Evolution and development of extraocular motor neurons, nerves and muscles in vertebrates.

The purpose of this review is to analyze the origin of ocular motor neurons, define the pattern of innervation of nerve fibers that project to the extraocular eye muscles (EOMs), describe congenital disorders that alter the development of ocular motor neurons, and provide an overview of vestibular pathway inputs to ocular motor nuclei. Six eye muscles are innervated by axons of three ocular motor neurons, the oculomotor (CNIII), trochlear (CNIV), and abducens (CNVI) neurons. Ocular motor neurons (CNIII) originate in the midbrain and innervate the ipsilateral orbit, except for the superior rectus and the levator palpebrae, which are contralaterally innervated. Trochlear motor neurons (CNIV) originate at the midbrain-hindbrain junction and innervate the contralateral superior oblique muscle. Abducens motor neurons (CNVI) originate variously in the hindbrain of rhombomeres r4-6 that innervate the posterior (or lateral) rectus muscle and innervate the retractor bulbi. Genes allow a distinction between special somatic (CNIII, IV) and somatic (CNVI) ocular motor neurons. Development of ocular motor neurons and their axonal projections to the EOMs may be derailed by various genetic causes, resulting in the congenital cranial dysinnervation disorders. The ocular motor neurons innervate EOMs while the vestibular nuclei connect with the midbrain-brainstem motor neurons.

Morphometry and anatomical variations of the inferior oblique muscle as relevant to the strabismus surgeries.

Effective outcome of inferior oblique (IO) corrective surgeries demands a detailed knowledge of morphometry and variations of IO. Our aim was to study and morphometrically define the surgical anatomy of the IO muscle and its variations. Also to provide easily identifiable surgical coordinates to locate, the IO origin and the oculomotor nerve entry point into the IO. Dissection was performed on 16 cadaveric orbits. IO anatomy, variations, morphometry and relevant surgical distances were measured using digital caliper. IO with multiple bellies was found in five specimens. The IO mean length was 33.1 ± 3.3 mm, width at origin was 3.1 ± 0.6 mm, and width at insertion was 8.8 ± 1.5 mm. For easy localization of origin, its distance from the palpable landmarks, Zygomatico-maxillary suture and fronto-maxillary suture was measured. The mean distance between IO and the optic nerve was 10 mm. Distance of the nerve to inferior oblique entry point to the origin and insertion of the inferior oblique was measured. The nerve to IO was 28 mm long. The mean distance of the nerve entry point to IO origin was 15.5 ± 2.3 mm and distance to IO insertion was 15.2 ± 2.8 mm. A muscular bridge between the Inferior rectus (IR) & IO was found in one case, affecting ~» of the IO length; the distal end of the bridge was 5 mm from the IO insertion. Origin of the IO can be localized on the orbital surface of maxilla, 1-2 cm from the point where zygomatico-maxillary suture cuts the inferior orbital margin and 1-2 cm from the fronto-maxillary suture. In 19% of the orbits, the IO length was less than 30 mm, which may cause traction injury in muscle transposition procedures. The width at insertion is useful as most corrective surgeries are performed at the insertion site. The nerve to IO consistently entered at the center of medial border. The nerve entry point is important surgically as myectomy is performed between it and the insertion point. The safe distance available from the optic nerve was 7 mm. Detailed morphometry of IO may aid surgeons in better surgical planning and execution.

The relative sizes of nuclei in the oculomotor complex vary by order and behaviour in birds.

