13 The brainstem and reticular formation
Case 13.1
A 16-year-old male presents with blurred vision following a concussion that he received in a motorcycle accident 1 month previous. He reports that he has no headaches, and no loss of sensation or strength in his hands, arms, or feet. During slow pursuit testing his eyes become slightly disconjugated. His saccades also overshoot during the fast return phase.
Case 13.2
A 65-year-old male presents with his wife who is concerned about her husband’s facial appearance. She claims that he does not look the same and has less facial expression than he used to. She has been noticing this for the last few weeks. On testing it is discovered that he cannot move the right side of his forehead or hold his right eye closed to gentle pressure.
Questions
• 13.2.1 Discuss the difference between upper and lower motor neuron lesions in general.
• 13.2.2 Discuss the different clinical signs when differentiating between an upper and a lower motor neuron lesion involving the facial nerve.
• 13.2.3 Discuss six differential diagnostic considerations for this gentleman.
Introduction
There is probably no more complicated area to study anatomically than the brainstem. Understanding the anatomy in a three-dimensional perspective is crucial for the application of clinical neurology. The reticular formation receives little attention in traditional neurology textbooks. It is an area that spans all levels of the brainstem, from the thalamus to the spinal cord, and is responsible for integrating information from the brain and periphery and linking sensory, motor, and autonomic nuclei of the brainstem. The reticular formation therefore mediates complex reflexes and functions such as eye movements, posture, feeding, breathing, homeostasis, arousal, sleep, control of vasomotor tone and cardiac output, and pain. The cranial nerves are very important as clinical windows into the functional state of various levels of the brainstem. The brainstem is also responsible for the control of vital functions like heart rate and respiration. This area, although complicated, promises access to a great amount of clinical information to those who spend the necessary investments of time and energy to thoroughly grasp the structure and functional relationships that compose the brainstem.
Anatomy of the brainstem
The brainstem is composed of the following anatomical areas (Figs 13.1, 13.2, and 13.3):
1. Midbrain or mesencephalon is contained between the cerebrum and the pons in an area which measures approximately 2.5 cm long;
2. Pons is contained between the midbrain and the medulla;
3. Medulla oblongata extends from the base of the pons to the first pair of cervical nerves. Caudally, the medulla is continuous with the medulla spinalis or the spinal cord.
We will approach the description of the brainstem by outlining the structures observed at various levels in cross-sectional dissections.
Input from primary afferents and their collaterals results in the following
1. Monosynaptic reflex involving the alpha motor neurons
4. Inhibition of contralateral homologues
5. Excitation of antagonist of contralateral homologues
7. Excitation of granular layer of the cerebellum, which leads to increased contralateral cortical integration via excitation of contralateral thalamus.
Mesencephalon
The structures of the mesencephalon can be observed in a cross-section of midbrain at the superior colliculus and the inferior colliculus (Figs 13.4 and 13.5).

Figure 13.4 A cross-sectional view of the mesencephalon at the superior colliculus.
(from Standring 2008 Gray’s Anatomy 40th edn. Edinburgh, Elsevier, with permission)

Figure 13.5 A cross-sectional view of the mesencephalon at the inferior colliculus.
(from Standring 2008 Gray’s Anatomy 40th edn. Edinburgh, Elsevier, with permission)
Periaqueductal grey area
The periaqueductal grey area is an area of neuron cell bodies that surrounds the cerebral aqueduct. It is continuous with the grey substance of the third ventricle.
Tectum
The tectum comprises the ‘roof’ or dorsal portion of the midbrain and contains the corpora quadrigemina, which includes the superior and inferior colliculi and all the substances that lie dorsal to the cerebral aqueduct in the midbrain area of the neuraxis. The superior colliculi are involved with visual reflexes, and project to the lateral geniculate bodies of the thalamus. The inferior colliculi are involved with reflexes associated with sound, and project to the medial geniculate bodies of the thalamus.
Tegmentum
The tegmentum consists of the bulk of the matter of the brainstem and comprises the area ventral to the cerebral aqueduct and fourth ventricle. It contains the bulk of the brainstem nuclei and the reticular formation of the midbrain, pons, and medulla.
Substantia nigra
The substantia nigra is a broad layer of pigmented neurons that separates the basis from the tegmentum. It extends from the upper surface of the pons to the hypothalamus. It projects to and receives projections from the neostriatum, thalamus, subthalamic nucleus, superior colliculi, and the reticular system of the brainstem. The neuron of this region utilise dopamine as a neurotransmitter.
Oculomotor nuclei
The oculomotor nuclei are the motor nuclei of the superior rectus, inferior rectus, and medial rectus muscles of the eye.
