Velocity Storage Network Research Articles

Measuring optokinetic after-nystagmus: potential for detecting patients with signs of visual dependence following concussion

Concussed patients with chronic symptoms commonly report dizziness during exposure to environments with complex visual stimuli (e.g. supermarket aisles, busy crossroads). Such visual induced dizziness is well-known in patients with vestibular deficits, in whom it indicates an overreliance on visual cues in sensory integration. Considering that optokinetic after-nystagmus (OKAN) reflects the response of the central network integrating visual and vestibular self-motion signals (velocity storage network), we investigated OKAN in 71 patients [17 (23.9%) females, 30.36 ± 9.05 years old] who suffered from persistent symptoms after a concussion and presented clinical signs suggesting visual dependence. Data were retrospectively compared with 21 healthy individuals [13 (61.9%) females, 26.29 ± 10.00 years old]. The median values of the slow cumulative eye position and of the time constant of OKAN were significantly higher in patients than in healthy individuals (slow cumulative eye position: 124.15 ± 55.61° in patients and 77.87 ± 45.63° in healthy individuals—p = 0.012; time constant: 25.17 ± 10.27 s in patients and 13.95 ± 4.92 s in healthy individuals—p = 0.003). The receiving operating curve (ROC) estimated on the time constant had an overall area under the curve of 0.73. Analysis of the ROC suggests that a test measuring the OKAN time constant could obtain a sensitivity of 0.73 and specificity of 0.72 in determining the origin of the visual-related disturbances in those patients (threshold 16.6 s). In a subset of 43 patients who also performed the Sensory Organization Test (SOT), the proposed OKAN test was twice as sensitive as the SOT. This study suggests that concussed patients with persisting visual symptoms may have an underlying impairment of the velocity storage mechanism and that measuring the OKAN time constant can objectify such impairment.

Is Vestibular Self-Motion Perception Controlled by the Velocity Storage? Insights from Patients with Chronic Degeneration of the Vestibulo-Cerebellum

BackgroundThe rotational vestibulo-ocular reflex (rVOR) generates compensatory eye movements in response to rotational head accelerations. The velocity-storage mechanism (VSM), which is controlled by the vestibulo-cerebellar nodulus and uvula, determines the rVOR time constant. In healthy subjects, it has been suggested that self-motion perception in response to earth-vertical axis rotations depends on the VSM in a similar way as reflexive eye movements. We aimed at further investigating this hypothesis and speculated that if the rVOR and rotational self-motion perception share a common VSM, alteration in the latter, such as those occurring after a loss of the regulatory control by vestibulo-cerebellar structures, would result in similar reflexive and perceptual response changes. We therefore set out to explore both responses in patients with vestibulo-cerebellar degeneration.Methodology/Principal FindingsReflexive eye movements and perceived rotational velocity were simultaneously recorded in 14 patients with chronic vestibulo-cerebellar degeneration (28–81yrs) and 12 age-matched healthy subjects (30–72yrs) after the sudden deceleration (90°/s2) from constant-velocity (90°/s) rotations about the earth-vertical yaw and pitch axes. rVOR and perceived rotational velocity data were analyzed using a two-exponential model with a direct pathway, representing semicircular canal activity, and an indirect pathway, implementing the VSM. We found that VSM time constants of rVOR and perceived rotational velocity co-varied in cerebellar patients and in healthy controls (Pearson correlation coefficient for yaw 0.95; for pitch 0.93, p<0.01). When constraining model parameters to use the same VSM time constant for rVOR and perceived rotational velocity, moreover, no significant deterioration of the quality of fit was found for both populations (variance-accounted-for >0.8).Conclusions/SignificanceOur results confirm that self-motion perception in response to rotational velocity-steps may be controlled by the same velocity storage network that controls reflexive eye movements and that no additional, e.g. cortical, mechanisms are required to explain perceptual dynamics.

