Theodore Raphan

Quantitative analysis of the velocity characteristics of optokinetic nystagmus and optokinetic after-nystagmus

1. Velocity characteristics of optokinetic nystagmus (OKN) and optokinetic after‐nystagmus (OKAN) induced by constant velocity full field rotation were studied in rhesus monkeys. A technique is described for estimating the dominant time constant of slow phase velocity curves and of monotonically changing data. Time constants obtained by this technique were used in formulating a model of the mechanism responsible for producing OKN and OKAN.

Role of the flocculus and paraflocculus in optokinetic nystagmus and visual-vestibular interactions: Effects of lesions

Summary1.Optokinetic nystagmus (OKN), optokinetic after-nystagmus (OKAN), vestibular nystagmus and visual-vestibular interactions were studied in monkeys after surgical ablation of the flocculus and paraflocculus. After bilateral flocculectomy the initial rapid rise in slow phase eye velocity of horizontal and vertical OKN was severely attenuated, and maximum velocities fell to the preoperative saturation level of OKAN. There is generally little or no upward OKAN in the normal monkey, and upward OKN was lost after bilateral lesions. Unilateral flocculectomy affected the rapid rise in horizontal velocity to both sides.2.Consistent with the absence of a rapid response to steps of surround velocity, animals were unable to follow acceleration of the visual field with eye accelerations faster than about 3–57 °/s2.3.The slow rise in OKN slow phase velocity to a steady state level was prolonged after operation. However, rates of rise were approximately equal for the same initial retinal slips before and after operation. The similarity in the time course of OKN when adjusted for initial retinal slip, and in the gain, saturation level and time course of OKAN before and after flocculectomy indicates that the lesions had not significantly altered the coupling of the visual system to the velocity storage integrator or its associated time constant.4.When animals were rotated in a subjectstationary visual surround after flocculectomy, they could not suppress the initial jump in eye velocity at the onset of the step. Despite this, they could readily suppress the subsequent nystagmus. The time constant of decline in the conflict situations was almost as short as in the normal monkey and was in the range of the peripheral vestibular time constant. This suggests that although the animals were unable to suppress rapid changes in eye velocity due to activation of direct vestibulo-oculomotor pathways, they had retained their ability to discharge activity from the velocity storage mechanism. Consistent with this, animals had no difficulty in suppressing OKAN after flocculectomy.5.Visual-vestibular interactions utilizing the velocity storage mechanism were normal after flocculectomy, as was nystagmus induced by rotation about a vertical axis or about axes tilted from the vertical. Also unaffected were the discharge of nystagmus caused by tilting the head out of the plane of the response and visual suppression of nystagmus induced by off-vertical axis rotation. The flocculus does not appear to play an important role in mediating these responses.6.The data before and after flocculectomy were simulated by a model which is homeomorphic to that presented previously. The model has direct pathways from the vestibular and visual systems. The visual and vestibular systems couple to a common velocity storage integrator. There is also a dump mechanism which shortens the time constant of the integrator when eye velocity exceeds surround velocity. An important element in the model is a nonlinearity that couples the visual system to the integrator. Approximate closed form relationships were established between the parameters of the nonlinearity and the dynamics of OKN and OKAN. The nonlinear element is assumed to receive a central representation of retinal slip as its input. Its output drives the velocity storage integrator. The model predicts the normal responses, and by removal of the direct pathway it simulates the data after flocculectomy. The nonlinearity explains why the storage integrator charges more slowly for larger initial retinal slips both in the normal animal and after flocculectomy. The model also predicts that surround velocity would be followed better during deceleration than acceleration. This is a result of activation of the dump mechanism which shortens the time constant of the velocity storage integrator, effectively discharging it. Activation of the dump mechanism is independent of the flocculus.7.Although the flocculus is closely linked to the vestibular system, its function in the monkey appears closely related to production of rapid changes in eye velocity from the visual system, either during slow phases of nystagmus or during ocular pursuit (Zee et al. 1981). It does not appear to cancel the horizontal VOR at the level of the vestibular nuclei, nor does it directly affect the dynamics of vestibular nystagmus, OKAN or the velocity storage mechanism.

