Alexander's Law During High-Speed, Yaw-Axis Rotation: Adaptation or Saturation?

Objective: Alexander's law (AL) states the intensity of nystagmus increases when gaze is toward the direction of the quick phase. What might be its cause? A gaze-holding neural integrator (NI) that becomes imperfect as the result of an adaptive process, or saturation in the discharge of neurons in the vestibular nuclei?Methods: We induced nystagmus in normal subjects using a rapid chair acceleration around the yaw (vertical) axis to a constant velocity of 200°/second [s] and then, 90 s later, a sudden stop to induce post-rotatory nystagmus (PRN). Subjects alternated gaze every 2 s between flashing LEDs (right/left or up/down). We calculated the change in slow-phase velocity (ΔSPV) between right and left gaze when the lateral semicircular canals (SCC) were primarily stimulated (head upright) or, with the head tilted to the side, stimulating the vertical and lateral SCC together.Results: During PRN AL occurred for horizontal eye movements with the head upright and for both horizontal and vertical components of eye movements with the head tilted. AL was apparent within just a few seconds of the chair stopping when peak SPV of PRN was reached. When slow-phase velocity of PRN faded into the range of 6–18°/s AL could no longer be demonstrated.Conclusions: Our results support the idea that AL is produced by asymmetrical responses within the vestibular nuclei impairing the NI, and not by an adaptive response that develops over time. AL was related to the predicted plane of eye rotations in the orbit based on the pattern of SCC activation.

Gaze Holding and the Neural Integrator

This chapter reviews the neural network that temporally integrates premotor, velocity-coded signals to achieve tonic contraction of the extraocular muscles to hold the eyes at an eccentric position in the orbits. The mechanical properties of the eye and its supporting tissues are quantified and related to the pulse-slide-step neural command for a saccadic change in eye position. The anatomical substrate and neuropharmacology of the neural integrator is reviewed, including nucleus prepositus hypoglossi, interstitial nucleus of Cajal and cerebellum. Mathematical and animal models for the neural integrator are discussed, addressing points about how a leaky or unstable integrator may arise. Clinical and laboratory evaluation of gaze holding is summarized. Effects of experimentally inactivating the neural integrator are compared with clinical disorders affecting gaze holding, including a discussion of the pathogenesis of gaze-evoked nystagmus and Alexander’s law. Compensatory mechanisms for a leaky neural integrator are discussed, including centripetal, rebound, and gaze-evoked nystagmus.

A Unifying Model-Based Hypothesis for the Diverse Waveforms of Infantile Nystagmus Syndrome

We expanded the original behavioral Ocular Motor System (OMS) model for Infantile Nystagmus Syndrome (INS) by incorporating common types of jerk waveforms within a unifying mechanism. Alexander’s law relationships were used to produce desired INS null positions and sharpness. At various gaze angles, these relationships influenced the IN slow-phase amplitudes differently, thereby mimicking the gaze-angle effects of INS patients. Transitions from pseudopendular with foveating saccades to jerk waveforms required replacing braking saccades with foveating fast phases and adding a resettable neural integrator in the pursuit pre-motor circuitry. The robust simulations of accurate OMS behavior in the presence of diverse INS waveforms demonstrate that they can all be generated by a loss of pursuit-system damping, supporting this hypothetical origin.

Alexander's Law and the Oculomotor Neural Integrator: Three-Dimensional Eye Velocity in Patients With an Acute Vestibular Asymmetry

According to Alexander's law (AL), the slow phase velocity of nystagmus of vestibular origin is dependent on horizontal position, with lower velocity when gaze is directed in the slow compared with the fast phase direction. Adaptive changes in the velocity-to-position neural integrator are thought to cause AL. Although these changes have been described for the horizontal neural integrator, nystagmus often includes vertical and torsional components, but the adaptive abilities of the vertical and torsional integrators have not been investigated. We measured 11 patients with a peripheral vestibular asymmetry and used second-order equations to describe how velocity varied with position. Horizontal velocity changed with horizontal position in accordance with AL and the second-order term for horizontal position was also significant. Whereas velocity decreased in the slow phase direction, it was relatively unchanged >10° into the fast phase direction. Vertical velocity was also highest in the vertical fast phase direction and the second-order term for vertical position was also significant, in that vertical velocity increased in the vertical fast phase direction, but was unchanging in the slow phase direction. Torsional velocity varied linearly with horizontal, but not vertical, position. These results show that the horizontal and vertical oculomotor neural integrators react to altered vestibular input by maintaining different integrating time constants depending on gaze direction.

Alexander's Law Revisited

Background: It is a common occurrence in the balance function laboratory to evaluate patients in the post-acute period following unilateral vestibular system impairment. It is important to be able to differentiate spontaneous nystagmus (SN) emanating from peripheral vestibular system impairments from asymmetric gaze-evoked nystagmus (GEN) that originates from central ocular motility impairment. Purpose: To describe the three elements of Alexander's Law (AL) that have been used to define SN from unilateral peripheral impairment. Additionally, a fourth element is described (i.e., augmentation of spontaneous nystagmus from unilateral peripheral vestibular system impairment) that differentiates nystagmus of peripheral vestibular system origin from nystagmus that originates from a central eye movement disorder. Research Design: Case reports Study Sample: Case data were obtained from two patients both showing a nystagmus that followed AL. Intervention: None Data Collection And Analysis: Videonystagmography (VNG), rotational, vestibular evoked myogenic potential (VEMP), and neuro-imaging studies were presented for each patient. Results: The nystagmus in Case 1 occurred as a result of a unilateral, peripheral, vestibular system impairment. The nystagmus was direction-fixed and intensified in the vision-denied condition. The nystagmus in Case 2, by appearance identical to that in Case 1, was an asymmetric gaze-evoked nystagmus originating from a space-occupying lesion in the cerebello-pontine angle. Unlike Case 1, the nystagmus did not augment in the vision-denied condition. Conclusions: Although nystagmus following AL usually occurs in acute peripheral vestibular system impairment, it can occur in cases of central eye movement impairment. The key element is whether the SN that follows AL is attenuated or augmented in the vision-denied condition. The SN from a unilateral peripheral vestibular system impairment should augment in the vision denied condition. An asymmetric GEN will either not augment, decrease in magnitude, or disappear entirely, in the vision-denied condition.