Spatial and temporal properties of eye movements produced by electrical stimulation of semicircular canal afferents

To investigate the characteristics of eye movements produced by electrical stimulation of semicircular canal afferents, we studied the spatial and temporal features of eye movements elicited by short-term lateral canal stimulation in two squirrel monkeys with plugged lateral canals, with the head upright or statically tilted in the roll plane. The electrically induced vestibuloocular reflex (eVOR) evoked with the head upright decayed more quickly than the stimulation signal provided by the electrode, demonstrating an absence of the classic velocity storage effect that improves the dynamics of the low-frequency VOR. When stimulation was provided with the head tilted in roll, however, the eVOR decayed more rapidly than when the head was upright, and a cross-coupled vertical response developed that shifted the eye's rotational axis toward alignment with gravity. These results demonstrate that rotational information provided by electrical stimulation of canal afferents interacts with otolith inputs (or other graviceptive cues) in a qualitatively normal manner, a process that is thought to be mediated by the velocity storage network. The observed interaction between the eVOR and graviceptive cues is of critical importance for the development of a functionally useful vestibular prosthesis. Furthermore, the presence of gravity-dependent effects (dumping, spatial orientation) despite an absence of low-frequency augmentation of the eVOR has not been previously described in any experimental preparation.

Resolution of Sensory Ambiguities for Gaze Stabilization Requires a Second Neural Integrator

The ability to simultaneously move in the world and maintain stable visual perception depends critically on the contribution of vestibulo-ocular reflexes (VORs) to gaze stabilization. It is traditionally believed that semicircular canal signals drive compensatory responses to rotational head disturbances (rotational VOR), whereas otolith signals compensate for translational movements [translational VOR (TVOR)]. However, a sensory ambiguity exists because otolith afferents are activated similarly during head translations and reorientations relative to gravity (i.e., tilts). Extra-otolith cues are, therefore, necessary to ensure that dynamic head tilts do not elicit a TVOR. To investigate how extra-otolith signals contribute, we characterized the temporal and viewing distance-dependent properties of a TVOR elicited in the absence of a lateral acceleration stimulus to the otoliths during combined translational/rotational motion. We show that, in addition to otolith signals, angular head position signals derived by integrating sensory canal information drive the TVOR. A physiological basis for these results is proposed in a model with two distinct integration steps. Upstream of the well known oculomotor velocity-to-position neural integrator, the model incorporates a separate integration element that could represent the "velocity storage integrator," whose functional role in the oculomotor system has so far remained controversial. We propose that a key functional purpose of the velocity storage network is to temporally integrate semicircular canal signals, so that they may be used to extract translation information from ambiguous otolith afferent signals in the natural and functionally relevant bandwidth of head movements.

The vestibulo-ocular reflex and velocity storage in spinocerebellar ataxia 8.

The autosomal dominant spinocerebellar ataxias (SCAs) are a group of neurodegenerative diseases characterized by progressive instability of posture and gait, incoordination, ocular motor dysfunction, and dysarthria due to degeneration of cerebellar and brainstem neurons. Among the more than 20 genetically distinct subtypes, SCA8 is one of several wherein clinical observations indicate that cerebellar dysfunction is primary, and there is little evidence for other CNS involvement. The aim of the present work was to study the decay of the horizontal vestibulo-ocular reflex (VOR) after a short period of constant acceleration to understand the pathophysiology of the VOR due to cerebellar Purkinje cell degeneration in SCA8. The VOR was recorded in patients with genetically defined SCA8 during rotation in the dark. Moderate to severely affected patients had a qualitatively intact VOR, but there were quantitative differences in the gain and dynamics compared to normal controls. During angular velocity ramp rotations, there was a reversal in the direction of the VOR that was more pronounced in SCA8 compared to controls. Modeling studies indicate that there are significant changes in the velocity storage network, including abnormal feedback of an eye position signal into the network that contributes to this reversal. These and other results will help to identify features that are diagnostic for SCA subtypes and provide new information about selective vulnerability of neurons controlling vestibular reflexes.

Otolith dysfunction in skew deviation after brain stem lesions

We investigated the horizontal and the vertical otolith-ocular reflex induced by off-vertical-axis rotation and subjective visual vertical in 14 patients with skew deviation due to brain stem lesion. Patients were divided into two groups: the group C ( N = 7) with caudal brain stem lesions and the group R ( N = 7) with rostral brain stem lesions as defined by the midpons level. The patient group was compared to a control group of 20 healthy subjects. The otolith-ocular reflex was evoked by constant velocity rotation in yaw plane around an axis tilted at 15 deg with respect to gravity. In group C, the horizontal off-vertical-axis nystagmus bias was negative i.e. anticompensatory to chair rotation, when directed toward the lesioned side. Furthermore, patients of group C were presenting with a significant tilt of subjective visual vertical. In group R, a vertical downward offset was induced predominantly in the hypotropic eye and in the direction of rotation away from the lesion. Finally, in patients of group R, horizontal and vertical modulation was increased for rotation away from the lesion. These results are discussed in terms of 1) asymmetrical horizontal and vertical dynamic otolith signals feeding the velocity storage network after brain stem lesion, 2) possible involvement of cerebellar function in OVAN modulation.

