The oculomotor system Please sit where you can examine a partner Michael E. Goldberg, M.D. meg2008@columbia.edu

First you tell them what your gonna tell them The anatomy of the extraocular muscles and nerves. The phenomenology of eye movements. The physiology of the extraocular muscles and nerves. The supranuclear control of eye movements: motor control and cognitive plans.

6 Muscles move the eyes Levator Palpebrae Superior Rectus Lateral Rectus Superior Oblique Medial Rectus Inferior Oblique Inferior Rectus

3 Cranial Nerves Control the Eye Levator Palpebrae Superior Rectus Inferior Rectus Nerve III: Oculomotor Superior Oblique Medial Rectus Inferior Oblique Lateral Rectus Nerve IV: Trochlear Nerve VI: Abducens

How the single eye moves Horizontal: Abduction (away from the nose) Adduction (toward the nose). Vertical: Elevation (the pupil moves up) Depression (the pupil moves down) Torsional: Intorsion: the top of the eye moves towards the nose Extorsion: the top of the eye moves towards the ear.

The obliques are counterintuitive Each oblique inserts behind the equator of the eye. The superior oblique rotates the eye downward and intorts it! The inferior oblique rotates the eye upward and extorts it. Vertical recti tort the eye as well as elevate or depress it.

Oblique action depends on orbital position The superior oblique depresses the eye when it is adducted (looking at the nose). The superior oblique intorts the eye when it is abducted (looking towards the ear)

Left fourth nerve palsy Hyperopia in central gaze. Worse on right gaze. Better on left gaze. Worse looking down to right Better looking up to right. Head tilt to right improves gaze. Head tilt to left worsens gaze.

Vertical rectus action depends on orbital position The superior rectus intorts the eye when it is adducted (looking at the nose). The superior rectus elevates the eye when it is abducted (looking towards the ear)

The types and purposes of eye movements Keep the eyes still when the head moves Rotational and translational vestibuloocular reflex Optokinetic reflex Keep the fovea on a slowly moving object Smooth pursuit Rapidly move the fovea from one object to another Saccade Change the depth plane of vision Divergence and convergence Confuse medical students and residents

The rotational vestibuloocular reflex. The semicircular canals provide a head velocity signal. The vestibuloocular reflex (VOR) provides an equal and opposite eye velocity signal to keep the eyes still in space when the head moves.

The three semicircular canals lie in 3 orthogonal planes Cochlear N Vestibular N Horizontal Canal Vestibulo- (Nerve VIII) Cochlea Posterior Vertical Anterior

The semicircular canals are functionally paired and sense rotation Horizontal canals: rotation in the horizontal plane Left anterior and right posterior canals (LARP): rotation in the vertical plane skewed 45° anteriorly to the left. Right anterior and left posterior canals (RALP): rotation in the vertical plane skewed 45° anteriorly to the right.

The semicircular canals and eye muscles are functionally paired The canals lie in roughly the same planes as the extraocular muscles: Horizontal canals: lateral and medial recti. LARP: left vertical recti, right obliques. RALP: right vertical recti, left obliques.

Vestibular Nystagmus

The vestibular signal habituates, and is supplemented by vision – the optokinetic response, so nystagmus in the light does not habituate.

Saccades move the fovea to a new position

The purposes of eye movements Keep the eyes still when the head moves Vestibuloocular reflex Optokinetic reflex Change what you are looking at ( move the fovea from one object to another) Saccade Keep an object on the fovea Fixation Smooth pursuit Change the depth plane of the foveal object Vergence – eyes move in different directions

Smooth pursuit matches eye velocity to target velocity

Listing’s Law Torsion must be constrained or else vertical lines would not remain vertical. Listing’s law accomplishes this: the axes of rotation of the eye from any position to any other position lie in a single plane, Listing’s plane. This is accomplished by moving the axis of rotation half the angle of the eye movement

Eye muscle nuclei Mesencephalic Reticular Formation Thalamus Superior Colliculus Inferior Colliculus III IV Cerebellum VI Pontine Nuclei Vestibular Nuclei

Oculomotor neurons describe eye position and velocity. Medial Lateral Abducens neuron Eye Position Medial - Lateral

The transformation from muscle activation to gaze Eye velocity and eye position are generated independently. For horizontal saccades eye velocity is generated in the paramedian pontine reticular formation. Eye position is generated in the medial vestibular nucleus and the prepositus hypoglossi by a neural network that integrates the velocity signal to derive the position signal.

Digression on Neural Integration Intuitively, you move your eyes from position to position. Higher centers describe a desired change in eye position, the saccadic position error. The pontine reticular formation changes the position error to a desired velocity. The vestibulo-ocular reflex also provides the desired velocity. In order to maintain eye position after the velocity signal has ended, this signal must be mathematically integrated.

