Based on physiological results, both neural and oculomotor, I propose the following simplified “imbalance principle” of nystagmus generation.
Nystagmus Is Due to an Asymmetry of Average Neural Activity between the Two Vestibular Nuclei (VN)
Evidence for this “imbalance principle” has come from the results of recordings of guinea pig single neurons in the two vestibular nuclei (VN) after TUVL [14
]. Acutely after TUVL there is a large imbalance in the average neural activity between the two VN, with the VN neurons on the lesioned side having a low or absent resting discharge, whereas neurons in the VN on the remaining healthy side having a normal or even elevated, average resting discharge. Thus, there is a major imbalance in average neural activity of the two VN. Corresponding to this neural imbalance, alert guinea pigs at this acute time after TUVL, show a strong nystagmus with quick phases beating away from the lesioned side [16
]. The activity of the stronger VN drives the SPV in a direction opposite to the stronger VN and this SPV is interspersed with quick phases (QPs) directed away from the lesioned side. Over about 30 h after TUVL the asymmetry in average resting activity between the two VN progressively diminishes [14
], and correspondingly, there is a progressive diminution of the nystagmus.
In healthy subjects at rest, it is assumed that the average neural activity is about the same in both vestibular nuclei (VN) since there is no nystagmus (Figure 3
A). If the average neural activity in one VN is greater than the other VN there will be a nystagmus with slow phases directed away from the VN with the larger average neural activity (the side of healthy ear) and QPs directed away from (opposite to) the side of the VN with the lower average neural activity (the affected ear). Such an asymmetry or imbalance or inequality in average neural activity can arise because of reduced input to the VN from the peripheral vestibular system of one ear or increased neural input to the other ear (Figure 3
B,C). Conditions which can cause such an average imbalance are e.g., horizontal angular acceleration (Figure 3
B) or unilateral vestibular loss (Figure 3
C). Such an imbalance between the VN activity will result in nystagmus with quick phases beating away from the side with the lower average neural activity.
This VN imbalance principle also explains why mastoid vibration stimulation of either mastoid in healthy subjects does not cause nystagmus; mastoid vibration will activate canal receptors in both labyrinths simultaneously because of the very effective transmission of vibration across the skull [17
], so both VN will have increased average neural activity but there will be no imbalance in average neural activity between the two VN and thus no nystagmus (Figure 3
D). This simultaneous activation of both horizontal canals is a unique stimulus—it can never happen during natural head movements. Cohen et al. showed simultaneous bilateral electrical stimulation of both horizontal canal nerves in cats caused no horizontal eye movement [5
] which they argued occurred because opposing eye muscles were simultaneously activated and so eye movement was cancelled.
This imbalance principle also explains why mastoid vibration causes SVIN after a patient with TUVL has compensated and so has minimal or absent spontaneous nystagmus (Figure 3
E). That absence of nystagmus implies that the average neural activity in both VN is about equal. The 100 Hz unilateral mastoid vibration stimulus on the healthy side will activate semicircular canal receptors and irregular afferents projecting to and activating the VN on the healthy side. However, there is no afferent neural input from the opposite (lesioned) labyrinth, so there is an imbalance in average neural activity between the two VN resulting in nystagmus with QPs directed away from the lesioned side. Stimulation of the mastoid of the affected ear will cause the vibration stimulus (represented by three lines near right labyrinth in D–H) to be transmitted through the skull very effectively and so this contralateral vibration stimulation will activate the canal and otolith receptors on the remaining (healthy side) and so will also result in an average neural imbalance between the two VN and so SVIN in the same direction for stimulation of either mastoid.
Semicircular canal neurons show progressively poorer response to vibration as the vibration frequency is increased above 100 Hz (Figure 2
D. However, a dehiscence of the semicircular canal (SCD) increases the fluid displacement caused by the stimulus [18
]. so high vibration frequencies such as 500 Hz will generate fluid displacements large enough to deflect the cilia and so sufficient to activate previously unresponsive afferents at 500 Hz [3
]. Semicircular canal neurons which were unresponsive to 500 Hz vibration with an intact bony labyrinth, respond vigorously to vibration at 500 Hz (and higher frequencies) after an experimental SCD [3
]. Correspondingly human SCD patients show SVIN to frequencies higher than the 100 Hz cut off in TUVL patients with intact bony labyrinths [8
This imbalance principle also explains why in some SCD patients (Figure 3
F) and some patients with MD (Figure 3
G), vibration causes a reverse SVIN with the quick phases of SVIN beating towards the affected ear (the ear with the SCD or MD—the labyrinth circled in Figure 3
) instead of away from the affected ear as occurs after TUVL. As a result of the enhanced semicircular canal neural response to vibration after SCD, unilateral mastoid vibration of a patient with an SCD will generate an imbalance between the two VN but now the VN on the side of the ear with the SCD will have a higher average firing rate than VN on the opposite side so, according to the imbalance principle, the quick phases will be driven towards the ear with the SCD since the VN on that side has the higher average neural activity (Figure 3
A similar account probably applies in some cases of MD; in the paralytic phase, MD may reduce the response of afferent neurons in the affected ear (and so result in imbalance of VN activity and SVIN with QPs away from the affected ear), but in the irritative phase the disease may enhance the response of afferent neurons [20
] and so result in nystagmus with QPs towards the affected ear. In both SCD and the irritative phase of MD, it is, on this account, an enhanced response which causes the imbalance in neural activity between the two VN and so drives QPs towards the affected ear (Figure 3
Physically blocking the membranous duct of a semicircular canal (called canal occlusion) reduces the capacity of the canal receptors and afferents to respond to angular acceleration stimulation and so the gain of the human vestibulo-ocular reflex is significantly attenuated [23
]. It is highly likely that the occlusion of a fully encased semicircular canal also reduces the response to low frequency skull vibration (although definite evidence of the effect of canal occlusion on the response of primary canal afferents to 100 Hz vibration (with intact bony labyrinth) has not yet been reported). So, the mastoid vibration in patients with unilateral semicircular canal occlusion would be expected to be attenuated and so result in a neural imbalance at the level of the VN. which would lead to SVIN with QPs away from the side of the occluded canal as has been reported [6
] (Figure 3