Canal-otolith interactions in the squirrel monkey vestibulo-ocular reflex and the influence of fixation distance

Natural head movements include angular and linear components of motion. Two classes of vestibulo-ocular reflex (VOR), mediated by the semicircular canals and otoliths (the angular and linear VOR, or AVOR and LVOR, respectively), compensate for head movements and help maintain binocular fixation on targets in space. In this study, AVOR/LVOR interactions were quantified during complex head motion over a broad range of fixation distances at a fixed stimulus frequency of 4.0 Hz. Binocular eye movements were recorded (search-coil technique) in squirrel monkeys while fixation distance (assessed by vergence) was varied using brief presentations of earth-fixed targets at various distances. Stimuli consisted of rotations around an earth-vertical axis and therefore always activated the AVOR. Horizontal and vertical AVORs were assessed when the head was centered over the axis of rotation and oriented upright (UP) and right-side-down (RD), respectively. AVOR gains increased slightly with increasing vergence in darkness, as expected given the small anterior position of the eyes in the head. Combined AVOR/LVOR responses were recorded when subjects were displaced eccentrically from the rotation axis. Eccentric rotations activated the AVOR just as when the head was centered, but added a translational stimulus which generated an LVOR component in response to interaural (IA) or dorsoventral (DV) tangential accelerations, depending on whether the head was UP or RD, respectively. When the head was eccentric and facing nose-out, the AVOR and LVOR produced ocular responses in the same plane and direction (coplanar and synergistic), and response magnitudes increased with increasing vergence. With the head facing nose-in, AVOR and LVOR response components were oppositely directed (coplanar and antagonistic). The AVOR dominated the response when fixation distance was far, and phase was compensatory for head rotation. As fixation distance decreased toward the rotation axis, responses declined to near zero, and when fixation distance approached even closer, the LVOR component dominated and response phase inverted. The same pattern was observed for both horizontal (head UP) and vertical (head RD) responses. The LVOR was recorded directly by rotating subjects eccentrically but in the nose-up (NU) orientation. The AVOR then generated torsional responses to head roll, coexistent with either horizontal or vertical LVOR responses to tangential acceleration when the subject was oriented head-out or right-side-out, respectively. Only the LVOR response components were modulated by vergence. A vectorial analysis of AVOR, LVOR, and combined responses supports the conclusion that AVOR and LVOR response components combine linearly during complex head motion. Received: 27 February 1997 / Accepted: 18 June 1997     

Eye movements and vestibular-nerve responses produced in the squirrel monkey by rotations about an earth-horizontal axis

Summary The eye movements produced by constant-speed rotations about an earth-horizontal axis (EHA) are similar in the alert squirrel monkey to those observed in other species. During EHA rotations, there are persistent eye movements, including a nonreversing nystagmus at lower rotation speeds and either a direction-reversing nystagmus or sinusoidal eye movements at higher rotation speeds. Horizontal eye movements are produced by barbecuespit (yaw) rotations, vertical eye movements by head-over-heels (pitch) rotations. The responses can be viewed as composed of a bias component, reflected in the nonreversing nature of the nystagmus, and a cyclic component, reflected in the periodic modulation of slow-phase eye velocity as head position varies. Vestibular-nerve recordings in the barbiturate-anesthetized monkey indicate that neither semicircular-canal nor otolith afferents give rise to a directionally specific dc signal which can account for the bias component. Apparently the appropriate dc signal has to be constructed centrally from a sinusoidal or ac peripheral input. The otolith organs are a likely source of this peripheral input, although contributions from the semicircular canals and from somatosensory receptors must also be considered. Our results suggest that the directional information required to distinguish rotation direction, rather than being contained in the discharge of individual otolith afferents, is encoded across a population of afferents. Possible sources of such information are the phase differences in the sinusoidal responses of otolith afferents differing in their functional polarization vectors.Supported by Grants NS 01330 from the National Institutes of Health and NGR-14-001-225 from the National Aeronautics and Space Administration     

Canal-otolith interactions driving vertical and horizontal eye movements in the squirrel monkey

