Unidirectional rotations produce asymmetric changes in horizontal VOR gain before and after unilateral labyrinthectomy in macaques

Abstract

Unilateral vestibular lesions cause marked asymmetry in the horizontal vestibulo-ocular reflex (VOR) during rapid head rotations, with VOR gain being lower for head rotations toward the lesion than for rotations in the opposite direction. Reducing this gain asymmetry by enhancing ipsilesional responses would be an important step toward improving gaze stability following vestibular lesions. To that end, there were two goals in this study. First, we wanted to determine whether we could selectively increase VOR gain in only one rotational direction in normal monkeys by exposing them to a training session comprised of a 3-h series of rotations in only one direction (1,000°/s² acceleration to a plateau of 150°/s for 1 s) while they wore 1.7 × magnifying spectacles. Second, in monkeys with unilateral vestibular lesions, we designed a paradigm intended to reduce the gain asymmetry by rotating the monkeys toward the side of the lesion in the same way as above but without spectacles. There were three main findings (1) unidirectional rotations with magnifying spectacles result in gain asymmetry in normal monkeys, (2) gain asymmetry is reduced when animals are rotated towards the side of the labyrinthectomy via the ipsilesional rotation paradigm, and (3) repeated training causes lasting reduction in VOR gain asymmetry.

Figure 1

Responses to rightward (positive) and leftward (negative) yaw head rotations (dashed, black) (1000°/s² to a peak head velocity of 150°/s). Eye responses are shown with the fast phases removed. Eye responses in the dark before training are in black. Monkey was then fitted with 1.7 X magnifying spectacles and trained with the unidirectional training paradigm in the counterclockwise direction. Post training eye responses are shown in gray.

Figure 2

Responses to ipsilesional (positive) and contralesional (negative) yaw head rotations (dashed, black) (1000°/sec² to a peak head velocity of 150°/sec). Eye responses are shown with the fast phases removed. Eye responses in the dark before the ipsilesional training paradigm are in black. Monkey 1 was trained with the ipsilesional training paradigm in the ipsilesional direction (training paradigm 2). Post training eye responses are shown in gray.

Figure 3

Data after the labyrinthectomy from each of the 3 animals before and after ipsilesional training. A (monkey 1), C (monkey 2) and E (monkey 3) show the contralesional G_A, ipsilesional G_A and SG_A for each monkey over the first 2 months after the labyrinthectomy. B (monkey 1), D (monkey 2) and F (monkey 3) show the contralesional G_V, ipsilesional G_V and SG_V for each monkey. Contralesional gain is denoted in black and ipsilesional gain is denoted in gray. S_GA and S_GV are shown with a dashed line. Dashed boxes denote the gains tested immediately before and after each ipsilesional training session. Pre refers to the gain tested before the ipsilesional training session and post refers to the gain values tested immediately after the ipsilesional training session. In every training session animals were trained by rotating them in the ipsilesional direction without magnifying spectacles. An asterisk denotes if there was a reduction in asymmetry after each ipsilesional training session (p < 0.05). In all animals there is was a general decline in the asymmetry over time.

Figure 4

Responses before and after the bidirectional training for each monkey. A (monkey 1), C (monkey 2) and E (monkey 3) show the contralesional G_A, ipsilesional G_A and SG_A for each monkey during the 3^rd month after the labyrinthectomy. B (monkey 1), D (monkey 2) and F (monkey 3) show the contralesional G_V, ipsilesional G_V and SG_V for each monkey. Contralesional gain is denoted in black and ipsilesional gain is denoted in gray. S_GA and S_GV are shown with a dashed line. Dashed boxes denote the gains tested immediately before and after each bidirectional training session. Pre refers to the gain tested before the bidirectional training session and post refers to the gain values tested immediately after the bidirectional training session. In every training session animals were trained by rotating them randomly in the ipsilesional and contralesional directions without magnifying spectacles. An asterisk denotes if there was a reduction in asymmetry after each bidirectional training session (p < 0.05).

Figure 5

Average long-term change in G_A (A) and G_V (B) for each labyrinthectomized monkey after the ipsilesional adaptation paradigm. Bars in black represent the gains in the contralesional direction. White bars represent the gain in the ipsilesional direction. Gray bars represent SG_A in A and SG_V in B. Before ipsilesional training there is a marked asymmetry in SG_A 7 days after the lesion. This asymmetry is still evident 4-5 weeks after the lesion (p > 0.1). At 7 weeks after the lesion, after 3-4 ipsilesional adaptation sessions, there is a marked reduction in SG_A (p < 0.01). This reduction in SG_A persists when tested 3 days later (p < 0.01). Before ipsilesional training there is a marked asymmetry in SG_V 7 days after the lesion. This asymmetry is still evident but markedly reduced 4-5 weeks after the lesion (p < 0.015). At 7 weeks after the lesion, after 3-4 ipsilesional adaptation sessions, there is a reduction in SG_V (p < 0.01). This reduction in SG_V, however, is not different from SG_V before the ipsilesional training sessions when tested 3 days later (p > 0.07).