Horizontal saccades are generated in the pons and medulla Thalamus Superior Colliculus Inferior Colliculus Medial longitudinal fasciculus III IV Cerebellum Paramedian Pontine Reticular Formation VI Vestibular Nuclei and Nucleus Prepositus Hypoglossi Pontine Nuclei

Neurons involved in the generation of a saccade `

Generating the horizontal gaze signal The medial rectus of one eye and the lateral rectus of the other eye must be coordinated. This coordination arises from interneurons in the abducens nucleus that project to the contralateral medial rectus nucleus via the medial longitudinal fasciculus.

. Left lateral rectus Right medial rectus Abducens nerve Abducens nucleus: motor neurons and interneurons. Left lateral rectus Right medial rectus Oculomotor nucleus and nerve: motor neurons only Medial longitudinal fasciculus Paramedian pontine reticular formation (saccade velocity) Nucleus of the dorsal raphe – ‘omnipause neurons – inhibit the burst neurons. Medial vestibular nucleus: eye position, VOR and smooth pursuit velocity Nucleus prepositus hypoglossi (eye position)

To reiterate Ocular motor neurons describe eye position and velocity. For smooth pursuit and the VOR the major signal is the velocity signal, which comes from the contralateral medial vestibular nucleus. The neural integrator in the medial vestibular nucleus and nucleus prepositus hypoglossi converts the velocity signal into a position signal which holds eye position. For horizontal saccades the paramedian pontine reticular formation converts the position signal from supranuclear centers into a velocity signal. This signal is also integrated by the medial vestibular nucleus and the nucleus prepositus hypoglossi. Abducens interneurons send the position and velocity signals to the oculomotor nucleus via the medial longitudinal fasciculus.

Vertical movements and vergence are organized in the midbrain Mesencephalic Reticular Formation Posterior commissure Thalamus Superior Colliculus Inferior Colliculus rIMLF III Medial Longitudinal Fasciculus IV Cerebellum Paramedian Pontine Reticular Formation VI Pontine Nuclei Vestibular Nuclei

Internuclear ophthalmoplegia The medial longitudinal fasciculus is a vulnerable fiber tract. It is often damaged in multiple sclerosis and strokes. The resultant deficit is internuclear ophthalmoplegia The horizontal version signal cannot reach the medial rectus nucleus, but the vergence signal can.

. Left lateral rectus Right medial rectus Abducens nerve Abducens nucleus: motor neurons and interneurons. Left lateral rectus Right medial rectus Oculomotor nucleus and nerve: motor neurons only Medial longitudinal fasciculus The horizontal version signal cannot reach the medial rectus motorneurons The vergence signal can reach the medial rectus motorneurons Internuclear ophthalmoplegia is a failure of horizontal version (saccades, smooth pursuit, optokinetic and vestibular nystagmus), with preservation of vergence

The one and a half syndrome If the lesion includes the abducens nucleus (or the caudal pprf and the mlf) the ipsilateral eye will not be able to abduct and the contralateral medial rectus will be disconnected from the horizontal gaze system.

Supranuclear control of saccades The brainstem can make a rapid eye movement all by itself (the quick phase of nystagmus). The supranuclear control of saccades requires controlling the rapid eye movement for cognitive reasons. In most cases saccades are driven by attention

Humans look at where they attend

Supranuclear control of saccades Superior Colliculus Reticular Formation

The superior colliculus drives the reticular formation with a signal that describes the impending saccade.

Supranuclear control of saccades Superior Colliculus Substantia Nigra Pars Reticulata Reticular Formation

The substantia nigra pars reticulata contains GABAergic neurons that discharge at a high tonic rate except at the time of a saccade

The substantia nigra inhibits the superior colliculus except around the time of a saccade

Supranuclear control of saccades Supplementary Eye Field Posterior Parietal Cortex Frontal Eye Field Caudate Nucleus Superior Colliculus Substantia Nigra Pars Reticulata Reticular Formation

Supranuclear Control of Saccades Superior colliculus drives the reticular formation to make contralateral saccades. The frontal eye fields and the parietal cortex drive the colliculus. The parietal cortex provides a salience signal, which is related to visual attention and can drive eye movements. The frontal eye field provides a clear motor signal. The substantia nigra inhibits the colliculus unless It is inhibited by the caudate nucleus Which is, in turn, excited by the frontal eye field.

Frontal Eye Field Visual Neuron Weak visual response when the monkey fixates Enhanced visual response when the monkey makes a saccade to the stimulus No response before a learned saccade in the dark No temporal relationship to the saccade, unlike the visual response synchronized to the stimulus

Frontal Eye Field Movement Neuron Temporal relationship to the saccade, unlike the visual response synchronized to the stimulus Weak visual response when the monkey fixates Big response before a learned saccade in the dark

The effect of lesions Monkeys with collicular or frontal eye field lesions make saccades with a slightly longer reaction time. Monkeys with combined lesions cannot make saccades at all. Humans with parietal lesions neglect visual stimuli, and make slightly hypometric saccades with longer reaction times. Often their saccades are normal: if they can see it they can make saccades to it. Humans with frontal lesions cannot make antisaccades.