The vestibulo-ocular reflex (VOR) was studied in three squirrel monkeys subjected to rotations with the head either centered over, or displaced eccentrically from, the axis of rotation. This was done for several different head orientations relative to gravity in order to determine how canal-mediated angular (aVOR) and otolithmediated linear (lVOR) components of the VOR are combined to generate eye movement responses in three-dimensional space. The aVOR was stimulated in isolation by rotating the head about the axis of rotation in the upright (UP), right-side down (RD), or nose-up (NU) orientations. Horizontal and vertical aVOR responses were compensatory for head rotation over the frequency range 0.25–4.0 Hz, with mean gains near 0.9. The horizontal aVOR was relatively constant across the frequency range, while vertical aVOR gains increased with increasing stimulation frequency. In the NU orientation, compensatory torsional aVOR responses were of relatively low gain (0.54) compared with horizontal and vertical responses, and gains remained constant over the frequency range. When the head was displaced eccentrically, rotation provided the same angular stimuli but added linear stimulus components, due to the centripetal and tangential accelerations acting on the head. By manipulating the orientation of the head relative to gravity and relative to the axis of rotation, the lVOR response could be combined with, or isolated from, the aVOR response. Eccentric rotation in the UP and RD orientations generated aVOR and lVOR responses which acted in the same head plane. Horizontal aVOR-lVOR interactions were recorded when the head was in the UP orientation and facing toward (nose-in) or away from (nose-out) the rotation axis. Similarly, vertical responses were recorded with the head RD and in the nose-out or nose-in positions. For both horizontal and vertical responses, gains were dependent on both the frequency of stimulation and the directions and relative amplitudes of the angular and linear motion components. When subjects were positioned nose-out, the angular and linear stimuli produced synergistic interactions, with the lVOR driving the eyes in the same direction as the aVOR. Gains increased with increasing frequency, consistent with an addition of broad-band aVOR and high-pass lVOR components. When subjects were nose-in, angular and linear stimuli generated eye movements in opposing directions, and gains declined with increasing frequency, consistent with a subtraction of the lVOR from the aVOR. This response pattern was identical for horizontal and vertical eye movements. aVOR and lVOR interactions were also assessed when the two components acted in orthogonal response planes. By rotating the monkeys into the NU orientation, the aVOR acted primarily in the roll plane, generating torsional ocular responses, while the translational (lVOR) component generated horizontal or vertical ocular responses, depending on whether the head was oriented such that linear accelerations acted along the interaural or dorsoventral axes, respectively. Horizontal and vertical lVOR responses were negligible at 0.25 Hz and increased dramatically with increasing frequency. Comparison of the combined responses (UP and RD orientations) with the isolated aVOR (head-centered) and lVOR (NU orientation) responses, indicates that these VOR components sum in a linear fashion during complex head motion.     

Non-linear interaction of angular and translational vestibulo-ocular reflex during eccentric rotation in the monkey

Eccentric sinusoidal rotation with the nose facing out or in leads to gain modulation of the vestibulo-ocular reflex (VOR), which is a result of an interaction between angular and translational VOR. There are conflicting reports with regard to the type of interaction. Combined angular and translational VOR during eccentric sinusoidal rotations over a wide range of target distances (12-180 cm), eccentricities (centric, 30 and 50 cm nose-out and nose-in eccentric) and frequencies (0.1-4 Hz) were studied in macaque monkeys trained to fixate earth-stationary light-emitting diode (LED) targets while binocular eye positions were measured using magnetic search coils. The monkeys were also exposed to sudden unpredictable position steps with peak accelerations of 500 degrees/s(2) using similar eccentricities and target distances. VOR gain enhancement during nose-out eccentric sinusoidal rotation was almost compensatory when the target was visible and was independent of stimulus frequency. Mean responses were still close to ideal when the target was extinguished; however, individual data showed increased variability. Sensitivities of the translational portion of the combined VOR were compensatory. These sensitivities were clearly reduced during nose-in eccentric sinusoidal rotation. Thus, especially for close targets at 4 Hz combined VOR was not compensatory, independent of target visibility. VOR elicited by sudden position steps showed a sequential response: (1) purely angular VOR (up to 40-45 ms); (2) additional translational VOR that was not modulated by target distance (45-65 ms); and (3) translational VOR weighted for target location (>65 ms). We conclude that angular and translational VOR have different latencies during transient accelerations and interact differently during agonistic (nose-out) and antagonistic stimulation (nose-in).     

The three-dimensional vestibulo-ocular reflex during prolonged microgravity

Single-case, longitudinal studies of the three-dimensional vestibulo-ocular response (VOR) were conducted with two spaceflight subjects over a 180-day mission. For reference, a control study was performed in the laboratory with 13 healthy volunteers. Horizontal, vertical and torsional VOR was measured during active yaw, pitch and roll oscillations of the head, performed during visual fixation of real and imaginary targets. The control group was tested in the head-upright position, and in the gravity-neutral, onside and supine positions. Binocular eye movements were recorded throughout using videooculography, yielding eye position in Fick co-ordinates. Eye velocity was calculated using quaternion algebra. Head angular velocities were measured by a head-mounted rate sensor. Eye/head velocity gain and phase were evaluated for the horizontal, vertical and torsional VOR. The inclination of Listing's plane was also calculated for each test session. Control group gain for horizontal and vertical VOR was distributed closely around unity during real-target fixation, and reduced by 30-50% during imaginary-target trials. Phase was near zero throughout. During head pitch in the onside position, vertical VOR gain did not change significantly. Analysis of up/down asymmetry indicated that vertical VOR gain for downward head movement was significantly higher than for upward head movement. Average torsional VOR gain with real-target fixation was significantly higher than with imaginary-target fixation. No difference in phase was found. In contrast to vertical VOR gain, torsional VOR gain was significantly lower in the gravity-neutral supine position. Spaceflight subjects showed no notable modification of horizontal or vertical VOR gain or phase during real-target fixation over the course of the mission. However, the up/down asymmetry of vertical VOR gain was inverted in microgravity. Torsional VOR gain was clearly reduced in microgravity, with some recovery in the later phase. After landing, there was a dip in gain during the first 24 h, with subsequent recovery to near baseline over the 13-day period tested. Listing's plane appeared to remain stable throughout the mission. The findings reflect various functions of the otolith responses. The reduced torsional VOR gain in microgravity is attributed to the absence of the gravity-dependent, dynamic stimulation to the otoliths (primarily utricles). On the other hand, the reversal of vertical VOR up/down gain asymmetry in microgravity is attributed to the off-loading of the constant 1-g bias (primarily to the saccules) on Earth. The observed increase in torsional VOR gain from the 1st to the 6th month in microgravity demonstrates the existence of longer-term adaptive processes than have previously been considered. Likely factors are the adaptive reweighting of neck-proprioceptive afferents and/or enhancement of efference copy.     

