Figure 1-26 Schematic illustration of the smooth pursuit system, showing the relevant cortical centers and their pathways for generating smooth pursuit eye movements. Note that this illustration is not meant to show the hypothetical scheme for the smooth pursuit system. Key: BPG = brainstem pursuit generator; CS = cerebellar structures; FEF = frontal eye field; MT/MST = middle temporal area/medial superior temporal area; PON = precerebellar pontine nuclei; PVC = primary visual
cortex; VN = vestibular nucleus. (Used with permission from Kline LB. Neuro-Ophthalmology Review Manual. 6th ed. Thorofare, NJ: Slack; 2008:54.)
For information on clinical disorders of the pursuit function, see Clinical Disorders of the Ocular Motor Systems in Chapter 7.
Brainstem
The supranuclear pathways for saccades and smooth pursuits eventually reach the brainstem neural network (via the SC and BG), which allows for conjugate eye movements. Following is a description of the important structures within the brainstem that allow for controlling gaze. In general, the midbrain is concerned with vertical eye movements and the pons with horizontal eye movements. Vertical and torsional saccades are generated from excitatory burst cells of the riMLF within the
midbrain. In contrast, the pathways for vertical vestibular and vertical smooth pursuit ascend from the medulla and pons to the midbrain via the MLF. Horizontal saccades are generated from excitatory burst cells within the PPRF, and horizontal smooth pursuit eye movements arise from the CN VI nucleus, which receives input from the vestibulocerebellum (see “Cerebellum” later in the chapter).
Vertical gaze is controlled through the midbrain. The primary gaze center is located in the riMLF (Fig 1-27). This area receives input from the medial and superior vestibular nuclei via the MLF and other internuclear connections. Other areas in the rostral midbrain, including the INC and the nucleus of Darkschewitsch, also modulate vertical motility. Burst cell input may come in part from the PPRF caudally but also locally within the riMLF. The INC (neural integrator for vertical and torsional gaze) receives signals from the riMLF and from the vestibular nuclei and projects to the motoneurons of the CN III and CN IV nuclei through the PC. Activity from the vertical gaze center is distributed to the CN III and CN IV nuclei. Information involved in upgaze crosses in the PC. Damage to this pathway results in the dorsal midbrain syndrome, a disorder that includes vertical gaze difficulty (most commonly, impaired supraduction), skew deviation, light–near pupillary dissociation, eyelid retraction, and convergence-retraction nystagmus (see Chapter 9).
Figure 1-27 Anatomical schemes for the synthesis of upward and downward movements (in red). From the vertical semicircular canals, primary afferents on the CN VIII synapse in the CN VIII nucleus (N) and ascend into the medial longitudinal fasciculus (MLF) and brachium conjunctivum (not shown) to contact the CN IV N, CN III N, and interstitial nucleus of Cajal (INC). (For clarity, only excitatory vestibular projections are shown.) The riMLF receives an inhibitory input from the RIP, which lies in the pons (for clarity, this projection is shown only for upward movements). Excitatory burst neurons in the riMLF project to the motoneurons of CN III and CN IV and send axon collaterals to the INC. Each riMLF
neuron sends axon collaterals to yoke-pair muscles (Hering’s law). Signals contributing to vertical smooth pursuit and eye–head tracking reach CN III from the y-group via the brachium conjunctivum and a crossing ventral tegmental tract. Key: CN III N = oculomotor nucleus; CN IV N = trochlear nucleus; CN VIII = vestibular nerve; CN VIII N = vestibular nuclei; io = inferior oblique subnucleus; ir = inferior rectus subnucleus; PC = posterior commissure; riMLF = rostral interstitial nucleus of the medial longitudinal fasciculus; RIP = nucleus raphe interpositus; so = superior oblique nucleus; sr =
superior rectus subnucleus. (Modified from Leigh RJ, Zee DS. The Neurology of Eye Movements. 4th ed. New York: Oxford University Press; 2006.)
Horizontal gaze is coordinated through the CN VI nucleus in the dorsal caudal pons (Fig 1-28). This nucleus receives tonic input from the contralateral horizontal semicircular canal through the medial and lateral vestibular nuclei. Burst information is supplied from the PPRF that is directly adjacent to the CN VI nucleus and MLF. The burst cells are normally inhibited by omnipause neurons located in the RIP. Saccades are thought to be initiated by supranuclear inhibition of the omnipause cells, which allows burst cell impulses to activate the horizontal and vertical gaze centers (Fig 1-29). To produce horizontal movement of both eyes, a signal to increase firing must be distributed to the ipsilateral lateral rectus and the contralateral medial rectus muscles. The lateral rectus muscle is supplied directly through ipsilateral CN VI. The contralateral medial rectus muscle is stimulated by interneurons that cross in the pons and ascend in the contralateral MLF. Therefore, pathology affecting the right MLF will result in a right internuclear ophthalmoplegia—a right (ipsilateral) adduction deficit with attempted left gaze—often accompanied by abducting nystagmus of the left (contralateral) eye and a skew deviation (see Chapter 8).
