the cuneate fasciculus end in the cuneate nucleus, which is located laterally and slightly rostrally to the gracile nucleus (see Fig. 7-3).

The myelinated axons of the cells in the gracile and cuneate nuclei pursue a curved course to the midline as internal arcuate fibers, which are clearly shown in Figure 7-4. After crossing the midline in the decussation of the medial lemnisci, these fibers turn rostrally in the medial lemniscus. This is one of the most conspicuous tracts of the brain stem, occupying the interval between the midline and the inferior olivary nucleus in the medulla (see Figs. 7-6 and 7-7). Fibers that conduct sensory signals from the contralateral foot are most ventral (i.e., adjacent to the pyramid). The opposite side of the body is then represented sequentially, so that fibers for the neck are in the most dorsal part of the medial lemniscus. After traversing the pons and midbrain, the tract ends in the lateral division


of the ventral posterior (VP1) nucleus of the thalamus. This is the thalamic nucleus for general somatic sensation.


FIGURE 7-2 Junction of the medulla and spinal cord. Corticospinal fibers are passing from the pyramidal decussation into the lateral corticospinal tract (Weigert stain). (See inside front cover of book for abbreviations used in figures in this chapter.)


FIGURE 7-3 Medulla at the rostral end of the pyramidal decussation (Weigert stain). For abbreviations see inside front cover of book.



FIGURE 7-4 Medulla at the caudal end of the inferior olivary nucleus (Weigert stain). For abbreviations see inside front cover of book.

Spinothalamic and Spinotectal Tracts

The spinothalamic tract for pain, temperature, and touch on the opposite side of the body continues into the medulla without appreciable change in position. This is also true of the spinotectal (or spinomesencephalic) tract, which conveys somesthetic data to the superior colliculus and the reticular formation of the midbrain. The two tracts soon merge to form the spinal lemniscus, which traverses the lateral area of the medulla dorsal to the inferior olivary nucleus (see Figs. 7-4, 7-5, 7-6, and 7-7). The spinothalamic fibers continue to the ventral posterior nucleus of the thalamus and send branches also to the intralaminar and posterior groups of nuclei of the thalamus. (The thalamic nuclei are described in Chapter 11.)

Spinoreticular Fibers

The spinoreticular tracts in the ventral and lateral white matter of the spinal cord continue into the brain stem, where their constituent axons synapse with cells of the reticular formation. They transmit sensory data, especially from the skin and internal organs. Some spinoreticular fibers are collateral branches of fibers of the spinothalamic tract. Axons of cells in the reticular formation project caudally to the spinal cord and rostrally to the thalamus.

There are at least three routes from the spinal cord to the thalamus and cerebral cortex. The medial lemniscus system proceeds without interruption, mainly to the ventral posterior thalamic nucleus, which, in turn, projects to the primary somatosensory area of the cerebral cortex. The neospinothalamic system, a mammalian pathway, consists of the axons of the tract cells that do not have collateral branches to the reticular formation. Sensory signals also reach the intralaminar group of thalamic nuclei through the paleospinothalamic system, which exists in all vertebrate animals. This less direct pathway consists of spinoreticular fibers (i.e., ones that are not collaterals of the spinothalamic tract) and reticulothalamic fibers, which are the rostrally projecting axons of neurons of the reticular formation. These ascending


fibers form the reticular formation end in the intralaminar nuclei, which project to the cerebral cortex generally. This diffuse pathway influences levels of consciousness and degrees of alertness, and it is also involved in the awareness (but not the localization) of pain.


FIGURE 7-5 Medulla at the level of transition between its closed and open parts (Weigert stain). For abbreviations see inside front cover of book.

Spinocerebellar Tracts

The dorsal and ventral spinocerebellar tracts, which carry proprioceptive signals mainly from the lower limb, are located near the lateral surface of the medulla (see Figs. 7-2, 7-3,7-4, 7-5, and 7-6). The dorsal tract, which is uncrossed, originates in the nucleus thoracicus (nucleus dorsalis or Clarke's column) of the thoracic and upper lumbar segments of the spinal cord. The ventral tract, on the other hand, is largely crossed, and most of its cells of origin are in the lumbosacral enlargement of the spinal cord. The dorsal spinocerebellar fibers enter the inferior cerebellar peduncle (see Figs. 7-7 and 7-8), and the ventral spinocerebellar tract continues through the pons and enters the cerebellum by way of the superior cerebellar peduncle. The spinocerebellar tracts serve the lower limb. For the upper limb, equivalent pathways involve the external cuneate nucleus.


External Cuneate Nucleus

The external or accessory cuneate nucleus is lateral to the cuneate nucleus (see Fig. 7-5). The afferents to the external cuneate nucleus are fibers that enter the spinal cord in cervical dorsal roots, and many of them are collateral branches of axons that end in the cuneate nucleus. Efferents from the external cuneate nucleus enter the cerebellum by way of the inferior peduncle. These cuneocerebellar fibers provide a pathway to the cerebellum from proprioceptive and other sensory endings in the neck and upper limb. The functions of the


external cuneate nucleus and cuneocerebellar tract are equivalent to those of the nucleus thoracicus and the dorsal spinocerebellar tract: both transmit proprioceptive signals along rapidly conducting axons to areas of cortex in and near the midline of the cerebellum (see Chapter 10).


FIGURE 7-6 Medulla at the mid-olivary level (Weigert stain). For abbreviations see inside front cover of book.


FIGURE 7-7 Rostral end of the medulla (Weigert stain). For abbreviations see inside front cover of book.



FIGURE 7-8 Caudal region of the pons (Weigert stain). For abbreviations see inside front cover of book.

Inferior Olivary Complex of Nuclei

Several groups of neurons in the medulla and pons are known as precerebellar nuclei. They receive afferents from various sources and project to the cerebellum. These nuclei include the components of the inferior olivary complex. The largest component is the inferior olivary nucleus, which is shaped like a crumpled bag or purse with the hilus facing medially (see Figs. 7-5, 7-6, and 7-7). The inferior olivary complex receives afferents from the contralateral dorsal horn of all levels of the spinal cord and from the ipsilateral red nucleus (in the midbrain) and cerebral cortex.

The central tegmental tract is in part a pathway from the red nucleus and the periaqueductal gray matter of the midbrain to the inferior olivary complex. The terminal part of the central tegmental tract forms a dense layer on the dorsal surface of the inferior olivary nucleus, best seen in Figure 7-7. The tract also contains fibers that ascend to the diencephalon from the reticular formation of the brain stem and from the solitary nucleus (of the medulla).

Olivocerebellar fibers constitute the projection from the inferior olivary complex. Fibers from the principal nucleus occupy its interior and leave through the hilus. After decussating in the midline, the strands of myelinated olivocerebellar fibers curve in a dorsolateral direction through the reticular formation and enter the inferior cerebellar peduncle, of which they are the largest single component (see Fig. 7-7). The inferior olivary complex is the source of climbing fibers, which terminate on and excite the Purkinje cells in all parts of the cerebellar cortex. Physiological studies indicate that the inferior olivary complex of nuclei channels into the cerebellum programs of instructions for


subsequent use in the coordination of learned patterns of movement.