Eye movements are a critical component of visually guided behaviours, allowing organisms to scan the environment and bring stimuli of interest to regions of acuity in the retina. Although the control and modulation of eye movements by cranial nerve nuclei are highly conserved across vertebrates, species variation in visually guided behaviour and eye morphology could lead to variation in the size of oculomotor nuclei. Here, we test for differences in the size and neuron numbers of the oculomotor nuclei among birds that vary in behaviour and eye morphology. Using unbiased stereology, we measured the volumes and numbers of neurons of the oculomotor (nIII), trochlear (nIV), abducens (nVI), and Edinger-Westphal (EW) nuclei across 71 bird species and analysed these with phylogeny-informed statistics. Owls had relatively smaller nIII, nIV, nVI and EW nuclei than other birds, which reflects their limited degrees of eye movements. In contrast, nVI was relatively larger in falcons and hawks, likely reflecting how these predatory species must shift focus between the central and temporal foveae during foraging and prey capture. Unexpectedly, songbirds had an enlarged EW and relatively more nVI neurons, which might reflect accommodation and horizontal eye movements. Finally, the one merganser we measured also has an enlarged EW, which is associated with the high accommodative power needed for pursuit diving. Overall, these differences reflect species and clade level variation in behaviour, but more data are needed on eye movements in birds across species to better understand the relationships among behaviour, retinal anatomy, and brain anatomy.

Intraoperative lateral rectus electromyographic recordings optimized by deep intraorbital needle electrodes.

OBJECTIVE: We demonstrate the advantages and safety of long, intraorbitally-placed needle electrodes, compared to standard-length subdermal electrodes, when recording lateral rectus electromyography (EMG) during intracranial surgeries. METHODS: Insulated 25 mm and uninsulated 13 mm needle electrodes, aimed at the lateral rectus muscle, were placed in parallel during 10 intracranial surgeries, examining spontaneous and stimulation-induced EMG activities. Postoperative complications in these patients were reviewed, alongside additional patients who underwent long electrode placement in the lateral rectus. RESULTS: In 40 stimulation-induced recordings from 10 patients, the 25 mm electrodes recorded 6- to 26-fold greater amplitude EMG waveforms than the 13 mm electrodes. The 13 mm electrodes detected greater unwanted volume conduction upon facial nerve stimulation, typically exceeding the amplitude of abducens nerve stimulation. Except for one case with lateral canthus ecchymosis, no clinical or radiographic complications occurred in 36 patients (41 lateral rectus muscles) following needle placement. CONCLUSIONS: Intramuscular recordings from long electrode in the lateral rectus offers more reliable EMG monitoring than 13 mm needles, with excellent discrimination between abducens and facial nerve stimulations, and without significant complications from needle placement. SIGNIFICANCE: Long intramuscular electrode within the orbit for lateral rectus EMG recording is practical and reliable for abducens nerve monitoring.

Macaque monkey trigeminal blink reflex circuits targeting levator palpebrae superioris motoneurons.

For normal viewing, the eyes are held open by the tonic actions of the levator palpebrae superioris (levator) muscle raising the upper eyelid. This activity is interrupted during blinks, when the eyelid sweeps down to spread the tear film or protect the cornea. We examined the circuit connecting the principal trigeminal nucleus to the levator motoneurons by use of both anterograde and retrograde tracers in macaque monkeys. Injections of anterograde tracer were made into the principal trigeminal nucleus using either a stereotaxic approach or localization following physiological characterization of trigeminal second order neurons. Anterogradely labeled axonal arbors were located both within the caudal central subdivision, which contains levator motoneurons, and in the adjacent supraoculomotor area. Labeled boutons made synaptic contacts on retrogradely labeled levator motoneurons indicating a monosynaptic connection. As the eye is also retracted through the actions of the rectus muscles during a blink, we examined whether these trigeminal injections labeled boutons contacting rectus motoneurons within the oculomotor nucleus. These were not found when the injection sites were confined to the principal trigeminal nucleus region. To identify the source of the projection to the levator motoneurons, we injected retrograde tracer into the oculomotor complex. Retrogradely labeled cells were confined to a narrow, dorsoventrally oriented cell population that lined the rostral edge of the principal trigeminal nucleus. Presumably these cells inhibit levator motoneurons, while other parts of the trigeminal sensory complex are activating orbicularis oculi motoneurons, when a blink is initiated by sensory stimuli contacting the face.

Accuracy and precision of small saccades.

