Pathophysiology of slow vertical saccades in progressive supranuclear palsy.

OBJECTIVES: To investigate the relative roles of burst neurons (which generate the saccadic command) and omnipause neurons (which gate the activity of burst neurons) in the pathogenesis of slow saccades in progressive supranuclear palsy (PSP). BACKGROUND: Experimental inactivation of mesencephalic burst neurons impairs vertical but not horizontal saccades. Experimental inactivation of omnipause neurons causes slowing of both horizontal and vertical saccades. Combining saccadic with vergence movements in healthy subjects induces small, high-frequency, conjugate oscillations, which indicate that omnipause neurons are inhibited. METHODS: The authors studied seven patients with PSP, six patients with other parkinsonian syndromes, and seven age-matched control subjects. They compared vertical saccades of similar sizes made with or without associated vergence movements. They compared the speed of vertical and horizontal saccades. RESULTS: Five patients with PSP and the six patients with other parkinsonian made vertical saccades in combination with horizontal vergence; all showed conjugate horizontal oscillations (29 to 41 Hz) during 27% to 93% of saccade-vergence trials. Vertical saccades made in conjunction with vergence movements were not speeded up or increased in size compared with saccades made between equidistant targets for the PSP or parkinsonian groups. Vertical saccades were slowed more than horizontal saccades in the PSP group (p < 0.005) but not in the parkinsonian group. CONCLUSIONS: Dysfunction of omnipause neurons ("gate dysfunction") is unlikely to be the primary cause of slow vertical saccades in progressive supranuclear palsy. Deficient generation of the motor command by midbrain burst neurons is the more likely cause.

Ocular responses to head rotations during mirror viewing.

The gain of the human vestibuloocular reflex (VOR) is influenced by the proximity of the object of regard. In six human subjects, we measured the eye rotations induced by passive, sinusoidal, horizontal head rotations at 2.0 Hz during binocular fixation of a stationary far target at 7 m; a stationary target close to the subject's near point of fixation (<15 cm); and the bridge of the subject's own nose, viewed through a mirror positioned so that, for each subject, the angle of vergence was similar to that during viewing of the near target. The median gain of compensatory eye movements for the group of subjects during far viewing was 0.99 (range 0.80-1.04), during near viewing was 1.21 (range 0.88-1.47), and during mirror viewing was 0.85 (range 0.71-1.01). The gain during near and mirror viewing was significantly different for each subject (P < 0.001) even though the vergence angles were similar. The lower gain values during mirror viewing can be attributed to the geometric relationship between the head rotation, the position of the eyes in the head, and the movement of the subject's virtual image in the mirror. To determine whether visually mediated eye movements were responsible for the observed gain values, we conducted a control experiment in which subjects were rotated using a sum-of-sines stimulus that minimized the effects of predictive visual tracking; differences of gain values between near- and mirror-viewing conditions were similar to those during rotation at 2 Hz. We conclude that, in these experiments, target proximity and vergence angle were not the key determinants of gain of the visuo-vestibular response during head rotation while viewing a near target but that contextual cues from motion vision were more important in generating the appropriate response.

Ocular oscillations induced by shifts of the direction and depth of visual fixation.

Shifts of the point of fixation between two targets aligned on one eye that are located near and far (Müller paradigm) stimulates a combined saccadic-vergence movement. In normal subjects, this test paradigm often induces saccadic oscillations of about 0.3 degrees at 20 to 30 Hz. We measured eye movements using the magnetic search coil technique in 2 patients recovering from viral opsoclonus-myoclonus syndrome, comparing saccadic-vergence responses to the Müller paradigm with conjugate saccades between distant targets. Both patients exhibited intermittent conjugate ocular oscillations of about 4 to 5 degrees amplitude at about 10 Hz. Combined saccadic-vergence movements induced these oscillations twice as often as did conjugate saccades. One patient also exhibited disjunctive ocular oscillations at 10 Hz while sustaining fixation on the near target. The Müller paradigm provides a useful clinical and experimental technique for inducing saccadic oscillations. The probable mechanism is that pontine omnipause neurons, which normally gate saccades, are inhibited during the sustained vergence movement that follows the saccadic component of the response to the Müller paradigm.

Saccades to sounds: effects of tracking illusory visual stimuli.

In 10 normal human subjects, we studied the accuracy of memory-guided saccades made to the remembered locations of visual targets and sounds. During the time of stimulus presentation, subjects were smoothly tracking a projected laser spot that was moving horizontally across a tangent screen, sinusoidally +/-15 degrees at 0.25 Hz. In one set of experiments, the laser spot moved across a 40 degrees x 28 degrees random dot display that moved synchronously in the vertical plane; this induced a strong illusion that the trajectory of the laser spot was diagonal (variant of Duncker illusion). In control experiments, the laser spot moved across the same display, which was stationary. The visual targets and speakers were at six locations (range +/-15 degrees ) in the horizontal plane. Saccades made to the remembered locations of targets presented during background motion (illusion) were significantly (P < 0.05) more inaccurate than with the background stationary (control) in 9 of 10 subjects for lights and in 6 of 10 subjects for sounds. As a group, the median change in errors due to the Duncker illusion was approximately 2.5 times greater for visual compared with acoustic targets (P < 0.001). These findings are consistent with electrophysiological studies which have shown that neurons in the primate lateral intraparietal area (LIP) may respond to both visual and auditory targets and these neurons are also influenced by the Duncker illusion during programming of memory-guided saccades.

