Editing Vestibulo-ocular reflex (section)

==Function==
[[Image:Vestibulo-ocular reflex EN.svg|thumb|300px]]

The vestibulo-ocular reflex is driven by signals arising from the vestibular system of the inner ear. The [[semicircular canals]] detect head rotation and provide the rotational component, whereas the [[otolith]]s detect head translation and drive the translational component. The signal for the horizontal rotational component travels via the [[vestibular nerve]] through the [[vestibular ganglion]] and end in the [[vestibular nuclei]] in the [[brainstem]]. From these nuclei, fibers cross to the [[abducens nucleus]] of the opposite side of the brain. Here, fibres synapse with 2 additional pathways. One pathway projects directly to the [[lateral rectus|lateral rectus muscle]] of the eye via the abducens nerve. Another nerve tract projects from the abducens nucleus by the [[medial longitudinal fasciculus]] to the [[oculomotor nucleus]] of the opposite side, which contains [[motor neuron]]s that drive eye muscle activity, specifically activating the [[medial rectus|medial rectus muscle]] of the eye through the [[oculomotor nerve]].

Another pathway (not in picture) directly projects from the vestibular nucleus through the [[ascending tract of Deiter's]] to the [[medial rectus|medial rectus muscle]] [[motor neuron]] of the same side. In addition there are inhibitory vestibular pathways to the ipsilateral abducens nucleus. However no direct vestibular neuron to medial rectus motoneuron pathway exists.<ref>{{cite journal | vauthors = Straka H, Dieringer N | title = Basic organization principles of the VOR: lessons from frogs | journal = Progress in Neurobiology | volume = 73 | issue = 4 | pages = 259–309 | date = July 2004 | pmid = 15261395 | doi = 10.1016/j.pneurobio.2004.05.003 | s2cid = 38651254 }}</ref>

Similar pathways exist for the vertical and torsional components of the VOR.

=== Oculomotor integrator ===
In addition to these direct pathways, which drive the velocity of eye rotation, there is an indirect pathway that builds up the position signal needed to prevent the eye from rolling back to center when the head stops moving. This pathway is particularly important when the head is moving slowly because here position signals dominate over velocity signals. David A. Robinson discovered that the eye muscles require this dual velocity-position drive, and also proposed that it must arise in the brain by mathematically integrating the velocity signal and then sending the resulting position signal to the motoneurons. Robinson was correct: the 'neural integrator' for horizontal eye position was found in the nucleus prepositus hypoglossi<ref name="Cannon1987">{{cite journal |vauthors=Cannon SC, Robinson DA |date=May 1987 |title=Loss of the neural integrator of the oculomotor system from brain stem lesions in monkey |journal=Journal of Neurophysiology |volume=57 |issue=5 |pages=1383–409 |doi=10.1152/jn.1987.57.5.1383 |pmid=3585473}}</ref> in the medulla, and the neural integrator for vertical and torsional eye positions was found in the [[interstitial nucleus of Cajal]]<ref name="Crawford1991#2">{{cite journal |vauthors=Crawford JD, Cadera W, Vilis T |date=June 1991 |title=Generation of torsional and vertical eye position signals by the interstitial nucleus of Cajal |journal=Science |volume=252 |issue=5012 |pages=1551–3 |bibcode=1991Sci...252.1551C |doi=10.1126/science.2047862 |pmid=2047862 |s2cid=15724175}}</ref> in the midbrain. The same neural integrators also generate eye position for other conjugate eye movements such as [[saccade]]s and [[smooth pursuit]].

The integrator is [[Leaky integrator|leaky]], with a characteristic leaking time of 20 s. For example, when the subject is sitting still and focusing on an object, and suddenly the light is turned off, the eyes would return to their neutral position in around 40 seconds even as the subject is attempting to keep the focus.<ref name="Robinson 33–45">{{Cite journal |last=Robinson |first=D A |date=March 1989 |title=Integrating with Neurons |url=https://www.annualreviews.org/doi/10.1146/annurev.ne.12.030189.000341 |journal=Annual Review of Neuroscience |language=en |volume=12 |issue=1 |pages=33–45 |doi=10.1146/annurev.ne.12.030189.000341 |pmid=2648952 |issn=0147-006X}}</ref><ref>{{Cite journal |last1=Sanchez |first1=Katherine |last2=Rowe |first2=Fiona J. |date=March 2018 |title=Role of neural integrators in oculomotor systems: a systematic narrative literature review |url=https://onlinelibrary.wiley.com/doi/10.1111/aos.13307 |journal=Acta Ophthalmologica |language=en |volume=96 |issue=2 |pages=e111–e118 |doi=10.1111/aos.13307 |pmid=27874249 |issn=1755-375X}}</ref>

