The brain stem consists of the medulla oblongata, pons and midbrain. The archaic term ‘bulb’ is applied to the brain stem in compound anatomical names given to nerve fibres originating from, or terminating in, the brain stem (e.g. ‘corticobulbar’ refers to axons that arise in the cerebral cortex and terminate in the brain stem). It is also used clinically to denote the medulla in such terms as ‘bulbar palsy’ and ‘pseudobulbar palsy’, which describe syndromes associated with medullary dysfunction.
The brain stem lies upon the basal portion of the occipital bone (clivus) and is connected to, and largely covered by, the cerebellum. Caudally, the medulla is continuous with the spinal cord just below the foramen magnum. Rostrally, the midbrain is continuous with the diencephalon of the forebrain.
The brain stem contains numerous ascending and descending fibre tracts. Some of these pass throughout its whole length, having their origin in the spinal cord or cerebral hemisphere, respectively; others have their origin or termination within brain stem nuclei. Certain of these brain stem nuclei receive fibres from, or send fibres into, cranial nerves, 10 pairs of which (III–XII) attach to the surface of the brain stem. These are known as the cranial nerve nuclei. In addition, the brain stem contains a complex and heterogeneous matrix of neurones known as the reticular formation, within which a number of individually identified nuclei exist. The reticular formation has several important functions, including control over the level of consciousness, the perception of pain and regulation of the cardiovascular and respiratory systems. It also has extensive connections with the cranial nerve nuclei, with the cerebellum, and with brain stem and spinal motor mechanisms, through which it influences movement, posture and muscle tone.
External features of the brain stem
Dorsal surface of the brain stem
The dorsal surface of the brain stem can be viewed if the overlying cerebellum is removed by cutting the three pairs of nerve fibre bundles, or peduncles, by which it is attached on each side (Figs 9.1, 9.2). On the dorsal surface of the medulla, the midline is marked by a dorsal median sulcus, continuous with that of the spinal cord. In the caudal part of the medulla, the dorsal columns (fasciculi gracilis and cuneatus, containing first-order sensory neurones) continue rostrally from the spinal cord to their termination in the nuclei gracilis and cuneatus, the locations of which are marked by two small elevations, the gracile and cuneate tubercles.
Figure 9.1 Dorsal aspect of the brain stem.
Figure 9.2 Lateral aspect of the brain stem.
The caudal two-thirds of the medulla contains the rostral continuation of the central canal of the spinal cord and is, therefore, sometimes referred to as the ‘closed’ portion of the medulla. In passing rostrally, the central canal moves progressively more dorsally until, in the rostral medulla, it opens out into the fourth ventricle. This portion is sometimes referred to as the ‘open’ medulla. The floor of the fourth ventricle forms a shallow, rhomboid depression on the dorsal surface of the rostral medulla and the pons. The transition from medulla to pons is not clearly delineated on the dorsal surface of the brain stem but, approximately, the caudal third of the floor of the fourth ventricle constitutes the dorsal aspect of the rostral medulla, while the rostral two-thirds of the ventricular floor is made up of the dorsal aspect of the pons. The fourth ventricle is widest at the level of the pontomedullary junction where a lateral recess extends to the lateral margin of the brain stem. At this point the small lateral aperture (foramen of Luschka) provides passage for CSF within the fourth ventricle to reach the subarachnoid space surrounding the brain. The lateral walls of the rostral part of the fourth ventricle are made up of the superiorand inferior cerebellar peduncles, connecting the brain stem with the cerebellum. In the rostral pons, the walls converge until, at the pontomesencephalic junction, the fourth ventricle becomes continuous with a small channel, the cerebral aqueduct, which passes throughout the length of the midbrain.
The dorsal aspect of the midbrain is marked by four paired elevations, the superior and inferior colliculi, which are parts of the visual and auditory systems, respectively. The trochlear nerve (IV cranial nerve) emerges immediately caudal to the inferior colliculus.