Arcuate Nucleus

The arcuate nucleus on the surface of the pyramid (see Fig. 7-4) receives collateral branches of corticospinal fibers. The axons of cells in the arcuate nucleus enter the cerebellum by way of the inferior cerebellar peduncle, which they reach by two routes. Some travel over the lateral surface of the medulla as the external arcuate fibers; the remainder run dorsally in the midline of the medulla and then laterally in the striae medullares in the floor of the fourth ventricle. The connections of the arcuate nucleus are similar to those of the pontine nuclei (in the ventral part of the pons; see Chapter 10). Both receive afferents from the ipsilateral cerebral cortex and project across the midline to the cerebellum.

Lateral Reticular Nucleus

This exceptionally distinct group of cells of the reticular formation is dorsal to the inferior olivary nucleus and medial to the spinal lemniscus, near the surface of the medulla (seeFigs. 7-4, 7-5, and 7-6). It receives afferents from the spinal cord and projects to the cerebellum. Other precerebellar reticular nuclei are described in Chapter 9.


Corticospinal (Pyramidal) Tract

The parent cell bodies of the corticospinal (pyramidal) tract are located in an area of cerebral cortex that occupies adjoining regions of the frontal and parietal lobes. Their axons traverse the subcortical white matter, the internal capsule, and the brain stem. In the medulla, each corticospinal tract is a compact body of white matter in the pyramid (see Figs. 7-4, 7-5, 7-6, and 7-7).

In most people, about 85% of corticospinal fibers cross over in the decussation of the pyramids. The rostral end of this decussation appears in Figure 7-3, and a bundle of axons passing through the gray matter from a pyramid to the opposite lateral corticospinal tract is shown in Figure 7-2. The 15% of nondecussating fibers continue into the ventral funiculus of the cord as the ventral corticospinal tract. Corticospinal fibers terminate in the base of the dorsal horn, the intermediate gray matter, and the ventral horn; a few synapse directly with motor neurons. Each pyramid contains approximately 1 million axons of varying size. The widest and most rapidly conducting ones come from the giant pyramidal cells of Betz in the primary motor area; these are the fibers believed to end in synaptic contact with the cell bodies of spinal motor neurons.

The corticospinal tracts are often thought of as having an exclusively motor function, and this is, indeed, their major function. Many axons of cortical origin arise in the primary somatosensory area (see Chapter 15); however, these modulate the transmission of sensory signals to the brain, by synapsing with neurons in the gracile and cuneate nuclei and in the dorsal horn of the spinal cord.

Tracts That Originate in the Midbrain

The central tegmental tract has already been mentioned as arising from the ipsilateral red nucleus and other gray areas of the midbrain. It terminates in the inferior olivary complex. A tiny bundle of axons from the contralateral red nucleus continues caudally as the rubrospinal tract, which comes to occupy a position ventral to the lateral corticospinal tract. In humans, this tract ends in the upper two cervical segments of the spinal cord.

The tectospinal tract originates in the superior colliculus of the midbrain, and the fibers cross at that level to the opposite side of the brain stem. The tract (see Fig. 5-10) is probably insignificantly small in humans. Tectobulbar fibers go from the superior colliculus to the reticular formation of the pons and upper medulla. They are involved in the control of eye movements (see Chapter 8).


Hypoglossal, Accessory, Vagus, and Glossopharyngeal Nerves

The hypoglossal nucleus, which contains motor neurons for the tongue muscles, is near the midline throughout most of the medulla in the central gray matter of the closed part (seeFig. 7-4) and beneath the hypoglossal trigone of the


rhomboid fossa (see Figs. 7-5, 7-6, and 7-7). The axons leaving the nucleus pass ventrally between the medial lemniscus and the inferior olivary nucleus (see Figs. 7-5 and 7-6) and then continue lateral to the pyramid, emerging as the rootlets of the hypoglossal nerve along the sulcus between the pyramid and the olive. The nucleus ambiguus lies within the reticular formation, dorsal to the inferior olivary nucleus (Figs. 7-5, 7-6, and 7-7). This important cell column supplies the muscles of the soft palate, pharynx, larynx, and upper esophagus through the cranial root of the accessory nerve and the vagus and glossopharyngeal nerves. It also contains parasympathetic neurons whose axons end in the cardiac ganglia and control the heart rate. The dorsal nucleus of the vagus nerve is the largest parasympathetic nucleus in the brain stem; it contains the cell bodies of preganglionic neurons that regulate the activities of smooth muscle and glandular elements of the thoracic and abdominal viscera. The nucleus lies lateral to the hypoglossal nucleus in the gray matter that surrounds the central canal (see Fig. 7-4) and extends rostrally beneath the vagal trigone of the rhomboid fossa (see Figs. 7-5, 7-6, and 7-7).

A bundle of visceral afferent fibers known as the solitary tract lies along the lateral side of the dorsal nucleus of the vagus nerve (see Figs. 7-5, 7-6, and 7-7). This tract consists of caudally directed axons from the inferior ganglia of the vagus and glossopharyngeal nerves and the geniculate ganglion of the facial nerve. The fibers terminate in the solitary nucleus (nucleus of the solitary tract), a column of cells that lies adjacent to and partly surrounds the tract. The vagal and glossopharyngeal afferents to the caudal part of the solitary nucleus have important roles in visceral reflexes. Fibers mediating the sense of taste (mostly from ganglia of the facial and glossopharyngeal nerves) go to the rostral end of the nucleus.

Vestibulocochlear Nerve

Nuclei in the rostral part of the medulla receive afferent axons from the cochlear and vestibular divisions of the eighth cranial nerve. The dorsal cochlear nucleus, lying on the base of the inferior cerebellar peduncle, is shown in Figure 7-7, and part of the ventral cochlear nucleus appears lateral to the peduncle in the same figure. Fibers leaving the cochlear nuclei are noted later in the description of the pons.

The vestibular nuclei, beneath the vestibular area of the rhomboid fossa, comprise the superior, lateral, medial, and inferior vestibular nuclei, which differ in their cytoarchitecture and connections. Whereas the superior nucleus is located in the pons (see Fig. 7-8), the remaining nuclei are located in the medulla (see Figs. 7-6 and 7-7). The vestibular nerve penetrates the brain stem ventral to the inferior cerebellar peduncle and medial and slightly rostral to the attachment of the cochlear nerve. Most vestibular nerve fibers end in the vestibular nuclei, but a few enter the cerebellum through the inferior peduncle. In addition to the primary vestibulocerebellar fibers, numerous secondary fibers proceed from the vestibular nuclei into the cerebellum through the inferior peduncle.

Vestibular nuclei project to the spinal cord by way of two tracts. The larger is the vestibulospinal tract (sometimes called the lateral vestibulospinal tract), for which the cells of origin are in the lateral vestibular nucleus. Vestibulospinal fibers run caudally, dorsal to the inferior olivary nucleus, in the position indicated in Figures 7-4 and 7-5. The tract is deflected ventrally at the level of the pyramidal decussation (see Figs. 7-2 and 7-3) and continues into the ipsilateral ventral funiculus of the spinal cord.