Despite recent advances on the mechanisms and purposes of fine oculomotor behavior, a rigorous assessment of the precision and accuracy of the smallest saccades is still lacking. Yet knowledge of how effectively these movements shift gaze is necessary for understanding their functions and is helpful in further elucidating their motor underpinnings. Using a combination of high-resolution eye-tracking and gaze-contingent control, here we examined the accuracy and precision of saccades aimed toward targets ranging from [Formula: see text] to [Formula: see text] eccentricity. We show that even small saccades of just 14-[Formula: see text] are very effective in centering the stimulus on the retina. Furthermore, we show that for a target at any given eccentricity, the probability of eliciting a saccade depends on its efficacy in reducing the foveal offset. The pattern of results reported here is consistent with current knowledge on the motor mechanisms of microsaccade production.

From Gaussian blobs to naturalistic videos: Comparison of oculomotor behavior across different stimulus complexities.

Research on eye movements has primarily been performed in two distinct ways: (1) under highly controlled conditions using simple stimuli such as dots on a uniform background, or (2) under free-viewing conditions with complex images, real-world movies, or even with observers moving around in the world. Although both approaches offer important insights, the generalizability among eye movement behaviors observed under these different conditions is unclear. Here, we compared eye movement responses to video clips showing moving objects within their natural context with responses to simple Gaussian blobs on a blank screen. Importantly, for both conditions, the targets moved along the same trajectories at the same speed. We measured standard oculometric measures for both stimulus complexities, as well as the effect of the relative angle between saccades and pursuit, and compared them across conditions. In general, eye movement responses were qualitatively similar, especially with respect to pursuit gain. For both types of stimuli, the accuracy of saccades and subsequent pursuit was highest when both eye movements were collinear. We also found interesting differences; for example, latencies of initial saccades to moving Gaussian blob targets were significantly faster compared to saccades to moving objects in video scenes, whereas pursuit accuracy was significantly higher in video scenes. These findings suggest a lower processing demand for simple target conditions during saccade preparation and an advantage for tracking behavior in natural scenes due to higher predictability provided by the context information.

Oculomotor behavior tracks the effect of ideological priming on deception.

The decision to lie to another person involves a conflict between one's own and others' interest. Political ideology may foster self-promoting or self-transcending values and thus may balance or fuel self vs. other related conflicts. Here, we explored in politically non-aligned participants whether oculomotor behavior may index the influence on moral decision-making of prime stimuli related to left and right-wing ideologies. We presented pictures of Italian politicians and ideological words in a paradigm where participants could lie to opponents with high vs. low socio-economic status to obtain a monetary reward. Results show that left-wing words decreased self-gain lies and increased other-gain ones. Oculomotor behavior revealed that gazing longer at politicians' pictures led participants to look longer at opponent's status-related information than at game's outcome-related information before the decision. This, in turn, caused participants to lie less to low status opponents. Moreover, after lying, participants averted their gaze from high status opponents and maintained it towards low status ones. Our results offer novel evidence that ideological priming influences moral decision-making and suggest that oculomotor behavior may provide crucial insights on how this process takes place.

New Cerebello-Cortical Pathway Involved in Higher-Order Oculomotor Control.

The cerebellum and the basal ganglia play an important role in the control of voluntary eye movement associated with complex behavior, but little is known about how cerebellar projections project to cortical eye movement areas. Here we used retrograde transneuronal transport of rabies virus to identify neurons in the cerebellar nuclei that project via the thalamus to supplementary eye field (SEF) of the frontal cortex of macaques. After rabies injections into the SEF, many neurons in the restricted region, the ventral aspects of the dentate nucleus (DN), the caudal pole of the DN, and the posterior interpositus nucleus (PIN) were labeled disynaptically via the thalamus, whereas no neuron labeling was found in the anterior interpositus nucleus (AIN). The distribution of the labeled neurons was dorsoventrally different from that of DN and PIN neurons labeled from the motor cortex. In the basal ganglia, a large number of labeled neurons were confined to the dorsomedial portion of the internal segment of the globus pallidus (GPi) as more neurons were labeled in the inner portion of the GPi (GPii) than in the outer portion of the GPi (GPio). This is the first evidence of a projection between cerebellum/basal ganglia and the SEF that could enable the cerebellum to modulate the cognitive control of voluntary eye movement.

The Importance of the Interaction Between Ocular Motor Function and Vision During Human Infancy.

