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With the wide spread of affordable virtual reality headsets, virtual environments are rapidly changing the way humans interact with reality. Understanding the effects of virtual environments on the mental and cognitive state is essential. In addition, defining methods for measuring and assessing visual fatigue in virtual environments is still needed. While eye movements are tightly coupled to the mental state, analysis of eye movement can add insights for safer virtual environments. Biomechanical analysis has been used extensively in the analysis of human movement. Simulation of different scenarios such as injuries and surgeries provided insights and solutions to problems that were otherwise impossible. This includes understanding the effects of changing insertion points of muscle on range of motion or how muscle activation can affect the motion produced. Extending the use of biomechanical simulation analysis into eye movement can be used to deepen our understanding of how virtual environments affect our visual and mental capabilities. This paper presents a thorough review on ocular biomechanics and ocular models in literature. We start with a brief introduction on the anatomy of the eye and eye kinematics. In addition, properties of the extraocular muscles (EOM) are described and the difference between EOMs and skeletal muscle is highlighted. The challenges facing biomechanical simulation and analysis of eye movement are presented along with the role of ocular models in assessing visual fatigue. Furthermore, the compatibility of available biomechanical tools to analyze ocular movements is discussed.

The aim of this study was to develop software that performs the optokinetic tracking assessment without the involvement of experimenters to increase the objectivity of the test. To check the effectiveness of the software, several videos were analyzed and the results were compared to those produced by two experimenters. Videos consisted of visual acuity and contrast sensitivity tests on normal animals and pigmented P23H rats (animal model of retinitis pigmentosa). Our software showed a reasonably high success rate: in approximately 78% of the cases, both the software program and the experimenters were in agreement, including the direction of rotation. The software detected 7% false positive cases, 10% false negative cases, and it was wrong in 5% of the cases. Decrease in visual function with age in pigmented P23H rats was observed from the first time interval, although minimum thresholds were found in visual parameters at advanced ages. We developed simple software based on current functions included in the Matlab image processing toolbox that was able to recognize, with a reasonably high percentage of success, the subtle head movements of the rodent produced when visual perception of the optokinetic optotype occurs

Posmatranje položaja očiju i njihove usklađenosti na najranijem uz- rastu je od izuzetne važnosti. Bitan preduslov za normalan razvoj vidne funkcije je paralelan položaj očiju. Razne devijacije ili skretanje oka, koje se mogu evidentirati već kod novorođenčadi i ukazivati na nedozrelost struktura centralnog nervnog sistema, istovremeno mogu biti i predik- tor pojave strabizma odnosno razrokosti. Učestalost ovog poremećaja kod dece je do 5%. S obzirom da se strabizam često susreće kod dece koja pokazuju poteškoće u savladavanju veština čitanja i pisanja, neophodno ga je što ranije otkriti kako bi se preduzele mere za pravovremenu korekciju. Inter- val između početka razrokosti i tretmana je ključni faktor za postizanje boljeg kvaliteta binokularnog vida. Cilj ovog rada je bio da utvrdi da li postoji povezanost između položa- ja očiju u budnom stanju i vestibulookularnog refleksa kod beba ispitanih neposredno po rođenju. Posmatranje položaja očiju u budnom stanju (POB) i testiranje vesti- bulo-okularnog refleksa (VOR), sprovedeno je u Institutu za ginekologiju i akušerstvo Kliničkog centra Srbije (IGA KCS), na uzorku od N=100 no- vorođenčadi. Kriterijumi za odabir ispitivanog uzorka su bili sledeći: uredne trudnoće, zdrava terminska novorođenčad, najviše vrednosti Apgar scor-a 9 ili 10, starosna dob novorođenčeta u vreme ispitivanja – 3. dan po rođenju, približno jednak broj novorođenčadi muškog i ženskog pola. U test situaciji, ispitivana beba je morala biti naspavana, u stanju optimalne relaksiranosti i kooperabilnosti. Kod sve novorođenčadi uzeti su podaci o polu, telesnoj težini (TT), telesnoj dužini (TD) i obimu glave (OG). Dobi- jeni podaci su dokumentovani uz pomoć digitalne kamere, zatim bodovani, statistički i deskriptivno obrađeni. Rezultati istraživanja su pokazali da ne postoji statistički zna- čajna povezanost između prisutnosti VOR s jedne strane, i položaja očiju kod novorođenčadi u budnom stanju, s druge strane. Dakle, stepen prisutno- sti pomenutog re, Observing the position of the eyes in the awake state and their alignment at the earliest age is of great importance. An essential prerequisite for normal visual development is parallel position of the eyes. Various deviations or deflections of the eye, that may already be recorded in newborns and indicate immaturity of the structure of the central nervous system, at the same time can be a predictor of occurrence of strabismus. The incidence of this disorder in children is up to 5%. Since the strabismus is frequently found in children who show difficulties in mastering the skills of reading and writing, it is necessary to detect it as early as possible in order to undertake certain exercises for timely correction. The interval between the onset of strabismus and the treatment is the key factor for achieving a better quality of binocular vision. The aim of this study was to determine whether there is a correlation between ocular alignment in the awake state and vestibulo-ocular reflex in healthy babies immediately after birth. Observation of ocular alignment in the awake state (OAA) and testing vestibulo-ocular reflex (VOR), were conducted at the Institute of Gynecology and Obstetrics, Clinical Center of Serbia, on a sample of N = 100 newborns. Criteria for the selection of tested sample were as follows: regular pregnancies and childbirth, healthy newborns, full-term newborns, maximum value of Apgar scores (9 or 10), infant age at the time of testing – the third day upon birth and approximately the same number of male and female babies. In the test situation, a baby who is tested should be rested and relaxed. Besides that, data on body mass on birth, body weight (BW), body length (BL) and head circumference (HC) were recorded for all newborns. The obtained results were recorded by means of a digital camera, then scored and statistically and descriptively processed.The research results showed that there was no statistically significant correlation between the presence