Fibers from the left and right medial vestibular nuclei account for most of those in each medial longitudinal fasciculus, a bundle that extends rostrally and caudally adjacent to the midline (see Figs. 7-2, 7-3, 7-4, 7-5, 7-6, and 7-7). The ascending fibers will be identified later in the discussion of the pons and midbrain. The small bundle of descending fibers, which are mainly from ipsilateral cell bodies, is sometimes called the medial vestibulospinal tract. Below the pyramidal decussation, it is joined by the nearby ventral corticospinal and tectospinal tracts.

Trigeminal Nerve

The trigeminal nerve contributes a tract and associated nucleus to the internal structure of the medulla. Many fibers of the trigeminal sensory root turn caudally on entering the pons. They constitute the spinal trigeminal tract, so named because many of these axons extend as far as the third cervical segment of the spinal


cord. The spinal tract transmits data for pain, temperature, and touch from the extensive area of distribution of the trigeminal nerve (most of the head; see Chapter 8). The tract also receives primary afferent fibers from the other three cranial nerves (facial, glossopharyngeal, and vagus) that have general somatic sensory functions. Axons leave the tract at all levels from the caudal pons to the second or third cervical segment of the spinal cord. They terminate in the spinal trigeminal nucleus (nucleus of the spinal trigeminal tract), which is located alongside and medial to the tract. The spinal trigeminal tract and its nucleus share several structural and functional characteristics with the dorsolateral tract of Lissauer and the outermost four laminae of the dorsal horn of the spinal gray matter, with which the nucleus is continuous.

The longest descending fibers in the spinal trigeminal tract are unmyelinated or thinly myelinated, and they carry signals relating to pain and temperature. The first synapses in the pathway for these types of sensation are, therefore, located in the most caudal part of the spinal trigeminal nucleus in the closed medulla and the uppermost cervical levels of the spinal cord.

The ventral trigeminothalamic tract (see Fig. 7-6) is a crossed fasciculus that arises from neurons in the spinal (and pontine) trigeminal nuclei and in the adjacent part of the reticular formation. It ends in the medial division of the ventral posterior nucleus of the thalamus (VPm). Conducting sensory signals from the opposite side of the head, the ventral trigeminothalamic tract is functionally comparable to the spinothalamic tract for the parts of the body below the neck.

Dorsal Pons (Tegmentum)

The main features seen in sections through the pons are its division into basal (ventral) and tegmental (dorsal) regions and the prominent cerebellar peduncles (see Figs. 7-8 and 7-9). The pontine tegmentum is structurally similar


to the medulla and midbrain. There are, therefore, tracts that were encountered in the medulla, together with components of several cranial nerves.


FIGURE 7-9 Section through the middle of the pons (Weigert stain). For abbreviations see inside front cover of book.


The medial lemniscus twists as it leaves the medulla, rotating in such a way that in the ventral pontine tegmentum, the fibers from the cuneate nucleus are medial to those from the gracile nucleus. Therefore, the somatotopic representation is neck, arm, trunk, and leg, in a medial-to-lateral sequence. The spinal lemniscus is near the lateral edge of the medial lemniscus throughout the pons (see Figs. 7-8, 7-9, and 7-10). The ventral spinocerebellar tract traverses the most lateral part of the tegmentum (see Fig. 7-8) and then curves dorsally and enters the cerebellum through the superior peduncle (see Figs. 7-9 and 7-11).

With respect to descending tracts, the central tegmental tract is medial to the fibers of the superior cerebellar peduncle at the level of the pontine isthmus (see Fig. 7-10), in the central area of the tegmentum at midpontine levels (see Fig. 7-9), and dorsal to the medial lemniscus in the caudal region of the pons (see Fig. 7-8). As in the medulla and spinal cord, the medial longitudinal fasciculus is located near the midline in the pontine tegmentum (see Figs. 7-8, 7-9, and 7-10).

The inferior cerebellar peduncles enter the cerebellum from the caudal part of the pons. At this level, they lie medial to the middle cerebellar peduncles and form the lateral walls of the fourth ventricle (see Fig. 7-8). Olivocerebellar fibers are the most numerous in the inferior peduncle, followed by fibers of the dorsal spinocerebellar tract. The region of the inferior cerebellar peduncle immediately adjoining the fourth ventricle consists of fibers that enter the cerebellum from the vestibular nerve and vestibular nuclei, together with fibers that arise in the parts of the cerebellum concerned with maintaining equilibrium. Most of the latter fibers terminate in the vestibular nuclei.

The superior cerebellar peduncles (see Fig. 7-9) consist mainly of fibers that originate in


cerebellar nuclei and enter the brain stem immediately caudal to the inferior colliculi of the midbrain. The fibers cross the midline at the level of the inferior colliculi in thedecussation of the superior cerebellar peduncles (see Figs. 7-10, 7-12, and 7-13). Most of these fibers continue rostrally to the thalamus, and the remainder end in the red nucleus and in the reticular formation. The superior cerebellar peduncle also contains fibers that enter the cerebellum: the ventral spinocerebellar tract and some axons from the mesencephalic trigeminal nucleus and the red nucleus.


FIGURE 7-10 Rostral part of the pons, including the isthmus region of the pontine tegmentum (Weigert stain). For abbreviations see inside front cover of book.


FIGURE 7-11 Part of a section through the middle of the pons at the level of the pontine and motor trigeminal nuclei (Weigert stain).


Vestibulocochlear Nerve

Fibers from the dorsal and ventral cochlear nuclei cross the pons to ascend in the lateral lemniscus of the opposite side. Most of the decussating fibers constitute the trapezoid body(see Fig. 7-8), which intersects the medial lemnisci. It is difficult to distinguish these slender bundles of acoustic fibers from nearby bundles of pontocerebellar fibers. The axons from the ventral cochlear nuclei end in the superior olivary nucleus (see Fig. 7-8), from which more ascending fibers are added to the auditory pathway. Fibers from the dorsal cochlear and superior olivary nuclei turn rostrally in the lateral part of the tegmentum to form the lateral lemniscus (see Fig. 7-8). This tract is lateral to the medial lemniscus in the first part of its course (see Fig. 7-9) and then moves dorsally to end in the inferior colliculus of the midbrain (see Figs. 7-10 and 7-12). The auditory pathway, which continues to the thalamus and cerebral cortex, is more fully described in Chapter 21.

One of the four vestibular nuclei, the superior vestibular nucleus, extends into the pons (see Fig. 7-8). Fibers from the vestibular nuclei, some crossed and some uncrossed, ascend in the medial longitudinal fasciculus, which is next to the midline and close to the floor of the fourth ventricle throughout the pons (see Figs. 7-8, 7-9, 7-10, 7-11, and 7-12). The fibers terminate mainly in the abducens, trochlear, and oculomotor nuclei, establishing connections that coordinate movements of the eyes with movements of the head.


The medial longitudinal fasciculus also contains other groups of fibers concerned with eye movements; these are discussed in Chapter 8.


FIGURE 7-12 Section that passes through the rostral end of the basal pons and the caudal ends of the inferior colliculi of the midbrain (Weigert stain). For abbreviations see inside front cover of book.

Facial and Abducens Nerves

The facial motor nucleus, which supplies the muscles of expression, is a prominent group of typical motor neurons in the ventrolateral part of the tegmentum (see Fig. 7-8). Axons arising from the nucleus course dorsomedially and then form a compact bundle, the internal genu, which loops over the caudal end of the abducens nucleus beneath the facial colliculus of the rhomboid fossa. The bundle of fibers that forms the genu then runs forward along the medial side of the abducens nucleus and curves again over its rostral end (see right side of Fig. 7-8). After leaving the genu, the fibers pass between the nucleus of origin and the spinal trigeminal nucleus, emerging as the motor root of the facial nerve at the junction of the pons and medulla.