Comparison between habituation of the cat vestibulo-ocular reflex by velocity steps and sinusoidal vestibular stimulation in the dark

Changes in the horizontal vestibulo-ocular reflex (VOR) in darkness were investigated in naive cats during: (1) repeated sessions of angular velocity steps, (2) one continuous 1-h session of sinusoidal oscillations at 0.01, 0.02, 0.04, or 0.12 Hz, and (3) repeated sessions of 1-h sinusoidal oscillations at 0.02 and 0.04 Hz. Before and after each vestibular training, the VOR response parameters elicited by both velocity steps and sinusoidal oscillations were measured in order to evaluate the transfer of habituation from one stimulus to the other. After training with velocity steps, the amplitude and duration of the VOR to velocity steps decreased by about 67% and 52%, respectively. This vestibular habituation transferred to the VOR response generated by sinusoidal oscillations, since a decrease in VOR gain was observed at 0.02 and 0.04 Hz, and an increase in phase lead was observed at 0.02, 0.04, and 0.08 Hz. After 1 h exposure to sinusoidal oscillations, the VOR gain was only reduced by 21-28%, whereas VOR phase lead decreased. The same changes were observed during subsequent sessions, with no retention of the response decrements from one session to the next. At the end of sinusoidal training, the amplitude of the VOR generated by velocity steps was slightly altered. After sinusoidal training, the weak changes in the VOR gain accompanied by a decrease in the VOR phase lead, and the absence of retention of these effects from one session to the next, suggest these changes are not characteristics of a vestibular habituation. Previous reports of vestibular habituation induced by repeated sinusoidal oscillations may be confounded by the fact that the angular velocity steps used for quantifying the effects may have been responsible for this habituation.     

Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. I. Normal responses.

The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in five squirrel monkeys with intact vestibular function. The VOR evoked by steps of acceleration in darkness (3,000 degrees /s(2) reaching a velocity of 150 degrees /s) began after a latency of 7.3 +/- 1.5 ms (mean +/- SD). Gain of the reflex during the acceleration was 14.2 +/- 5.2% greater than that measured once the plateau head velocity had been reached. A polynomial regression was used to analyze the trajectory of the responses to steps of acceleration. A better representation of the data was obtained from a polynomial that included a cubic term in contrast to an exclusively linear fit. For sinusoidal rotations of 0.5-15 Hz with a peak velocity of 20 degrees /s, the VOR gain measured 0.83 +/- 0.06 and did not vary across frequencies or animals. The phase of these responses was close to compensatory except at 15 Hz where a lag of 5.0 +/- 0.9 degrees was noted. The VOR gain did not vary with head velocity at 0.5 Hz but increased with velocity for rotations at frequencies of >/=4 Hz (0. 85 +/- 0.04 at 4 Hz, 20 degrees /s; 1.01 +/- 0.05 at 100 degrees /s, P < 0.0001). No responses to these rotations were noted in two animals that had undergone bilateral labyrinthectomy indicating that inertia of the eye had a negligible effect for these stimuli. We developed a mathematical model of VOR dynamics to account for these findings. The inputs to the reflex come from linear and nonlinear pathways. The linear pathway is responsible for the constant gain across frequencies at peak head velocity of 20 degrees /s and also for the phase lag at higher frequencies being less than that expected based on the reflex delay. The frequency- and velocity-dependent nonlinearity in VOR gain is accounted for by the dynamics of the nonlinear pathway. A transfer function that increases the gain of this pathway with frequency and a term related to the third power of head velocity are used to represent the dynamics of this pathway. This model accounts for the experimental findings and provides a method for interpreting responses to these stimuli after vestibular lesions.     