Ventral surface of the brain stem
On the ventral surface of the medulla, prominent longitudinal columns, the pyramids, run on either side of the ventral median fissure (Figs 9.3, 9.4). The pyramid gives its name to the underlying pyramidal or corticospinal tract, which consists of descending fibres originating from the ipsilateral cerebral cortex. In the caudal medulla, 75–90% of these fibres cross over in the decussation of the pyramids (Figs 9.3-9.5), partly obscuring the ventral median fissure as they do so, to form the lateral corticospinal tract of the spinal cord. Lateral to the pyramid lies an elongated elevation, the olive, within which lies the inferior olivary nucleus. This has connections primarily with the cerebellum and is involved in the control of movement.
Figure 9.3 Ventral aspect of the brain stem.
Figure 9.4 Ventral aspect of the brain stem showing the decussation of the pyramids.
Figure 9.5 Transverse section through the caudal medulla at the level of the decussation of the pyramids. The sections shown in Figs 9.5-9.13 have been stained by the Weigert–Pal method. Areas rich in nerve fibres stain darkly, while areas rich in cell bodies are relatively pale.
The transition from medulla to pons is clearly delineated on the ventral surface of the brain stem. The ventral part of the pons is dominated by a transverse system of fibres (the transverse pontine fibres or pontocerebellar fibres) that originate from cells in the ventral pons (pontine nuclei) and pass through the contralateral middle cerebellar peduncle to enter the cerebellar hemisphere. The pontine nuclei receive corticopontine fibres from the cerebral cortex (including the motor cortex) and constitute an important connection between cerebral and cerebellar cortices involved in the coordination of movement. The massive system of transverse pontine fibres obscures the underlying corticospinal tract.
The ventral surface of the midbrain consists, on either side, of a large column of descending fibres, the crus cerebri or basis pedunculi. In the midline, the two crura cerebri are separated by a depression called the interpeduncular fossa. The crus cerebri is continuous rostrally with the internal capsule of the cerebral hemisphere (Fig. 1.23) and consists of corticobulbar and corticospinal fibres that have left the cerebral hemisphere via the internal capsule on their way to the brain stem and spinal cord. They are primarily motor in function.
External features of the brain stem
The brain stem consists of the medulla oblongata, pons and midbrain.
On the dorsal aspect of the brain stem can be seen the dorsal columns, the floor of the fourth ventricle and the superior and inferior colliculi.
The dorsal aspect of the rostral medulla and the pons form the floor of the fourth ventricle; the lateral and median apertures of the fourth ventricle permit the passage of CSF into the subarachnoid space. The cerebral aqueduct runs through the midbrain, beneath the colliculi.
On the ventral aspect of the brain stem can be seen the pyramids, transverse pontine fibres and the crura cerebri.
The inferior, middle and superior cerebellar peduncles connect the cerebellum to the medulla, pons and midbrain, respectively.
Internal structure of the brain stem
At the transition from spinal cord to medulla, the pattern of grey and white matter undergoes considerable rearrangement (Fig. 9.5). The ventral horn becomes much attenuated. The dorsal horn is replaced by the caudal part of the trigeminal sensory nucleus (nucleus of the spinal tract of the trigeminal nerve). The trigeminal sensory nucleus is regarded as the brain stem homologue of the dorsal horn since it receives primary afferent fibres conveying general sensation from the head, which enter the brain stem in the trigeminal nerve. It is a large nucleus that extends the whole length of the brain stem and into the upper segments of the spinal cord. This latter, caudal part of the trigeminal nucleus is particularly associated with the modalities of pain and temperature. The trigeminal nerve attaches to the pons and, therefore, fibres that terminate in the parts of the trigeminal nucleus caudal to this level descend in a tract (the spinal tract of the trigeminal) which lies immediately superficial to the nucleus.