===Example===
For instance, if the head is turned clockwise as seen from above, then excitatory impulses are sent from the semicircular canal on the right side via the vestibular nerve through [[Scarpa's ganglion]] and end in the right [[vestibular nuclei]] in the brainstem. From this nuclei excitatory fibres cross to the left abducens nucleus. There they project and stimulate the lateral rectus of the left eye via the abducens nerve. In addition, by the medial longitudinal fasciculus and [[oculomotor nuclei]], they activate the medial rectus muscles on the right eye. As a result, both eyes will turn counter-clockwise.

Furthermore, some neurons from the right vestibular nucleus directly stimulate the right medial rectus motor neurons, and inhibits the right abducens nucleus.

=== Integrated neural control ===
The VOR is controlled by a neural integrator. The neuron from each horizontal semicircular canal fires at a rate of <math>(90 + 0.4 \dot H) \; \mathrm{Hz}</math>, where <math>\dot H</math> is the sensed horizontal angular velocity of the semicircular canal. The [[Motor neuron|motoneuron]] commanding the horizontal eye muscles fires at a rate of <math>(4 \;\mathrm{Hz / deg}) \theta + (1.0 \;\mathrm{Hz / (deg/sec)}) \dot \theta </math>, where <math>\theta</math> is the horizontal turning angle, and <math>\dot \theta </math> is its horizontal angular speed. The two terms account for the elasticity and viscosity of ocular tissue.<ref name="Robinson 33–45"/>

The rotational [[moment of inertia]] of the eye is negligible, as individuals wearing weighted contact lens that increases the rotational moment of inertia almost 100-fold still has the same VOR (p.&nbsp;94 <ref name=":1">{{Cite book |last=Tweed |first=Douglas |title=Microcosms of the brain: what sensorimotor systems reveal about the mind |date=2003 |publisher=Oxford University Press |isbn=978-0-19-850735-2 |location=Oxford; New York}}</ref>).

===Speed===
The vestibulo-ocular reflex needs to be fast: for clear vision, head movement must be compensated almost immediately; otherwise, vision corresponds to a photograph taken with a shaky hand. Signals are sent from the semicircular canals using only three neurons, called the ''three neuron arc''. This results in eye movements that lag head movement by less than 10 ms.<ref>{{cite journal | vauthors = Aw ST, Halmagyi GM, Haslwanter T, Curthoys IS, Yavor RA, Todd MJ | title = Three-dimensional vector analysis of the human vestibuloocular reflex in response to high-acceleration head rotations. II. responses in subjects with unilateral vestibular loss and selective semicircular canal occlusion | journal = Journal of Neurophysiology | volume = 76 | issue = 6 | pages = 4021–30 | date = December 1996 | pmid = 8985897 | doi = 10.1152/jn.1996.76.6.4021 }}</ref> The vestibulo-ocular reflex is one of the fastest reflexes in the human body.

=== VOR suppression ===
When a person tracks the movement of something with both their eyes and head together, the VOR is counterproductive to the goal of keeping the gaze and head angle aligned. Research indicates that there exists mechanisms in the brain to suppress the VOR using the active visual (retinal) feedback obtained by watching the object in motion.<ref>{{cite web|url=http://psycnet.apa.org/record/1980-24636-001|title=PsycNET|website=psycnet.apa.org|language=en|access-date=2018-05-15}}</ref> In the absence of visual feedback, such as when the object passes behind an opaque barrier, humans can continue to visually track the apparent position of the object using anticipatory (extra-retinal) systems within the brain, and the VOR is also suppressed during this activity. The VOR can even be cognitively suppressed, such as when following an imagined target with the eyes and head together, although the effect tends to be less dramatic than with visual feedback.<ref>{{cite journal | vauthors = Ackerley R, Barnes GR | title = The interaction of visual, vestibular and extra-retinal mechanisms in the control of head and gaze during head-free pursuit | journal = The Journal of Physiology | volume = 589 | issue = Pt 7 | pages = 1627–42 | date = April 2011 | pmid = 21300755 | pmc = 3099020 | doi = 10.1113/jphysiol.2010.199471 }}</ref>