Figure 1-28 Anatomical scheme for the synthesis of signals for horizontal eye movements (excitatory pathway indicated in red and inhibitory pathway in black). From the horizontal semicircular canal, primary afferents of the vestibular nerve (CN VIII) project mainly to neurons of the vestibular nerve nucleus (CN VIII N), which then send an excitatory connection to the contralateral abducens nucleus (CN VI N) and an inhibitory projection to the ipsilateral CN VI N. CN VI N innervates the ipsilateral lateral rectus (LR) muscle, and the contralateral oculomotor nerve nucleus (CN III N) via the medial longitudinal fasciculus (MLF). Eye position information (the output of the neural integrator) reaches the abducens from neurons within the nucleus prepositus hypoglossi (NPH) and adjacent CN VIII N. The anatomical sections on the right correspond to the levels indicated by the 2 arrows pointing toward the schematic on the left. Key: ATD = ascending tract of Deiters; CN VI = abducens nerve; CN VII = facial nerve; CTT = central tegmental tract; EBN = excitatory burst neurons; IBN = inhibitory burst neurons; ICP = inferior cerebellar peduncle; I CN VIII N = inferior vestibular nucleus; MedRF = medullary reticular formation; MR = medial rectus muscle; MVN = medial vestibular nucleus; PPRF = pontine paramedian reticular formation;
SVN = superior vestibular nucleus. (Modified from Leigh RJ, Zee DS. The Neurology of Eye Movements. 4th ed. New York: Oxford
University Press; 2006.)
Figure 1-29 Schematic of the brainstem network for saccade generation. Motoneurons innervating horizontally acting extraocular muscles receive saccadic commands from burst neurons in the paramedian pontine reticular formation (PPRF). Motoneurons innervating vertically acting extraocular muscles receive saccadic commands from burst neurons in the midbrain’s rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). Both sets of burst neurons are modulated by omnipause neurons that lie in the pontine nucleus raphe interpositus (RIP). A saccade is initiated by a trigger signal that inhibits omnipause neurons; subsequently, hypothetical latch neurons, which receive input from burst neurons, inhibit omnipause neurons until the saccade is complete. Minus signs indicate inhibition. (Modified with permission
from Leigh RJ, Zee DS. The Neurology of Eye Movements. 4th ed. New York: Oxford University Press; 2006.)
The distribution of infranuclear (ocular motor cranial nuclei and nerves) as well as supranuclear information requires internuclear communication within the brainstem. The most important of these pathways, the MLF, runs in 2 parallel columns from the spinal cord to an area of the midbrain PC that is located dorsomedial to the red nucleus and rostral to the INC. The bulk of the fibers contributing to the MLF have their origin in the vestibular nuclei. The projections from the superior vestibular nucleus are ipsilateral, and those from the medial vestibular nucleus are contralateral. The MLF also receives interneurons originating from the contralateral CN VI nucleus. Additional vertical pathways include the brachium conjunctivum and the ascending tract of Deiters. The latter pathway runs lateral to the MLF and conveys signals from CN VIII nuclei ipsilaterally to the medial rectus subnucleus in the midbrain, modulating the vestibular response during near fixation.
To maintain eccentric gaze, additional tonic input must be provided to the yoke muscles that hold the eye in position. This additional input is provided by integrating the velocity signal provided by the burst neuron activity. For horizontal eye movements, integration takes place in the NPH, located adjacent to the medial vestibular nucleus at the pontomedullary junction, with input from the cerebellum. Neural integration for vertical eye movements involves the INC in addition to the cerebellum. Pathology affecting the neural integrator (often metabolic, associated with alcohol consumption or anticonvulsant medication) results in failure to maintain eccentric gaze, recognized clinically as gaze-evoked nystagmus.
Vestibular ocular system
The output of the vestibular nuclei provides both the major infranuclear input into ocular motility and the major tonic input into eye position. This system has one of the shortest arcs in the nervous system, producing a fast response with extremely short latency. The hair cells of the semicircular canals alter their firing in response to relative movement of the endolymph (Fig 1-30). The signal is produced by a change in velocity (head acceleration) in any one of 3 axes. The information is then conveyed to the vestibular nuclei (located laterally in the rostral medulla) via the inferior and superior vestibular nerves. An additional contribution to the vestibular nerve is from hair cells in the macula acoustica of the utricle and saccule. Calcium carbonate crystals within the otoliths respond to linear acceleration (most important, gravity) to orient the body. The vestibular nerve and the output of the membranous labyrinth (the cochlear nerve) make up the CN VIII complex and exit the petrous bone through the internal auditory meatus. CN VIII traverses the subarachnoid space within the cerebellopontine angle. Within the medulla, the vestibular information synapses in the medial, lateral, and superior vestibular nuclei. Tonic information from the horizontal canal crosses directly to the contralateral gaze center within the CN VI nucleus in the dorsal medial aspect of the caudal pons just under the fourth ventricle. Tonic information from the anterior and posterior canals travels rostrally through several of the important internuclear connections to innervate the vertical gaze center in the rostral midbrain. Medial and inferior vestibular nuclei, as well as the NPH and the inferior olivary nucleus, project to the nodulus (a central nucleus of the cerebellum) and the ventral uvula. This pathway, which projects back to the vestibular nuclei, is responsible for the velocity storage mechanism (that is, the mechanism that maintains the vestibular signal beyond the output of the primary vestibular neurons).
Figure 1-30 Vestibular system. A, Schematic of the mammalian labyrinth. The crista of the lateral semicircular canal is shown but not labeled (with the canal projecting forward). B, Top: Motion transduction by the vestibular hair cells. At rest,