The Antisaccade Task

The Antisaccade Task Look away from a stimulus. The parietal cortex has a powerful signal describing the attended stimulus. The colliculus does not respond to this signal. The frontal motor signal drives the eyes away from the stimulus. Patients with frontal lesions cannot ignore the stimulus, but must respond to the parietal signal

Substantia Nigra Pars Reticulata Antisaccades Supplementary Eye Field Posterior Parietal Cortex Frontal Eye Field Caudate Nucleus Superior Colliculus Substantia Nigra Pars Reticulata Reticular Formation

A classical view of the saccadic system Supplementary Eye Field Posterior Parietal Cortex Frontal Eye Field Caudate Nucleus Superior Colliculus Substantia Nigra Pars Reticulata Reticular Formation

What does the saccadic system have to do beyond finding the target and driving the eyes? Adjust the neural signal to compensate for muscular weakness: a greater neural signal is necessary for the same saccadic movement. Adjust for the elastic restoring forces in the orbit: eccentric eye positions are held against the elastic restoring force. The cerebellum provides these adjustments.

Adjusting the saccadic signal for muscular weakness Kommerell’s case. (G Kommerell, D Olivier, and H Theopold Adaptive programming of phasic and tonic components in saccadic eye movements. Investigations of patients with abducens palsy. Invest Ophthalmol. 1976 15: 657-660.) A diabetic patient had a macular hemorrhage in one eye and a diabetic sixth in the other. The ophthalmologist patched the poorly seeing, normally moving eye. After a day, the normally seeing eye began to move normally. Behind the patch, the poorly seeing eye was making much larger eye movements than the normally seeing eye. The neural signal had been increased to compensate for the muscular weakness of the seeing eye.

Hering’s law The eyes receive equal innervation. The innervation necessary to drive the weak eye adequately overdrives the strong eye. The visual error in the weak eye induces a change in the innervation. Because the strong eye is patched, the brain does not know that the increased innervation leads to a visual error. The cerebellum corrects the saccadic signal to eliminate the visual error.

Saccadic adaptation is a laboratory trick to mimic muscular weakness You are blind during a saccade. We ask the subject to make a saccade. During the saccade the computer moves the saccade target. The first eye movement is inaccurate, and the subject has to make a corrective saccade to capture the target. Gradually the system adjusts the saccadic amplitude the so it can capture the target in one saccade.

Humans adapt their saccade amplitude quickly 20-15 Target Step 25 20 Saccade Amplitude (Deg.) 15 20 40 60 Trial number

A patient with a spinocerebellar degeneration cannot adapt his saccades 25 20-15 Target Step 20 Saccade Amplitude (Deg.) 15 20 40 60 Trial number

Putting the cerebellum into the saccadic system

Supplementary Eye Field Posterior Parietal Cortex Frontal Eye Field Dorsolateral pontine nuclei Caudate Nucleus Superior Colliculus Substantia Nigra Pars Reticulata Cerebellar vermis Fastigial nucleus Reticular Formation

A second cerebellar function in the control of saccades The orbit has elastic restoring forces which keep the eyes in an equilibrium position. Different forces are needed for the same amplitude of saccade when the eye moves toward the center of the orbit than when it moves toward the edge of the orbit. The cerebellum adjusts the forces necessary to make the same amplitude saccade from different orbital positions. Patients with cerebellar disorders make saccades are too big when they are done in the direction of the orbital forces, and too small when they are made against the orbital forces.

Supranuclear control of pursuit: pursuit matches eye velocity to target velocity Middle temporal and middle superior temporal (MT and MST) provide the velocity signal Frontal Eye Field provides the trigger to start the pursuit. Striate Cortex Nucleus reticularis tegmenti pontis Cerebellum vermis and flocculus Vestibular nucleus

Smooth pursuit Requires cortical areas that compute target velocity, the nucleus reticularis tegmenti pontis, and the cerebellum. Utilizes many of the brainstem structures for the vestibuloocular reflex Requires attention to the target.

Clinical deficits of smooth pursuit Cerebellar and brainstem disease Specific parietotemporal or frontal lesions Any clinical disease with an attentional deficit – Alzheimer’s or any frontal dementia, schizophrenia.

Finally, you tell them what you told them Saccades, smooth pursuit, the vestibuloocular and optokinetic reflexes have some shared and some independent neural substrates. Eye velocity and eye position are generated by different neural systems Horizontal and vertical eye movements are generated by separate neural systems. The oculomotor system provides a convenient bedside tool for looking at Muscular problems (myasthenia gravis) Brain stem problems (internuclear ophthalmoplegia) Cortical problems (frontal and parietal lesions) It’s easy!