The neurophysiological substrate for the cervico-ocular reflex in the squirrel monkey

Passive rotation of the trunk with respect to the head evoked cervico-ocular reflex (COR) eye movements in squirrel monkeys. The amplitude of the reflex varied both within and between animals, but the eye movements were always in the same direction as trunk rotation. In the dark, the COR typically had a gain of 0.3–0.4. When animals fixated earth-stationary targets during low-frequency passive neck rotation or actively tracked moving visual targets with head movements, the COR was suppressed. The COR and vestibulo-ocular reflex (VOR) summed during passive head-on-trunk rotation producing compensatory eye movements whose gain was greater than 1.0. The firing behavior of VOR-related vestibular neurons and cerebellar flocculus Purkinje cells was studied during the COR. Passive neck rotation produced changes in firing rate related to neck position and/or neck velocity in both position-vestibular-pause neurons and eye-head-vestibular neurons, although the latter neurons were much more sensitive to the COR than the former. The neck rotation signals were reduced or reversed in direction when the COR was suppressed. Flocculus Purkinje cells were relatively insensitive to COR eye movements. However, when the COR was suppressed, their firing rate was modulated by neck rotation. These neck rotation signals summed with ocular pursuit signals when the head was used to pursue targets. We suggest that the neural substrate that produces the COR includes central VOR pathways, and that the flocculus plays an important role in suppressing the reflex when it would cause relative movement of a visual target on the retina. Electronic Publication     

Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. III. Responses after labyrinthectomy

The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral labyrinthectomy. Spontaneous nystagmus was measured at the beginning and end of each testing session. During the period that animals were kept in darkness (4 days), the nystagmus at each of these times measured approximately 20 degrees /s. Within 18-24 h after return to the light, the nystagmus (measured in darkness) decreased to 2.8 +/- 1.5 degrees /s (mean +/- SD) when recorded at the beginning but was 20.3 +/- 3.9 degrees /s at the end of the testing session. The latency of the VOR measured from responses to steps of acceleration (3,000 degrees /s(2) reaching a velocity of 150 degrees /s) was 8.4 +/- 0.3 ms for responses to ipsilesional rotations and 7.7 +/- 0.4 ms for contralesional rotations. During the period that animals were kept in darkness after the labyrinthectomy, the gain of the VOR measured during the steps of acceleration was 0.67 +/- 0.12 for contralesional rotations and 0.39 +/- 0.04 for ipsilesional rotations. Within 18-24 h after return to light, the VOR gain for contralesional rotations increased to 0.87 +/- 0.08, whereas there was only a slight increase for ipsilesional rotations to 0.41 +/- 0. 06. A symmetrical increase in the gain measured at the plateau of head velocity was noted after the animals were returned to light. The VOR evoked by sinusoidal rotations of 2-15 Hz, +/-20 degrees /s, showed a better recovery of gain at lower (2-4 Hz) than at higher (6-15 Hz) frequencies. At 0.5 Hz, gain decreased symmetrically when the peak amplitude was increased from 20 to 100 degrees /s. At 10 Hz, gain was decreased for ipsilesional half-cycles and increased for contralesional half-cycles when velocity was raised from 20 to 50 degrees /s. A model incorporating linear and nonlinear pathways was used to simulate the data. Selective increases in the gain for the linear pathway accounted for the recovery in VOR gain for responses at the velocity plateau of the steps of acceleration and for the sinusoidal rotations at lower peak velocities. The increase in gain for contralesional responses to steps of acceleration and sinusoidal rotations at higher frequencies and velocities was due to an increase in the contribution of the nonlinear pathway. This pathway was driven into cutoff and therefore did not affect responses for rotations toward the lesioned side.     

Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. IV. Responses after spectacle-induced adaptation

The horizontal angular vestibuloocular reflex (VOR) evoked by sinusoidal rotations from 0.5 to 15 Hz and acceleration steps up to 3,000 degrees /s(2) to 150 degrees /s was studied in six squirrel monkeys following adaptation with x2.2 magnifying and x0.45 minimizing spectacles. For sinusoidal rotations with peak velocities of 20 degrees /s, there were significant changes in gain at all frequencies; however, the greatest gain changes occurred at the lower frequencies. The frequency- and velocity-dependent gain enhancement seen in normal monkeys was accentuated following adaptation to magnifying spectacles and diminished with adaptation to minimizing spectacles. A differential increase in gain for the steps of acceleration was noted after adaptation to the magnifying spectacles. The gain during the acceleration portion, G(A), of a step of acceleration (3,000 degrees /s(2) to 150 degrees /s) increased from preadaptation values of 1.05 +/- 0.08 to 1.96 +/- 0.16, while the gain during the velocity plateau, G(V), only increased from 0.93 +/- 0.04 to 1.36 +/- 0.08. Polynomial fits to the trajectory of the response during the acceleration step revealed a greater increase in the cubic than the linear term following adaptation with the magnifying lenses. Following adaptation to the minimizing lenses, the value of G(A) decreased to 0.61 +/- 0.08, and the value of G(V) decreased to 0.59 +/- 0.09 for the 3,000 degrees /s(2) steps of acceleration. Polynomial fits to the trajectory of the response during the acceleration step revealed that there was a significantly greater reduction in the cubic term than in the linear term following adaptation with the minimizing lenses. These findings indicate that there is greater modification of the nonlinear as compared with the linear component of the VOR with spectacle-induced adaptation. In addition, the latency to the onset of the adapted response varied with the dynamics of the stimulus. The findings were modeled with a bilateral model of the VOR containing linear and nonlinear pathways that describe the normal behavior and adaptive processes. Adaptation for the linear pathway is described by a transfer function that shows the dependence of adaptation on the frequency of the head movement. The adaptive process for the nonlinear pathway is a gain enhancement element that provides for the accentuated gain with rising head velocity and the increased cubic component of the responses to steps of acceleration. While this model is substantially different from earlier models of VOR adaptation, it accounts for the data in the present experiments and also predicts the findings observed in the earlier studies.     

