Yves Sauvé, PhD, Associate Professor of Ophthalmology and Visual Sciences University of Alberta

1. Calgary Vision Event 2015 Review of visual neurology Intense, practical, in-depth review of clinical visual neurology. Emphasis on CNS control of extra-ocular muscles (EOM) in vestibular-ocular and optokinetic reflexes. Saturday September 19th 2015 Yves Sauvé, PhD, Associate Professor of Ophthalmology and Visual Sciences University of Alberta

2. The only visually-dependent event in vision is?

3. Retina circuits Zele AJ, Cao D. Vision under mesopic and scotopic illumination. Front Psychol 2015 Jan 22;5:1594.

4. Center surround antagonistic visual receptive fields

5. Visual receptive field size and visual acuity

6. Professor David Heeger, NYU

7. Visual input to the cortex first arrives in V1 and comes from the LGN

8. Two streams of visual processing Dorsal (parietal) stream: magnocellular system (magno=large). “Where, when, how” motion, form, stereopsis. Pathway: large M-type retinal ganglion cells to magnocellular layers of LGN & visual cortex, then to middle temporal part of posterior parietal cortex Ventral (temporal) stream: parvocellular system (parvo = small): “What” (colour, object recognition). Pathway: small P-type as well as large M-type retinal ganglion cells to parvocellular layers of LGN & visual cortex (blobs and inter-blobs), then to V4 in temporal cortex.

9. We do not see the visual world as it is Hermann Grid Illusion #1

10. The intersections of the white "streets" in A are surrounded by more white than in B. This results in more inhibition from the surround in on-center, off-surround receptive fields in A than B: therefore A appears more white than B. A B Peter Keyser: The Joy of Visual Illusions (http://www.yorku.ca/eye/toc.htm)

11. Our conscious representation of the visual world is ultimately a subjective creation of our brain Neuron. 2001 May;30(2):319-33. The prefrontal cortex--an update: time is of the essence. Fuster JM

12. There are well-defined brain pathways underlying vision and movement without any awareness Spering M, Carrasco M. Acting without seeing: eye movements reveal visual processing without awareness. Trends Neurosci. 2015 Apr;38(4):247-58. doi:10.1016/j.tins.2015.02.002. Epub 2015 Mar 10. Review.

13. Retinal projections to primary visual centers

14. On the menu • Saccades • Smooth pursuit movements • Optokinetic reflex • Vestibulo-ocular Reflex (VOR) • Vergence and accommodation

15. Control of eye movements Fundamentals The eyeball must be moved so that the image of the target falls on the fovea (the part of the retina with the highest density of photoreceptors, the largest projection to the visual cortex and therefore the highest visual acuity). E.g. written characters are only recognized if foveated. The extra-ocular muscles (four recti, two obliques) must be co-activated in specific combinations to move the eye up/down & left/right. The eyeball has a low mass and little resistance to rotation within the eye socket. Unlike the limbs, the eyeball doesn’t have to resist or move external loads. Extra-ocular motor units are the smallest and fastest in the human body (10-20 muscle fibres per motor axon).

16. Five separate anatomical movement systems have been identified and each is characterized by a particular type of eye movement. • Saccades:"jumps of 0.2 sec. duration, then hold at new position, with mini-saccades 2) Smooth pursuit movements: slow tracking of visual targets. Cannot be made in absence of target (e.g. it's impossible to move eyes smoothly around a static scene).

17. 3) Optokinetic reflex: sensory input is visual, eyes fixate a sequence of objects moving slowly with respect to head, e.g. landscape viewed from car window. Slow phase (like smooth pursuit) maintains fixation on an object. Fast phase (saccade) in direction of head motion relative to scene. Slow pursuit movement in one direction, saccade back is called “nystagmus”. By definition, direction of nystagmus is that of fast (saccadic) phase. 4) Vestibulo-ocular reflex: response to head rotation mediated by vestibular apparatus. Fast phase in direction of head movement, slow phase opposite.

18. 5) Vergence: eyes move towards each other to foveate near objects. This is linked to accommodation (i.e. focussing of the lens) for near and far vision. Mediated by superior colliculus and cortical eye fields.

19. Functional neuroanatomy of the 5 eye movement systems • Saccadic system: Visual (striate) cortex & posterior parietal cortex perceive target. Supplementary and frontal eye fields activate saccade generators in brainstem and superior colliculi (though the ability to generate saccades gradually recovers after a complete lesion of the colliculi). Cerebellum probably adjusts gain of transmission in these pathways. 2 & 3) Smooth pursuit & optokinetic reflex systems: Visual cortex, frontal eye fields, pons, cerebellar floccular lobe, pontine gaze center, oculomotor neurons. 4. Vestibulo-ocular reflex (VOR) system: Vestibular apparatus, vestibular nuclei, abducens nuclei, oculomotor nuclei. 5. Vergence system: Midbrain area near oculomotor nucleus

20. Saccades

21. Generation of “reflex” saccades 1. target changes 3. The pause in firing of the omnipause neurons removes their inhibition of neurons in the paramedianpontine reticular formation PPRF. These elicit a burst of activity in the extra-ocular muscles PPH 4. activity in nucleus prepositus hypoglossi PPH terminates the phasic part of the saccade and holds the new position Omnidirectional pause neurons are so called because they pause during saccades in a given direction 2. hill of activity in SC shifts

22. Smooth pursuit movements

23. Fukushima K, Fukushima J, Warabi T, Barnes GR. Cognitive processes involved in smooth pursuit eye movements: behavioral evidence, neural substrate and clinical correlation. Front Syst Neurosci. 2013 Mar 19;7:4.