The abducens nucleus innervates the lateral rectus muscle of the eye and also contains internuclear neurons. It is located beneath the facial colliculus, as noted previously (see Fig. 7-8). The efferent motor fibers of the nucleus proceed ventrally with a caudal inclination and leave the brain stem as the abducens nerve between the pons and the pyramid of the medulla (see Fig. 6-1). The internuclear neurons have axons that travel in the contralateral medial longitudinal fasciculus to the division of the oculomotor nucleus that supplies the medial rectus muscle. This arrangement provides for simultaneous contraction of the lateral rectus and contralateral medial rectus when the eyes move in the horizontal plane.

Trigeminal Nerve

The spinal trigeminal tract and nucleus are located in the lateral part of the tegmentum of the caudal half of the pons (see Fig. 7-8), lateral to the fibers of the facial nerve. The pontine tegmentum also contains two other trigeminal nuclei (see Fig. 7-11). The pontine trigeminal nucleus (also known as the chief or principal


nucleus) is located at the rostral end of the spinal trigeminal nucleus. It receives fibers for touch, especially discriminative touch. Fibers from the pontine trigeminal nucleus project to the thalamus, along with fibers from the spinal nucleus, in the ventral trigeminothalamic tract (see Figs. 7-9 and 7-10). A dorsal trigeminothalamic tract, consisting of crossed and uncrossed fibers, originates exclusively in the pontine trigeminal nuclei. (Alternatively, all the trigeminothalamic fibers are said to compose the trigeminal lemniscus.) Themotor nucleus, which is medial to the pontine trigeminal nucleus (see Fig. 7-11), contains the motor neurons that supply the muscles of mastication and a few other muscles.


FIGURE 7-13 Midbrain at the level of the rostral ends of the inferior colliculi (Weigert stain). For abbreviations see inside front cover of book.

The mesencephalic trigeminal nucleus is a slender column of cells beneath the lateral edge of the rostral part of the fourth ventricle (see Figs. 7-9 and 7-10), extending into the midbrain. These unipolar cells are unusual because they are cell bodies of primary sensory neurons and the only such cells in the central nervous system. The axons of the unipolar neurons form the mesencephalic tract of the trigeminal nerve (see Figs. 7-9 and 7-10); most are distributed through the mandibular division of the nerve to proprioceptive endings in the muscles of mastication.

Ventral or Basal Pons

The basal or ventral part of the pons (see Figs. 7-8, 7-9, and 7-10) is especially large in humans because of its connections with the cortices of the cerebral and cerebellar hemispheres. The basal part of the pons consists of longitudinal and transverse fiber bundles and the pontine nuclei, which are collections of neurons that lie among the bundles. The longitudinal bundles are numerous and small at rostral levels (see Figs. 7-9 and 7-10), but many coalesce as they approach the medulla (see Fig. 7-8).

The longitudinal fasciculi are descending fibers that enter the pons from the basis pedunculi


of the midbrain. Many are corticospinal fibers that pass through the pons to reassemble as the pyramids of the medulla. Numerous corticopontine fibers, which originate in widespread areas of cerebral cortex and establish synaptic contact with cells of the pontine nuclei of the same side, are also present. Except in the caudal one third of the pons, where large regions of pontine gray matter are present (see Fig. 7-8), the pontine nuclei are small groups of cells scattered among the longitudinal and transverse fasciculi (see Figs. 7-9 and 7-10). The axons of the neurons of the pontine nuclei cross the midline, forming the conspicuous transverse bundles of pontocerebellar fibers, and enter the cerebellum through the middle cerebellar peduncle. The activities of the cerebral cortex are thus made available to the cerebellar cortex through the relay in the pontine nuclei. The cerebellar cortex influences motor areas in the frontal lobe of the cerebral hemisphere through a pathway that includes the dentate nucleus of the cerebellum and the ventral lateral nucleus of the thalamus. The well-developed circuit linking the cerebral and cerebellar cortices contributes to the precision and efficiency of voluntary movements.


The internal structure of the midbrain is shown in Figures 7-12, 7-13, 7-14, and 7-15. The sections shown in Figures 7-12 and 7-13 are through the inferior colliculi. The planes of the sections are such that Figure 7-12 includes the basal pons, and Figure 7-13 shows the extreme rostral lip of the basal pons (see Fig. 7-1). Figures 7-14 and 7-15 show more rostral levels that include the superior colliculi and certain thalamic nuclei that are in the same transverse plane.

For descriptive purposes, the midbrain is divided into the following regions (see Fig. 7-14): the tectum, which consists of the paired inferior and superior colliculi (corpora quadrigemina); the basis pedunculi, which is a dense mass of descending fibers; and the substantia nigra, which is a prominent zone of gray matter immediately dorsal to the basis pedunculi. The remainder of the midbrain comprises the tegmentum,


which contains fiber tracts, the prominent red nuclei, and the periaqueductal gray matter surrounding the cerebral aqueduct. The term cerebral peduncle refers to all of the midbrain on each side, exclusive of the tectum.


FIGURE 7-14 Midbrain at the level of the superior colliculi (Weigert stain). For abbreviations see inside front cover of book.


FIGURE 7-15 Midbrain at the level of the rostral ends of the superior colliculi. The section also includes parts of the thalamus and some cortex of the temporal lobes (Weigert stain). For abbreviations see inside front cover of book.


Inferior Colliculus

The inferior colliculus is a large nucleus of the auditory pathway. Fibers of the lateral lemniscus envelop and enter the nucleus (see Fig. 7-12). Fibers leaving the inferior colliculus traverse the inferior brachium to reach the medial geniculate body of the thalamus (see Figs. 7-13, 7-14, and 7-15), which, in turn, projects to the auditory cortex in the temporal lobe. Commissural fibers are present between the inferior colliculi, accounting partly for the bilateral cortical projection from each ear.

Some axons from the inferior colliculus pass forward into the superior colliculus. From the latter site, through a polysynaptic pathway described in Chapter 8, auditory signals reach cranial nerve nuclei that supply the extraocular muscles, and a few tectospinal fibers influence spinal motor neurons in the cervical region. A pathway is thereby established for reflex turning of the eyes and head toward the source of an unexpected sound.

Superior Colliculus

The superior colliculus (see Figs. 7-14 and 7-15) has a complex structure consisting of seven alternating layers of white and gray matter; its connections are with the visual system. Corticotectal fibers come from the visual cortex in the occipital lobe, from adjacent parietal cortex, and from an area of the frontal lobe called the frontal eye field. The corticotectal fibers (which are ipsilateral) make up most of the superior brachium, which reaches the superior colliculus by passing between the pulvinar and the medial geniculate body of the thalamus (see Figs. 7-14 and 7-15). Through collicular efferents (to be described), this connection between the cortex and the superior colliculus is responsible for both voluntary and involuntary movements of the eyes and head, as when rapidly shifting the direction of gaze (saccadic movements) or when following objects passing across the visual field (smooth


pursuit movements). Corticotectal fibers that originate in the occipital cortex also participate in the ocular response of accommodation (i.e., thickening of the lens and constriction of the pupil), which accompanies convergence of the eyes when viewing a near object.