Horizontal vestibuloocular reflex evoked by high-acceleration rotations in the squirrel monkey. II. Responses after canal plugging.

The horizontal angular vestibuloocular reflex (VOR) evoked by high-frequency, high-acceleration rotations was studied in four squirrel monkeys after unilateral plugging of the three semicircular canals. During the period (1-4 days) that animals were kept in darkness after plugging, the gain during steps of acceleration (3, 000 degrees /s(2), peak velocity = 150 degrees /s) was 0.61 +/- 0.14 (mean +/- SD) for contralesional rotations and 0.33 +/- 0.03 for ipsilesional rotations. Within 18-24 h after animals were returned to light, the VOR gain for contralesional rotations increased to 0. 88 +/- 0.05, whereas there was only a slight increase in the gain for ipsilesional rotations to 0.37 +/- 0.07. A symmetrical increase in the gain measured at the plateau of head velocity was noted after animals were returned to light. The latency of the VOR was 8.2 +/- 0. 4 ms for ipsilesional and 7.1 +/- 0.3 ms for contralesional rotations. The VOR evoked by sinusoidal rotations of 0.5-15 Hz, +/-20 degrees /s had no significant half-cycle asymmetries. The recovery of gain for these responses after plugging was greater at lower than at higher frequencies. Responses to rotations at higher velocities for frequencies >/=4 Hz showed an increase in contralesional half-cycle gain, whereas ipsilesional half-cycle gain was unchanged. A residual response that appeared to be canal and not otolith mediated was noted after plugging of all six semicircular canals. This response increased with frequency to reach a gain of 0.23 +/- 0.03 at 15 Hz, resembling that predicted based on a reduction of the dominant time constant of the canal to 32 ms after plugging. A model incorporating linear and nonlinear pathways was used to simulate the data. The coefficients of this model were determined from data in animals with intact vestibular function. Selective increases in the gain for the linear and nonlinear pathways predicted the changes in recovery observed after canal plugging. An increase in gain of the linear pathway accounted for the recovery in VOR gain for both responses at the velocity plateau of the steps of acceleration and for the sinusoidal rotations at lower peak velocities. The increase in gain for contralesional responses to steps of acceleration and sinusoidal rotations at higher frequencies and velocities was due to an increase in the gain of the nonlinear pathway. This pathway was driven into inhibitory cutoff at low velocities and therefore made no contribution for rotations toward the ipsilesional side.     

The human horizontal vestibulo-ocular reflex in response to high-acceleration stimulation before and after unilateral vestibular neurectomy

Summary The normal horizontal vestibulo-ocular reflex (HVOR) is largely generated by simultaneous stimulation of the two horizontal semicircular canals (HSCCs). To determine the dynamics of the HVOR when it is generated by only one HSCC, compensatory eye movements in response to a novel vestibular stimulus were measured using magnetic search coils. The vestibular stimulus consisted of low-amplitude, high-acceleration, passive, unpredictable, horizontal rotations of the head with respect to the trunk. While these so called head “impulses” had amplitudes of only 15–20 degrees with peak velocities up to 250 deg/s, they had peak accelerations up to 3000 deg/s/s. Fourteen humans were studied in this way before and after therapeutic unilateral vestibular neurectomy; 10 were studied 1 week or 1 year afterwards; 4 were studied 1 week and 1 year afterwards. The results from these 14 patients were compared with the results from 30 normal control subjects and with the results from one subject with absent vestibular function following bilateral vestibular neurectomy. Compensatory eye rotation in normal subjects closely mirrored head rotation. In contrast there was no compensatory eye rotation in the first 170 ms after the onset of head rotation in the subject without vestibular function. Before unilateral vestibular neurectomy all the patients' eye movement responses were within the normal control range. One week after unilateral vestibular neurectomy however there was a symmetrical bilateral HVOR deficit. The asymmetry was much more profound than has been shown in any previous studies. The HVOR generated in response to head impulses directed away from the intact side largely by ampullofugal disfacilitation from the single intact HSCC (ignoring for the moment the small contribution to the HVOR from stimulation of the vertical SCCs), was severely deficient with an average gain (eye velocity/head velocity) of 0.25 at 122.5 deg/sec head velocity (normal gain=0.94+/−0.08). In contrast the HVOR generated in response to head impulses directed toward the intact side, largely by ampullopetal excitation from the single intact HSCC, was only mildly (but nonetheless significantly) deficient, with an average gain of 0.80 at 122.5 deg/sec head velocity. At these accelerations there was no significant improvement in the average HVOR velocity gain in either direction over the following year. These results indicate that ampullopetal excitation from one HSCC can, even in the absence of ampullofugal disfacilitation from the opposite HSCC, generate a near normal HVOR in response to high-acceleration stimulation. Furthermore, since ampullofugal disfacilitation on its own, can only generate an inadequate HVOR in response to high-acceleration stimulation, it may under some normal circumstances make little contribution to the bilaterally generated HVOR.     