Vertical nystagmus in normal subjects: effects of head position, nicotine and scopolamine.

We measured gaze stability in darkness of four normal humans using the search coil technique. Subjects were tested first with their heads erect, and then with their heads positioned 180 degrees upside-down. In each position, subjects held their head stationary for one minute, and then actively performed pitch rotations for 20 sec. All subjects showed sustained chin-beating nystagmus in the upside-down position. Each subject showed a significant increase of slow-phase velocity directed towards their brow after 40 sec in the inverted versus erect position. Pitch head rotation had little effect on subsequent nystagmus, except for transient reversal in one subject. The sustained changes of vertical eye drifts induced by 180 deg change of head position suggest that otolithic factors may contribute to vertical nystagmus in normals. The subjects were retested after wearing a nicotine patch for 2 hours. In three subjects, nicotine induced brow-beating nystagmus; adopting a head-hanging position increased this nystagmus in two subjects. In a third session, subjects were tested after wearing a scopolamine patch for 2 hours; results were generally similar to the control condition. We conclude that normal subjects may show chin-beating ("downbeating") nystagmus in a head-hanging position in darkness, reflecting a normal, physiological change in otolithic inputs brought about by the head orientation.

Conjugate ocular oscillations during shifts of the direction and depth of visual fixation.

PURPOSE: To characterize dynamic properties of combined saccade-vergence eye movements that occur as the point of visual fixation is shifted between objects lying in different directions and at different depths. METHODS: Using the scleral search-coil technique, eye movements were measured in 10 normal subjects as they made voluntary, disjunctive gaze shifts comprising a range of saccades and vergence movements. RESULTS: By analyzing eye acceleration records, the authors identified small-amplitude (0.2-0.7 degrees), high-frequency (23-33 Hz), conjugate horizontal oscillations of the eyes during the vergence movement that followed the initial saccade. When the shift of the fixation point required a large vergence component (17 degrees , every subject showed these oscillations; they were present in approximately a third of responses. Approximately 5% of responses showed oscillations that had horizontal and vertical components. Oscillations were less prominent with shifts that had smaller vergence components and were absent after saccades made between targets located at optical infinity. CONCLUSIONS: These findings suggest that a common mechanism gates both the saccadic and vergence components of disjunctive gaze shifts, a likely candidate being the pontine omnipause neurons. When a saccade is immediately followed by a prolonged vergence movement, the omnipause neurons remain silent, leading to small-amplitude saccadic oscillations. Shifts in the point of visual fixation that require a large vergence movement may be a useful experimental strategy to induce saccadic oscillations.

Tests of two hypotheses to account for different-sized saccades during disjunctive gaze shifts.

Rapid shifts of the point of visual fixation between objects that lie in different directions and at different depths require disjunctive eye movements. We tested whether the saccadic component of such movements is equal for both eyes (Hering's law) or is unequal. We compared the saccadic pulses of abducting and adducting movements when horizontal gaze was shifted from a distant to a near target aligned on the visual axis of one eye (Müller paradigm) in ten normal subjects. We similarly compared horizontal saccades made between two distant targets lying in the same field of movement as during the Müller paradigm tests, and between targets lying symmetrically on either side of the midline, at near side of the midline, at near or far. We measured the ratio of the amplitude of the movements of each eye in corresponding directions due to the saccadic component, as well as corresponding ratios of peak velocity and peak acceleration. In response to a Müller test paradigm requiring about 17 degrees of vergence, the change in position of the unaligned eye was typically twice the size of the corresponding movement of the aligned eye. The ratio of peak velocities for the unaligned/aligned eyes was about 1.5, which was greater than for saccades made between distant targets. The ratio of peak acceleration for unaligned/aligned eyes was about 1.0 during shifts from near to far and about 1.3 for shifts from far to near, these values being similar to corresponding ratios for saccades between distant targets. These measurements of peak acceleration indicate that the saccadic pulses sent to each eye during the Müller paradigm are more equal than would be deduced by comparing the changes in eye position. We retested five subjects to compare directly the peak acceleration of saccades made during the Müller paradigm with similar-sized "conjugate" saccades made between targets at optical infinity. Saccades made during the Müller paradigm were significant slower (P < 0.005) than similar-sized conjugate saccades; this indicated that the different-sized movements during Müller paradigm are not simply due differences in saccadic pulse size but are also influenced by the concurrent vergence movement. A model for saccade-vergence interactions, which incorporates equal saccadic pulses for each eye, and differing contributions from convergence and divergence, accounts for many of these findings.