VS 117
Professor Clifton Schor
Thursday 4/15/99
Notes by Khoa Truong

Announcements:
1) These are the last 3 lectures; Read Chapters 14 (Saccades), 15 (Pursuits), 11 (Nystagmus)
2) The Final Exam is on Tuesday May 18 (12:30 - 3:30)in 277 Cory; it will cover Chapters 5, 7-9, 11, 14, 15, 22 and the neurological work up in the reader appendix on the website; it's not comprehensive; whew guys =)
3) There will be graphical analysis on the final
4) There will be videos shown in the last day of class

I. Finish up Chapter 9 (Supranuclear Control of Gaze and Interconnections)

Introduction - Final Common Pathway
The final common pathway is composed of the 3rd, 6th, and 4th nerve. These nerves convey information for all types and classes of eye movements. However, they do not orchestrate complex patterns like Herring's, conjugate movements or vergence movements of the eyes. You need a choreographing or orchestrating center above the motor nuclei to indicate which muscles are going to work together to get the eyes to move in the appropriate manner. You need to activate the agonist and inhibit the antagonist simultaneously. Accordingly, these centers are needed to control these complex actions. There are supranuclear regions that control patterns of eye movements, duration, velocity, and coordination of eye muscles.

Control of Horizontal and Vertical Saccades
For saccades, there is a region for horizontal saccades called the (PPRF). This is a diagram representing the PPRF (paramedian pontine reticular formation) and its relation to motor nuclei.

The PPRF is located in the pons within the vicinity of the sixth nerve and it controls horizontal saccades. The right half of the brain controls rightward saccades and the left half of the brain controls leftward saccades. The PPRF projects axons to a group of muscles to make the two eyes saccade at the same time and the same direction (Hering's law?; also it controls the saccade velocity, duration and amplitude. There's also the dorsal and lateral pontine region that's not shown on here that controls pursuit eye movements. Vertical saccades are controlled by the riMLF (rostral interstitial nucleus of the MLF) in the pretectal region. Right around the 3rd nerve itself, there are neurons that control convergence (near response cells). Anterior to the 3rd nerve, we have vertical eye position and convergence and posterior to 3rd nerve, right around the 6th nerve we have horizontal saccades eye movements and pursuits in all directions. Also down in the 8th nerve, there is a region that controls smooth eye movements. This region converts burst to tonic position control for smooth eye movements.

The PPRF controlling saccades contains burst cells that get the eye moving very quickly to overcome ????????viscosity, but we also need tonic cells to hold the eye in the new position. There is a horizontal integrator called the Prepositus located by the PPRF and there is a vertical integrator ???????????????????????called the Nucleus of Cajal. These integrators take the burst innervation and integrate to give us a tonic innervation????????????????????????. The PPRF projects to the horizontal integrator and together, they project to the sixth nerve nucleus which is the lateral gaze center that ??????????? the ipsilateral lateral rectus and ?????????????????to contralateral medial rectus. For vertical movers, the riMLF has bursters that project to the Nucleus of Cajal to be integrated then they project to the 3rd and 4th nerve to ???????? vertical eye movements.

This diagram shows the connections of the riMLF and it shows how the riMLF is going to project to the Cajal Nucleus. The burst and tonic innervation project to the 4th nerve nucleus and 3rd nerve nucleus to activate the vertical recti and the obliques to control vertical eye position. Also there is input from vestibular sources to give us vertical eye position.

Lesions and Clinical Syndromes
You can have lesions almost anywhere in the brain stem and depending on the site of the lesion, you are going to get a characteristic pattern of abnormal eye movements. If the lesions affect motor nuclei, you will get specific eye muscles that are disabled but if they affect the supranuclear region, you will get groups gaze palsies where you will unable to move your eyes in a certain direction of gaze. So it's not that the muscles that are not functioning but the supranuclear orchestration of eye movements are not functioning. ????y??????????????????????????????????????????????????????????????To tell the difference, let's take the medial rectus. The medial rectus may work just fine during convergence but it may not work during lateral version so it cannot adduct the eye. That tells you that the motor neurons for the 3rd nerve for the medial rectus are functioning but innervation is not getting to the 3rd nerve during certain types of eye movements. Thus, it's a supranuclear problem.

The diagram below is a schematic illustrating the connections between the lateral gaze centers III, IV and VI cranial nerves. The fibers that connect the supranuclear regions to the motor nuclei are called the medial longitudinal fasciculus (MLF). These are examples of various lesions affecting eye mobility (ophthalmoplegia) and the resulting symptoms. An opthalmoplegia by definition is any lesion that disrupts these fibers thus disconnecting the pre-motor from the motor nuclei and it basically describes an immobile eye.

The first lesion affects the 3rd nerve itself and it is called complete or nuclear ophthalmoplegia. In this case, the 3rd nerve is no longer projecting to the left eye and results in a fixed dilated pupil and a droopy lid. The functions of the 3rd nerve nucleus are innervation to the medial rectus, inferior oblique, and superior rectus so damage to this 3rd nerve nucleus will not affect the lateral rectus and superior oblique. The superior rectus will still work on that side if the nucleus is damaged but if the nerve is damaged then the superior rectus would not work.