Ultrastructure of vestibular commissural neurons related to velocity storage in the monkey

The angular vestibulo-ocular reflex maintains gaze during head movements. It is thought to be mediated by two components: direct and velocity storage pathways. The direct angular vestibulo-ocular reflex is conveyed by a three neuron chain from the labyrinth to the ocular motoneurons. The indirect pathway involves a more complex neural network that utilizes a portion of the vestibular commissure. The purpose of the present study was to identify the ultrastructural characteristics of commissural neurons in the medial vestibular nucleus that are related to the velocity storage component of the angular vestibulo-ocular reflex. Ultrastructural studies of degenerating medial vestibular nucleus neurons were conducted in monkeys following midline section of rostral medullary commissural fibers with subsequent behavioral testing. After this lesion, oculomotor and vestibular functions attributable to velocity storage were abolished, whereas the direct angular vestibulo-ocular reflex pathway remained intact. Since this damage was functionally discrete, degenerating neurons were interpreted as potential participants in the velocity storage network. Ultrastructural observations indicate that commissural neurons related to velocity storage are small and medium sized cells having large nuclei with deep indentations and relatively little cytoplasm, which are located in the lateral crescents of rostral medial vestibular nucleus. The morphology of degenerating dendritic profiles varied. Some contained numerous round or tubular mitochondria in a pale cytoplasmic matrix with few other organelles, while others had few mitochondria but many cisterns and vacuoles in dense granular cytoplasm. The commissural nature of these cells was further suggested by the presence of two different types of degenerating axon terminals in the rostral medial vestibular nucleus: those with a moderate density of large spherical synaptic vesicles, and those with pleomorphic, primarily ellipsoid synaptic vesicles. The recognition of two types of degenerating terminals further supports our interpretation that at least two morphological types of commissural neurons participate in the velocity storage network. The degenerating boutons formed contacts with a variety of postsynaptic partners. In particular, synapses were observed between degenerating boutons and non-degenerating dendrites, and between intact terminals and degenerating dendrites. However, degenerating pre- and postsynaptic elements were rarely observed in direct contact, suggesting that additional neurons are interposed in the indirect pathway commissural system. On the basis of these ultrastructural observations, it is concluded that vestibular commissural neurons involved in the mediation of velocity storage have distinguishing ultrastructural features and synaptology, that are different from those of direct pathway neurons.

The ultrastructure of GABA-immunoreactive vestibular commissural neurons related to velocity storage in the monkey

The purpose of the present study was to visualize the synaptic interactions of GABAergic neurons involved in the mediation of velocity storage. In the previous report, ultrastructural studies of degenerating neurons were conducted following midline section of rostral medullary commissural fibers with subsequent behavioral testing. The midline lesion caused functionally discrete damage to the velocity storage component, but not to the direct pathway, of the angular vestibulo-ocular reflex, and the degenerating neurons were interpreted as potential participants in the velocity storage network. We concluded that at least some of the commissural axons mediating velocity storage originate from clusters of neurons in the lateral crescents of the rostral medial vestibular nucleus. In the present report, immunocytochemical evidence is presented that many vestibular commissural neurons, putatively involved in mediating velocity storage, are GABAergic. These cells have large nuclei, small round or narrow tubular mitochondria, occasional cisterns and vacuoles, but few other organelles. Their axons are thinly-myelinated, and terminate in boutons containing mitochondria of similar ultrastructural appearance and a moderate density of round/pleomorphic synaptic vesicles. Such terminals often form axoaxonic synapses, and less frequently axodendritic contacts, with non-GABAergic elements. On the basis of the present results, we conclude that a portion of the commissural neurons of the velocity storage pathway is GABAergic. The observation of GABAergic axoaxonic synapses in this pathway is interpreted as a structural basis for presynaptic inhibition of medial vestibular nucleus circuits by velocity storage-related commissural neurons. Conversely, substantial ultrastructural evidence for postsynaptic inhibition of non-GABAergic commissural cells argues for a dual role for GABAergic terminals mediating velocity storage: presynaptic inhibition of non-GABAergic vestibular cells by GABAergic velocity storage commissural axons, and postsynaptic inhibition of non-GABAergic velocity storage cells by GABAergic axons. Both pre- and postsynaptic inhibitory arrangements could provide the morphologic basis for disinhibitory activation of the velocity storage network within local neuronal circuits.