Numerous studies have demonstrated the impact of imposed abnormal visual experience on the postnatal development of the visual system. These studies have provided fundamental insights into the mechanisms underlying neuroplasticity and its role in clinical care. However, the ocular motor responses of postnatal human infants largely define their visual experience in dynamic three-dimensional environments. Thus, the immature visual system needs to control its own visual experience. This review explores the interaction between the developing motor and sensory/perceptual visual systems, together with its importance in both typical development and the development of forms of strabismus and amblyopia.

The Amniote Oculomotor Complex.

The oculomotor (OM) complex is a combination of somatic and parasympatethic neurons. The correct development and wiring of this cranial pair is essential to perform basic functions: eyeball and eyelid movements, pupillary constriction, and lens accommodation. The improper formation or function of this nucleus leads pathologies such as strabismus. We describe the OM organization and function in different vertebrate brains, including chick, mouse, and human. The morphological localization is detailed, as well as the spatial relation with the trochlear nucleus in order to adjust some misleading anatomical topographic descriptions. We detailed the signaling processes needed for the specification of the OM neurons. The transcriptional programs driven the specification and differentiation of these neurons are partially determined. We summarized recent genetic studies that have led to the identification of guidance mechanisms involved in the migration, axon pathfinding, and targeting of the OM neurons. Finally, we overviewed the pathology associated to genetic malformations in the OM development and related clinical alterations. Anat Rec, 302:446-451, 2019. © 2018 Wiley Periodicals, Inc.

Saccade metrics reflect decision-making dynamics during urgent choices.

A perceptual judgment is typically characterized by constructing psychometric and chronometric functions, i.e., by mapping the accuracies and reaction times of motor choices as functions of a sensory stimulus feature dimension. Here, we show that various saccade metrics (e.g., peak velocity) are similarly modulated as functions of sensory cue viewing time during performance of an urgent-decision task. Each of the newly discovered functions reveals the dynamics of the perceptual evaluation process inherent to the underlying judgment. Remarkably, saccade peak velocity correlates with statistical decision confidence, suggesting that saccade kinematics reflect the degree of certainty with which an urgent perceptual decision is made. The data were explained by a race-to-threshold model that also replicates standard performance measures and cortical oculomotor neuronal activity in the task. The results indicate that, although largely stereotyped, saccade metrics carry subtle but reliable traces of the underlying cognitive processes that give rise to each oculomotor choice.

Encoding of error and learning to correct that error by the Purkinje cells of the cerebellum.

The primary output cells of the cerebellar cortex, Purkinje cells, make kinematic predictions about ongoing movements via high-frequency simple spikes, but receive sensory error information about that movement via low-frequency complex spikes (CS). How is the vector space of sensory errors encoded by this low-frequency signal? Here we measured Purkinje cell activity in the oculomotor vermis of animals during saccades, then followed the chain of events from experience of visual error, generation of CS, modulation of simple spikes, and ultimately change in motor output. We found that while error direction affected the probability of CS, error magnitude altered its temporal distribution. Production of CS changed the simple spikes on the next trial, but regardless of the actual visual error, this change biased the movement only along a vector that was parallel to the Purkinje cell's preferred error. From these results, we inferred the anatomy of a sensory-to-motor adaptive controller that transformed visual error vectors into motor-corrections.

Electrophysiology of Extraocular Cranial Nerves: Oculomotor, Trochlear, and Abducens Nerve.

The utility of extraocular cranial nerve electrophysiologic recordings lies primarily in the operating room during skull base surgeries. Surgical manipulation during skull base surgeries poses a risk of injury to multiple cranial nerves, including those innervating extraocular muscles. Because tumors distort normal anatomic relationships, it becomes particularly challenging to identify cranial nerve structures. Studies have reported the benefits of using intraoperative spontaneous electromyographic recordings and compound muscle action potentials evoked by electrical stimulation in preventing postoperative neurologic deficits. Apart from surgical applications, electromyography of extraocular muscles has also been used to guide botulinum toxin injections in patients with strabismus and as an adjuvant diagnostic test in myasthenia gravis. In this article, we briefly review the rationale, current available techniques to monitor extraocular cranial nerves, technical difficulties, clinical and surgical applications, as well as future directions for research.