Some fibers of the optic tract reach the superior colliculus by way of the superior brachium and constitute the afferent limb of a reflex pathway that assists in turning the eyes and head to follow an object moving across the field of vision. In addition, spinotectal fibers terminate in the superior colliculus and transmit data from general sensory endings, especially those in the skin. These connections presumably serve to direct the eyes and head toward sources of cutaneous stimuli. Another source of afferents to the superior colliculus is the pars reticulata of the substantia nigra, which thereby connects the corpus striatum (see Chapter 12) with the parts of the midbrain that control movements of the eyes and head.

Efferents from the superior colliculus are distributed to the spinal cord and nuclei of the brain stem. The few fibers destined for the spinal cord curve around the periaqueductal gray matter, cross to the opposite side in the dorsal tegmental decussation, and continue caudally near the midline as the tectospinal tract. Efferents to the brain stem, known astectobulbar fibers, are, for the most part, directed bilaterally. They go to the pretectal area, the accessory oculomotor nuclei, and the paramedian pontine reticular formation. These regions project to the nuclei of the nerves that supply the eye muscles. (Neural control of these muscles is discussed in Chapter 8.) Other efferent fibers from the superior colliculus terminate in the reticular formation near the motor nucleus of the facial nerve, providing a reflex pathway for protective closure of the eyelids when there is a sudden visual stimulus.

The superior colliculi are interconnected by the commissure of the superior colliculi (see Fig. 7-14). The posterior commissure is a robust bundle that runs transversely, just dorsal to the transition between the cerebral aqueduct and the third ventricle. A small piece of this commissure is included in the section shown in Figure 7-15. Fibers in the posterior commissure come from the superior colliculus and from the following nearby smaller nuclei: pretectal area, habenular nuclei (in the epithalamus of the diencephalon), and the accessory oculomotor nuclei of the midbrain (which are reviewed in Chapter 9).

Pretectal Area

The pretectal area consists of four pairs of small nuclei rostral to the lateral edge of the superior colliculus. One of the pretectal nuclei, the olivary pretectal nucleus, receives fibers from both retinas by way of the ipsilateral optic tract and the superior brachium. Axons arising in the olivary pretectal nucleus go to the Edinger-Westphal nucleus of each side. The latter nucleus is the source of the preganglionic parasympathetic fibers in the oculomotor nerve. The pretectal area is thereby included in a reflex pathway for constriction of the pupils in response to increased intensity of light. The pretectal area also has connections that implicate it in pathways for the control of eye movements, including convergence (seeChapter 8).


Fasciculi Proceeding to the Thalamus

The medial lemniscus traverses the midbrain in the lateral area of the tegmentum to its termination in the ventral posterior nucleus of the thalamus (see Figs. 7-13, 7-14, and 7-15). The spinal lemniscus is dorsolateral to the medial lemniscus; this spatial relation is continued from the pontine tegmentum. Spinotectal fibers leave the spinal lemniscus to enter the superior colliculus and the periaqueductal gray matter. The spinothalamic fibers continue into the diencephalon, where they end in the ventral posterior and other thalamic nuclei. Some spinothalamic fibers send branches into the periaqueductal gray matter of the midbrain.

Red Nucleus and Associated Tracts

The red nucleus is egg shaped (round in transverse section) and extends from the caudal limit of the superior colliculus into the subthalamic region of the diencephalon. The nucleus is more vascular than the surrounding tissue and is named for its pinkish hue in a fresh specimen. Myelinated axons that pass through the red nucleus give it a punctate appearance in Weigertstained sections (see Figs. 7-14 and 7-15).


Afferent fibers from the contralateral cerebellum reach the red nucleus by way of the superior cerebellar peduncle and its decussation (see Fig. 7-13). Corticorubral fibers come from the motor areas of the ipsilateral cerebral hemisphere. Many other afferents to the red nucleus have been detected in animals, but their significance in the human brain is not known.

The red nucleus gives rise to a small number of axons that cross the midline in the ventral tegmental decussation and continue through the brain stem into the lateral funiculus of the spinal cord as the rubrospinal tract. This is a minor pathway in the human brain, and its few fibers terminate in the first two segments of the cervical spinal gray matter. In laboratory animals, some descending fibers from the red nucleus end in the facial motor nucleus and in those nuclei of the reticular formation that project to the cerebellum. In addition to these crossed projections, large numbers of rubroolivary fibers travel in the ipsilateral central tegmental tract to terminate in the inferior olivary complex of nuclei, which projects across the midline to the cerebellum.


The midbrain contains nuclei of three cranial nerves as well as certain tracts that originate in the sensory nuclei of cranial nerves in the medulla and pons.

Vestibulocochlear Nerve

The lateral lemniscus was identified in the discussion of the inferior colliculus. The medial longitudinal fasciculus is adjacent to the midline (see Figs. 7-12, 7-13, 7-14, and 7-15) in the same general position as at lower levels. Most of its fibers originate in vestibular nuclei, and those that reach the midbrain end in the trochlear, oculomotor, and accessory oculomotor nuclei. The fasciculus also contains the axons of internuclear neurons, which connect the abducens, trochlear, and oculomotor nuclei.

Trigeminal Nerve

The trigeminal lemniscus, comprising fibers from the spinal and pontine trigeminal nuclei, is medial to the medial lemniscus (see Figs. 7-12, 7-13, 7-14, and 7-15). Themesencephalic nucleus of the trigeminal nerve continues from the pons into the lateral region of the periaqueductal gray matter up to the level of the superior colliculus.

Trochlear and Oculomotor Nerves

The trochlear nucleus is located in the periaqueductal gray matter at the level of the inferior colliculus, where it lies just dorsal to the medial longitudinal fasciculus (see Fig. 7-13). Fibers from the nucleus curve dorsally around the periaqueductal gray matter, with a caudal slope (see Figs. 7-10 and 7-12). On reaching the dorsal surface of the brain stem, the fibers decussate in the superior medullary velum and emerge as the trochlear nerve just below the inferior colliculi. The trochlear nerve supplies the superior oblique muscle of the eye.

The oculomotor nucleus is actually a group of subnuclei in and adjacent to the midline in the ventral part of the periaqueductal gray matter at the level of the superior colliculus. The paired nuclei have a V-shaped outline in sections (see Figs. 7-14 and 7-15). Bundles of axons from the nucleus curve ventrally through the tegmentum, with many of them passing through the red nucleus (see Fig. 7-14), and then emerge along the side of the interpeduncular fossa to form the oculomotor nerve (see Figs. 6-1 and 7-15). The oculomotor nerve supplies four of the six extraocular muscles (all except the lateral rectus and superior oblique) and the striated fibers of the levator palpebrae superioris muscle, which raises the upper eyelid. Distinct subnuclei supply the individual muscles. The oculomotor nuclear complex includes a functionally different parasympathetic component, the Edinger-Westphal nucleus, concerned with the ciliary and sphincter pupillae muscles of the eye (see Chapter 8).