In the ventral medulla, the majority of fibres of the pyramid undergo decussation and then pass laterally, dorsally and caudally to form the lateral corticospinal tract.
On the ventral surface of the mid-medulla the pyramids are prominent, above their decussation. On the dorsal surface, the ascending fibres of the dorsal columns reach their termination in the gracile and cuneate nuclei, which appear beneath their respective tracts (Fig. 9.6). The dorsal columns consist of first-order sensory neurones; the cell bodies of these neurones lie in the dorsal root ganglia of spinal nerves and have central processes that ascended ipsilaterally through the cord and into the medulla. They terminate in the nuclei gracilis and cuneatus, upon the cell bodies of second-order neurones. The axons of the second-order neurones course ventrally and medially as internal arcuate fibres, decussating in the midline. Thereafter, they turn rostrally forming a distinct tract, the medial lemniscus, which runs through the rostral medulla, the pons and midbrain to terminate upon third-order neurones in the ventral posterior nucleus of the thalamus.
Figure 9.6 Transverse section through the mid-medulla at the level of the great sensory decussation.
Passing into the rostral medulla a number of new features appear, mostly related to the ventricular system and cerebellar connections. On the ventral surface of the medulla, the descending fibres of the pyramids remain conspicuous. Immediately dorsal to the medial aspect of the pyramid lie the ascending fibres of the medial lemniscus, on either side of the midline (Fig. 9.7). Dorsolateral to the pyramid and lateral to the medial lemniscus is the inferior olivary nucleus, lying within the prominence of the olive. The inferior olivary nucleus has roughly the form of a crenated bag with an opening, or hilum, facing medially, through which afferent and efferent fibres pass. The nucleus is concerned with the control of movement and receives afferents from the motor and sensory cortices of the cerebral hemisphere and from the red nucleus of the midbrain. Its main efferent connection is to the cerebellum via the inferior cerebellar peduncle. Within the cerebellum, axons originating from the inferior olivary nucleus, known as climbing fibres, end in excitatory synapses in the dentate nucleus and upon Purkinje cells of the cerebellar cortex.
Figure 9.7 Transverse section through the rostral medulla at the level of the inferior olivary nucleus.
Dorsal to the inferior olivary nucleus and lateral to the medial lemniscus lie second-order sensory fibres ascending to the ventral posterior thalamus from the trigeminal nucleus (the trigeminothalamic tractor trigeminal lemniscus) and from the spinal cord (spinothalamic fibres, referred to in the brain stem as the spinal lemniscus).
The dorsal surface of the rostral medulla forms part of the floor of the fourth ventricle. Both immediately and deep beneath the floor of the ventricle lie a number of cranial nerve nuclei, some of which can be clearly identified in simply stained sections, others of which cannot. Immediately beneath the ventricular floor, just lateral to the midline, lies the hypoglossal nucleus, which contains motor neurones innervating the muscles of the tongue via the hypoglossal nerve. Lateral to the hypoglossal nucleus lies the dorsal motor nucleus of the vagus, containing preganglionic parasympathetic neurones that run in the vagus nerve. The most caudal aspect of the ventricular floor is known as the area postrema. At this point, the blood–brain barrier, which limits the passage of certain chemicals from the blood to the brain, is absent. This region is the central site of action of substances that cause vomiting (emetics). In the lateral part of the floor of the fourth ventricle are located the vestibular nuclei, which receive primary afferent fibres from the vestibular nerve. Ventromedial to the hypoglossal nucleus, close to the midline, is located the medial longitudinal fasciculus. This consists of both ascending and descending fibres and can be identified also in the pons and midbrain. Within the brain stem, it links the vestibular nuclei with the nuclei supplying the extraocular muscles (abducens, trochlear and oculomotor nuclei) and subserves the coordination of head and eye movements.