===Gain===
The "gain" of the VOR is defined as the change in the eye angle divided by the change in the head angle during the head turn. Ideally the gain of the rotational VOR is 1.0. The gain of the horizontal and vertical VOR is usually close to 1.0, but the gain of the torsional VOR (rotation around the line of sight) is generally low.<ref name="Crawford1991"/> The gain of the translational VOR has to be adjusted for distance, because of the geometry of motion parallax. When the head translates, the angular direction of near targets changes faster than the angular direction of far targets.<ref name="Angelaki2004"/>

If the gain of the VOR is wrong (different from 1)—for example, if eye muscles are weak, or if a person puts on a new pair of eyeglasses—then head movement results in image motion on the retina, resulting in blurred vision. Under such conditions, [[motor learning]] adjusts the gain of the VOR to produce more accurate eye motion. This is what is referred to as VOR adaptation.

Nearsighted people who habitually wear negative spectacles have lower VOR gain. Farsighted people or [[Aphakia|aphakes]] who habitually wear positive spectacle have higher VOR gain. People who habitually wear contact lens show no change in VOR gain. Monocular, disconjugate adaptation of the VOR is possible, for example, after [[Extraocular muscles|extraocular muscle]] [[palsy]]. (p.&nbsp;27 <ref>{{Cite book |last1=Leigh |first1=R. John |title=The neurology of eye movements |last2=Zee |first2=David S. |date=1991 |publisher=F.A. Davis Co |isbn=978-0-8036-5528-7 |edition=Ed. 2 |series=Contemporary neurology series |location=Philadelphia}}</ref>)

The phase of the VOR can also adapt.<ref>{{Cite journal |last1=Kramer |first1=PhillipD. |last2=Shelhamer |first2=Mark |last3=Zee |first3=DavidS. |date=1995 |title=Short-term adaptation of the phase of the vestibulo-ocular reflex (VOR) in normal human subjects |url=http://link.springer.com/10.1007/BF00241127 |journal=Experimental Brain Research |language=en |volume=106 |issue=2 |pages=318–326 |doi=10.1007/BF00241127 |pmid=8566196 |issn=0014-4819}}</ref>

=== Leak ===
The oculomotor integrator is a leaky integrator, with a characteristic leaking time of ~20 s. If the leaking time is too low, some form of adaptation occurs to "patch the leak" to raise the leaking time. It is hypothesized that the leaking integrator is constructed by a feedback circuit with a gain of slightly below 1, and adaptation occurs by adjusting the gain of the feedback circuit. The hypothesis is tested by using an specially patterned [[optokinetic drum]] that simulates the visual effect of having a very leaky oculomotor integrator. After 1 hour of viewing, the integrator becomes "anti-leaky", meaning that its value grows exponentially even in the absence of input. The eye motion becomes positive-feedback, meaning that if it is slightly to the left of a fixation target, it would drift even further to the left, and similarly for the right. It is also accompanied by nausea.<ref>{{Cite journal |last1=Kramer |first1=Phillip D. |last2=Shelhamer |first2=Mark |last3=Zee |first3=David S. |date=1995-01-01 |title=Short-term adaptation of the phase of the vestibulo-ocular reflex (VOR) in normal human subjects |url=https://doi.org/10.1007/BF00241127 |journal=Experimental Brain Research |language=en |volume=106 |issue=2 |pages=318–326 |doi=10.1007/BF00241127 |issn=1432-1106}}</ref> (p.&nbsp;84 <ref name=":1" />)