The second lesion affects the 6th nerve projection to the lateral rectus referred to as abducens palsy. The right eye will not be able to turn to the right. The right eye can move nasally but not temporally. This is the most common lesion because this would result in extreme esotropia so the patient would go right to the neurologist.

The third lesion is an internuclear ophthalmoplegia (meaning between nuclei), sometimes abbreviated INO. In this case, it is a unilateral anterior INO. The 6th nerve is really a lateral gaze center so it is projecting to the ipsilateral lateral rectus then it sends an interneuron and crosses over to the contralateral medial rectus. If you block just the interneuron, then the left eye will be unable to move to the right. If both interneurons get damaged, then both eyes will not be able to move medially (bilateral INO). This is a limitation of adduction, but if you ask the patient to converge, both eyes will turn in quite easily. This is because convergence is signaled by a motor nucleus that is anterior to the 3rd nerve and it does not project through VI. If the lesion is caudal to the 3rd nerve nucleus, you will affect lateral gaze. If the lesion is rostral to the 3rd nerve nucleus, you will affect convergence. When you affect convergence near response cells, you also affect vertical gaze due to its close proximity to the riMLF.

The fourth lesion is called One-and-a-half syndrome, and in this example it blocks the lateral gaze center of the left side and the interneuron on the right side. Normally, the left lateral gaze center allows the eyes to move leftward and when that is blocked completely, neither eye can move to the left. There is still a projection to the right lateral rectus so the left will be completely immobilized and the right eye can look outward.

The fifth lesion is called Foville's Syndrome or Posterior INO. If you block just the right lateral gaze center then neither eye can look to the right, but both eyes can look to the left. The 6th nerve nucleus is really a lateral gaze center controlling the movement of both eyes to the ipsilateral side and depending on where the lesion occurs it's going to block parts of that lateral gaze mechanism.

Parinaud's syndrome is a vertical gaze palsy where the eyes have trouble looking up or sometimes down. It is also associated with deficits of convergence, but the patient can look left and right very easily. These lesions are rostral to the 3rd nerve nucleus in the region of the pretectum. A paresis is a partial loss of function to a nerve such as multiple sclerosis, while a palsy and paralysis are equivalent.

Chapter 14 (Saccade Initiation and Tracking)

Introduction to Saccades and their function
Saccades are the most studied type of eye movements because they occur in all animals with mobile. Their main function is to shift gaze quickly from one direction to another. The name comes from a French term describing the movement of a horse's head caused by tugging on the bridal as seen on the diagram on the left.

Saccades have many different functions. 1) They help us read by shifting our gaze quickly from one group of words to another. In clinic, we analyze reading by counting the number of forward and regressive saccades during the reading process. The above right diagram shows typical saccade pattern during reading a passage of words. What are important are the number of saccades and number of regressions. For reading evaluation, look at motor patterns and retention. 2) Another function is to perform visual searches through saccade scan paths. When we examine a pattern such as a person's face, there are certain features that tend to attract our attention like the eyes and the mouth. The diagram above shows a saccadic eye movement of a person's face.
3) When you are not pursuing fast enough, catch-up saccades help foveate during fast pursuits. Many catch-up saccades produce cog-wheel pursuits. 4) We only move our eyes 15 degrees at most, so gaze direction is controlled by rotation of the eyes and head. When we look at a peripheral target, initially the eyes saccade ahead and when the head moves in that direction, the eyes counter-roll in the head but maintain their new position is space. So saccades work with head to change our direction of gaze and the superior colliculus coordinate the two actions.

Saccadic Suppression
The purpose of saccades is to foveate the target and place it on the region of highest visual acuity to enhance visual performance. However, during a saccade, visual acuity is reduced. We are partially blind during a saccade. Try to look back and forth between your eyes while looking in a mirror and you will never see your eyes move, however you can see someone elses eyes move while they perform this task. There are four different factors that account for this partial blindness during a saccade. 1) The biggest of these factors is called backward masking. It is simply the suppression of vision caused by a later event. The new stimulus actually gets transmitted to the visual pathways more rapidly than the previous target so that the new target gets to the cortex sooner than the old target does and masks it. The new target suppresses the visibility of the old target. It accounts for most of the loss of vision during a saccade. 2) The second factor is the smearing of the retinal image because the saccade is travelling at 100 to 1000 degrees/second. 3) Saccadic suppression is an active inhibition of vision by 20 percent; and it starts about 50 milliseconds before the saccade starts. 4) There is a lag of vitreous in the eye because of the inertia of the vitreous and that tugs on the retina causing a shearing force that reduces visibility. There is a functional reason for having reduced vision during a saccade. When we look from one direction to another, we have to recalculate the head-centric visual direction but it takes time to make that calculation so the reduced vision allows time for this to occur without distorting perception. If we didn't have this reduced vision, we would see the world jumping around. Saccadic suppression is to allow us to see a stable world during saccades.