Effects of walking velocity on vertical head and body movements during locomotion

Abstract Trunk and head movements were characterized over a wide range of walking speeds to determine the relationship between stride length, stepping frequency, vertical head translation, pitch rotation of the head, and pitch trunk rotation as a function of gait velocity. Subjects (26–44 years old) walked on a linear treadmill at velocities of 0.6–2.2 m/s. The head and trunk were modeled as rigid bodies, and rotation and translation were determined using a video-based motion analysis system. At walking speeds up to 1.2 m/s there was little head pitch movement in space, and the head pitch relative to the trunk was compensatory for trunk pitch. As walking velocity increased, trunk pitch remained approximately invariant, but a significant head translation developed. This head translation induced compensatory head pitch in space, which tended to point the head at a fixed point in front of the subject that remained approximately invariant with regard to walking speed. The predominant frequency of head translation and rotation was restricted to a narrow range from 1.4 Hz at 0.6 m/s to 2.5 Hz at 2.2 m/s. Within the range of 0.8–1.8 m/s, subjects tended to increase their stride length rather than step frequency to walk faster, maintaining the predominant frequency of head movement at close to 2.0 Hz. At walking speeds above 1.2 m/s, head pitch in space was highly coherent with, and compensatory for, vertical head translation. In the range 1.2–1.8 m/s, the power spectrum of vertical head translation was the most highly tuned, and the relationship between walking speed and head and trunk movements was the most linear. We define this as an optimal range of walking velocity with regard to head-trunk coordination. The coordination of head and trunk movement was less coherent at walking velocities below 1.2 m/s and above 1.8 m/s. These results suggest that two mechanisms are utilized to maintain a stable head fixation distance over the optimal range of walking velocities. The relative contribution of each mechanism to head orientation depends on the frequency of head movement and consequently on walking velocity. From consideration of the frequency characteristics of the compensatory head pitch, we infer that compensatory head pitch movements may be produced predominantly by the angular vestibulocollic reflex (aVCR) at low walking speeds and by the linear vestibulocollic reflex (lVCR) at the higher speeds.

Role of the otolith organs in generation of horizontal nystagmus: effects of selective labyrinthine lesions

Selective labyrinthine lesions were made to study the origin of excitation in the labyrinth during off-vertical axis rotation. Plugging the semicircular canals abolishes the response to rotation about a vertical axis, but optokinetic after-nystagmus (OKAN) and the sustained horizontal nystagmus induced by off-vertical axis rotation (OVAR) are maintained. After cutting the nerves of the lateral semicircular canals, neither horizontal OKAN nor the continuous horizontal nystagmus associated with off-axis rotation can be induced, although vertical OKN, OKAN and vestibular nystagmus are intact. This supports the theory that labyrinthine activity responsible for the nystagmus induced by OVAR arises in the otolith organs and couples to the oculomotor system through the velocity storage mechanism.

Habituation and adaptation of the vestibuloocular reflex: a model of differential control by the vestibulocerebellum

SummaryWe habituated the dominant time constant of the horizontal vestibuloocular reflex (VOR) of rhesus and cynomolgus monkeys by repeated testing with steps of velocity about a vertical axis and adapted the gain of the VOR by altering visual input with magnifying and reducing lenses. After baseline values were established, the nodulus and ventral uvula of the vestibulocerebellum were ablated in two monkeys, and the effects of nodulouvulectomy and flocculectomy on VOR gain adaptation and habituation were compared. The VOR time constant decreased with repeated testing, rapidly at first and more slowly thereafter. The gain of the VOR was unaffected. Massed trials were more effective than distributed trials in producing habituation. Regardless of the schedule of testing, the VOR time constant never fell below the time constant of the semicircular canals (≈5 s). This finding indicates that only the slow component of the vestibular response, the component produced by velocity storage, was habituated. In agreement with this, the time constant of optokinetic after-nystagmus (OKAN) was habituated concurrently with the VOR. Average values for VOR habituation were obtained on a per session basis for six animals. The VOR gain was adapted by natural head movements in partially habituated monkeys while they wore ×2.2 magnifying or ×0.5 reducing lenses. Adaptation occurred rapidly and reached about ±30%, similar to values obtained using forced rotation. VOR gain adaptation did not cause additional habituation of the time constant. When the VOR gain was reduced in animals with a long VOR time constant, there were overshoots in eye velocity that peaked at about 6–8 s after the onset or end of constant-velocity rotation. These overshoots occurred at times when the velocity storage integrator would have been maximally activated by semicircular canal input. Since the activity generated in the canals is not altered by visual adaptation, this finding indicates that the gain element that controls rapid changes in eye velocity in the VOR is separate from that which couples afferent input to velocity storage. Nodulouvulectomy caused a prompt and permanent loss of habituation, returning VOR time constants to initial values. VOR gain adaptation, which is lost after flocculectomy, was unaffected by nodulouvulectomy. Flocculectomy did not alter habituation of the VOR or of OKAN. Using a simplified model of the VOR, the decrease in the duration of vestibular nystagmus due to habituation was related to a decrement in the dominant time constant of the velocity storage integrator (1/h0). Nodulouvulectomy, which reversed habituation, would be effected by decreasing h0, thereby increasing the VOR time constant. Small values of h0 would cause velocity storage to approach an ideal integrative process, leading the system to become unstable. By controlling the VOR time constant through habituation, the nodulus and uvula can stabilize the slow component of the VOR. VOR gain adaptation was related to a modification of the direct vestibular path gain g1, without altering the coupling to velocity storage g0 or its time constant (1/h0). The mismatched direct- and indirect-pathway gains simulated the overshoots in the dynamic response to a step in velocity, that were observed experimentally. We conclude that independent distributed elements in the VOR modify its dynamic response, under control of separate parts of the vestibulocerebellum.