=== Disruption by ethanol ===
{{Anchor|Nystagmus}}
{{Main|Positional alcohol nystagmus}}
[[File:Semicircular Canals.png|thumb|Orientation of three semicircular canals in the head.]]
[[Ethanol]] consumption can disrupt the VOR, reducing dynamic visual acuity.<ref>{{cite journal |vauthors=Schmäl F, Thiede O, Stoll W |date=September 2003 |title=Effect of ethanol on visual-vestibular interactions during vertical linear body acceleration |url=https://onlinelibrary.wiley.com/doi/abs/10.1097/01.ALC.0000087085.98504.8C |journal=Alcoholism: Clinical and Experimental Research |volume=27 |issue=9 |pages=1520–6 |doi=10.1097/01.ALC.0000087085.98504.8C |pmid=14506414}}</ref> In normal conditions, the cupula and the endolymph are equal in density (both are approximately that of water). After ingesting ethanol, the ethanol diffuses into the cupula before it diffuses into the endolymph, because it is closer to blood capillaries. This makes the cupula temporarily lighter. In this state, if a person lies down with right cheek touching the ground, then the cupula in the left ear would float towards the left, creating an illusory sense of slow left-to-right head rotation. To compensate for this, the VOR moves the eyes right-to-left slowly, until it reaches the limit, and the eyes then pull to the right rapidly (nystagmus). This is the [[positional alcohol nystagmus]], phase I (PAN I). The unusual vestibular stimulation also caused motion sickness symptoms: illusions of bodily rotations, dizziness, and nausea. These symptoms subside in a few seconds after assuming an upright posture.<ref name=":0">{{Cite journal |last1=Money |first1=K. E. |last2=Myles |first2=W. S. |date=February 1974 |title=Heavy water nystagmus and effects of alcohol |url=https://www.nature.com/articles/247404a0 |journal=Nature |language=en |volume=247 |issue=5440 |pages=404–405 |doi=10.1038/247404a0 |pmid=4544739 |issn=1476-4687}}</ref>

After some time, the density of cupula and endolymph equalizes, removing the nystagmus effect. After ethanol is fully metabolized, the cupula returns to normal density first, creating nystagmus in the opposite direction (PAN II) during the [[hangover]].<ref name=":0" />

As predicted, [[heavy water]] (1.1 density of water) consumption has the exact opposite nystagmus effect compared to ethanol consumption. Consuming a mixture of heavy water (<math>4 \;\mathrm{ml/kg}</math>) and ethanol (<math>2 \;\mathrm{ml/kg}</math>) largely cancels out the effect.<ref name=":0" /> [[Macroglobulinemia|Macroglobulinaemia]], or consuming [[glycerol]] (1.26 density of water), have similar effects as heavy water.<ref>{{Cite journal |last=Brandt |first=Thomas |date=1991 |title=MAN IN MOTION: HISTORICAL AND CLINICAL ASPECTS OF VESTIBULAR FUNCTION: A REVIEW |url=https://academic.oup.com/brain/article-lookup/doi/10.1093/brain/114.5.2159 |journal=Brain |language=en |volume=114 |issue=5 |pages=2159–2174 |doi=10.1093/brain/114.5.2159 |pmid=1933240 |issn=0006-8950}}</ref><ref>{{Citation |last=Brandt |first=Thomas |title=Positional nystagmus/vertigo with specific gravity differential between cupula and endolymph (buoyancy hypothesis) |date=2003 |work=Vertigo: Its Multisensory Syndromes |pages=285–289 |editor-last=Brandt |editor-first=Thomas |url=https://doi.org/10.1007/978-1-4757-3801-8_17 |access-date=2024-07-06 |place=New York, NY |publisher=Springer |language=en |doi=10.1007/978-1-4757-3801-8_17 |isbn=978-1-4757-3801-8|doi-access=free }}</ref><ref>{{Cite journal |last1=Rietz |first1=Robert |last2=Troia |first2=Barbara W. |last3=Yonkers |first3=Anthony J. |last4=Norris |first4=Thomas W. |date=September 1987 |title=Glycerol-induced Positional Nystagmus in Human Beings |url=https://aao-hnsfjournals.onlinelibrary.wiley.com/doi/10.1177/019459988709700306 |journal=Otolaryngology–Head and Neck Surgery |language=en |volume=97 |issue=3 |pages=282–287 |doi=10.1177/019459988709700306 |issn=0194-5998}}</ref>