1.1 General Architecture
1.4.5 Premotor Control of Eye Movements
Five different eye movement types – saccades, vestibulo-ocular reflex, optokinetic reflex, smooth pursuit eye movements,
convergence – and gaze stabilization can be differentiated in humans. They are generated in different neuronal networks and their efferent premotor pathways converge on motor neurons of the eye muscles and continue to the orbit as a short common pathway before terminating (Fig. 1.11).
Consequently, damage to one premotor pathway or to an indi- vidual premotor region of the brain can lead to a relatively selective loss of one eye movement type, while the others remain intact (Leigh and Zee 2006).
1.4.5.1 Saccades
Information about a gaze target is transmitted via different rostral regions of the brain to the superior colliculus, and then these neurons in the deep layers of the colliculus proj- ect to premotor centers in the reticular formation, which in turn activate motor neurons of the eye muscles, thus gener- ating a rapid eye movement (saccade) (Fig. 1.11). This results in the generation of horizontal saccades in the para- median pontine reticular formation (PPRF), while verti- cal and torsional saccades are generated in the mesencephalic reticular formation. The paramedian pontine reticular for- mation comprises anatomically the nucleus reticularis pon- tis caudalis and contains the premotor neurons for horizontal saccades to both sides, as well as inhibiting glycinergic omnipause neurons located near the midline and control the triggering of saccades in all directions (Fig. 1.10;
Büttner-Ennever and Horn 2004). Efferent connections from the PPRF exist to the abducens nerve nucleus, the prepositus hypoglossal nucleus, the medial vestibular nucleus, and to motor neurons of the cervical muscles that are activated on changes in gaze direction. Unilateral damage to the parame- dian pontine reticular formation therefore leads to horizon- tal gaze paresis to one side, while a lesion located in proximity to the midline is associated with complete gaze paresis (Leigh and Zee 2006).
Premotor neurons for vertical and torsional saccades are located in the rostral interstitial nucleus of the medial lon- gitudinal fasciculus (riMLF) and in the interstitial nucleus of Cajal (INC) (Fig. 1.4a and p. 19). The riMLF and adja- cent INC are embedded in the fibers of the medial longitudi- nal fasciculus, inferior to the thalamus and dorsolateral to the rostral pole of the oculomotor nucleus (Büttner-Ennever and Horn 2004). In addition to projections to motoneurons of the vertically moving eye muscles in the oculomotor and tro- chlear nuclei, the riMLF and INC have efferent connections to cell groups of the paramedian tract in the pons and medulla, as well as to vestibular nuclei and the spinal cord via the medial longitudinal fasciculus. Bilateral lesions of the riMLF lead to vertical gaze paresis, mostly upward or downward and – in rare cases – to isolated down gaze paresis due to the presence of very small lesions (Leigh and Zee 2006).
1.4 Internal Architecture 19
1.4.5.2 Vestibulo-ocular Reflex
The vestibulo-ocular reflex occurs in the form of a slow compensatory eye movement in response to excitation of the semicircular canals (rotation of the head), interrupted by rapid return saccades of the eyes (Fig. 1.11). Repeatedly occurring compensatory and saccadic eye movements are described as “nystagmus”; the direction is defined by the direction of the fast (saccadic) phase of the nystagmus.
While return saccades are generated via premotor pathways of the saccadic system, the compensatory movement is gen- erated via a short and therefore very rapidly reacting three neuron arc: primary afferents from the semicircular canals activate secondary neurons in the rostral third of the ves- tibular nuclei monosynaptically, which then directly acti- vate the motor neurons of one eye muscle pair (superior oblique muscle and inferior rectus muscle; superior rectus muscle and inferior oblique muscle; lateral rectus muscle and the internuclear neurons in the abducens nerve nucleus, the medial rectus muscle motoneurons). In this process excitatory vestibular pathways cross to contralateral, while inhibitory pathways remain ipsilateral (Fig. 1.12). Nearly all of these neuronal connections project via the medial longitudinal fasciculus. The inhibiting vestibuloocular con- nections of the horizontal system use glycine as transmitter, while GABA is used by the vertical systems (Büttner- Ennever and Gerrits 2004; Highstein and Holstein 2006).