The cingular vocalization pathway in the squirrel monkey

Summary In 39 squirrel monkeys (Saimiri sciureus), the effects of various brain lesions on vocalizations elicited from the precallosal cingulate gyrus were tested. It was found that lesions abolishing the cingular vocalization completely can be traced from the stimulation site continuously down to the laryngeal motoneurons in the nucleus ambiguus. The pathway thus determined (Fig. 4) travels from the precallosal cingulate gyrus through the frontal white matter and enters the internal capsule from a dorsolateral position. The pathway then follows this structure in a medio-caudal direction down to the caudal diencephalon. Here, the effective lesions leave the corticospinal tract and ascend dorsally into the periaqueductal grey. The pathway follows this structure to its end where it sweeps lateral through the parabrachial area and then descends through the lateral pons and ventrolateral medulla to the nucleus ambiguus.In nine of the animals, in addition, the effects of bilateral anterior cingular lesions on vocalizations elicited in other brain areas were tested. It was found that the only vocalization-eliciting area which becomes ineffective after destruction of the anterior cingulate gyrus is the postero-medial orbital cortex.Abbreviations a nucl. accumbens - aa area anterior amygdalae - ab nucl. basalis amygdalae - ac nucl. centralis amygdalae - al nucl. lateralis amygdalae - am nucl. medialis amygdalae - an nucl. anterior thalami - aq griseum centralis - bc brachium conjunctivum - ca caudatum - cb cerebellum - cc corpus callosum - cen nucl. centralis superior Bechterew - ci capsula interna - cin cingulum - cl claustrum - coa commissura anterior - coli colliculus inferior - cols colliculus superior - cop commissura posterior - cr corpus restiforme - csp tractus corticospinalis - db fasciculus diagonalis Brocae - dbc decussatio brachii conjunctivi - f fornix - gc gyrus cinguli - gl geniculatum laterale - gm geniculatum mediale - gp globus pallidus - gr gyrus rectus - gs gyrus subcallosus - h area tegmentalis (Forel) - ha habenula - hi tractus habenulo-interpeduncularis - hip hippocampus - hya hypothalamus anterior - hyv hypothalamus ventromedialis - in nucl. interpeduncularis - lap nucl. lateralis posterior thalami - lem lemniscus medialis - lm fasciculus longitudinalis medialis - m nucl. mammillaris - md nucl. medialis dorsalis thalami - mt tractus mammillothalamicus - nst nucl. striae terminalis - nts nucl. solitarius - oi oliva inferior - ol fasciculus olfactorius (Zuckerkandl) - os oliva superior - p pedunculus cerebri - pmc brachium pontis - po griseum pontis - pro area praeoptica - pu nucl. pulvinaris - put putamen - re formatio reticularis mesencephali - rep nucl. reticularis tegmenti pontis - rl nucl. reticularis lateralis - rub nucl. ruber - s septum - sm stria medullaris - sn substantia nigra - st stria terminalis - sto stria olfactoria lateralis - tec tractus tegmentalis centralis - trz corpus trapezoideum - va nucl. ventralis anterior thalami - ves nucl. vestibularis - vpl nucl. ventralis posterior lateralis th. - vpm nucl. ventralis posterior medialis th. - zi zona incerta - II tractus opticus - IIchde chiasma n. opticorum - III nucl. n. oculomotorii and n. oculomotorius - IV nucl. n. trochlearis - VI n. abducens - VII nucl. n. facialis and n. facialis - VIII n. acusticus - XII nucl. n. hypoglossi     