The vestibuloocular reflex can be manually elicited by tilting or rotating the head. Manual techniques serve their purpose well and is the golden standard in the clinical work, but they lack control of velocity and movement pattern. However, motion simulation platforms enable automatic control of both velocity and movement pattern. One motion simulation platform, named BIRGIT, has been built at the Department of Clinical Neurosciences at Karolinska Institutet but has not yet been in service and require a performance evaluation. The objectives with this thesis is to evaluate the accuracy and precision of BIRGIT and evaluate how bodyweight and movement direction impact the performance. The thesis also evaluate whether it is possible to stabilize the head of the patient during the acceleration phase. Repeated measurements of acceleration with different loads, desired ac- celeration, direction and motion type (rotational and translational), are per- formed. Dummies are used to simulate bodyweight in the performance study and real persons are used in the head stabilization study. Analysis of variance (ANOVA) is the main statistical tool. The results suggest that the platform does not perform equally at dif- ferent load or directions and that there is a bias between desired and true acceleration. The main problems are an inclination of the rails, upon which the chair is mounted, that causes differences between directions and an un- desirable performance characteristic for rotational motions. The stabilization study suggest that the head can be stabilized., Den vestibulo-okul ̈ara reflexen kan framkallas genom att manuellt rotera eller rycka p ̊a huvudet. Att manuellt framkalla reflexen fungerar i de flesta sam- manhang va ̈l och a ̈r standard i m ̊anga underso ̈kningar. Dock g ̊ar det inte att till fullo kontrollera vare sig hastighet eller ro ̈relsebana perfekt. Emellertid g ̊ar detta att kontrollera genom att anva ̈nda sig av en s ̊a kallad ro ̈relsesimu- leringsplatform. En s ̊adan platform, d ̈opt till BIRGIT, har byggts vid Institutionen f ̈or kliniska neurovetenskaper vid Karolinska Institutet. Denna har ej bo ̈rjat anva ̈ndas ̈annu d ̊a dess prestanda fo ̈rst beho ̈ver utv ̈arderas. Syftet med denna uppsats ̈ar att utva ̈rdera precision och noggrannhet hos BIRGIT. Dessutom, att utv ̈ardera hur kroppsvikt och ro ̈relseriktning inverkar p ̊a prestandan. I arbetet ing ̊ar ̈aven att testa om det a ̈r m ̈ojligt att stabilisera huvudet under accelerationsfasen. Repeterade ma ̈tningar av sann acceleration med olika last, riktning, bo ̈rac- celeration och r ̈orelsetyp (rotation eller sidledes) genomfo ̈rdes. Testdockor anva ̈ndes fo ̈r att simulera lasten i prestandatesterna och riktiga testpersoner anva ̈ndes i huvudstabiliseringsdelen. Variansanalys (ANOVA) var det hu- vudsakliga statistiska verktyget. Resultatet antyder att last och ro ̈relseriktning inverkar p ̊a acceleratio- nen och prestandan och att den sanna accelerationen alltigenom a ̈r la ̈gre a ̈n bo ̈raccelerationen. Det finns tv ̊a sto ̈rre problem hos plattformen, det fo ̈rsta a ̈r att uppha ̈ngningen till stolen lutar och detta resulterar i en skillnad mellan riktningarna (det g ̊ar fortare nedf ̈ors). Det andra problemet a ̈r ett cykliskt uppfo ̈rande na ̈r flera rotationsr ̈orelser skall fo ̈lja p ̊a varandra. Stabiliseringsstudien visade att det g ̊ar att stabilisera huvudet.