Red nucleus
These bilateral structures are ovoid groups of nuclei composed of two different cell types, the magnocellular and parvocellular groups of neurons. The magnocellular neurons are large, multipolar cells located in the caudal area of the red nuclear mass. These neurons receive bilateral projections both from sensorimotor cortical areas via the corticorubral tracts and from collaterals via the corticospinal tracts. The cortical projections and their target neurons in the red nucleus are somatotopically organised. Axon projections from the magnocellular neurons form the rubrospinal tracts, which cross in the brainstem and project in a somatotopically organised fashion, mainly to the interneurons of the intermediate grey areas of the spinal cord. Some rubrospinal fibres terminate directly on ventral horn motor neurons as well. Some axons that form the rubrospinal tracts terminate on neurons in the pontomedullary reticular formation and the motor nuclei of various cranial nerves, forming the rubroreticular system and the rubrobulbar tracts, respectively (Brown 1974). Reciprocal, bilateral projections to the superior colliculi are also present and form the rubrotectal tracts (Fig. 13.6). The rubrospinal and corticospinal tracts form the lateral motor system of the spinal cord. The medial motor system is composed of the reticulospinal and vestibulospinal tracts.
The parvocellular neurons of the red nucleus are small pyramidal- and spherical-shaped neurons, mostly located in the rostral areas of the red nuclear mass. These neurons receive projections from the dentate nucleus of the contralateral cerebellum, and from the ipsilateral globus pallidus pars externa, substantia nigra, and subthalamic nuclei. These neurons project to the ipsilateral thalamus (Fig. 13.6).
Medial longitudinal fasciculus (MLF)
This structure is a highly myelinated axon tract that descends from the interstitial nucleus of Cajal in the lateral wall of the third ventricle through the midbrain, pons, and medulla to the spinal cord where it becomes continuous with the anterior intersegmental fasciculus. The MLF acts as a major communications conduit between all of the cranial nerve nuclei and all related structures including the reticular formations of the mesencephalon, pons, and medulla. The medial vestibulospinal tract axons project with the MLF to the spinal cord (Brodal et al. 1962). Other axons from the vestibular nuclei ascend in the MLF to more rostral structures including the extraocular cranial nuclei. The MLF is the first fibre tract in the developing embryo to become myelinated and probably acts as a major pathway providing stimulus to developing neurons in the early stages of embryonic development.
Medial lemnisci
The medial lemniscus is a bundle of axons that forms a triangular structure medial to the spinothalamic tract. The bundles are formed from axons of the contralateral dorsal column nuclei, the nucleus gracilis and cuneatus, which have decussated and formed the internal arcuate fibres which become continuous with the medial lemnisci. The fibres are joined by axons of the trigeminal sensory nucleus to project to the ipsilateral thalamus. Axons from the dorsal column nuclei terminate on neurons in the ventral posterior lateral nucleus of the thalamus, whereas axons from the trigeminal sensory nucleus terminate on neurons in the ventral posterior medial nucleus of the thalamus (Guyton & Hall 1996).
Crus cerebri
This semilunar structure, also referred to as the basis, is located anterior to the substantia nigra and is composed of the corticospinal, corticonuclear, and corticopontine fibre tracts. The corticospinal fibres terminate on the ventral horn neurons of the contralateral spinal cord. The corticonuclear fibres terminate mainly on contralateral cranial nerve nuclei throughout the brainstem. The corticopontine fibres are composed of projections from the frontal and temporal cortical areas and terminate on the interneurons of the nuclei pontis. These nuclei then project mostly to the contralateral cerebellum.
Pons
The structures of the pons can be observed through a cross-section at the level of the trigeminal nerves (Fig. 13.7), just superior to the cerebral peduncles.

Figure 13.7 A cross-sectional view of the pons at the level of the trigeminal nerves.
(from Standring 2008 Gray’s Anatomy 40th edn. Edinburgh, Elsevier, with permission)
Superior cerebellar peduncle
This structure, which is also referred to as the brachium conjunctivum, proceeds from the upper white substance of the cerebellar hemisphere to the tegmentum where it completely decussates at the level of the inferior colliculus. It is composed of:
1. Dentatorubral and dentatothalamic fibres, both of which terminate contralaterally in the red nucleus and the thalamus, respectively;
2. Fibres of the ventral or anterior spinocerebellar tract projecting to the cerebellum from the spinal cord; and
3. Fibres of the uncinate fasciculus that contains fibres from the fastigial nucleus that will terminate in the lateral vestibular nucleus (Chusid 1982).
Anterior (ventral) spinocerebellar tract
These tracts form bilateral structures that ascend in the spinal cord in the ventral lateral fasciculi. They terminate in the vermis and intermediate zones of the ipsilateral cerebellum. These tracts relay information to the cerebellum about what information or commands have arrived at the ventral horn cells. These pathways are part of the efference copy mechanism of the cerebellar motor system.
Lateral lemnisci
This tract carries fibres from the contralateral dorsal cochlear nucleus to the inferior colliculus.