Short-term vestibulo-ocular reflex adaptation in humans

We investigated the effect of short-term vestibulo-ocular reflex (VOR) adaptation in normal human subjects on the dynamic properties of the velocity-to-position ocular motor integrator that holds positions of gaze. Subjects sat in a sinusoidally rotating chair surrounded by an optokinetic nystagmus drum. The movement of the visual surround (drum) was manipulated relative to the chair to produce an increase (× 1.7 viewing), decrease (× 0.5, × 0 viewing), or reversal (× (-2.5) viewing) of VOR gain. Before and after 1 h of training, VOR gain and gaze-holding after eccentric saccades in darkness were measured. Depending on the training paradigm, eccentric saccades could be followed by centrifugal drift (after × 0.5 viewing), implying an unstable integrator, or by centripetal drift [after × 1.7 or × (-2.5) viewing], implying a leaky integrator. The changes in the neural integrator appear to be context specific, so that when the VOR was tested in non-training head orientations, both the adaptive change in VOR gain and the changes in the neural integrator were much smaller. The changes in VOR gain were on the order of 10% and the induced drift velocities were several degrees per secend at 20 deg eccentric positions in the orbit. We propose that (1) the changes in the dynamic properties of the neural integrator reflect an attempt to modify the phase (timing) relationships of the VOR and (2) the relative directions of retinal slip and eye velocity during head rotation determine whether the integrator becomes unstable (and introduces more phase lag) or leaky (and introduces less phase lag).Visiting scientist from: 1 INSERM-U94. 16, avenue du Doyen Lépine, F-69500 Bron, France     

Modulation of the vestibulo-ocular reflex by serotonin in the rat

The effects of intraventricular injection of serotonin (5-HT) and its agonists and antagonists on the amplitude of the vestibulo-ocular reflex were studied in chronic implanted rats. 5-HT (10^–5 M) triggers an increase of the amplitude of the reflex which lasts 30 min. Similar results are obtained when N,N-dimethyl-5-methoxytryptamine (10^–3 M) is introduced into the ventricular cannula. The increasing effects observed both with 5-HT and N,N-dimethyl-5-methyoxy-tryptamine are abolished by methiothepin, a potent antagonist of 5-HT receptors. Injection of indirect agonists like pargyline, a monoamine oxidase inhibitor, or fluoxetine, a potent inhibibitor of 5-HT reuptake, is followed by an increase of the amplitude of the vestibulo-ocular reflex. These results indicate that 5-HT can modulate the activity of the vestibulo-ocular pathway and muscular tone of extraocular muscles. Location and involvement of various modulating 5-HT sites are discussed.     

The latency of the cat vestibulo-ocular reflex before and after short- and long-term adaptation

Latencies of normal and adapted feline vestibulo-ocular reflex (VOR) were studied in five cats by applying ± 20°/s horizontal head velocity steps (4000°/s₂ acceleration) and measuring the elicited horizontal or vertical reflex eye responses. Normal VOR latency was 13.0 ms ± 1.9 SD. Short-term adaptation was then accomplished by using 2 h of paired horizontal sinusoidal vestibular stimulation and phase-synchronized vertical optokinetic stimulation (cross-axis adaptation). For long-term adaptation, cats wore ×0.25 or ×2.2 magnifying lenses for 4 days. The cats were passively rotated for 2 h/day and allowed to walk freely in the laboratory or their cages for the remainder of the time. The latency of the early (primary) adaptive response was 15.2ms±5.2 SD for crossaxis adaptation and 12.5 ms±3.9 SD for lens adaptation. This short-latency response appeared within 30 min after beginning the adaptation procedure and diminished in magnitude overnight. A late (secondary) adaptive response with latency of 76.8 ms±7.0 SD for cross-axis adaptation and 68.1 ms±8.8 SD for lens adaptation appeared after approximately 2 h of adaptation. It had a more gradual increase in magnitude than the primary response and did not diminish in magnitude overnight. These data suggest that brainstem VOR pathways are a site of learning for adaptive VOR modification, since the primary latency is short and has a similar latency to that of the normal VOR.     

Unilateral intra-perilymphatic infusion of substance P enhances ipsilateral vestibulo-ocular reflex gains in the sinusoidal rotation test

Previous studies have reported localization of substance P (SP) within the inner ear and that SP exists abundantly within vestibular endorgans. While SP's functional role in the inner ear remains unclear, SP can act as a neuromodulator in the CNS and directly influences neuronal excitability. We hypothesized that SP might influence neuronal excitability within the vestibular periphery. The present study used the sinusoidal rotation test to investigate the influence of SP after its local application in the guinea pig unilateral inner ear. A tiny hole was made adjacent to the round window in the right ears of Hartley white guinea pigs that had normal tympanic membranes and Preyer reflexes. An osmotic pump infused SP (10⁻⁴ M, 10⁻³ M, and 10⁻² M), neurokinin-1 (NK-1) receptor antagonist (10⁻³ M) alone, or SP (10⁻³ M) + NK-1 receptor antagonist (10⁻³ M) through this hole, with rotation tests performed before, and 12 h and 24 h after the treatment. Results were used to calculate the vestibulo-ocular reflex (VOR) gains. After administration of 10⁻³ M and 10⁻² M SP, significant increases in the VOR gains were noted at 12 h after treatment, with these gains disappearing by 24 h after treatment. This increase was not observed when there was simultaneous NK-1 receptor antagonist administration. There were also no changes in the VOR gains noted after administration of 10⁻⁴ M SP or the NK-1 receptor antagonist alone. These results indicate the possibility that SP may act on vestibular endorgans as an excitatory factor via the NK-1 receptors.     