The vestibuloocular reflex can be manually elicited by tilting or rotating the head. Manual techniques serve their purpose well and is the golden standard in the clinical work, but they lack control of velocity and movement pattern. However, motion simulation platforms enable automatic control of both velocity and movement pattern. One motion simulation platform, named BIRGIT, has been built at the Department of Clinical Neurosciences at Karolinska Institutet but has not yet been in service and require a performance evaluation. The objectives with this thesis is to evaluate the accuracy and precision of BIRGIT and evaluate how bodyweight and movement direction impact the performance. The thesis also evaluate whether it is possible to stabilize the head of the patient during the acceleration phase. Repeated measurements of acceleration with different loads, desired ac- celeration, direction and motion type (rotational and translational), are per- formed. Dummies are used to simulate bodyweight in the performance study and real persons are used in the head stabilization study. Analysis of variance (ANOVA) is the main statistical tool. The results suggest that the platform does not perform equally at dif- ferent load or directions and that there is a bias between desired and true acceleration. The main problems are an inclination of the rails, upon which the chair is mounted, that causes differences between directions and an un- desirable performance characteristic for rotational motions. The stabilization study suggest that the head can be stabilized., Den vestibulo-okul ̈ara reflexen kan framkallas genom att manuellt rotera eller rycka p ̊a huvudet. Att manuellt framkalla reflexen fungerar i de flesta sam- manhang va ̈l och a ̈r standard i m ̊anga underso ̈kningar. Dock g ̊ar det inte att till fullo kontrollera vare sig hastighet eller ro ̈relsebana perfekt. Emellertid g ̊ar detta att kontrollera genom att anva ̈nda sig av en s ̊a kallad ro ̈relsesimu- leringsplatform. En s ̊adan platform, d ̈opt till BIRGIT, har byggts vid Institutionen f ̈or kliniska neurovetenskaper vid Karolinska Institutet. Denna har ej bo ̈rjat anva ̈ndas ̈annu d ̊a dess prestanda fo ̈rst beho ̈ver utv ̈arderas. Syftet med denna uppsats ̈ar att utva ̈rdera precision och noggrannhet hos BIRGIT. Dessutom, att utv ̈ardera hur kroppsvikt och ro ̈relseriktning inverkar p ̊a prestandan. I arbetet ing ̊ar ̈aven att testa om det a ̈r m ̈ojligt att stabilisera huvudet under accelerationsfasen. Repeterade ma ̈tningar av sann acceleration med olika last, riktning, bo ̈rac- celeration och r ̈orelsetyp (rotation eller sidledes) genomfo ̈rdes. Testdockor anva ̈ndes fo ̈r att simulera lasten i prestandatesterna och riktiga testpersoner anva ̈ndes i huvudstabiliseringsdelen. Variansanalys (ANOVA) var det hu- vudsakliga statistiska verktyget. Resultatet antyder att last och ro ̈relseriktning inverkar p ̊a acceleratio- nen och prestandan och att den sanna accelerationen alltigenom a ̈r la ̈gre a ̈n bo ̈raccelerationen. Det finns tv ̊a sto ̈rre problem hos plattformen, det fo ̈rsta a ̈r att uppha ̈ngningen till stolen lutar och detta resulterar i en skillnad mellan riktningarna (det g ̊ar fortare nedf ̈ors). Det andra problemet a ̈r ett cykliskt uppfo ̈rande na ̈r flera rotationsr ̈orelser skall fo ̈lja p ̊a varandra. Stabiliseringsstudien visade att det g ̊ar att stabilisera huvudet.