Nystagmus induced by stimulation of the nucleus of the optic tract in the monkey

Summary1. The nucleus of the optic tract (NOT) was electrically stimulated in alert rhesus monkeys. In darkness stimulation evoked horizontal nystagmus with ipsilateral slow phases, followed by after-nystagmus in the same direction. The rising time course of the slow phase velocity was similar to the slow rise in optokinetic nystagmus (OKN) and to the charge time of optokinetic after-nystagmus (OKAN). The maximum velocity of the steady state nystagmus was approximately the same as that of OKAN, and the falling time course of the after-nystagmus paralled OKAN. 2. Increases in frequency and duration of stimulation caused the rising and falling time constants of the nystagmus and after-nystagmus to become shorter. Changes in the falling time constant of the after-nystagmus were similar to changes in the time constant of OKAN produced by increases in the velocity or duration of optokinetic stimulation. 3. Stimulus-induced nystagmus was combined with OKN, OKAN and per- and post-rotatory nystagmus. The slow component of OKN as well as OKAN could be prolonged or blocked by stimulation, leaving the rapid component of OKN unaffected. Activity induced by electrical stimulation could also sum with activity arising in the semicircular canals to reduce or abolish post-rotatory nystagmus. 4. Positive stimulus sites for inducing nystagmus were located in the posterolateral pretectum. This included portions of NOT that lie in and around the brachium of the superior colliculus and adjacent regions of the dorsal terminal nucleus (DTN). 5. The data indicate that NOT stimulation had elicited the component of OKN which is responsible for the slow rise in slow phase velocity and for OKAN. The functional implication is that NOT, and possibly DTN, are major sources of visual information related to retinal slip in the animals yaw plane for semicircular canal-related neurons in the vestibular nuclei. Analyzed in terms of a model of OKN and OKAN (Cohen et al. 1977; Waespe et al. 1983), the indirect pathway, which excites the velocity storage mechanism in the vestibular system to produce the slow component of OKN and OKAN, lies in NOT in the monkey, as it probably also does in cat, rat and rabbit. Pathways carrying activity for the rapid rise in slow phase velocity during OKN or for ocular pursuit appear to lie outside NOT.

The vestibulo-ocular reflex in three dimensions

The purpose of this paper is to review the kinematics and dynamics of the vestibulo-ocular reflex (VOR) in three dimensions. We give a brief, didactic tutorial on vectors and matrices and their importance as representational schemes for describing the kinematics and dynamics of the angular and linear accelerations that activate the vestibular system. We show how the vectors associated with angular and linear head accelerations are transformed by the peripheral and central vestibular systems to drive the oculomotor system to produce eye movements in three-dimensional space. We also review critical questions and controversies related to the compensatory and orientation behavior of the VOR. One such question is how the central vestibular system distinguishes tilts of the head, which generate interaural linear acceleration from translations along the interaural axis. Another question is how the velocity-position integrator is implemented centrally. The review has been placed in the context of a model that explains the behavior of the VOR in three dimensions. Model processes have been related to peripheral and central neural behavior in order to gain insight into the nature of the three-dimensional organization and the controversial questions that are addressed.

Organizational Principles of Velocity Storage in Three Dimensions

1. Optokinetic nystagmus was elicited in alert monkeys by movement of the visual surround in their horizontal or yaw plane, and optokinetic after-nystagmus was recorded in darkness. The animals were upright or were statically tilted at various angles from the upright. While upright, the OKAN was horizontal, and there were no vertical or roll components. When animals were tilted to either side or forward or back, vertical or roll components appeared both in the primary and secondary OKAN. Such components were also observed during nystagmus and after-nystagmus induced by electrical stimulation of the nucleus of the optic tract. The characteristics of the cross-coupled components indicated that they were mediated through the velocity storage mechanism in the vestibulo-ocular reflex. 2. A principle was inferred that explained the appearance of cross-coupled vertical or roll components in the primary and secondary OKAN: With the animal in a tilted position, a vector of eye velocity during OKN along the body-vertical axis was converted during primary OKAN toward a spatial-vertical axis with the same sense by a right hand rule. Thus, slow phase velocity along a vector toward the top of the animals head during horizontal OKN rotated so that it tended to be directed spatially upward during primary OKAN. The reverse was true for OKN with a velocity vector directed toward the animals feet. It rotated during primary OKAN so that it tended to be aligned with the direction of gravity. The vector of velocity during secondary OKAN was opposite to the direction of the vector during primary OKAN and was approximately aligned with spatial vertical. 3. OKN and OKAN were elicited about the animals pitch and roll axes while they were upright and statically tilted at various angles away from the spatial vertical. There was a graded increase in the strength of vertical and roll OKN and OKAN and in the falling time constant of OKAN as the animals were tilted so that the axis of pitch or roll eye movements was moved toward alignment with the spatial vertical. Thus, velocity storage during pure vertical and roll nystagmus was similar to that during yaw OKN and OKAN in tilted positions: it was maximal along the pitch and roll axes when these axes were aligned with gravity. 4. The data indicate that the gravitational field is of fundamental importance in imposing a spatial reference onto the velocity storage integrator.(ABSTRACT TRUNCATED AT 400 WORDS)