Middle cerebellar peduncle
These bilateral structures, which are also referred to as the brachium ponti, are the largest of the cerebellar peduncles. They carry fibres from the pontine nuclei to the contralateral neocerebellum. They are a component of the corticopontocerebellar pathways.
Reticular formation
The reticular formation of the pons is continuous with the reticular formations of the medulla and the mesencephalon. This area receives input from virtually all areas of the neuraxis and projects widely throughout the neuraxis. (See below for more detail.)
Fourth ventricle
This cavity is bounded by the pons and medulla ventrally and by the cerebellum dorsally. It is continuous with the cerebral aqueduct above and the central canal of the medulla below and has a capacity for cerebrospinal fluid (CSF) of about 20 ml. The floor of the fourth ventricle, which is also referred to as the rhomboid fossa, is formed by the dorsal surfaces of the pons and medulla. The fourth ventricle acts as a component of the CSF system (Chusid 1982).
Medulla
Structures of the medulla can be viewed by cross-sections at:
Structures found at a cross-section at the inferior olive (fig. 13.8)
Choroid plexus of 4th
This structure is also referred to as the tela choroidea of the fourth ventricle and is composed of a layer of pia matter that has become highly vascularised. The choroid plexus produces CSF.
Inferior cerebellar peduncle
These bilateral structures, which are also referred to as the restiform bodies, ascend laterally from the walls of the fourth ventricles to enter the cerebellum between the superior and middle cerebellar peduncles. They carry fibres of the following tracts:
1. Olivocerebellar tract, which arises from neurons of the contralateral superior olivary nucleus and projects to the cerebellar hemispheres and vermis;
2. Dorsal spinocerebellar tract, which arises from neurons in the area of Clark’s column of the spinal cord to project to the interpositus nuclear region and the palaeocerebellar cortex;
3. Dorsal external arcuate fibres from the nuclei gracilis and cuneatus;
4. Ventral external arcuate fibres from the lateral reticular nuclei of the medulla; and
5. Vestibulocerebellar tract, which arises from the vestibular nuclei and projects to the flocculonodular lobe of the cerebellum.
Cuneate nucleus
These structures are located bilaterally, lateral and superior to the nuclei gracilis. They are composed of neurons that receive proprioceptive information from the arms and shoulders. Axons from these nuclei project via the internal arcuate fibres where they decussate to form the medial lemnisci projecting ultimately to the contralateral thalamus.
Accessory cuneate nucleus
These structures receive axons from muscle spindles and joint receptors transmitting unconscious proprioception from the arms and shoulders to the ipsilateral cerebellum. The axons from these nuclear cells form the cuneocerebellar tracts via the external arcuate fibres.
Lateral spinothalamic tract
Nucleus tractus solitarius
The single most important component of the autonomic nervous system from a manipulatory point of view is the nucleus tractus solitarius (NTS, or solitary nucleus). The NTS receives afferent inputs from the viscera in addition to somatic and limbic structures and very heavy projections from the vestibular system. It mediates supraspinal visceral reflexes and contains a map of the viscera including the gastrointestinal system, cardiorespiratory system, and taste sensation.
These tracts are located medial and anterior to the ventral spinocerebellar tracts in the ventral lateral fasciculus of the spinal cord. They are formed by axons projecting from neurons located in the contralateral dorsal horn area. These neurons project their axons via the anterior white commissure to the opposite lateral spinothalamic tract where they terminate on the ipsilateral thalamus to the tract in which they ascend.
Inferior olivary nucleus
These bilateral groups of nuclei are located within the olive of the medulla. They receive projections from the cortex, from other brainstem nuclei, from the ipsilateral parvocellular red nucleus, and from the ipsilateral spinal cord. These neurons project axons, referred to as climbing fibres, via the inferior cerebellar peduncles to all areas of the cerebellar cortex. These structures are part of a group of projections and nuclei referred to as the inferior olivary nuclear complex, which forms a complicated loop from the cerebellar cortex to the dentate nucleus to the contralateral red nucleus to the inferior olivary nucleus and back to the contralateral cerebellar cortex (Fig. 13.9)
Dorsal motor nucleus of the vagus nerve (DMN)
These nuclei are located bilaterally, dorsal and lateral to the hypoglossal nuclei. These nuclei supply the preganglionic parasympathetic axons of the vagus and spinal accessory nerves.
Solitary tract nucleus
These nuclei are also referred to as the nuclei of the tractus solitarius (NTS). These nuclei are located ventrolaterally to the motor nuclei of the vagus nerve and run the full length of the medulla. All cranial visceral afferent nerves project to the NTS. The rostral portion of the NTS, which is referred to as the gustatory nucleus, receives projections from the special visceral afferent nerves (CN VII, CN IX, CN X) for taste. The caudal portion of the NTS, which is referred to as the cardiorespiratory nucleus, receives projections from the general visceral afferent fibres of CN IX and CN X.