The dorsolateral part of the rostral medulla is dominated by the inferior cerebellar peduncle, or restiform body. This consists of fibres passing between the medulla and the cerebellum. Prominent among these are olivocerebellar fibres, connections between the vestibular nuclei and the cerebellum, and the fibres of the dorsal spinocerebellar tract, conveying proprioceptive information from the limbs. On the dorsal and lateral aspects of the inferior cerebellar peduncle lie the dorsal and ventral cochlear nuclei, which receive afferent fibres from the cochlear nerve. Deep beneath the ventricular floor, just dorsal to the inferior olivary nucleus, is located the nucleus ambiguus. This sends motor fibres into the glossopharyngeal, vagus and accessory nerves and, thence, to the muscles of the pharynx and larynx.
The pons may be divided into a ventral, or basal, portion and a dorsal portion, also known as the tegmentum. The ventral portion is marked by numerous transversely oriented fascicles of pontocerebellar fibres that originate from scattered cell groups, the pontine nuclei, and pass into the contralateral side of the cerebellum through the massive middle cerebellar peduncle (brachium pontis) (Figs 9.8-9.10). Corticospinal fibres (which continue into the medullary pyramid) appear as small, separate bundles running longitudinally between the fascicles of transverse pontine fibres.
Figure 9.8 Transverse section through the caudal pons.
Figure 9.9 Transverse section through the mid-pons at the level of the trigeminal nerve.
Figure 9.10 Transverse section through the rostral pons.
The ascending fibres of the medial lemniscus become separated from the pyramid and displaced dorsally, together with the spinal lemniscus and trigeminothalamic tract (trigeminal lemniscus), by intervening transverse pontocerebellar fibres. The medial lemniscus also rotates through 90° so that it lies almost horizontally, marking the boundary between ventral and tegmental portions of the pons. In the caudal pons (Fig. 9.8), an additional group of transversely running fibres is located ventral to the ascending lemniscal fibres but dorsal to the pontocerebellar fibres. This is the trapezoid body, which consists of acoustic fibres crossing the brain stem from the cochlear nuclei. They ascend into the midbrain as the lateral lemniscus and terminate in the inferior colliculus.
Beneath the floor of the fourth ventricle, in the pontine tegmentum, lie a number of cranial nerve nuclei. These include the abducens nucleus (innervating the lateral rectus muscle), the facial motor nucleus(innervating the muscles of facial expression) and the trigeminal motor nucleus (innervating the muscles of mastication), which each supply motor axons to their respective cranial nerves. Also the trigeminal sensory nucleus, already encountered in the medulla, reaches its maximum extent in the pons, adjacent to the origin of the trigeminal nerve.
In the rostral part of the pons (Fig. 9.10) the superior cerebellar peduncles form the lateral walls of the fourth ventricle, the thin superior medullary velum spanning between them to form its roof. The superior peduncle contains some cerebellar afferent fibres, such as the ventral spinocerebellar tract, which conveys proprioceptive information from the limbs. It consists mainly, however, of ascending cerebellar efferents concerned with the coordination of movement, that are destined for the red nucleus of the midbrain and the ventral lateral nucleus of the thalamus. The superior cerebellar peduncles converge towards the midline as they pass into the midbrain.
The midbrain is formally divided into dorsal and ventral portions at the level of the cerebral aqueduct. The dorsal portion is known as the tectum, which consists largely of the inferior and superior colliculi(corpora quadrigemina). The ventral portion of the midbrain is known as the tegmentum. It is bounded ventrally by the massive fibre system of the crus cerebri. The term cerebral peduncle is sometimes used as a synonym for crus cerebri, but strictly speaking, the cerebral peduncle refers to the whole of the ventral midbrain, on either side, excluding the tectum.
In the caudal part of the midbrain, the inferior colliculus constitutes part of the ascending acoustic (auditory) projection. Ascending auditory fibres run in the lateral lemniscus, which terminates in the inferior colliculus. Efferent fibres from the colliculus terminate in the medial geniculate nucleus of the thalamus, which in turn projects to the auditory cortex of the temporal lobe.