The substantia nigra is a large nucleus situated between the tegmentum and the basis pedunculi throughout the midbrain (see Figs. 7-13, 7-14, and 7-15) and extending into the subthalamic region of the diencephalon. The black color is caused by the dopaminergic neurons of the pars compacta, adjacent to the tegmentum. These cells contain cytoplasmic inclusion granules of melanin pigment. The melanin granules are few at birth; their numbers increase rapidly during


childhood and then more slowly throughout life. The pigment, which is present in albinos, is also known as neuromelanin to distinguish it from the pigment of skin. It is probably a byproduct of the metabolism of dopamine, which is the neurotransmitter used by these cells. The substantia nigra is connected with the corpus striatum, a large body of gray matter in the forebrain, and it is included in the functional system known as the basal ganglia.


Parkinson's Disease

The importance of the substantia nigra is apparent when the disturbances of motor function in Parkinson's disease (paralysis agitans) are considered. The clinical features of this crippling disorder are muscular rigidity, a slow tremor, and bradykinesia (or poverty of movement). The last is manifest as a masklike face, difficulty in initiating movements, and loss of associated involuntary movements such as swinging the arms when walking. All three features combine to cause a shuffling gait, with a tendency to fall forward and difficulty in stopping. The most consistent pathological finding in Parkinson's disease is degeneration of the melanin-containing cells in the pars compacta of the substantia nigra. Most cases of Parkinson's disease have no known cause, but a few are caused by poisons, including manganese compounds (industrial exposure in some mines) and MPTP (1-methyl-4-phenyl-1,2,4,6-tetrahydropyridine), a compound present in illegally manufactured heroin. Some drugs (see below) can cause transient parkinsonian symptoms by blocking the normal actions of dopamine at synapses.

Biochemical and histochemical research in the 1960s provided the basis for modern medical therapy. The normally high concentrations of dopamine in the substantia nigra and striatum are greatly reduced in patients with Parkinson's disease. Administration of dopamine might replace the regulatory action of the substantia nigra on the striatum, but this amine does not cross the blood-brain barrier. Therefore, a metabolic precursor that does gain access to brain tissue is used instead. This precursor is L-dopa (L-dihydroxyphenylalanine; also called levodopa), and its conversion to dopamine occurs in the surviving neurons of the pars compacta. The administration of L-dopa does not stop the loss of neurons, but it does relieve the motor abnormalities in Parkinson's disease until there are not enough nigral neurons left to deliver dopamine to the striatum.

Other drugs used to treat parkinsonism include anticholinergic agents and inhibitors of an enzyme that degrades dopamine. The former work indirectly by suppressing the actions of the cholinergic interneurons of the striatum.

The traditional surgical treatment of Parkinson's disease consists of destroying parts of the brain that are overactive when there is not enough dopaminergic modulation of the striatum. Clinical experimentation in the 1940s and 1950s led to the adoption of either the globus pallidus or the ventral lateral nucleus of the thalamus as the site of choice for such lesions, but transient relief of parkinsonian symptoms followed either surgical or spontaneous pathological damage almost anywhere in the base of the cerebral hemisphere. Magnetic resonance imaging (MRI; seeChapter 4) allows for electrical recording and stimulation at anatomically known sites in the diencephalon and corpus striatum, so it is now possible to locate lesions more accurately than in earlier years of the disease process. Surgical ablations in the thalamus (thalamotomy)relieve tremor and rigidity but not bradykinesia. With lesions in the ventral medial part of the globus pallidus (pallidotomy), relief of rigidity and bradykinesia takes place. In recent years, symptomatic relief has been achieved with stimulating electrodes chronically implanted in the pallidum, thalamus, or subthalamic nucleus.

In the 1980s and 1990s, many attempts were made to treat patients with Parkinson's disease by transplanting cells potentially capable of secreting dopamine (taken from aborted human fetuses) into the corpus striatum. Clinical follow-up and postmortem studies, which became available in the early 1990s, showed that symptomatic relief was usually transient. Experimentation with human fetal transplants has continued, and it is now generally agreed that any resulting clinical improvement is minor and seldom lasts for more than a few months except in some younger patients. Trials involving sham-operated patients indicate that transient improvement is a placebo effect. Other current research in the field of therapeutic grafting is directed toward the potential use of genetically modified cells that might produce dopamine and form appropriate synaptic connections in the corpus striatum.

The major source of fibers afferent to the pars compacta is the striatum (a part of the corpus


striatum comprising the caudate nucleus and the putamen of the lentiform nucleus). The efferent fibers from the pars compacta go to the striatum. These connections form part of a larger piece of neuronal circuitry, discussed in Chapters 12 and 23.

The region of the substantia nigra bordering the basis pedunculi consists of cells that lack pigment and is called the pars reticulata. It is a detached part of the internal segment of the globus pallidus, which is part of the corpus striatum (see Chapter 12). The pars reticulata contains neurons that project to the same thalamic nuclei that receive input from the pallidum, and it also sends fibers to the superior colliculus, providing a pathway whereby the basal ganglia participate in the control of eye movements.

Ventral Tegmental Area

The ventral tegmental area is another population of dopaminergic neurons, on the medial aspect of the cerebral peduncle, between the substantia nigra and the red nucleus (see Fig. 7-15). The axons of these cells end in the hypothalamus, amygdala, hippocampal formation, nucleus accumbens, and elsewhere. These projections, sometimes called the mesolimbic dopaminergic system, have been intensively studied in animals because their actions are blocked by drugs that are used in the clinical management of patients with schizophrenia and other mental disorders. The drugs antagonize dopamine at its postsynaptic receptors, and their most serious adverse effect is a syndrome that resembles Parkinson's disease.


The basis pedunculi (crus cerebri) consists of fibers of the pyramidal and corticopontine systems (see Figs. 7-13, 7-14, and 7-15 and Chapter 23).

Corticospinal fibers constitute the middle three fifths of the basis pedunculi; the somatotopic arrangement is that of fibers for the neck, arm, trunk, and leg in a medial-to-lateral direction.

Corticobulbar (corticonuclear) fibers are located between the corticospinal and frontopontine tracts, but many leave the basis pedunculi and continue to their destinations through the tegmentum of the midbrain and pons. The majority of the corticobulbar fibers end in the reticular formation near the motor nuclei of cranial nerves (the trigeminal and facial motor nuclei, nucleus ambiguus, and hypoglossal nucleus). A few of the fibers make direct synaptic contacts with the motor neurons in these nuclei. In addition to these pathways, which have obvious motor functions, corticobulbar fibers to the pontine and spinal trigeminal nuclei and to the solitary nucleus are present. Axons of cortical origin that end in the gracile and cuneate nuclei are also classified as corticobulbar. Thus, corticobulbar connections are involved in modulating the transmission of sensory information rostrally from the brain stem as well as in the control of movement.

Corticopontine fibers are divided into two large bundles. The frontopontine tract occupies the medial one-fifth of the basis pedunculi. The lateral one fifth consists of theparietotemporopontine tract, which contains fibers from the parietal, occipital, and temporal lobes. Corticopontine fibers end in the basal pons, synapsing with the neurons of the pontine nuclei.

Visceral Pathways in the Brain Stem

The ascending visceral pathways in the spinal cord are situated in the ventral and ventrolateral funiculi. They may be considered to be parts of the spinothalamic and spinoreticular tracts. Signals of visceral origin reach the reticular formation, thalamus, and hypothalamus.