The vestibuloocular reflex can be manually elicited by tilting or rotating the head. Manual techniques serve their purpose well and is the golden standard in the clinical work, but they lack control of velocity and movement pattern. However, motion simulation platforms enable automatic control of both velocity and movement pattern. One motion simulation platform, named BIRGIT, has been built at the Department of Clinical Neurosciences at Karolinska Institutet but has not yet been in service and require a performance evaluation. The objectives with this thesis is to evaluate the accuracy and precision of BIRGIT and evaluate how bodyweight and movement direction impact the performance. The thesis also evaluate whether it is possible to stabilize the head of the patient during the acceleration phase. Repeated measurements of acceleration with different loads, desired ac- celeration, direction and motion type (rotational and translational), are per- formed. Dummies are used to simulate bodyweight in the performance study and real persons are used in the head stabilization study. Analysis of variance (ANOVA) is the main statistical tool. The results suggest that the platform does not perform equally at dif- ferent load or directions and that there is a bias between desired and true acceleration. The main problems are an inclination of the rails, upon which the chair is mounted, that causes differences between directions and an un- desirable performance characteristic for rotational motions. The stabilization study suggest that the head can be stabilized., Den vestibulo-okul ̈ara reflexen kan framkallas genom att manuellt rotera eller rycka p ̊a huvudet. Att manuellt framkalla reflexen fungerar i de flesta sam- manhang va ̈l och a ̈r standard i m ̊anga underso ̈kningar. Dock g ̊ar det inte att till fullo kontrollera vare sig hastighet eller ro ̈relsebana perfekt. Emellertid g ̊ar detta att kontrollera genom att anva ̈nda sig av en s ̊a kallad ro ̈relsesimu- leringsplatform. En s ̊adan platform, d ̈opt till BIRGIT, har byggts vid Institutionen f ̈or kliniska neurovetenskaper vid Karolinska Institutet. Denna har ej bo ̈rjat anva ̈ndas ̈annu d ̊a dess prestanda fo ̈rst beho ̈ver utv ̈arderas. Syftet med denna uppsats ̈ar att utva ̈rdera precision och noggrannhet hos BIRGIT. Dessutom, att utv ̈ardera hur kroppsvikt och ro ̈relseriktning inverkar p ̊a prestandan. I arbetet ing ̊ar ̈aven att testa om det a ̈r m ̈ojligt att stabilisera huvudet under accelerationsfasen. Repeterade ma ̈tningar av sann acceleration med olika last, riktning, bo ̈rac- celeration och r ̈orelsetyp (rotation eller sidledes) genomfo ̈rdes. Testdockor anva ̈ndes fo ̈r att simulera lasten i prestandatesterna och riktiga testpersoner anva ̈ndes i huvudstabiliseringsdelen. Variansanalys (ANOVA) var det hu- vudsakliga statistiska verktyget. Resultatet antyder att last och ro ̈relseriktning inverkar p ̊a acceleratio- nen och prestandan och att den sanna accelerationen alltigenom a ̈r la ̈gre a ̈n bo ̈raccelerationen. Det finns tv ̊a sto ̈rre problem hos plattformen, det fo ̈rsta a ̈r att uppha ̈ngningen till stolen lutar och detta resulterar i en skillnad mellan riktningarna (det g ̊ar fortare nedf ̈ors). Det andra problemet a ̈r ett cykliskt uppfo ̈rande na ̈r flera rotationsr ̈orelser skall fo ̈lja p ̊a varandra. Stabiliseringsstudien visade att det g ̊ar att stabilisera huvudet.