24. Optokinetic reflex http://www.optometry.co.uk/uploads/articles/cet-2013/april-5-2013-cet-2.pdf

25. Optokinetic reflex

26. Rotation of the head results in rotation of the eyes at the same speed, but in the opposite direction. This stabilizes the image on the retina. Mediated by brainstem nuclei input from the vestibular system output to extra-ocular muscles Vestibulo-ocular reflex (VOR)

27. Vestibulo-ocular reflex (VOR)

28. Vestibulo-ocular reflex (VOR) Vestibular apparatus: the part of the inner ear labyrinth concerned with detection of head orientation and movement. 1) semicircular canals (rotational acceleration sensors), Arranged in 3 mutually perpendicular planes. Angular acceleration causes endolymph in the semicircular canals to move, deflecting hair cells in the ampulla http://en.wikipedia.org/wiki/Vestibular_system http://www.tutis.ca/Senses/L10Balance/L10Balance.swf

29. Vestibulo-ocular reflex (VOR) During head movements sensory signals from left and right horizontal semicircular canals are reciprocal. Interneurons in the brainstem vestibular nuclei take this reciprocity into account.

30. Vestibulo-ocular reflex (VOR) head velocity • The vestibulo-ocular reflex (VOR) is mediated by brainstem nuclei which also receive inputs from cerebellum and visual centers. • In humans, neurons in the vestibular nuclei respond to a sudden and maintained change in rotational velocity of the head, with a time constant of adaptation of 15 s (i.e. the firing rate initially rapidly changes, then exponentially returns toward the rest state, reducing the change by 63% in 15 seconds). firing rate change 63% drop 15 sec

31. Vestibulo-ocular reflex (VOR): nystagmus in response to head acceleration, automatically maintains eye fixation, even with eyes closed. Combines with optokinetic reflex (e.g. subject motionless, visual field moves.... nystagmus; e.g. watching scenery from car. Optokinetic reflex dominates eye stabilization in slow head movements (e.g. up to 1 Hz); VOR dominates as head acceleration becomes more rapid ( >1 Hz). post-rotatory nystagmus: vestibular nystagmus occurs during acceleration to constant velocity, then declines over next 15 sec. During deceleration, endolymph deflects cupula. When rotation ceases, endolymph is stationary in canal, but cupula now takes another 15 sec. to return to rest position; nystagmus (and illusions of motion) persist for this time.

32. VOR can be elicited by caloric stimulation: warm or cold water (37 + 5oC) is infiltrated into external auditory canal. This causes convection currents in endolymph, deflecting the vestibular hair cells, leading to vertigo and nystagmus. The temperature change may also directly activate the vestibular nerve endings. Used clinically to assess vestibular function, and also, in extreme form (iced water) as test for brain-death for organ transplant approval. Adaptation over 2 - 3 weeks.The sensitivity of the VOR is state-dependent and tends to decline over days and weeks if the vestibular apparatus is constantly over-stimulated. Mechanism: presynaptic inhibition of transmission interneurons. Occurs in Labyrinthitis, Meniere's disease (gradual destruction of vestibular nerves), after labyrinthectomy, and in occupational groups such as aircraft & ship personnel, ballerinas, ice skaters etc. Note that in rapid spins, skaters minimise head motion by fixating for most of spin, then rapid and equal accel. + decel. (avoiding accumulated post-rotatory nystagmus). Reversing prisms experiment: VOR suppressed after 2 weeks, and reversed after 3-4 weeks. Shows that pathway includes interneurons whose transmission is adjustable ("plasticity").

33. Adaptation of VOR: hypothesized mechanisms. • Ito hypothesis • There is an indirect reflex loop from vestibular nuclei to motoneurons via cerebellar cortex. A mismatch between head and eye velocity in the slow phase of nystagmus is signaled by climbing fibre input which modifies the gain of transmission through this indirect loop. • Miles-Lisberger hypothesis: • During slow phase of nystagmus, PCs receive • a motor (efference) copy of eye velocity signal • vestibular input signalling head velocity. • If there is a difference (mismatch), the PCs are activated. This activity is a “teaching signal” that alters the gain of transmission of vestibular input through the vestibular nuclei to the motoneurons.

34. Are you still focusing? Vergence reflex

35. Accommodation reflex

36. Reflex versus voluntary (learned) “reflex” saccades LGN: lateral geniculate nucleus, SC: superior colliculus PPRF: paramedian pontine reticular formation, riMLF: rostral interstitial nucleus of medial longitudinal fasciculus “voluntary” saccades FEF: frontal eye field PEF: Posterior eye field

37. Eye movements, an overview http://www.tutis.ca/Senses/L11EyeMovements/L11EyeMovements.swf • Tutis Vilis; University of Western Ontario

38. How are you looking? • Of course you are all looking great • But HOW are you looking? • Dr. Arthur ProchazkaUniversity of Alberta • Dr. Charles Boulet • Black Diamond • TutisVilis • University of Western Ontario http://www.ualberta.ca/~aprochaz/ http://dvvc.ca http://www.tutis.ca/Senses/index.htm file://localhost/Users/yvessauve/Documents/talks and slides/2015 Calgary Sept/L11EyeMovements.swf

39. Derek Bok Panchantra