Psychophysiological and oculomotoric changes during emotion elicitation

With an aim to examine behavioural and physiological changes during emotion elicitation, 30 participants were shown audio, video or audio-video versions of movie clips depicting anger, fear, happiness, sadness, surprise and neutral expressions. While watching these stimuli, the eye-tracking glass was used to record oculomotoric changes. Heart rate, blood volume and respiration rate were also recorded. After viewing each clip the participants had to label and rate the emotion depicted in the movie clip. The data was analyzed with respect to valence, motoric direction and arousal dimensions of emotions. Findings of the behavioural data and corresponding change in the respiration rate suggest that fear is the only emotion that equally impacted participants psychologically as well as physiologically. The number of fixations and saccades for positive and negative emotions differed significantly (AU)

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Role of neural integrators in oculomotor systems: a systematic narrative literature review.

PURPOSE: To evaluate the role of neural integrators (NI) in the oculomotor system. METHODS: A literature search was carried out using several electronic databases during the months of June 2014 to March 2015. The following keywords were used to generate focused results: 'neural integrators', 'gaze-holding', 'oculomotor integration', 'impaired gaze-holding', 'gaze evoked nystagmus' and 'gaze dysfunction'. Further materials were found through searching relevant articles within reference lists. Seventy-one articles were sourced for this review which analysed animal and human subjects and network models; 45 were studies of humans, 16 studies of primates, three studies of felines and one study from rats and network models. The remaining articles were literature reviews. RESULTS: The horizontal and vertical, including torsional, NI are located logically in the brainstem, nearby their appropriate target extraocular motoneuron nuclei for stable eye position in eccentric position. The nucleus prepositus hypoglossi (NPH) and medial vestibular nuclei (MVN) are closely linked at the caudal pons and dorsal rostral medulla, integrating horizontal conjugate eye movement. The interstitial nucleus of Cajal (INC) integrates vertical and torsional eye movement at the upper midbrain. The integrator time constant is averaged to 25 seconds in human horizontal and animal vertical NI to perform its function. Case reports revealed that dysfunction of horizontal NI also resulted in vertical ocular deviations, indicating some overlap of horizontal and vertical gaze control. Furthermore, pharmacological inactivation of NI exposed a population of inhibitory neurotransmitters that permits its mechanism of action; allowing for smooth conjugate movement. CONCLUSIONS: Neural integrators operate to integrate eye velocity and eye position information to provide signals to extraocular motoneurons to attain and maintain a new position. Therefore, NI allow image stabilization during horizontal and vertical eye movements at eccentric positions for comfortable single vision.

[Neuroanatomy of the Oculomotor System]. / Neuroanatomie des okulomotorischen Systems.

After just a clinical examination, the experienced neurologist can assign specific symptoms quite precisely to distinct lesions within the brain and other parts of the nervous system, on the basis of his neuroanatomical knowledge. This also holds true for lesions affecting the oculomotor system. The aim of this article is to give a comprehensive overview of the neuroanatomical basis of the oculomotor system, in order to facilitate the precise spatial assignment of potential lesions affecting the control of eye movements. After a brief introduction, the components of the system are discussed, including the extraocular muscles and their innervating nerves. The following section will then cover the control of eye movements and will specifically address distinct patterns of eye movements and areas within the central nervous system controlling these. This article also gives a brief overview of the intraocular muscles and their control.

Ocular Motor Function in Children with Spastic Hemiplegia Evaluated by the Ocular Motor Score.

