Our main finding is that the speed and size of vertical saccades were influenced by the eye position at which the movement starts in all of our PSP patients. The pattern of this dependence of saccadic metrics on orbital position varied from patient to patient, but was generally different from the mild effect of upward gaze on upward saccades in healthy subjects noted in a prior study3
and confirmed in our control subjects (). These findings raise questions about the pathogenesis and clinical significance of the dependency of vertical saccades on the starting eye position.
Current models for the brainstem generation of saccades are based on the electrophysiological properties of burst neurons.11,12
Excitatory burst neurons for vertical saccades lie in the RIMLF;13
their discharge properties correlate closely with the saccades that they generate. The rate of discharge (spikes per second) corresponds with eye speed, and the total number of spikes in the burst corresponds with the total change in eye position. Application of these electrophysiological studies, and of current models they engendered,14
indicate that the number of spikes generated by burst neurons dictates the size of saccades, rather than any specified eye position in the orbit. Our findings argue that such a model is incomplete and requires modification to incorporate the influence of either starting eye position in the orbit or vestibular inputs, or both.
Could the effects that we noted () be accounted for by orbital biomechanical factors? This certainly bears consideration in older individuals, such as our cohort, for whom orbital biomechanical properties show substantial changes, resulting inprogressive limitation of the vertical range of eye movements, especially upward, after the age of 60 years.6
Several of our findings argue against this being the main determinant of orbital dependency of saccades in PSP. First, reduction of saccade amplitude and peak velocity was often bidirectional, whereas a unidirectional effect would be expected from mechanical factors, such as the reported progressive slowing of upward saccades as starting position moved into the upward field.3
Second, it is well known that even when vertical saccades can no longer be generated, PSP patients may still show a full range of vertical movements in response to pitch head rotations.
Thus, the evidence points strongly to a central cause for the orbital dependency of saccadic metrics in PSP. One candidate to account for this is the interstitial nucleus of Cajal, which is important for vertical gaze control and which is affected in this disorder.15
Inactivation of the INC limits the range of vertical saccades without substantially affecting their velocity;8
such a restriction of range might then be superimposed on the slowing and hypometria that follows RIMLF lesions.7
The INC receives inputs from the vestibular system, including the otoliths, which might determine the range and speed of vertical eye movements.16,17
Changing the orbital starting position for testing is much more easily achieved in PSP by head rotation than by patients’ attempts to direct their gaze at a visual target. Nonetheless, in PSP–PD 8 we were able to compare the effects of starting position achieved by either head rotation or a shift of the positions of the visual stimuli; effects on saccade amplitude and peak velocity were quantitatively similar. Taken together, these results challenge simple “displacement” models for the brainstem generation of saccades,14
and suggest that the discharge of burst neurons or components of the neural integrator are influenced by current eye position or head position, as well as the desired change in eye position.
For clinicians, these results have three important implications. First, testing of vertical saccades should be performed with the eyes in three starting positions, corresponding to the central, upper, and lower field of gaze; our study indicates that saccade behavior may change according to the field of gaze in which the movements are made. Second, there is a need to extend the present studies to other disorders that impair vertical gaze to determine whether affected patients also show an orbital dependency of their saccadic palsy.Finally, the effect of different starting eye positions on saccade amplitude and speed needs to be taken into account in any drug trial for PSP that uses eye movements as a therapeutic index.