The vestibuloocular reflex can be manually elicited by tilting or rotating the head. Manual techniques serve their purpose well and is the golden standard in the clinical work, but they lack control of velocity and movement pattern. However, motion simulation platforms enable automatic control of both velocity and movement pattern. One motion simulation platform, named BIRGIT, has been built at the Department of Clinical Neurosciences at Karolinska Institutet but has not yet been in service and require a performance evaluation. The objectives with this thesis is to evaluate the accuracy and precision of BIRGIT and evaluate how bodyweight and movement direction impact the performance. The thesis also evaluate whether it is possible to stabilize the head of the patient during the acceleration phase. Repeated measurements of acceleration with different loads, desired ac- celeration, direction and motion type (rotational and translational), are per- formed. Dummies are used to simulate bodyweight in the performance study and real persons are used in the head stabilization study. Analysis of variance (ANOVA) is the main statistical tool. The results suggest that the platform does not perform equally at dif- ferent load or directions and that there is a bias between desired and true acceleration. The main problems are an inclination of the rails, upon which the chair is mounted, that causes differences between directions and an un- desirable performance characteristic for rotational motions. The stabilization study suggest that the head can be stabilized., Den vestibulo-okul ̈ara reflexen kan framkallas genom att manuellt rotera eller rycka p ̊a huvudet. Att manuellt framkalla reflexen fungerar i de flesta sam- manhang va ̈l och a ̈r standard i m ̊anga underso ̈kningar. Dock g ̊ar det inte att till fullo kontrollera vare sig hastighet eller ro ̈relsebana perfekt. Emellertid g ̊ar detta att kontrollera genom att anva ̈nda sig av en s ̊a kallad ro ̈relsesimu- leringsplatform. En s ̊adan platform, d ̈opt till BIRGIT, har byggts vid Institutionen f ̈or kliniska neurovetenskaper vid Karolinska Institutet. Denna har ej bo ̈rjat anva ̈ndas ̈annu d ̊a dess prestanda fo ̈rst beho ̈ver utv ̈arderas. Syftet med denna uppsats ̈ar att utva ̈rdera precision och noggrannhet hos BIRGIT. Dessutom, att utv ̈ardera hur kroppsvikt och ro ̈relseriktning inverkar p ̊a prestandan. I arbetet ing ̊ar ̈aven att testa om det a ̈r m ̈ojligt att stabilisera huvudet under accelerationsfasen. Repeterade ma ̈tningar av sann acceleration med olika last, riktning, bo ̈rac- celeration och r ̈orelsetyp (rotation eller sidledes) genomfo ̈rdes. Testdockor anva ̈ndes fo ̈r att simulera lasten i prestandatesterna och riktiga testpersoner anva ̈ndes i huvudstabiliseringsdelen. Variansanalys (ANOVA) var det hu- vudsakliga statistiska verktyget. Resultatet antyder att last och ro ̈relseriktning inverkar p ̊a acceleratio- nen och prestandan och att den sanna accelerationen alltigenom a ̈r la ̈gre a ̈n bo ̈raccelerationen. Det finns tv ̊a sto ̈rre problem hos plattformen, det fo ̈rsta a ̈r att uppha ̈ngningen till stolen lutar och detta resulterar i en skillnad mellan riktningarna (det g ̊ar fortare nedf ̈ors). Det andra problemet a ̈r ett cykliskt uppfo ̈rande na ̈r flera rotationsr ̈orelser skall fo ̈lja p ̊a varandra. Stabiliseringsstudien visade att det g ̊ar att stabilisera huvudet.