Baclofen and velocity storage: a model of the effects of the drug on the vestibulo-ocular reflex in the rhesus monkey.

1. Baclofen had a characteristic effect on vestibular and optokinetic nystagmus in rhesus monkeys. Each aspect of nystagmus that is dependent on the velocity‐storage mechanism in the vestibulo‐ocular reflex (v.o.r.) was altered by the drug: (a) Baclofen reduced the dominant time constant of the v.o.r. in a dose‐dependent manner up to 5 mg/kg, the highest dosage used. The alteration in v.o.r. time constant began within 15 min of injection, was maximal between 1 and 4 h, and lasted for 14‐18 h. This effect mirrors changes in plasma levels of baclofen after oral doses in humans (Faigle, Keberle & Agen, 1980). (b) Slow‐phase velocities of steady‐state nystagmus induced by rotation about axes tilted from the vertical (off‐vertical axis rotation, o.v.a.r.) were reduced after baclofen and could not be maintained at previous levels. (c) There was a dose‐dependent decline in the steady‐state gain of optokinetic nystagmus (o.k.n.), and at the highest dosages little o.k.n. was induced. In parallel, the peak velocity and falling time constant of optokinetic after‐nystagmus (o.k.a.n.) were reduced. Since baclofen is a GABA agonist, systems utilizing GABA and acting on GABAB receptors appear to produce inhibitory control of velocity storage. 2. The step gain of the v.o.r., measured at the beginning and end of constant‐velocity rotation in darkness, was unaffected by baclofen, as were saccades, quick phases of nystagmus, and the ability to hold positions of fixation or to generate linear slow phases of nystagmus. This indicates that it is possible to use baclofen to manipulate the dominant time constant of the v.o.r. and of o.k.a.n. in relative isolation from effects on other oculomotor components. 3. Baclofen caused a dose‐dependent reduction in the initial jump in eye velocity at the onset of o.k.n., suggesting that the initial jump is also under inhibitory control of GABAB receptors. However, there were still occasional slow phases with velocities up to 30‐40 deg/s after baclofen, and animals were capable of visually suppressing the v.o.r. This indicates that pathways responsible for causing rapid changes in slowphase velocity were capable of functioning, at least intermittently, in the presence of the drug.(ABSTRACT TRUNCATED AT 400 WORDS)

Vestibular control of sympathetic activity. An otolith-sympathetic reflex in humans

It has been proposed that a vestibular reflex originating in the otolith organs and other body graviceptors modulates sympathetic activity during changes in posture with regard to gravity. To test this hypothesis, we selectively stimulated otolith and body graviceptors sinusoidally along different head axes in the coronal plane with off-vertical axis rotation (OVAR) and recorded sympathetic efferent activity in the peroneal nerve (muscle sympathetic nerve activity, MSNA), blood pressure, heart rate, and respiratory rate. All parameters were entrained during OVAR at the frequency of rotation, with MSNA increasing in nose-up positions during forward linear acceleration and decreasing when nose-down. MSNA was correlated closely with blood pressure when subjects were within ±90° of nose-down positions with a delay of 1.4 s, the normal latency of baroreflex-driven changes in MSNA. Thus, in the nose-down position, MSNA was probably driven by baroreflex afferents. In contrast, when subjects were within ±45° of the nose-up position, i.e., when positive linear acceleration was maximal along the naso-ocipital axis, MSNA was closely related to gravitational acceleration at a latency of 0.4 s. This delay is too short for MSNA changes to be mediated by the baroreflex, but it is compatible with the delay of a response originating in the vestibular system. We postulate that a vestibulosympathetic reflex, probably originating mainly in the otolith organs, contributes to blood pressure maintenance during forward linear acceleration. Because of its short latency, this reflex may be one of the earliest mechanisms to sustain blood pressure upon standing.