Gravity and the vertical vestibulo-ocular reflex

Summary We studied the vertical vestibulo-ocular reflex (VOR) and vertical visual-vestibular interaction induced by voluntary pitch in the upright and onside positions in eight normal human subjects. Subjects were trained to produce sinusoidal (0.4 to 1.6 Hz) pitch head movements guided by a frequency modulated sound signal. Eye and head movements were recorded with a magnetic search coil. There was no significant difference between the pooled average gain (eye velocity/head velocity) of the vertical VOR in the upright and onside positions. Vertical VOR gain in any position could be more or less than 1.0 for individual subjects. By contrast, gain with an earth-fixed visual target was always near 1.0. Asymmetries in the gain of upward and downward VOR, pursuit and fixation suppression of the VOR were found in individual subjects, but in the group of normal subjects there was no significant difference between gain of up and down eye movements induced by vestibular, visual or visual-vestibular stimulation in any position. We conclude that during voluntary pitch otolith signals are not critical for normal functioning of the vertical VOR.     

The squirrel monkey vestibulo-ocular reflex and adaptive plasticity in yaw,pitch, and roll

Summary The vestibulo-ocular reflex (VOR) was studied in adult squirrel monkeys before and after adaptation to magnifying and minifying viewing conditions. Monkeys were subjected to broadband (0.05–0.71 Hz) conditioning rotation for six hours in head yaw, pitch, and roll on separate occasions, and the VORs in these three planes were studied in darkness to assess adaptive plasticity in the reflexes. The gain of the horizontal VOR (H-VOR) averaged 0.8 across the frequency bandwidth studied (0.025–4 Hz). Phase was near 0° from 4 to around 0.1 Hz, but developed a progressive lead as frequency declined further. Normal vertical VOR (V-VOR) gain climbed from 0.6 at 0.025 Hz to near 1 as frequency increased to 4 Hz. Phase lead was more pronounced at low frequencies than in the H-VOR. The normal torsional VOR (T-VOR) qualitatively resembled the V-VOR, showing similar phase but lower gains (0.3–0.7) across the frequency bandwidth. These findings suggest that the dynamics of the V-VOR and T-VOR resemble canal characteristics more closely than does the H-VOR. After adaptation to visual minification and conditioning rotation (0.5X for yaw and pitch, 0X for roll), gain decreased in each of the planes of conditioning. Similarly, gain increased in the plane of conditioning after adaptation to visual magnification (2X). The adaptive changes were greater at low (0.025–1 Hz) than at high (2.5–4 Hz) frequencies, and were more robust when gain was driven downward than upward. However, control (sham) adaptation experiments showed that VOR gain tended to drop slightly over 6 h in the absence of adaptive drive to do so, suggesting that the gain modifications may be more symmetric when referenced to the control. Adaptive VOR gain enhancement or decrement in the plane of conditioning did not result in systematic and parallel changes in orthogonal VOR planes.     

Impairments in the initial horizontal vestibulo-ocular reflex of older humans

To determine age-related changes, the initial horizontal vestibulo-ocular reflex (VOR) of 11 younger normal subjects (aged 20–32 years) was compared with that of 12 older subjects (aged 58–69 years) in response to random transients of whole-body acceleration of 1,000 and 2,800°/s² delivered around eccentric vertical axes ranging from 10 cm anterior to 20 cm posterior to the eyes. Eye and head positions were sampled at 1,200 Hz using magnetic search coils. Subjects fixed targets 500 cm or 15 cm distant immediately before the unpredictable onset of rotation in darkness. For all testing conditions, younger subjects exhibited compensatory VOR slow phases with early gain (eye velocity/head velocity, interval 35–45 ms from onset of rotation) of 0.90±0.02 (mean ± SEM) for the higher head acceleration, and 0.79±0.02 for the lower acceleration. Older subjects had significantly (P<0.0001) lower early gain of 0.77±0.04 for the higher head acceleration and 0.70±0.02 for the lower acceleration. Late gain (125–135 ms from onset of rotation) was similar for the higher and lower head accelerations in younger subjects. Older subjects had significantly lower late gain at the higher head acceleration, but gain similar to the younger subjects at the lower acceleration. All younger subjects maintained slow-phase VOR eye velocity to values ≥200°/s throughout the 250-ms rotation, but, after an average of 120 ms rotation (mean eccentricity 13°), 8 older subjects consistently had abrupt declines (ADs) in slow-phase VOR velocity to 0°/s or even the anticompensatory direction. These ADs were failures of the VOR slow phase rather than saccades and were more frequent with the near target at the higher acceleration. Slow-phase latencies were 14.4±0.4 ms and 16.8±0.4 ms for older subjects at the higher and lower accelerations, significantly longer than comparable latencies of 10.0±0.5 ms and 12.0±0.6 ms for younger subjects. Late VOR gain modulation with target distance was significantly attenuated in older subjects only for the higher head acceleration. Electronic Publication