Posmatranje položaja očiju i njihove usklađenosti na najranijem uz- rastu je od izuzetne važnosti. Bitan preduslov za normalan razvoj vidne funkcije je paralelan položaj očiju. Razne devijacije ili skretanje oka, koje se mogu evidentirati već kod novorođenčadi i ukazivati na nedozrelost struktura centralnog nervnog sistema, istovremeno mogu biti i predik- tor pojave strabizma odnosno razrokosti. Učestalost ovog poremećaja kod dece je do 5%. S obzirom da se strabizam često susreće kod dece koja pokazuju poteškoće u savladavanju veština čitanja i pisanja, neophodno ga je što ranije otkriti kako bi se preduzele mere za pravovremenu korekciju. Inter- val između početka razrokosti i tretmana je ključni faktor za postizanje boljeg kvaliteta binokularnog vida. Cilj ovog rada je bio da utvrdi da li postoji povezanost između položa- ja očiju u budnom stanju i vestibulookularnog refleksa kod beba ispitanih neposredno po rođenju. Posmatranje položaja očiju u budnom stanju (POB) i testiranje vesti- bulo-okularnog refleksa (VOR), sprovedeno je u Institutu za ginekologiju i akušerstvo Kliničkog centra Srbije (IGA KCS), na uzorku od N=100 no- vorođenčadi. Kriterijumi za odabir ispitivanog uzorka su bili sledeći: uredne trudnoće, zdrava terminska novorođenčad, najviše vrednosti Apgar scor-a 9 ili 10, starosna dob novorođenčeta u vreme ispitivanja – 3. dan po rođenju, približno jednak broj novorođenčadi muškog i ženskog pola. U test situaciji, ispitivana beba je morala biti naspavana, u stanju optimalne relaksiranosti i kooperabilnosti. Kod sve novorođenčadi uzeti su podaci o polu, telesnoj težini (TT), telesnoj dužini (TD) i obimu glave (OG). Dobi- jeni podaci su dokumentovani uz pomoć digitalne kamere, zatim bodovani, statistički i deskriptivno obrađeni. Rezultati istraživanja su pokazali da ne postoji statistički zna- čajna povezanost između prisutnosti VOR s jedne strane, i položaja očiju kod novorođenčadi u budnom stanju, s druge strane. Dakle, stepen prisutno- sti pomenutog re, Observing the position of the eyes in the awake state and their alignment at the earliest age is of great importance. An essential prerequisite for normal visual development is parallel position of the eyes. Various deviations or deflections of the eye, that may already be recorded in newborns and indicate immaturity of the structure of the central nervous system, at the same time can be a predictor of occurrence of strabismus. The incidence of this disorder in children is up to 5%. Since the strabismus is frequently found in children who show difficulties in mastering the skills of reading and writing, it is necessary to detect it as early as possible in order to undertake certain exercises for timely correction. The interval between the onset of strabismus and the treatment is the key factor for achieving a better quality of binocular vision. The aim of this study was to determine whether there is a correlation between ocular alignment in the awake state and vestibulo-ocular reflex in healthy babies immediately after birth. Observation of ocular alignment in the awake state (OAA) and testing vestibulo-ocular reflex (VOR), were conducted at the Institute of Gynecology and Obstetrics, Clinical Center of Serbia, on a sample of N = 100 newborns. Criteria for the selection of tested sample were as follows: regular pregnancies and childbirth, healthy newborns, full-term newborns, maximum value of Apgar scores (9 or 10), infant age at the time of testing – the third day upon birth and approximately the same number of male and female babies. In the test situation, a baby who is tested should be rested and relaxed. Besides that, data on body mass on birth, body weight (BW), body length (BL) and head circumference (HC) were recorded for all newborns. The obtained results were recorded by means of a digital camera, then scored and statistically and descriptively processed.The research results showed that there was no statistically significant correlation between the presence

Vestibulo-ocular reflexes are the fastest compensatory reflex systems. One of these is the translational vestibulo-ocular reflex (TVOR) which stabilizes the gaze at a given fixation point during whole body translations. For a proper response of the TVOR the eyes have to counter rotate in the head with a velocity that is inversely scaled to viewing distance of the target. It is generally assumed that scaling of the TVOR is automatically coupled to vergence angle at the brainstem level. However, different lines of evidence also argue that in humans scaling of the TVOR also depends on a mechanism that pre-sets gain on a priori knowledge of target distance. To discriminate between these two possibilities we used a real target paradigm with vergence angle coupled to distance and a virtual target paradigm with vergence angle dissociated from target distance. We compared TVOR responses in six subjects who underwent lateral sinusoidal whole-body translations at 1 and 2. Hz. Real targets varied between distance of 50 and 22.4. cm in front of the subjects, whereas the virtual targets consisting of a green and red light emitting diode (LED) were physically located at 50. cm from the subject. Red and green LED's were dichoptically viewed. By shifting the red LED relative to the green LED we created a range of virtual viewing distances where vergence angle changed but the ideal kinematic eye velocity was always the same. Eye velocity data recorded with virtual targets were compared to eye velocity data recorded with real targets. We also used flashing targets (flash frequency 1. Hz, duration 5. ms). During the real, continuous visible targets condition scaling of compensatory eye velocity with vergence angle was nearly perfect. During viewing of virtual targets, and with flashed targets compensatory eye velocity only weakly correlated to vergence angle, indicating that vergence angle is only partially coupled to compensatory eye velocity during translation. Our data suggest that