Physiologically important visceral sensory fibers reach the solitary nucleus in the medulla by way of the vagus and glossopharyngeal nerves (see Chapter 8). The solitary nucleus also receives afferents for taste, mainly through the glossopharyngeal and facial nerves. Ascending fibers from the solitary nucleus travel ipsilaterally in the central tegmental tract and terminate in the hypothalamus and in the most medial part of the ventral posterior medial nucleus of the thalamus. From the latter site, information with respect to taste is relayed to a cortical taste area in the parietal and insular lobes. A small solitariospinal tract, which originates in the solitary nucleus and nearby parts of the reticular formation, terminates on


preganglionic autonomic neurons in the spinal cord and possibly also on neurons that supply respiratory muscles. Some axons ascend from nuclei of the reticular formation to the hypothalamus in the dorsal longitudinal fasciculus, which also contains descending fibers (see next paragraph and Chapter 11).


Anatomical and Clinical Correlations

Vascular lesions are among the more important causes of damage to the brain. Hemorrhage into the brain stem usually has serious consequences (such as sudden death or coma) because the escaping blood destroys regions of the reticular formation that control the vital functions of respiration, circulation, and consciousness. Some effects of large lesions in the brain stem are discussed in Chapter 9. Vascular occlusion can cause smaller destructive lesions, resulting in neurological signs that depend on the location and size of the affected region. Symptoms and clinical signs can indicate the level of a lesion in the brain stem as well as the medial, lateral, dorsal, or ventral location of the lesion. The level is deduced largely from the anatomy of the nuclei of the affected cranial nerves. Interruption of motor or sensory pathways or connections with the cerebellum can establish the lateral, medial, dorsal, or ventral position of a lesion. Clinical imaging of the brain stem, especially MRI, is valuable but is less precise and, consequently, less accurate than deductions based on knowledge of neuroanatomy.

There are two descending pathways whose cells of origin are located in the hypothalamus. Mamillotegmental fibers originate in the mamillary body of the hypothalamus; they terminate in the reticular formation of the midbrain, which projects to autonomic nuclei in the brain stem and spinal cord. Fibers from other hypothalamic nuclei, notably the paraventricular nucleus, run caudally in the dorsal longitudinal fasciculus, a bundle of mostly unmyelinated fibers in the periaqueductal gray matter of the midbrain. Some terminate in the reticular formation of the brain stem and the dorsal nucleus of the vagus nerve, and the hypothalamospinal fibers proceed to autonomic nuclei in the spinal cord. Thus, impulses of hypothalamic origin reach the preganglionic sympathetic and sacral parasympathetic neurons both directly and through relays in the reticular formation. Clinical evidence indicates that fibers influencing the sympathetic nervous system descend ipsilaterally through the lateral part of the medulla.

The following examples are presented to show the correlation between clinical syndromes and the locations of some lesions in the brain stem. Table 7-1 provides a summary. Information contained in Chapters 8, 9, and 10 is needed in order to appreciate all the data in the table.

The medial medullary syndrome results from occlusion of a medullary branch of the vertebral artery; the size of the infarction depends on the distribution of the particular artery involved. In the example shown in Figure 7-16, the affected area includes the pyramid and most of the medial lemniscus on one side. The lesion extends far enough laterally to include fibers of the hypoglossal nerve as they pass between the medial lemniscus and the inferior olivary nucleus. A patient with this lesion has contralateral hemiparesis as well as impairment of the sensations of position and movement and of discriminative touch on the opposite side of the body. Paralysis of the tongue muscles is ipsilateral. This is an example of “crossed” or “alternating” paralysis, in which whereas the body below the neck is affected on the side opposite the lesion, muscles supplied by a cranial nerve are affected on the same side as the lesion.

Occlusion of a vessel supplying the lateral area of the medulla results in the lateral medullary (Wallenberg's) syndrome. Typically, the occluded vessel is a medullary branch of the posterior inferior cerebellar artery. The infarcted area (Fig. 7-17) includes (a) the base of the inferior cerebellar peduncle and vestibular nuclei, causing dizziness, cerebellar ataxia, and nystagmus; (b) the spinal trigeminal tract and its nucleus, causing ipsilateral loss of pain and temperature sensibility in the area of distribution of the trigeminal nerve; (c) the spinothalamic tract, causing contralateral loss of pain and temperature sensation below the neck; or (d) the nucleus ambiguus, causing paralysis of the muscles of the soft palate, pharynx, and


larynx on the side of the lesion, with difficulty in swallowing and phonation. The descending pathway to the intermediolateral cell column of the spinal cord is usually included in the area of degeneration, thereby causing Horner's syndrome (i.e., constricted pupil and drooping of the upper eyelid [ptosis]) and warm, dry skin of the face, all on the side of the lesion. Cerebellar signs are more pronounced if infarction of part of the cerebellum is added to that of the medulla (posterior inferior cerebellar artery thrombosis). Partial syndromes such as that of Avellis (see Table 7-1) are caused by smaller lesions in the lateral part of the medulla.

TABLE 7-1 Some Clinical Syndromes Caused by Localized Lesions in the Brain Stem

Clinical Features

Site of Lesion

Name of Syndrome
and Other Comments

Ipsilateral hypoglossal palsy with contralateral hemiplegia

Ventromedial medulla, including pyramid and axons of hypoglossal nerve

Medial medullary syndrome (see Fig. 7-16)

Vertigo, ataxia, paralysis of the ipsilateral palate and vocal cord, loss of pain and thermal sensation on the same side of face and opposite side of body, ipsilateral Horner's syndrome, and loss of facial sweating

Lateral medulla (territory of posterior inferior cerebellar artery), including the vestibular nuclei inferior cerebellar peduncle, nucleus ambiguus, spinal trigeminal tract and nucleus, spinothalamic tract, and fibers descending to preganglionic sympathetic neurons

Wallenberg's syndrome (see Fig. 7-17and Chapters 8 and 24); smaller lesions cause partial syndromes (see next row of this table for an example)

Paralysis of the ipsilateral palate and vocal cord and loss of pain and thermal sensation on same side of face and opposite side of body

Lateral medulla, including nucleus ambiguus, spinal trigeminal tract and nucleus, and spinothalamic tract

Avellis' syndrome; caused by a lesion in the ventral part of the shaded area in Fig. 7-17

Ipsilateral lower motor neuron facial paralysis with contralateral hemiplegia

Pons, including facial motor nucleus and descending motor fibers

Millard-Gübler syndrome (see Fig. 7-19)

Ipsilateral lower motor neuron facial paralysis, ipsilateral conjugate gaze paralysis, and transient contralateral hemiparesis

Dorsomedial pons, including abducens nucleus, facial motor nucleus and axons, dorsal to the descending motor fibers

Foville's syndrome (see Figs. 7-20 and8-5)

Ipsilateral abducens nerve palsy with contralateral hemiparesis

Ventral pons, including axons (not the nucleus) of the abducens nerve and descending motor fibers

Raymond's syndrome (see Fig. 7-18)

Ipsilateral oculomotor nerve palsy with contralateral hemiplegia or hemiparesis

Ventral part of cerebral peduncle, including axons of oculomotor nerve and descending motor fibers in the basis pedunculi

Weber's syndrome (see Fig. 7-21)

Ipsilateral oculomotor nerve palsy with contralateral hemiparesis and tremor

Cerebral peduncle, with oculomotor axons and descending motor fibers and extending dorsally to include the red nucleus and fibers from the contralateral side of the cerebellum

Benedikt's syndrome (see Fig. 7-21and Chapter 10); the tremor resembles a cerebellar tremor

Paralysis of conjugate upward gaze without paralysis of convergence

Dorsal midbrain; typically a pineal tumor pressing on the posterior commissure, pretectal area, and superior colliculi

Parinaud's syndrome (see Chapter 8and Fig. 8-6)



FIGURE 7-16 Site of a lesion producing the medial medullary syndrome. This lesion transects axons of the medial lemniscus, the pyramid, and the hypoglossal nerve.