Differences in optokinetic and vestibular ocular reflex performance in teleosts and their relationship to different life styles.

Horizontal eye movements in response to vestibular and optokinetic stimulation were investigated in 20 species of marine and fresh water teleosts. Most species performed spontaneous saccadic eye movements in light and in darkness. Successive saccades occurred either at irregular intervals and in different directions (few species), or in bursts of smaller saccades in one direction followed by saccades in the opposite direction (majority of species). Thus, in the latter group the lines of sight shifted cyclically from one side to the other about every 10-15 s. Eye movement responses in goldfish and toadfish were prototypical for two major functional groups. Optokinetic and vestibular nystagmus in the goldfish were much more regular and attained significantly higher gains than in the oyster toadfish. Optokinetic afternystagmus (OKAN) and per-/postrotatory nystagmus lasted about 10-12 s in the goldfish, but only 2-3 s in the oyster toadfish. Bilateral labyrinthectomy in goldfish resulted in optokinetic gains and OKAN durations that were very close to those of intact toadfish. These results indicate the presence (in goldfish) and the absence (in toadfish) of a functioning velocity storage network, respectively. Other non-ostariophysan teleosts failed to show a 'goldfish-like' response pattern as well. Ostariophysan species differed in their reflex performance as well. A 'goldfish-like' response pattern was observed in five of the seven cypriniform species and in two of the four characiform species but not in the four siluriform species. Positively correlated, combined response properties suggest that some species are better equipped for gaze stabilization at higher velocities than other species. These behavioral differences may parallel different specializations in locomotor pattern and mode of life. Absence of a functioning velocity storage network in bottom-dwelling teleosts (as in Amphibia) may be related to the sporadic, slow locomotion of these species and the resulting small requirements for continuous gaze stabilization during self-motion at higher velocities.

Differences in the central organization of gaze stabilizing reflexes between frog and turtle

1. Compensatory eye and head movements, and responses of central vestibular neurons of frogs and turtles were investigated. 2. Eye movements (head restrained) evoked by optokinetic stimulation reach low peak slow phase velocities in both species: 1.5 °/s in frog and ca. 4 °/s in turtle. The optimal working range of the ocular optokinetic system is restricted to stimulus velocities <1 °/s. Optokinetic-afternystagmus (OKAN) of the eyes is absent in frog (n = 14) and can be present in turtle (one out of five animals). 3. Head movements evoked by optokinetic stimuli reach higher velocities in both species than the eyes and gaze is stabilized by head movements up to 80% of the stimulus velocity within the different working ranges (up to ca. 4 °/s in frog and up to ca. 25 °/s in turtle). Head OKAN is absent in frog (n = 23) and present in turtle (n = 10). OKAN head velocity in turtle decays linearly with apparent time constants between 6 and 12 s (for 20 °/s stimulus velocity). 4. Vestibular per/postrotatory nystagmus (PRN) of the head is short in frog (2–4 s in duration) compared to that in the turtle, where PRN head velocity decays linearly with apparent time constants between 7 and 11s (for 20 °/s velocity steps). Parametric similarities of OKAN and PRN and almost perfect cancellation of head PRN by head OKAN for velocity steps below 30 °/s in the turtle suggest a common neuronal storage for optokinetically and vestibularly evoked head velocity signals. 5. Eye-head coordination is very similar in both species. Fast phases resetting the position of eyes and head are coupled. The major contribution of the ocular motor system is restricted to brief transient periods (at the onset of compensatory movements; after each fast phase) during which the neck motor system more slowly accelerates the head. 6. Responses of central vestibular neurons to velocity steps have short time constants (1–4 s) in alert frogs and optokinetic stimuli modulate the activity of these neurons only exceptionally (2 out of 82). In the turtle, apparent time constants are longer (between 6 and 14 s, mean ca. 9 s) and resting activity of 10 out of 11 neurons was optokinetically modulated. 7. Like the behavioral data, vestibular unit data contain evidence for a functioning velocity storage network in turtles, but not in frogs. These differences in the properties of gaze stabilizing reflexes are discussed in relation with the differing demands that result from differences in the locomotory repertoires of the two species.