Saccades in progressive supranuclear palsy - maladapted, irregular, curved, and slow.

Abstract

Slowed and curved rapid eye movements, saccades, are the well-known features of progressive supranuclear palsy (PSP). We hypothesized that the saccades in PSP are not only slow and curved, but they are also irregular and have timing deficits. We tested this hypothesis in 12 patients with PSP by measuring vertical and horizontal visually guided saccades using a limbus tracker. Both, horizontal and vertical saccades were slow and had irregular trajectory and velocity profiles, but deficits were much more robust in vertical saccades. The irregularity in the saccade velocity was due to premature interruptions that either completely stopped the eyes, or moved the eyes at much slower velocity along or in the opposite direction of the ongoing saccade. The direction of the eyes' trajectory was often changed after the interruption. We simulated a conductance based single-compartment model of the burst neurons embedded in local feedback circuit for saccade generation. This model mimicked anatomical and physiological realism, while allowing the liberty to selectively change the activation of individual burst neurons or the pause neurons. The PSP saccades were comparable to the simulations during reduced activity of the inhibitory and excitatory burst neurons. PSP saccades are due to the paucity in burst generation at the excitatory and imprecise timing signal from the inhibitory burst neurons. Premature discharge of the inhibitory burst neuron further leads to breaks in the saccade trajectory, and maladaptive superior colliculus activity leading to aberrant saccades changing the intended trajectory of the ongoing saccade.