The vertical vestibulo-ocular pathways further innervate
the prepositus nucleus via collaterals, cell groups of the paramedian tracts, the interstitial nucleus of Cajal, and the rostral interstitial nucleus of the medial longitudinal fas- ciculus. Furthermore, a group of vestibulo-ocular second- ary neurons in the medial and inferior vestibular nuclei send collaterals via the contralateral medial vestibulospinal tract to the spinal cord ending on motor neurons of the cer- vical muscles. Purely vestibulospinal pathways project from the lateral vestibular nucleus ipsilaterally in the lat- eral vestibulospinal tract and innervate the cervical muscu- lature (Fig. 1.8 and p. 13) (Shinoda et al. 2006).
1.4.5.3 Optokinetic Reflex
The vestibulo-ocular reflex is complemented by the optoki- netic system, which is activated by large-field visual stimuli moving across the retina, e.g. movement from the surrounding world (Fig. 1.11). Two anatomic systems play an important role in the generation of the resulting compensatory eye move- ment, the optokinetic reflex: the accessory optic system (see
‘Retinal Inputs’ p. 5) and the pretectum with the nucleus of the optic tract (see p. 24). Retinal signals are transmitted to the vestibular nuclei via the nucleus of the optic and the accessory optic nuclei via different parallel pathways and with involve- ment of the prepositus nucleus. From the vestibular nuclei the same premotor pathways as those for the vestibulo-ocular reflex are used for optokinetic responses (Fig. 1.11).
1 Saccades
2 Vestibulo-ocular reflex (VOR)
3 Optokinetic reflex (OKN)
4 Smooth pursuit Eye movements
5 Vergence
6 Gaze stabilization PPRF
riMLF Vestibular nuclei Accessory optic nuclei Nucleus of the optic tract Vestibular nuclei
Pretectum MRF
Interstitial nucleus of Cajal Prepositus hypoglossal nucleus
Motor neurons
Eye muscle
SC Frontal eye fields Basal ganglia
Retina
Floccular region
?
Vestibular nuclei
Floccular region Pontine
nuclei Visual cortex
Fig. 1.11 Block diagram illustrating the premotor pathways of eye move- ments. Five eye movement types and gaze stabilization can be differenti- ated. They are generated via separate premotor pathways that converge, on motoneurons in the eye muscle nuclei. Some of the same premotor
pathways are used by different eye movement types (vestibulo-ocular and optokinetic reflexes). riMLF rostral interstitial nucleus of the medial lon- gitudinal fasciculus, PPRF paramedian pontine reticular formation, SC superior colliculus, MRF mesencephalic reticular formation
20 1 Neuroanatomy of the Brainstem
1.4.5.4 Smooth Pursuit Eye Movements
Signal processing for smooth pursuit eye movements, which permit the constant representation of a small mov- ing gaze target on the fovea, is initiated via corticopon- tine-cerebellar pathways. In this process visual information is transmitted from the retina through the lateral genicu- late nucleus to the primary visual cortex to be transformed into the respective smooth pursuit eye movements via activated parietotemporal visual cortex areas, the frontal eye fields, pontine nuclei, cerebellum and vestibular nuclei (other areas than those for the vestibulo-ocular reflex) (Fig. 1.11). In addition, parallel pathways project through the nucleus of the optic tract to the pontine nuclei and the nucleus reticularis tegmenti pontis (Fig. 1.14c), which corresponds in humans to the nucleus papilliformis together with the pontine gray supralemniscal process (Olszewski and Baxter 1982). Cell groups of the pons around the corticopontine and the descending fiber bun- dles of the corticospinal tract are described as pontine nuclei. Based on their anatomic location they are divided into different subnuclei, these subnuclei do not represent functional unities. The dorsolateral and adjacent dorso- medial pontine nuclei constitute the primary components of the pathways for smooth pursuit eye movements (Thier and Möck 2006).