The mammalian oculomotor nucleus receives a strong γ-aminobutyric acid (GABA)ergic synaptic input, whereas such projections have rarely been reported in fish. In order to determine whether this synaptic organization is preserved across vertebrates, we investigated the GABAergic projections to the oculomotor nucleus in the goldfish by combining retrograde transport of biotin dextran amine, injected into the antidromically identified oculomotor nucleus, and GABA immunohistochemistry.The main source of GABAergic afferents to the oculomotor nucleus was the ipsilateral anterior octaval nucleus, with only a few, if any, GABAergic neurons being located in the contralateral tangential and descending nuclei of the octaval column. In mammals there is a nearly exclusive ipsilateral projection from vestibular neurons to the oculomotor nucleus via GABAergic inhibitory inputs; thus, the vestibulooculomotor GABAergic circuitry follows a plan that appears to be shared throughout the vertebrate phylogeny. The second major source of GABAergic projections was the rhombencephalic reticular formation, primarily from the medial area but, to a lesser extent, from the inferior area. A few GABAergic oculomotor projecting neurons were also observed in the ipsilateral nucleus of the medial longitudinal fasciculus. The GABAergic projections from neurons located in both the reticular formation surrounding the abducens nucleus and the nucleus of the medial reticular formation have primarily been related to the control of saccadic eye movements. Finally, all retrogradely labeled internuclear neurons of the abducens nucleus, and neurons in the cerebellum (close to the caudal lobe), were negative for GABA. These data suggest that the vestibuloocular and saccadic inhibitory GABAergic systems appear early in vertebrate phylogeny to modulate the firing properties of the oculomotor nucleus motoneurons.

Cerebellar motor learning is required to obtain procedural skills. Studies have provided supportive evidence for a potential role of kinase-mediated long-term depression (LTD) at the parallel fiber to Purkinje cell synapse in cerebellar learning. Recently, phosphatases have been implicated in the induction of potentiation of Purkinje cell activities in vitro, but it remains to be shown whether and how phosphatase-mediated potentiation contributes to motor learning. Here, we investigated its possible role by creating and testing a Purkinje cell-specific knockout of calcium/calmodulin-activated protein-phosphatase-2B (L7-PP2B). The selective deletion of PP2B indeed abolished postsynaptic long-term potentiation in Purkinje cells and their ability to increase their excitability, whereas LTD was unaffected. The mutants showed impaired "gain-decrease" and "gain-increase" adaptation of their vestibulo-ocular reflex (VOR) as well as impaired acquisition of classical delay conditioning of their eyeblink response. Thus, our data indicate that PP2B may indeed mediate potentiation in Purkinje cells and contribute prominently to cerebellar motor learning.

Background: The spinocerebellar ataxias (SCAs) are clinically and genetically heterogeneous. Currently, 27 forms are known, with the causative gene identified in 16. Although the majority of dominant pedigrees worldwide have SCAs 1, 2, 3, 6 or 8, new SCAs continue to be delineated. We describe a new disorder: SCA 30. Method(s): An Australian family of Anglo-Celtic ethnicity manifested a relatively pure, slowly evolving ataxia. Six affected and four unaffected members were personally examined in a standardised fashion. MRI and nerve conduction studies were performed in two. An autosomal genome-wide linkage study was undertaken, and an in silico analysis of potential candidate genes in the linkage region was performed. Result(s): The six affected members had a relatively pure, slowly evolving ataxia developing in mid to late life, with only minor pyramidal signs and no evidence of neuropathy. All had hypermetric saccades with normal vestibulo-ocular reflex gain. Only one displayed (slight) gaze-evoked nystagmus. MRI showed cerebellar atrophy with preservation of nodulus/uvula and brainstem. Linkage analysis excluded currently known SCAs and identified a logarithm (base 10) of odds score of 3.0 at chromosome 4q34.3-q35.1, distinct from all previously reported loci. In silico prioritisation identified the gene ODZ3 as the most likely contender. Conclusion(s): SCA 30 is a previously undescribed cause of (relatively) pure adult-onset autosomal dominant cerebellar ataxia. The responsible gene is yet to be determined, but ODZ3 is a plausible candidate.

Background: The spinocerebellar ataxias (SCAs) are clinically and genetically heterogeneous. Currently, 27 forms are known, with the causative gene identified in 16. Although the majority of dominant pedigrees worldwide have SCAs 1, 2, 3, 6 or 8, new SCAs continue to be delineated. We describe a new disorder: SCA 30. Method(s): An Australian family of Anglo-Celtic ethnicity manifested a relatively pure, slowly evolving ataxia. Six affected and four unaffected members were personally examined in a standardised fashion. MRI and nerve conduction studies were performed in two. An autosomal genome-wide linkage study was undertaken, and an in silico analysis of potential candidate genes in the linkage region was performed. Result(s): The six affected members had a relatively pure, slowly evolving ataxia developing in mid to late life, with only minor pyramidal signs and no evidence of neuropathy. All had hypermetric saccades with normal vestibulo-ocular reflex gain. Only one displayed (slight) gaze-evoked nystagmus. MRI showed cerebellar atrophy with preservation of nodulus/uvula and brainstem. Linkage analysis excluded currently known SCAs and identified a logarithm (base 10) of odds score of 3.0 at chromosome 4q34.3-q35.1, distinct from all previously reported loci. In silico prioritisation identified the gene ODZ3 as the most likely contender. Conclusion(s): SCA 30 is a previously undescribed cause of (relatively) pure adult-onset autosomal dominant cerebellar ataxia. The responsible gene is yet to be determined, but ODZ3 is a plausible candidate.