Lesions in the basal region of the pons or the midbrain may produce alternating paralysis, similar to that described for the medial medullary syndrome. Figure 7-18 shows an area of infarction in one side of the caudal region of the pons, resulting from occlusion of a pontine branch of the basilar artery, causing Raymond's syndrome. Interruption of corticospinal and other descending motor fibers causes contralateral hemiparesis. Inclusion of abducens nerve fibers in the lesion causes paralysis of the lateral rectus muscle on the ipsilateral side, resulting in a medial strabismus or squint. More laterally and dorsally located lesions (Fig. 7-19) involve descending motor fibers and the motor nucleus and axons of the facial nerve. In the resulting Millard-Gübler syndrome, contralateral hemiparesis and ipsilateral facial paralysis are present.


FIGURE 7-17 Site of a lesion producing a lateral medullary syndrome. This lesion (the one described by Wallenberg) involves the vestibular nuclei and inferior cerebellar peduncle, spinal trigeminal tract and nucleus, spinothalamic tract, and nucleus ambiguus and descending fibers that control the sympathetic innervation of the eye and face. Smaller lesions spare certain functions such as those of the vestibular system and cerebellum, the laryngeal and pharyngeal muscles, or the sympathetic control of the iris.

A more dorsally and medially located pontine lesion can involve the abducens nucleus together with the nearby motor fibers of the facial nerve or the facial motor nucleus (see Fig. 7-8). In the resulting Foville's syndrome, patients have ipsilateral paralysis of the facial muscles and of the lateral rectus muscle, which is supplied


by the abducens nerve. In addition, the medial rectus muscle of the contralateral eye fails to contract when a conjugate lateral eye movement is attempted but does contract when the eyes converge to look at a near object. The effect of the lesion on the contralateral medial rectus is caused by destruction of internuclear neurons. These, which occur alongside the motor neurons in the abducens nucleus, have axons that cross the midline, ascend in the medial longitudinal fasciculus, and stimulate the motor neurons in the oculomotor subnucleus for the medial rectus muscle. (The complex neural connections for conjugate eye movements are explained in Chapter 8 and summarized in Fig. 8-5.) Sensory and motor tracts are ventral to a lesion causing Foville's syndrome and, typically, there is a contralateral hemiparesis of brief duration caused by transient ischemia or pressure (Fig. 7-20).


FIGURE 7-18 Site of a lesion in the basal pons involving corticospinal and other descending motor fibers and fibers of the abducens nerve. This lesion results in Raymond's syndrome. This lesion spares the abducens nucleus and the nucleus and axons of the facial nerve.


FIGURE 7-19 Site of a lesion in the caudal part of the pons involving descending motor fibers and the axons and nucleus of the facial nerve but sparing the nucleus and axons of the abducens nerve. This lesion results in the Millard-Gübler syndrome.


FIGURE 7-20 Site of a lesion causing Foville's syndrome. Involvement of the abducens nucleus causes paralysis of the contralateral medial rectus in addition to the ipsilateral lateral rectus muscle. The motor nucleus and axons of the facial nerve are also destroyed, and the lesion extends ventrally to cause partial damage to corticospinal and other descending motor tracts.



FIGURE 7-21 Site of a lesion in the rostral midbrain involving corticospinal and other descending motor fibers and the axons of the oculomotor nerve. This lesion results in Weber's syndrome.

The position of a vascular lesion in the basal region of a cerebral peduncle, which can follow occlusion of a branch of the posterior cerebral artery, is shown in Figure 7-21. This causes Weber's syndrome, consisting of contralateral hemiparesis caused by interruption of corticospinal and other descending motor fibers and ipsilateral paralysis of ocular muscles because of inclusion of oculomotor nerve fibers in the infarcted area. Affected patients have paralysis of all the extraocular muscles except the lateral rectus and superior oblique. The most obvious signs are loss of ability to raise the upper eyelid and lateral strabismus, together with dilatation of the pupil because of interruption of parasympathetic fibers that control the sphincter pupillae muscle. A lesion that extends farther dorsally than the one in Figure 7-21 involves cerebellar efferent fibers, causing a tremor, similar to that associated with cerebellar disorders, in the paretic contralateral limbs. The condition is then known as Benedikt's syndrome.

Suggested Reading

Bassetti C, Bogousslavsky J, Mattle H, Bernasconi A. Medial medullary stroke: report of seven patients and review of the literature. Neurology 1997;48:882-890.

Damier P, Hirsch EC, Agid Y, et al. The substantia nigra of the human brain. Brain 1999;122:1421-1448.

Defer GL, Geny C, Ricolfi F, et al. Long-term outcome of unilaterally transplanted Parkinsonian patients, 1: clinical approach. Brain 1996;119:41-50.

Finnis KW, Starreveld YP, Parrent AG, et al. Three-dimensional database of subcortical electrophysiology for image-guided stereotactic functional neurosurgery. IEEE Trans Med Imaging 2003;22:93-104.

Freed CR, Greene PE, Breeze RE, et al. Transplantation of embryonic dopamine neurons for severe Parkinson's disease. N Engl J Med 2001;344:710-719.

Hirsch WL, Kemp SS, Martinez AJ, et al. Anatomy of the brainstem: correlation of in vitro MR images with histologic sections. Am J Neuroradiol 1989;10:923-928.


Landau WM. Artificial intelligence: the brain transplant cure for parkinsonism. Neurology 1990;40:733-740.

Nathan PW, Smith MC. The rubrospinal and central tegmental tracts in man. Brain 1982;105:223-269.

Nathan PW, Smith MC. The location of descending fibres to sympathetic neurons supplying the head and neck. J Neurol Neurosurg Psychiatr 1986;49:187-194.

Nieuwenhuys R, Voogd J, van Huijzen C. The Human Central Nervous System. A Synopsis and Atlas, 3rd ed. Berlin: Springer-Verlag, 1988.

Olszewski J, Baxter D. Cytoarchitecture of the Human Brain Stem, 2nd ed. Basel: S Karger, 1954; reprint, 1982.

Riley HA. An Atlas of the Basal Ganglia, Brain Stem and Spinal Cord. New York: Hafner, 1960.

Vuilleumier P, Bogousslavsky J, Regli E. Infarction of the lower brainstem: clinical, aetiological and MRItopographical correlations. Brain 1995;118:1013-1025.

Wolf JK. The Classical Brain Stem Syndromes. Springfield, IL: Thomas, 1971.