PURPOSE: To assess the ocular motor functions in children with spastic hemiplegia by using the Ocular Motor Score (OMS). MATERIAL: This study included 34 children, median age 11 years. The children were divided into 3 groups according to the underlying brain lesion; group 1 malformations, group 2 white matter damage of immaturity (WMDI), and group 3 cortical/subcortical lesions. METHODS: The OMS protocol consists of 15 different subtests evaluating ocular motor functions. The OMS is divided into 2 parts, a static and a dynamic. The results from each subtest are scored 0, 0.3, 0.5, or 1, according to the level of disturbance, where 0 corresponds to normal function and 1 represents the maximum disability in the certain subtest. A total OMS (tOMS) between 0 and 15 can be obtained. RESULTS: The median tOMS in the whole spastic hemiplegia group was 2.5 (range 1.3-5.8). The highest median tOMS 5.2 was seen in group 1, in the children with malformations. Strabismus was found in 45% (15/34) of the children, with an equal percentage in all 3 groups. CONCLUSIONS: The children with spastic hemiplegia had a median tOMS of 2.7 and the highest median tOMS was seen in children with malformations. The OMS protocol is easy to use clinically and gives a quick overview of the patient´s ocular motor functions.

Usefulness of intraoperative electromyographic monitoring of oculomotor and abducens nerves during skull base surgery.

BACKGROUND: Intraoperative neurophysiologic monitoring of the extraocular cranial nerve (EOCN) is not commonly performed because of technical difficulty and risk, reliability of the result and predictability of the postoperative function of the EOCN. METHODS: We performed oculomotor nerve (CN III) and abducens nerve (CN VI) intraoperative monitoring in patients with skull base surgery by recording the spontaneous muscle activity (SMA) and compound muscle action potential (CMAP). Two types of needle electrodes of different length were percutaneously inserted into the extraocular muscles with the free-hand technique. We studied the relationships between the SMA and CMAP and postoperative function of CN III and CN VI. RESULTS: A total of 23 patients were included. Nineteen oculomotor nerves and 22 abducens nerves were monitored during surgery, respectively. Neurotonic discharge had a positive predictive value of less than 50% and negative predictive value of more than 80% for postoperative CN III and CN VI dysfunction. The latency of patients with postoperative CN III dysfunction was 2.79 ± 0.13 ms, longer than that with intact CN III function (1.73 ± 0.11 ms). One patient had transient CN VI dysfunction, whose CMAP latency (2.54 ms) was longer than that of intact CN VI function (2.11 ± 0.38 ms). There was no statistically significant difference between patients with paresis and with intact function. CONCLUSIONS: The method of intraoperative monitoring of EOCNs described here is safe and useful to record responses of SMA and CMAP. Neurotonic discharge seems to have limited value in predicting the postoperative function of CN III and CN VI. The onset latency of CMAP longer than 2.5 ms after tumor removal is probably relevant to postoperative CN III and CN VI dysfunction. However, a definite quantitative relationship has not been found between the amplitude and stimulation intensity of CMAP and the postoperative outcome of CN III and CN VI.

Ocular Motor Nerve Development in the Presence and Absence of Extraocular Muscle.

Purpose: To spatially and temporally define ocular motor nerve development in the presence and absence of extraocular muscles (EOMs). Methods: Myf5cre mice, which in the homozygous state lack EOMs, were crossed to an IslMN:GFP reporter line to fluorescently label motor neuron cell bodies and axons. Embryonic day (E) 11.5 to E15.5 wild-type and Myf5cre/cre:IslMN:GFP whole mount embryos and dissected orbits were imaged by confocal microscopy to visualize the developing oculomotor, trochlear, and abducens nerves in the presence and absence of EOMs. E11.5 and E18.5 brainstems were serially sectioned and stained for Islet1 to determine the fate of ocular motor neurons. Results: At E11.5, all three ocular motor nerves in mutant embryos approached the orbit with a trajectory similar to that of wild-type. Subsequently, while wild-type nerves send terminal branches that contact target EOMs in a stereotypical pattern, the Myf5cre/cre ocular motor nerves failed to form terminal branches, regressed, and by E18.5 two-thirds of their corresponding motor neurons died. Comparisons between mutant and wild-type embryos revealed novel aspects of trochlear and oculomotor nerve development. Conclusions: We delineated mouse ocular motor nerve spatial and temporal development in unprecedented detail. Moreover, we found that EOMs are not necessary for initial outgrowth and guidance of ocular motor axons from the brainstem to the orbit but are required for their terminal branching and survival. These data suggest that intermediate targets in the mesenchyme provide cues necessary for appropriate targeting of ocular motor axons to the orbit, while EOM cues are responsible for terminal branching and motor neuron survival.