The superior colliculus of the rostral midbrain is part of the visual system. Its main afferents are corticotectal fibres originating from the visual cortex of the occipital lobe and from the frontal eye field of the frontal lobe. These inputs are concerned with controlling movements of the eyes, such as those occurring when a moving object is followed (smooth pursuit) or when the direction of the gaze is altered (saccadic eye movements). In addition, corticotectal fibres from the visual cortex are involved in the accommodation reflex (Ch. 10).
A small number of visual fibres running in the optic tract terminate just rostral to the superior colliculus, in the pretectal nucleus. This nucleus has connections with parasympathetic neurones controlling the smooth muscle of the eye and is part of the circuit mediating the pupillary light reflex (Ch. 10).
Ventral to the colliculi, the cerebral aqueduct runs the length of the midbrain. Surrounding the aqueduct is a pear-shaped arrangement of grey matter, the periaqueductal (or central) grey. In the ventral part of the periaqueductal grey, at the levels of the inferior and superior colliculi, respectively, lie the trochlear and oculomotor nuclei, which innervate the extraocular muscles controlling eye movements. Close to the nuclei runs the medial longitudinal fasciculus, which links them to the abducens nucleus in the pons and is important in the control of gaze.
At the level of the inferior colliculus (Figs 9.11, 9.12), the central portion of the tegmentum is dominated by the superior cerebellar peduncles (brachium conjunctivum). These fibres originate in the cerebellum, coursing ventromedially as they run into the midbrain. Beneath the inferior colliculus, the superior cerebellar peduncles decussate in the midline. Rostral to the decussation, at the level of the superior colliculus (Fig. 9.13), the central portion of the tegmentum is occupied by the red nucleus, in which some of the fibres of the superior cerebellar peduncle terminate. The red nucleus is involved in motor control. Its other major source of afferents is the motor cortex of the frontal lobe. Efferent fibres from the red nucleus cross in the ventral tegmental decussation and descend to the spinal cord in the rubrospinal tract. In addition, the red nucleus projects to the inferior olivary nucleus of the medulla, via the central tegmental tract.
Figure 9.11 Transverse section through the brain stem at the level of the pontine–mesencephalic junction.
Figure 9.12 Transverse section through the caudal midbrain at the level of the inferior colliculus.
Figure 9.13 Transverse section through the rostral midbrain at the level of the superior colliculus.
The most ventral part of the midbrain tegmentum is occupied by the substantia nigra. A subdivision of this nucleus, known as the pars compacta, consists of pigmented, melanin-containing neurones that synthesise dopamine as their transmitter. These neurones project to the caudate nucleus and putamen of the basal ganglia in the forebrain (Ch. 14). Degeneration of the pars compacta of the substantia nigra is associated with Parkinson’s disease. The other, non-pigmented, subdivision of the substantia nigra is called the pars reticulata. It is considered to be a functional homologue of the medial segment of the globus pallidus, which is also part of the basal ganglia.
Ventral to the substantia nigra lies the massive crus cerebri. This consists entirely of descending cortical efferent fibres that have left the cerebral hemisphere by traversing the internal capsule. Approximately the middle 50% of the crus consists of corticobulbar and corticospinal fibres. The corticobulbar fibres end predominantly in or near the motor cranial nerve nuclei of the brain stem. The corticospinal (pyramidal) fibres traverse the pons to enter the medullary pyramid and, thence, the corticospinal tracts.
On either side of the corticobulbar and corticospinal fibres, the crus cerebri contains corticopontine fibres that originate from widespread regions of the cerebral cortex and terminate in the pontine nuclei of the ventral pons. From the pontine nuclei connections are established with the cerebellum, via the middle cerebellar peduncle, that are involved in the coordination of movement.