Friedreich ataxia (FRDA), the commonest of the inherited ataxias, is a multisystem neurodegenerative condition that affects ocular motor function. We assessed eye movement abnormalities in 20 individuals with genetically confirmed FRDA and compared these results to clinical measures. All subjects were assessed with infrared oculography. Fifteen individuals underwent a full protocol of eye movement recordings. Ten subjects were analysed using two-dimensional scleral coil equipment and five using three-dimensional scleral coil recording equipment. We also recorded visual quality of life, Sloan low contrast letter acuity and Friedreich Ataxia Rating Scale scores to compare to the visual measures. Whilst saccadic velocity was essentially normal, saccadic latency was prolonged. The latency correlated with clinical measures of disease severity, including the scores for the Friedreich Ataxia Rating Scale and the Sloan low contrast letter acuity tests. Fixation abnormalities consisting of square wave jerks and ocular flutter were common, and included rare examples of vertical square wave jerks. Vestibular abnormalities were also evident in the group, with markedly reduced vestibulo-ocular reflex gain and prolonged latency. The range of eye movement abnormalities suggest that neurological dysfunction in FRDA includes brainstem, cortical and vestibular pathways. Severe vestibulopathy with essentially normal saccadic velocity are hallmarks of FRDA and differentiate it from a number of the dominant spinocerebellar ataxias. The correlation of saccadic latency with FARS score raises the possibility of its use as a biomarker for FRDA clinical trials. © The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

Friedreich ataxia (FRDA), the commonest of the inherited ataxias, is a multisystem neurodegenerative condition that affects ocular motor function. We assessed eye movement abnormalities in 20 individuals with genetically confirmed FRDA and compared these results to clinical measures. All subjects were assessed with infrared oculography. Fifteen individuals underwent a full protocol of eye movement recordings. Ten subjects were analysed using two-dimensional scleral coil equipment and five using three-dimensional scleral coil recording equipment. We also recorded visual quality of life, Sloan low contrast letter acuity and Friedreich Ataxia Rating Scale scores to compare to the visual measures. Whilst saccadic velocity was essentially normal, saccadic latency was prolonged. The latency correlated with clinical measures of disease severity, including the scores for the Friedreich Ataxia Rating Scale and the Sloan low contrast letter acuity tests. Fixation abnormalities consisting of square wave jerks and ocular flutter were common, and included rare examples of vertical square wave jerks. Vestibular abnormalities were also evident in the group, with markedly reduced vestibulo-ocular reflex gain and prolonged latency. The range of eye movement abnormalities suggest that neurological dysfunction in FRDA includes brainstem, cortical and vestibular pathways. Severe vestibulopathy with essentially normal saccadic velocity are hallmarks of FRDA and differentiate it from a number of the dominant spinocerebellar ataxias. The correlation of saccadic latency with FARS score raises the possibility of its use as a biomarker for FRDA clinical trials. © The Author (2008). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.

The dynamic contribution of the otoliths to the human ocular torsion response was examined during passive sinusoidal body roll about an earth-horizontal axis (varying otolith input) and about an earth-vertical axis (unvarying otolith input). At a fixed amplitude of 25°, the stimulus frequency was varied from 0.05 to 0.4Hz. The otoliths affected the ocular torsion response in three different ways. First, the gain of the slow component velocity was slightly, but consistently, higher with varying otolith input as compared to unvarying otolith inputs. Second, and more importantly, contribution of the otoliths improved the response dynamics by reducing the phase lead at frequencies up to 0.20Hz. Third, the nystagmus showed considerably less anti-compensatory saccades with varying otolith input than with unvarying otolith input, even though the slow component velocity was lower in the latter. We conclude that the primary concern of the otolith-oculomotor system is to stabilize eye position in space rather than to prevent retinal blur.