1. The oculomotor system Please sit where you can examine a partner
Michael E. Goldberg, M.D.

2. 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.

3. 6 Muscles move the eyes Levator Palpebrae Superior Rectus
Lateral Rectus
Superior Oblique
Medial Rectus
Inferior Oblique
Inferior Rectus

4. 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

5. 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.

6. 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.

7. 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)

8. 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.

9. 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)

10. 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

11. 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.

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

13. 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.

14. 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.

15. Vestibular Nystagmus

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

17. Saccades move the fovea to a new position

18. 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

19. Smooth pursuit matches eye velocity to target velocity

20. 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

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

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

23. 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.

24. 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.

25. 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

26. Neurons involved in the generation of a saccade`

27. 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.

28. . 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)

29. 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.

30. 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

31. 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.

32. . 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

33. 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.

34. 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

35. Humans look at where they attend

36. Supranuclear control of saccades
Superior Colliculus
Reticular Formation

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

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

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

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

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

42. 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.

43. 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

44. 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

45. 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.

46. The Antisaccade Task

47. 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

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

49. 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

50. 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.

51. 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 : )
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.

52. 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.

53. 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.

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

55. A patient with a spinocerebellar degeneration cannot adapt his saccades25
20-15 Target Step 20
Saccade Amplitude (Deg.) 15 20 40 60
Trial number

56. Putting the cerebellum into the saccadic system

57. 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

58. 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.

59. 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

60. 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.

61. 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.

62. 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!