Dynamics of Saccades
The latency of saccades takes 200 msec so it takes 1/5 second to begin the execution of a saccade. Once the saccade starts it takes anywhere from 25-100 msec to complete depending on its amplitude (see the main sequence below). The only latencies that are longer are accommodation and pupil changes because the ciliary body and iris are really sluggish. Saccades take more time than other eye movements because they are ballistic and has to calculate the whole movement and change of direction prior to making the movement. During the latency or refractory period, it is impossible to modify the impending saccade with new stimuli. You have to complete a saccade before you can start a new one. This diagram above shows that a saccade cannot be modified during its latency period. It should be noticed that the inter-saccadic interval remains constant despite the different durations of target jumps.

Now it turns out that there is some degree of modification during the latency period until the last 90 msec before a saccade. But for the most part, saccades have to be completed before a new saccade can be programmed so there can be a maximum of 5 saccades per second.

Saccades are also ballistic; once a saccade is triggered, during its flight it cannot be modified. It's like firing a bullet from a gun; not like a guided missile. They are extremely fast. Saccades of 2 degrees are 100 degrees/second and saccades of 15 degrees go up to 1000 degrees/second. They are also very short; the 2 degree saccades are 20 msec in duration and the 15 degree is about 100 msec. The below diagram shows the main sequence for saccades plotting velocity vs. magnitude on the left and duration vs. magnitude. These plots basically shows us the activity of the burst cells.

There are three cell types that control saccades. One is the burst cell; they control the initial acceleration of the eye. There are two components of the burst that are importation. The spike frequency determines the velocity of the saccade and the duration of the burst determines the amplitude. So a lot of spikes per second will have a high velocity and a long duration burst will have a large amplitude. Pulse and burst are used interchangeably; burst describes the innervation and the actual movement of the eye during the burst. The burst innervation gets integrated by the Prepositus and it gives us the horizontal saccade step. The step holds the eye in the new position to oppose the stiffness of the antagonist. The burst is overcoming viscosity of the muscle and the step is the tonic component opposing stiffness of the antagonist. The third cell is called the omnipause cell; they are basically the clutch of the oculomotor system. The pause cells turn on the bursters. So whenever the pause cells are firing (they fire continuously most of the time) the eye remains still but when the pause cells turn off for brief periods; this allows the bursters to fire. So the pause cell determines the duration of the pulse by turning off for a brief period. The same pause cells also control the bursters for accommodation and vergence by linking this with saccadic eye movements. So the pause cells are crucial for timing and synchronization and getting all the bursters for several motor systems to act together for a critical durations of time. The other thing that has to happen during a saccade is Sherington's Law of Reciprocal Innervation. If you want to move your eye laterally, the lateral rectus has to increase innervation and the medial rectus has to decrease innervation. During a saccade, the antagonist is actually totally shut off completely. So to speed up a saccade, the antagonist is shut off to restrict that motion. At the end of the saccade, you turn on the new step innervation for that particular direction of gaze. The pause neuron helps control the duration by inhibiting the antagonist and the agonist has pulse innervation.

Dysmetria are errors in eye movements. Hypometric errors undershoot and a hypermetric overshoot a target. Most of the time our saccades are hypometric. This is done intentionally so the eye moves near to the desired position then corrects it by moving it closer in the same direction. It takes more time to make a corrective saccade in the opposite direction. A glissade is a sliding movement and this can be used to correct the eye movement when the pulse component produces a different eye position that the step component. An example of a step-pulse mismatch is Gaze evoked nystagmus. This occurs when you are intoxicated from alcohol and police offices look for this when they suspect your driving under the influence. The tonic integrators don't work very well when you are intoxicated. Below are diagrams demonstrating various saccadic abnormalities and some us these will seen in the video in class next week.

Horizontal saccades are controlled in PPRF and the PPRF innervates saccades to the ipsilateral side. That PPRF gets innervation from two regions: the superior colliculus (the tectal region on the contralateral side) and the frontal eye fields on the contralateral side. The frontal eye fields when stimulated will drive saccades to the opposite side. So if you stimulate the left frontal eye field; it will drive saccadic eye movements to the right. For vertical eye movements, you will need to stimulate both hemispheres of the cortex. The frontal eye fields also control gaze and head information. The colliculus is more of a motor area; it controls how big the saccade should be. The colliculus has a retinotopic map and the rostral pole represents the fovea. So when that region is active, that is a fixation site that keeps saccades from occurring. This rostral pole stimulates pause neurons in the brain stem to hold the eye still. A lateral saccade will shift the colliculus activity caudally. The right colliculus causes eye movements to the left. Vertial saccades are controlled by medial to lateral locations of the colliculus. Medial causes upward saccades while lateral is downward saccades. You can get rid of the colliculus or the frontal eye field and still have saccades; but if you get rid of both the colliculus and FEF, saccades can not occur. Below is a motor map diagram of the superior colliculus and depending where the stimulus is, it determines the magnitude and direction of the saccade.
Thus the superior colliculus controls change of fixation from any starting direction of gaze.