1.4.5.5 Convergence
In convergence, the only type of normally occurring disconjugate eye movements, motor neurons of the medial and inferior rectus muscles of both eyes are activated simultaneously. The premotor connections for convergence have not been extensively investigated thus far. Premotor neurons are assumed to be located in an area dorsomedial to the oculomotor nerve nucleus and in the pretectum (Fig. 1.11). Additional premotor pathways for convergence are found in the vestibular nuclei. Activation of the otoliths as a result of linear acceleration (e.g. on a toboggan) auto- matically produces compensatory convergence eye move- ments whose amplitude is dependent upon the distance from the point of visual fixation. In this connection an inde- pendent monosynaptic activation of medial rectus motor neurons also occurs from the ipsilateral ventrolateral ves- tibular nucleus via the ascending tract of Deiters.
1.4.5.6 Gaze Stabilization
On completion of an eye movement, velocity signals in the motor neurons must be converted into a position signal to maintain the eyes in a stable position. An important role regarding this integrator function is assumed by the
LR MR LR
III
MLF INT
HC VI
Vestibular nuclei
– +
IO+
III
MLF AC Vestibular nuclei
– + +SR
IV
MLF
–IR –SO
III
MLF PC Vestibular nuclei
– + SR
IR+
IV
MLF
SO+ IO
a b c
Fig. 1.12 Representation of pathways for the vestibulo-ocular reflex.
Primary afferents of the semicircular canals are relayed to excitatory (red) and inhibitory secondary neurons (black axons) in the vestibular nuclei; these in turn travel to the motor neurons of the respective eye muscles, which they activate (red, with red arrow) while inhibiting their antagonists (gray, dotted line arrow). Shown here is the pulling direction of eye muscle, not the muscles themselves. On excitation of the horizontal canal (a) internuclear neurons (INT) in addition to lateral rectus muscle (LR) motoneurons are activated in the abducens nucleus
(VI), which then excite the medial rectus muscle (MR) neurons in the contralateral oculomotor nucleus (III). The result of bilateral activation of the anterior semicircular canal (b) is an upward eye movement, while activation of the posterior canal (c) leads to a downward movement. IV trochlear nerve nucleus, VI abducens nerve nucleus, IO inferior oblique muscle, SO superior oblique muscle, IR inferior rectus muscle, SR superior rectus muscle, AC anterior canal, HC horizontal canal, MLF medial longitudinal fasciculus, PC posterior canal
1.4 Internal Architecture 21
prepositus nucleus for horizontal (McCrea and Horn 2006), and by the interstitial nucleus of Cajal for vertical and tor- sional eye movements (Horn 2006). The prepositus nucleus is located medially on the floor of the fourth ventricle between the abducens nucleus and the hypoglossal nucleus, and the interstitial nucleus of Cajal lies dorsolateral to the oculomotor nerve nucleus. Both nuclei have reciprocal con- nections to the respective premotor neurons of the horizon- tal and vertical/torsional saccadic and vestibular system, as well as to the cerebellar flocculus (Fig. 1.11). The eye posi- tion signal is presumed to be transmitted via their projec- tions to the respective motor neurons in the abducens nucleus or the oculomotor and trochlear nuclei. It is further assumed that the recently described paramedian tract neurons near the midline in close proximity to the raphe
nuclei in the pons and medulla, play a key role in the feed- back control for maintaining gaze position, because they also receive input from all premotor areas and in turn proj- ect to the cerebellar flocculus. An injury to these neurons may serve in some cases to explain gaze stability distur- bances (Büttner-Ennever and Horn 1996).