The reticular formation consists of a complex matrix of neurones that extends throughout the length of the brain stem. This is, in phylogenetic terms, a relatively old part of the brain stem and its neurones fulfil a number of important functions, some of which are necessary for survival. The reticular formation has widespread afferent and efferent connections with other parts of the CNS, which reflect its complex and multimodal functions. Some reticular neurones have long axons that ascend and descend for considerable distances within the brain stem, allowing profuse interaction with other neuronal systems. Within the reticular formation a number of individual nuclei are recognised. Some functions are subserved, however, by more dispersed networks that do not correspond exactly to anatomically identified nuclei. The latter applies to the so-called respiratory and cardiovascular centres. These consist of diffuse neuronal networks located within the medullary and caudal pontine reticular formation that control respiratory movements and cardiovascular function.
Brain stem lesions
A unilateral brain stem lesion caused by stroke, tumour or multiple sclerosis causes ipsilateral cranial nerve dysfunction, contralateral spastic hemiparesis, hyperreflexia and an extensor plantar response (upper motor neurone lesion), contralateral hemisensory loss and ipsilateral incoordination (Fig. 9.14). A bilateral lesion destroys the ‘vital centres’ for respiration and the circulation, leading to coma and death. Multiple sclerosis can affect eye movements through demyelination of the medial longitudinal fasciculus, which interferes with conjugate ocular deviation. Typically, on horizontal gaze, the abducting eye moves normally but the adducting eye fails to follow. Adduction is preserved on convergence. Internuclear ophthalmoplegia is the term used to describe this disorder (Fig. 9.15).
Figure 9.14 Brain stem lesion.
Figure 9.15 Internuclear ophthalmoplegia.
Internal structure of the brain stem
Cranial nerves III–XII attach to the brain stem, their fibres either originating from, or terminating in, the cranial nerve nuclei.
The reticular formation controls the level of consciousness, the cardiovascular system and the respiratory system.
Ascending sensory systems pass through the brain stem en route to the thalamus. First-order proprioceptive fibres in the dorsal columns relay in the dorsal column nuclei. Second-order fibres decussate to form the medial lemniscus. Spinothalamic fibres form the spinal lemniscus. Second-order fibres originating in the trigeminal sensory nucleus constitute the trigeminothalamic tract (trigeminal lemniscus).
Descending fibre systems end in the brain stem, pass through it and originate within it.
Corticobulbar fibres terminate in the midbrain, pons and medulla. The corticospinal tract runs through the crus cerebri, the basal part of the pons and the medullary pyramid; 75–90% of fibres cross in the pyramidal decussation to form the lateral corticospinal tract.
The reticular formation, red nucleus and vestibular nuclei give rise to descending fibres that pass to the spinal cord.
Descending reticulospinal tracts originate from the medullary and pontine reticular formation (Ch. 8). These predominantly influence muscle tone and posture. Some of the ascending fibres of the reticular formation constitute the reticular activating system. These neurones receive input, either directly or indirectly, from multiple sensory sources. Through the intermediary of thalamic nuclei, they cause activation of the cerebral cortex and heightened arousal.
The raphé nuclei are a group of midline nuclei that extend throughout the length of the brain stem. Many of the neurones of these nuclei are serotonergic, utilising serotonin (5-hydroxytryptamine, 5-HT) as their transmitter. Their axons are widely distributed throughout the CNS. In particular, ascending fibres to forebrain structures are involved in the neural mechanisms of sleep, and descending fibres to the spinal cord are involved in the modulation of nociceptive mechanisms.
The locus coeruleus is a group of pigmented neurones that lies in the brain stem tegmentum of the caudal midbrain and rostral pons. It is the principal noradrenergic cell group of the brain. It projects to many areas of the CNS. Ascending fibres project to the cerebellum, hypothalamus, thalamus, limbic structures and cerebral cortex. Descending fibres project widely throughout the brain stem and spinal cord. The locus coeruleus, like the raphé nuclei, has been implicated in the neural mechanisms regulating sleep, particularly REM (rapid eye movement) sleep.