Nucleus ambiguus
These bilateral nuclei are located ventromedially to the spinal nucleus of the trigeminal nerve and run longitudinally throughout the medulla. The neurons of these nuclei supply the branchial motor output of the glossopharyngeal (CN IX), the vagus (CN X), and the spinal accessory (CN XI) nerves.
Vagus nerve
These nerves exit the rostral medulla ventrolaterally from the pontomedullary junction as several rootlets between the inferior olive and the inferior cerebellar peduncle. The nerves exit the skull via the jugular foramen. The nerves supply the preganglionic parasympathetic output to all structures below the neck including the heart, lungs, pancreas, liver, kidneys, and gastrointestinal tract, and the branchial motor supply to the pharyngeal muscles and the muscles of the larynx.
Pyramids
These bilateral structures are found on the ventral surface of the medulla from the pontomedullary junction to the pyramidal decussation. They are formed by the axons of the motor output neurons of the cortex that largely involve the pyramidal neurons. These axons will form the corticospinal tracts of the spinal cord.
Hypoglossal nerve
These nerves exit the medulla ventromedially between the pyramids and inferior olivary nuclei. The hypoglossal nerve exits the skull via the hypoglossal canal and supplies the motor axons to the tongue.
Structures found in a cross-section at the lemniscal decussation (fig. 13.10)
Fasciculus gracilis
These bilateral tracts run dorsally in the medulla medial to the cuneate fasciculi. They are formed by the axons of the dorsal root ganglion cells that detect proprioception and touch in the lower limbs and trunk, usually below the T6 level. The axons enter the spinal cord via the dorsal root and ascend ipsilaterally in the fasciculus gracilis to the gracile nucleus.
Gracile nucleus
These bilateral nuclei are located caudally and medially to the cuneate nuclei. These nuclei receive the axons of the fasciculus gracilis, which have arisen from the dorsal root ganglion cells detecting proprioception and touch in the lower limbs and trunk. The neurons project their axons via the internal arcuate fibres where they decussate and terminate in the contralateral ventral posterior lateral nucleus of the thalamus.
Fasciculus cuneatus
These bilateral structures are located dorsally in the medulla, lateral to the fasciculus gracilis. They are formed by the axons of the dorsal root ganglion cells that detect proprioception and touch in the upper limbs and trunk, usually above the T6 level. The axons enter the spinal cord via the dorsal root and ascend ipsilaterally in the fasciculus cuneatus to the cuneate nucleus. These fibres transmit information related to two-point discrimination, vibration sense, unconscious and conscious proprioception, as well as joint position sense.
Decussation of lemnisci
Axons from the nucleus cuneatus and nucleus gracilis form the internal arcuate fibres that cross in the decussation and continue from there as the medial lemniscus.
Structures found at a cross-section through pyramidal decussation (fig. 13.11)
Anterior corticospinal tracts
These bilateral tracts are contained in the pyramids of the medulla until the decussation of the pyramids where they do not decussate but continue ipsilaterally in the ventral medial portion of the ventral fasciculus of the spinal cord. These tracts relay motor information to the muscles of the trunk, spine, and proximal limbs.
The reticular formation (RF)
The reticular formation receives little attention in traditional neurology textbooks. It is an area that spans all levels of the brainstem, from the thalamus to the spinal cord, and is responsible for integrating information from the brain and periphery and linking sensory, motor, and autonomic nuclei of the brainstem. The reticular formation therefore mediates complex reflexes and functions such as eye movements, posture, feeding, breathing, homeostasis, arousal, sleep, control of vasomotor tone and cardiac output, and pain. The reticular formation is composed of continuous groups of neurons interconnected via polysynaptic pathways that can be both crossed and uncrossed in nature. The RF receives projections from virtually all sensory modalities and projects to all areas of the neuraxis including direct projections to the cortex (Webster 1978).
The parabrachial nucleus
The parabrachial nucleus (PBN) is an important structure that integrates sensory input from the reticular formation and projects that information to relay and intralaminar nuclei in the thalamus. This nucleus is also involved in the reticular activation system that maintains consciousness. The PBN maintains reciprocal connections with the following systems:
The cerebellopontine angle
The cerebellopontine angle forms a triangle between the lateral aspect of the pons, the cerebellum, and the inner third of the petrous ridge of the temporal bone.
Cranial nerve (CN) V (motor) is at the rostral border while CN IX is at the caudal border. CN VI ascends at its medial edge, and CN VII and VIII traverse it before entering the internal auditory meatus.
Afferent projections to the RF include:
Efferent projections from the RF include:
• Projections to autonomic nuclei and intermediolateral (IML) column;
• Direct projections to the thalamus and cortex; and
• Direct projections to other areas of the reticular system.

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